Megalencephalic leukoencephalopathy with subcortical cysts: Characterization of disease variants.

PubMed

Hamilton, Eline M C; Tekturk, Pinar; Cialdella, Fia; van Rappard, Diane F; Wolf, Nicole I; Yalcinkaya, Cengiz; Çetinçelik, Ümran; Rajaee, Ahmad; Kariminejad, Ariana; Paprocka, Justyna; Yapici, Zuhal; Bošnjak, Vlatka Mejaški; van der Knaap, Marjo S

2018-04-17

To provide an overview of clinical and MRI characteristics of the different variants of the leukodystrophy megalencephalic leukoencephalopathy with subcortical cysts (MLC) and identify possible differentiating features. We performed an international multi-institutional, cross-sectional observational study of the clinical and MRI characteristics in patients with genetically confirmed MLC. Clinical information was obtained by questionnaires for physicians and retrospective chart review. We included 204 patients with classic MLC, 187 of whom had recessive mutations in MLC1 (MLC1 variant) and 17 in GLIALCAM (MLC2A variant) and 38 patients with remitting MLC caused by dominant GLIALCAM mutations (MLC2B variant). We observed a relatively wide variability in neurologic disability among patients with classic MLC. No clinical differences could be identified between patients with MLC1 and MLC2A. Patients with MLC2B invariably had a milder phenotype with preservation of motor function, while intellectual disability and autism were relatively frequent. Systematic MRI review revealed no MRI features that distinguish between MLC1 and MLC2A. Radiologic improvement was observed in all patients with MLC2B and also in 2 patients with MLC1. In MRIs obtained in the early disease stage, absence of signal abnormalities of the posterior limb of the internal capsule and cerebellar white matter and presence of only rarefied subcortical white matter instead of true subcortical cysts were suggestive of MLC2B. Clinical and MRI features did not distinguish between classic MLC with MLC1 or GLIALCAM mutations. Absence of signal abnormalities of the internal capsule and cerebellar white matter are MRI findings that point to the remitting phenotype. Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stathakis, S; Defoor, D; Linden, P

Purpose: To study the frequency of Multi-Leaf Collimator (MLC) leaf failures, investigate methods to predict them and reduce linac downtime. Methods: A Varian HD120 MLC was used in our study. The hyperterminal MLC errors logged from 06/2012 to 12/2014 were collected. Along with the hyperterminal errors, the MLC motor changes and all other MLC interventions by the linear accelerator engineer were recorded. The MLC dynalog files were also recorded on a daily basis for each treatment and during linac QA. The dynalog files were analyzed to calculate root mean square errors (RMS) and cumulative MLC travel distance per motor. Anmore » in-house MatLab code was used to analyze all dynalog files, record RMS errors and calculate the distance each MLC traveled per day. Results: A total of 269 interventions were recorded over a period of 18 months. Of these, 146 included MLC motor leaf change, 39 T-nut replacements, and 84 MLC cleaning sessions. Leaves close to the middle of each side required the most maintenance. In the A bank, leaves A27 to A40 recorded 73% of all interventions, while the same leaves in the B bank counted for 52% of the interventions. On average, leaves in the middle of the bank had their motors changed approximately every 1500m of travel. Finally, it was found that the number of RMS errors increased prior to an MLC motor change. Conclusion: An MLC dynalog file analysis software was developed that can be used to log daily MLC usage. Our eighteen-month data analysis showed that there is a correlation between the distance an MLC travels, the RMS and the life of the MLC motor. We plan to use this tool to predict MLC motor failures and with proper and timely intervention, reduce the downtime of the linac during clinical hours.« less

Messier: A Detailed NVM-Based DIMM Model for the SST Simulation Framework.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Awad, Amro; Voskuilen, Gwendolyn Renae; Rodrigues, Arun F.

2017-02-01

DRAM technology is the main building block of main memory, however, DRAM scaling is becoming very challenging. The main issues for DRAM scaling are the increasing error rates with each new generation, the geometric and physical constraints of scaling the capacitor part of the DRAM cells, and the high power consumption caused by the continuous need for refreshing cell values. At the same time, emerging Non- Volatile Memory (NVM) technologies, such as Phase-Change Memory (PCM), are emerging as promising replacements for DRAM. NVMs, when compared to current technologies e.g., NAND-based ash, have latencies comparable to DRAM. Additionally, NVMs are non-volatile,more » which eliminates the need for refresh power and enables persistent memory applications. Finally, NVMs have promising densities and the potential for multi-level cell (MLC) storage.« less

A multi-characteristic based algorithm for classifying vegetation in a plateau area: Qinghai Lake watershed, northwestern China

NASA Astrophysics Data System (ADS)

Ma, Weiwei; Gong, Cailan; Hu, Yong; Li, Long; Meng, Peng

2015-10-01

Remote sensing technology has been broadly recognized for its convenience and efficiency in mapping vegetation, particularly in high-altitude and inaccessible areas where there are lack of in-situ observations. In this study, Landsat Thematic Mapper (TM) images and Chinese environmental mitigation satellite CCD sensor (HJ-1 CCD) images, both of which are at 30m spatial resolution were employed for identifying and monitoring of vegetation types in a area of Western China——Qinghai Lake Watershed(QHLW). A decision classification tree (DCT) algorithm using multi-characteristic including seasonal TM/HJ-1 CCD time series data combined with digital elevation models (DEMs) dataset, and a supervised maximum likelihood classification (MLC) algorithm with single-data TM image were applied vegetation classification. Accuracy of the two algorithms was assessed using field observation data. Based on produced vegetation classification maps, it was found that the DCT using multi-season data and geomorphologic parameters was superior to the MLC algorithm using single-data image, improving the overall accuracy by 11.86% at second class level and significantly reducing the "salt and pepper" noise. The DCT algorithm applied to TM /HJ-1 CCD time series data geomorphologic parameters appeared as a valuable and reliable tool for monitoring vegetation at first class level (5 vegetation classes) and second class level(8 vegetation subclasses). The DCT algorithm using multi-characteristic might provide a theoretical basis and general approach to automatic extraction of vegetation types from remote sensing imagery over plateau areas.

Evaluation of dosimetric effect caused by slowing with multi-leaf collimator (MLC) leaves for volumetric modulated arc therapy (VMAT)

PubMed Central

Wang, Iris Z.; Kumaraswamy, Lalith K.; Podgorsak, Matthew B.

2016-01-01

Background This study is to report 1) the sensitivity of intensity modulated radiation therapy (IMRT) QA method for clinical volumetric modulated arc therapy (VMAT) plans with multi-leaf collimator (MLC) leaf errors that will not trigger MLC interlock during beam delivery; 2) the effect of non-beam-hold MLC leaf errors on the quality of VMAT plan dose delivery. Materials and methods. Eleven VMAT plans were selected and modified using an in-house developed software. For each control point of a VMAT arc, MLC leaves with the highest speed (1.87-1.95 cm/s) were set to move at the maximal allowable speed (2.3 cm/s), which resulted in a leaf position difference of less than 2 mm. The modified plans were considered as ‘standard’ plans, and the original plans were treated as the ‘slowing MLC’ plans for simulating ‘standard’ plans with leaves moving at relatively lower speed. The measurement of each ‘slowing MLC’ plan using MapCHECK®2 was compared with calculated planar dose of the ‘standard’ plan with respect to absolute dose Van Dyk distance-to-agreement (DTA) comparisons using 3%/3 mm and 2%/2 mm criteria. Results All ‘slowing MLC’ plans passed the 90% pass rate threshold using 3%/3 mm criteria while one brain and three anal VMAT cases were below 90% with 2%/2 mm criteria. For ten out of eleven cases, DVH comparisons between ‘standard’ and ‘slowing MLC’ plans demonstrated minimal dosimetric changes in targets and organs-at-risk. Conclusions For highly modulated VMAT plans, pass rate threshold (90%) using 3%/3mm criteria is not sensitive in detecting MLC leaf errors that will not trigger the MLC leaf interlock. However, the consequential effects of non-beam hold MLC errors on target and OAR doses are negligible, which supports the reliability of current patient-specific IMRT quality assurance (QA) method for VMAT plans. PMID:27069458

Automatic detection of MLC relative position errors for VMAT using the EPID-based picket fence test

NASA Astrophysics Data System (ADS)

Christophides, Damianos; Davies, Alex; Fleckney, Mark

2016-12-01

Multi-leaf collimators (MLCs) ensure the accurate delivery of treatments requiring complex beam fluences like intensity modulated radiotherapy and volumetric modulated arc therapy. The purpose of this work is to automate the detection of MLC relative position errors  ⩾0.5 mm using electronic portal imaging device-based picket fence tests and compare the results to the qualitative assessment currently in use. Picket fence tests with and without intentional MLC errors were measured weekly on three Varian linacs. The picket fence images analysed covered a time period ranging between 14-20 months depending on the linac. An algorithm was developed that calculated the MLC error for each leaf-pair present in the picket fence images. The baseline error distributions of each linac were characterised for an initial period of 6 months and compared with the intentional MLC errors using statistical metrics. The distributions of median and one-sample Kolmogorov-Smirnov test p-value exhibited no overlap between baseline and intentional errors and were used retrospectively to automatically detect MLC errors in routine clinical practice. Agreement was found between the MLC errors detected by the automatic method and the fault reports during clinical use, as well as interventions for MLC repair and calibration. In conclusion the method presented provides for full automation of MLC quality assurance, based on individual linac performance characteristics. The use of the automatic method has been shown to provide early warning for MLC errors that resulted in clinical downtime.

Myosin‑II heavy chain and formin mediate the targeting of myosin essential light chain to the division site before and during cytokinesis

PubMed Central

Feng, Zhonghui; Okada, Satoshi; Cai, Guoping; Zhou, Bing; Bi, Erfei

2015-01-01

MLC1 is a haploinsufficient gene encoding the essential light chain for Myo1, the sole myosin‑II heavy chain in the budding yeast Saccharomyces cerevisiae. Mlc1 defines an essential hub that coordinates actomyosin ring function, membrane trafficking, and septum formation during cytokinesis by binding to IQGAP, myosin‑II, and myosin‑V. However, the mechanism of how Mlc1 is targeted to the division site during the cell cycle remains unsolved. By constructing a GFP‑tagged MLC1 under its own promoter control and using quantitative live‑cell imaging coupled with yeast mutants, we found that septin ring and actin filaments mediate the targeting of Mlc1 to the division site before and during cytokinesis, respectively. Both mechanisms contribute to and are collectively required for the accumulation of Mlc1 at the division site during cytokinesis. We also found that Myo1 plays a major role in the septin‑dependent Mlc1 localization before cytokinesis, whereas the formin Bni1 plays a major role in the actin filament–dependent Mlc1 localization during cytokinesis. Such a two‑tiered mechanism for Mlc1 localization is presumably required for the ordered assembly and robustness of cytokinesis machinery and is likely conserved across species. PMID:25631819

An increase or a decrease in myosin II phosphorylation inhibits macrophage motility

PubMed Central

1991-01-01

Myosin II purified from mammalian non-muscle cells is phosphorylated on the 20-kD light chain subunit (MLC20) by the Ca2+/calmodulin-dependent enzyme myosin light chain kinase (MLCK). The importance of MLC20 phosphorylation in regulating cell motility was investigated by introducing either antibodies to MLCK (MK-Ab) or a Ca2+/calmodulin- independent, constitutively active form of MLCK (MK-) into macrophages. The effects of these proteins on cell motility were then determined using a quantitative chemotaxis assay. Chemotaxis is significantly diminished in macrophages containing MK-Ab compared to macrophages containing control antibodies. Moreover, there is an inverse relationship between the number of cells that migrate and the amount of MK-Ab introduced into cells. Interestingly, there is also an inverse relationship between the number of cells that migrate and the amount of MK- introduced into cells. Other experiments demonstrated that MK-Ab decreased intracellular MLC20 phosphorylation while MK- increased MLC20 phosphorylation. MK- also increased the amount of myosin associated with the cytoskeleton. These data demonstrate that the regulation of MLCK is an important aspect of cell motility and suggest that MLC20 phosphorylation must be maintained within narrow limits during translational motility by mammalian cells. PMID:2071674

TH-AB-202-02: Real-Time Verification and Error Detection for MLC Tracking Deliveries Using An Electronic Portal Imaging Device

DOE Office of Scientific and Technical Information (OSTI.GOV)

J Zwan, B; Central Coast Cancer Centre, Gosford, NSW; Colvill, E

2016-06-15

Purpose: The added complexity of the real-time adaptive multi-leaf collimator (MLC) tracking increases the likelihood of undetected MLC delivery errors. In this work we develop and test a system for real-time delivery verification and error detection for MLC tracking radiotherapy using an electronic portal imaging device (EPID). Methods: The delivery verification system relies on acquisition and real-time analysis of transit EPID image frames acquired at 8.41 fps. In-house software was developed to extract the MLC positions from each image frame. Three comparison metrics were used to verify the MLC positions in real-time: (1) field size, (2) field location and, (3)more » field shape. The delivery verification system was tested for 8 VMAT MLC tracking deliveries (4 prostate and 4 lung) where real patient target motion was reproduced using a Hexamotion motion stage and a Calypso system. Sensitivity and detection delay was quantified for various types of MLC and system errors. Results: For both the prostate and lung test deliveries the MLC-defined field size was measured with an accuracy of 1.25 cm{sup 2} (1 SD). The field location was measured with an accuracy of 0.6 mm and 0.8 mm (1 SD) for lung and prostate respectively. Field location errors (i.e. tracking in wrong direction) with a magnitude of 3 mm were detected within 0.4 s of occurrence in the X direction and 0.8 s in the Y direction. Systematic MLC gap errors were detected as small as 3 mm. The method was not found to be sensitive to random MLC errors and individual MLC calibration errors up to 5 mm. Conclusion: EPID imaging may be used for independent real-time verification of MLC trajectories during MLC tracking deliveries. Thresholds have been determined for error detection and the system has been shown to be sensitive to a range of delivery errors.« less

Embryonic essential myosin light chain regulates fetal lung development in rats.

PubMed

Santos, Marta; Moura, Rute S; Gonzaga, Sílvia; Nogueira-Silva, Cristina; Ohlmeier, Steffen; Correia-Pinto, Jorge

2007-09-01

Congenital diaphragmatic hernia (CDH) is currently the most life-threatening congenital anomaly the major finding of which is lung hypoplasia. Lung hypoplasia pathophysiology involves early developmental molecular insult in branching morphogenesis and a late mechanical insult by abdominal herniation in maturation and differentiation processes. Since early determinants of lung hypoplasia might appear as promising targets for prenatal therapy, proteomics analysis of normal and nitrofen-induced hypoplastic lungs was performed at 17.5 days after conception. The major differentially expressed protein was identified by mass spectrometry as myosin light chain 1a (MLC1a). Embryonic essential MLC1a and regulatory myosin light chain 2 (MLC2) were characterized throughout normal and abnormal lung development by immunohistochemistry and Western blot. Disruption of MLC1a expression was assessed in normal lung explant cultures by antisense oligodeoxynucleotides. Since early stages of normal lung development, MLC1a was expressed in vascular smooth muscle (VSM) cells of pulmonary artery, and MLC2 was present in parabronchial smooth muscle and VSM cells of pulmonary vessels. In addition, early smooth muscle differentiation delay was observed by immunohistochemistry of alpha-smooth muscle actin and transforming growth factor-beta1. Disruption of MLC1a expression during normal pulmonary development led to significant growth and branching impairment, suggesting a role in branching morphogenesis. Both MLC1a and MLC2 were absent from hypoplastic fetal lungs during pseudoglandular stage of lung development, whereas their expression partially recovered by prenatal treatment with vitamin A. Thus, a deficiency in contractile proteins MLC1a and MLC2 might have a role among the early molecular determinants of lung hypoplasia in the rat model of nitrofen-induced CDH.

SU-G-BRA-17: Tracking Multiple Targets with Independent Motion in Real-Time Using a Multi-Leaf Collimator

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ge, Y; Keall, P; Poulsen, P

Purpose: Multiple targets with large intrafraction independent motion are often involved in advanced prostate, lung, abdominal, and head and neck cancer radiotherapy. Current standard of care treats these with the originally planned fields, jeopardizing the treatment outcomes. A real-time multi-leaf collimator (MLC) tracking method has been developed to address this problem for the first time. This study evaluates the geometric uncertainty of the multi-target tracking method. Methods: Four treatment scenarios are simulated based on a prostate IMAT plan to treat a moving prostate target and static pelvic node target: 1) real-time multi-target MLC tracking; 2) real-time prostate-only MLC tracking; 3)more » correcting for prostate interfraction motion at setup only; and 4) no motion correction. The geometric uncertainty of the treatment is assessed by the sum of the erroneously underexposed target area and overexposed healthy tissue areas for each individual target. Two patient-measured prostate trajectories of average 2 and 5 mm motion magnitude are used for simulations. Results: Real-time multi-target tracking accumulates the least uncertainty overall. As expected, it covers the static nodes similarly well as no motion correction treatment and covers the moving prostate similarly well as the real-time prostate-only tracking. Multi-target tracking reduces >90% of uncertainty for the static nodal target compared to the real-time prostate-only tracking or interfraction motion correction. For prostate target, depending on the motion trajectory which affects the uncertainty due to leaf-fitting, multi-target tracking may or may not perform better than correcting for interfraction prostate motion by shifting patient at setup, but it reduces ∼50% of uncertainty compared to no motion correction. Conclusion: The developed real-time multi-target MLC tracking can adapt for the independently moving targets better than other available treatment adaptations. This will enable PTV margin reduction to minimize health tissue toxicity while remain tumor coverage when treating advanced disease with independently moving targets involved. The authors acknowledge funding support from the Australian NHMRC Australia Fellowship and NHMRC Project Grant No. APP1042375.« less

Myosin light chain 2-based selection of human iPSC-derived early ventricular cardiac myocytes.

PubMed

Bizy, Alexandra; Guerrero-Serna, Guadalupe; Hu, Bin; Ponce-Balbuena, Daniela; Willis, B Cicero; Zarzoso, Manuel; Ramirez, Rafael J; Sener, Michelle F; Mundada, Lakshmi V; Klos, Matthew; Devaney, Eric J; Vikstrom, Karen L; Herron, Todd J; Jalife, José

2013-11-01

Applications of human induced pluripotent stem cell derived-cardiac myocytes (hiPSC-CMs) would be strengthened by the ability to generate specific cardiac myocyte (CM) lineages. However, purification of lineage-specific hiPSC-CMs is limited by the lack of cell marking techniques. Here, we have developed an iPSC-CM marking system using recombinant adenoviral reporter constructs with atrial- or ventricular-specific myosin light chain-2 (MLC-2) promoters. MLC-2a and MLC-2v selected hiPSC-CMs were purified by fluorescence-activated cell sorting and their biochemical and electrophysiological phenotypes analyzed. We demonstrate that the phenotype of both populations remained stable in culture and they expressed the expected sarcomeric proteins, gap junction proteins and chamber-specific transcription factors. Compared to MLC-2a cells, MLC-2v selected CMs had larger action potential amplitudes and durations. In addition, by immunofluorescence, we showed that MLC-2 isoform expression can be used to enrich hiPSC-CM consistent with early atrial and ventricular myocyte lineages. However, only the ventricular myosin light chain-2 promoter was able to purify a highly homogeneous population of iPSC-CMs. Using this approach, it is now possible to develop ventricular-specific disease models using iPSC-CMs while atrial-specific iPSC-CM cultures may require additional chamber-specific markers. © 2013.

Mechanistic studies of a cell-permeant peptide designed to enhance myosin light chain phosphorylation in polarized intestinal epithelia.

PubMed

Almansour, Khaled; Taverner, Alistair; Eggleston, Ian M; Mrsny, Randall J

2018-06-10

Tight junction (TJ) structures restrict the movement of solutes between adjacent epithelial cells to maintain homeostatic conditions. A peptide, termed PIP 640, with the capacity to regulate the transient opening of intestinal TJ structures through an endogenous mechanism involving the induction of myosin light chain (MLC) phosphorylation at serine 19 (MLC-pS 19 ) has provided a promising new method to enhance the in vivo oral bioavailability of peptide therapeutics. PIP 640 is a decapeptide composed of all D-amino acids (rrdykvevrr-NH 2 ) that contains a central sequence designed to emulates a specific domain of C-kinase potentiated protein phosphatase-1 inhibitor-17 kDa (CPI-17) surrounded by positively-charged amino acids that provide a cell penetrating peptide (CPP)-like character. Here, we examine compositional requirements of PIP 640 with regard to its actions on MLC phosphorylation, its intracellular localization to TJ structures, and its interactions with MLC phosphatase (MLCP) elements that correlate with enhanced solute uptake. These studies showed that a glutamic acid and tyrosine within this peptide are critical for PIP 640 to retain its ability to increase MLC-pS 19 levels and enhance the permeability of macromolecular solutes of the size range of therapeutic peptides without detectable cytotoxicity. On the other hand, exchange of the aspartic acid for alanine and then arginine resulted in an increasingly greater bias toward protein phosphatase-1 (PP1) relative to MLCP inhibition, an outcome that resulted in increased paracellular permeability for solutes in the size range of therapeutic peptides, but with a significant increase in cytotoxicity. Together, these data further our understanding of the composition requirements of PIP 640 with respect to the desired goal of transiently altering the intestinal epithelial cell paracellular barrier properties through an endogenous mechanism, providing a novel approach to enhance the oral bioavailability of poorly absorbed therapeutic agents of < ~ 5 kDa. Copyright © 2018 Elsevier B.V. All rights reserved.

Genetics Home Reference: megalencephalic leukoencephalopathy with subcortical cysts

MedlinePlus

... is unable to correctly transport GlialCAM and MLC1 proteins to cell junctions. It is unknown how a lack of functional MLC1 or GlialCAM protein at cell junctions in the brain impairs brain development and ...

Blackcomb: Hardware-Software Co-design for Non-Volatile Memory in Exascale Systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schreiber, Robert

Summary of technical results of Blackcomb Memory Devices We explored various different memory technologies (STTRAM, PCRAM, FeRAM, and ReRAM). The progress can be classified into three categories, below. Modeling and Tool Releases Various modeling tools have been developed over the last decade to help in the design of SRAM or DRAM-based memory hierarchies. To explore new design opportunities that NVM technologies can bring to the designers, we have developed similar high-level models for NVM, including PCRAMsim [Dong 2009], NVSim [Dong 2012], and NVMain [Poremba 2012]. NVSim is a circuit-level model for NVM performance, energy, and area estimation, which supports variousmore » NVM technologies, including STT-RAM, PCRAM, ReRAM, and legacy NAND Flash. NVSim is successfully validated against industrial NVM prototypes, and it is expected to help boost architecture-level NVM-related studies. On the other side, NVMain is a cycle accurate main memory simulator designed to simulate emerging nonvolatile memories at the architectural level. We have released these models as open source tools and provided contiguous support to them. We also proposed PS3-RAM, which is a fast, portable and scalable statistical STT-RAM reliability analysis model [Wen 2012]. Design Space Exploration and Optimization With the support of these models, we explore different device/circuit optimization techniques. For example, in [Niu 2012a] we studied the power reduction technique for the application of ECC scheme in ReRAM designs and proposed to use ECC code to relax the BER (Bit Error Rate) requirement of a single memory to improve the write energy consumption and latency for both 1T1R and cross-point ReRAM designs. In [Xu 2011], we proposed a methodology to design STT-RAM for different optimization goals such as read performance, write performance and write energy by leveraging the trade-off between write current and write time of MTJ. We also studied the tradeoffs in building a reliable crosspoint ReRAM array [Niu 2012b]. We have conducted an in depth analysis of the circuit and system level design implications of multi-layer cross-point Resistive RAM (MLCReRAM) from performance, power and reliability perspectives [Xu 2013]. The objective of this study is to understand the design trade-offs of this technology with respect to the MLC Phase Change Memory (MLCPCM).Our MLC ReRAM design at the circuit and system levels indicates that different resistance allocation schemes, programming strategies, peripheral designs, and material selections profoundly affect the area, latency, power, and reliability of MLC ReRAM. Based on this analysis, we conduct two case studies: first we compare MLC ReRAM design against MLC phase-change memory (PCM) and multi-layer cross-point ReRAM design, and point out why multi-level ReRAM is appealing; second we further explore the design space for MLC ReRAM. Architecture and Application We explored hybrid checkpointing using phase-change memory for future exascale systems [Dong 2011] and showed that the use of nonvolatile memory for local checkpointing significantly increases the number of faults covered by local checkpoints and reduces the probability of a global failure in the middle of a global checkpoint to less than 1%. We also proposed a technique called i2WAP to mitigate the write variations in NVM-based last-level cache for the improvement of the NVM lifetime [Wang 2013]. Our wear leveling technique attempts to work around the limitations of write endurance by arranging data access so that write operations can be distributed evenly across all the storage cells. During our intensive research on fault-tolerant NVM design, we found that ECC cannot effectively tolerate hard errors from limited write endurance and process imperfection. Therefore, we devised a novel Point and Discard (PAD) architecture in in [ 2012] as a hard-error-tolerant architecture for ReRAM-based Last Level Caches. PAD improves the lifetime of ReRAM caches by 1.6X-440X under different process variations without performance overhead in the system's early life. We have investigated the applicability of NVM for persistent memory design [Zhao 2013]. New byte addressable NVM enables fast persistent memory that allows in-memory persistent data objects to be updated with much higher throughput. Despite the significant improvement, the performance of these designs is only 50% of the native system with no persistence support, due to the logging or copy-on-write mechanisms used to update the persistent memory. A challenge in this approach is therefore how to efficiently enable atomic, consistent, and durable updates to ensure data persistence that survives application and/or system failures. We have designed a persistent memory system, called Klin, that can provide performance as close as that of the native system. The Klin design adopts a non-volatile cache and a non-volatile main memory for constructing a multi-versioned durable memory system, enabling atomic updates without logging or copy-on-write. Our evaluation shows that the proposed Kiln mechanism can achieve up to 2X of performance improvement to NVRAM-based persistent memory employing write-ahead logging. In addition, our design has numerous practical advantages: a simple and intuitive abstract interface, microarchitecture-level optimizations, fast recovery from failures, and no redundant writes to slow non-volatile storage media. The work was published in MICRO 2013 and received Best Paper Honorable Mentioned Award.« less

Isolation and characterization of ventricular-like cells derived from NKX2-5eGFP/w and MLC2vmCherry/w double knock-in human pluripotent stem cells.

PubMed

Yamauchi, Kaori; Li, Junjun; Morikawa, Kumi; Liu, Li; Shirayoshi, Yasuaki; Nakatsuji, Norio; Elliott, David A; Hisatome, Ichiro; Suemori, Hirofumi

2018-01-01

Human pluripotent stem cell (hPSC)-derived cardiomyocytes (CMs) are a promising source for cell transplantation into the damaged heart, which has limited regenerative ability. Many methods have been developed to obtain large amounts of functional CMs from hPSCs for therapeutic applications. However, during the differentiation process, a mixed population of various cardiac cells, including ventricular, atrial, and pacemaker cells, is generated, which hampers the proper functional analysis and evaluation of cell properties. Here, we established NKX2-5 eGFP/w and MLC2v mCherry/w hPSC double knock-ins that allow for labeling, tracing, purification, and analysis of the development of ventricular cells from early to late stages. As with the endogenous transcriptional activities of these genes, MLC2v-mCherry expression following NKX2-5-eGFP expression was observed under previously established culture conditions, which mimic the in vivo cardiac developmental process. Patch-clamp and microelectrode array electrophysiological analyses showed that the NKX2-5 and MLC2v double-positive cells possess ventricular-like properties. The results demonstrate that the NKX2-5 eGFP/w and MLC2v mCherry/w hPSCs provide a powerful model system to capture region-specific cardiac differentiation from early to late stages. Our study would facilitate subtype-specific cardiac development and functional analysis using the hPSC-derived sources. Copyright © 2017 Elsevier Inc. All rights reserved.

Rho-kinase signaling controls nucleocytoplasmic shuttling of class IIa Histone Deacetylase (HDAC7) and transcriptional activation of orphan nuclear receptor NR4A1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Compagnucci, Claudia; Barresi, Sabina; Petrini, Stefania

2015-04-03

Rho-kinase (ROCK) has been well documented to play a key role in RhoA-induced actin remodeling. ROCK activation results in myosin light chain (MLC) phosphorylation either by direct action on MLC kinase (MLCK) or by inhibition of MLC phosphatase (MLCP), modulating actin–myosin contraction. We found that inhibition of the ROCK pathway in induced pluripotent stem cells, leads to nuclear export of HDAC7 and transcriptional activation of the orphan nuclear receptor NR4A1 while in cells with constitutive ROCK hyperactivity due to loss of function of the RhoGTPase activating protein Oligophrenin-1 (OPHN1), the orphan nuclear receptor NR4A1 is downregulated. Our study identify amore » new target of ROCK signaling via myosin phosphatase subunit (MYPT1) and Histone Deacetylase (HDAC7) at the nuclear level and provide new insights in the cellular functions of ROCK. - Highlights: • ROCK regulates nucleocytoplasmic shuttling of HDAC7 via phosphorylation of MYPT1. • Nuclear export of HDAC7 and upregulation of NR4A1 occurs with low ROCK activity. • High levels of ROCK activity due to OPHN1 loss of function downregulate NR4A1.« less

Myosin light chain 2-based selection of human iPSC-derived early ventricular cardiac myocytes

PubMed Central

Bizy, Alexandra; Guerrero-Serna, Guadalupe; Hu, Bin; Ponce-Balbuena, Daniela; Willis, B. Cicero; Zarzoso, Manuel; Ramirez, Rafael J.; Sener, Michelle F.; Mundada, Lakshmi V.; Klos, Matthew; Devaney, Eric J.; Vikstrom, Karen L.; Herron, Todd J.; Jalife, José

2014-01-01

Applications of human induced pluripotent stemcell derived-cardiac myocytes (hiPSC-CMs) would be strengthened by the ability to generate specific cardiac myocyte (CM) lineages. However, purification of lineage-specific hiPSC-CMs is limited by the lack of cell marking techniques. Here, we have developed an iPSC-CM marking system using recombinant adenoviral reporter constructs with atrial- or ventricular-specific myosin light chain-2 (MLC-2) promoters. MLC-2a and MLC-2v selected hiPSC-CMs were purified by fluorescence-activated cell sorting and their biochemical and electrophysiological phenotypes analyzed. We demonstrate that the phenotype of both populations remained stable in culture and they expressed the expected sarcomeric proteins, gap junction proteins and chamber-specific transcription factors. Compared to MLC-2a cells, MLC-2v selected CMs had larger action potential amplitudes and durations. In addition, by immunofluorescence, we showed that MLC-2 isoform expression can be used to enrich hiPSC-CM consistent with early atrial and ventricularmyocyte lineages. However, only the ventricular myosin light chain-2 promoter was able to purify a highly homogeneous population of iPSC-CMs. Using this approach, it is now possible to develop ventricular-specific disease models using iPSC-CMs while atrial-specific iPSC-CM cultures may require additional chamber-specific markers. PMID:24095945

Disrupting MLC1 and GlialCAM and ClC-2 interactions in leukodystrophy entails glial chloride channel dysfunction

NASA Astrophysics Data System (ADS)

Hoegg-Beiler, Maja B.; Sirisi, Sònia; Orozco, Ian J.; Ferrer, Isidre; Hohensee, Svea; Auberson, Muriel; Gödde, Kathrin; Vilches, Clara; de Heredia, Miguel López; Nunes, Virginia; Estévez, Raúl; Jentsch, Thomas J.

2014-03-01

Defects in the astrocytic membrane protein MLC1, the adhesion molecule GlialCAM or the chloride channel ClC-2 underlie human leukoencephalopathies. Whereas GlialCAM binds ClC-2 and MLC1, and modifies ClC-2 currents in vitro, no functional connections between MLC1 and ClC-2 are known. Here we investigate this by generating loss-of-function Glialcam and Mlc1 mouse models manifesting myelin vacuolization. We find that ClC-2 is unnecessary for MLC1 and GlialCAM localization in brain, whereas GlialCAM is important for targeting MLC1 and ClC-2 to specialized glial domains in vivo and for modifying ClC-2’s biophysical properties specifically in oligodendrocytes (OLs), the cells chiefly affected by vacuolization. Unexpectedly, MLC1 is crucial for proper localization of GlialCAM and ClC-2, and for changing ClC-2 currents. Our data unmask an unforeseen functional relationship between MLC1 and ClC-2 in vivo, which is probably mediated by GlialCAM, and suggest that ClC-2 participates in the pathogenesis of megalencephalic leukoencephalopathy with subcortical cysts.

Magnolol Inhibits Human Glioblastoma Cell Migration by Regulating N-Cadherin.

PubMed

Cheng, Yu-Chen; Tsao, Min-Jen; Chiu, Chen-Yang; Kan, Po-Chieh; Chen, Ying

2018-06-01

Glioblastoma is a primary malignant brain tumor with a poor prognosis. An effective treatment for glioblastoma is needed. Magnolol is a natural compound from Magnolia officinalis suggested to have antiproliferative activity. The aim of this research was to investigate the anticancer effects of magnolol in glioma, with an emphasis on migration and the underlying mechanism. Magnolol decreased the expression of focal adhesion-related proteins and inhibited LN229 and U87MG glioma cell migration. The levels of phosphorylated myosin light chain (p-MLC), phosphorylated myosin light chain kinase and myosin phosphatase target subunit 1 were reduced in response to magnolol treatment. In addition, immunostaining and membrane fractionation showed that the distribution of N-cadherin at the glioma cell membrane was decreased by magnolol. In an orthotropic xenograft animal model, magnolol treatment not only inhibited tumor progression but also reduced p-MLC and N-cadherin protein expression. In conclusion, magnolol reduces cell migration, potentially through regulating focal adhesions and N-cadherin in glioma cells. Magnolol is a potential candidate for glioma treatment.

SU-E-T-604: Penumbra Characteristics of a New InCiseâ„¢ Multileaf Collimator of CyberKnife M6â„¢ System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hwang, M; Jang, S; Ozhasoglu, C

2015-06-15

Purpose: The InCise™ Multileaf Collimator (MLC) of CyberKnife M6™ System has been released recently. The purpose of this study was to explore the dosimetric characteristics of the new MLC. In particular, the penumbra characteristics of MLC fields at varying locations are evaluated. Methods: EBT3-based film measurements were performed with varying MLC fields ranging from 7.5 mm to 27.5 mm. Seventeen regions of interests (ROIs) were identified for irradiation. These are regions located at the central area (denoted as reference field), at the left/right edge areas of reference open field, at an intermediate location between central and edge area. Single beammore » treatment plans were designed by using the MultiPlan and was delivered using the Blue Phantom. Gafchromic films were irradiated at 1.5 cm depth in the Blue Phantom and analyzed using the Film Pro software. Variation of maximum dose, penumbra of MLC-defined fields, and symmetry/flatness were calculated as a function of locations of MLC fields. Results: The InCise™ MLC System showed relatively consistent dose distribution and penumbra size with varying locations of MLC fields. The measured maximum dose varied within 5 % at different locations compared to that at the central location and agreed with the calculated data well within 2%. The measured penumbrae were in the range of 2.9 mm and 3.7 mm and were relatively consistent regardless of locations. However, dose profiles in the out-of-field and in-field regions varied with locations and field sizes. Strong variation was seen for all fields located at 55 mm away from the central field. The MLC leakage map showed that the leakage is dependent on position. Conclusion: The size of penumbra and normalized maximum dose for MLC-defined fields were consistent in different regions of MLC. However, dose profiles in the out-field region varied with locations and field sizes.« less

Carbachol-induced rabbit bladder smooth muscle contraction: roles of protein kinase C and Rho kinase.

PubMed

Wang, Tanchun; Kendig, Derek M; Smolock, Elaine M; Moreland, Robert S

2009-12-01

Smooth muscle contraction is regulated by phosphorylation of the myosin light chain (MLC) catalyzed by MLC kinase and dephosphorylation catalyzed by MLC phosphatase. Agonist stimulation of smooth muscle results in the inhibition of MLC phosphatase activity and a net increase in MLC phosphorylation and therefore force. The two pathways believed to be primarily important for inhibition of MLC phosphatase activity are protein kinase C (PKC)-catalyzed CPI-17 phosphorylation and Rho kinase (ROCK)-catalyzed myosin phosphatase-targeting subunit (MYPT1) phosphorylation. The goal of this study was to determine the roles of PKC and ROCK and their downstream effectors in regulating MLC phosphorylation levels and force during the phasic and sustained phases of carbachol-stimulated contraction in intact bladder smooth muscle. These studies were performed in the presence and absence of the PKC inhibitor bisindolylmaleimide-1 (Bis) or the ROCK inhibitor H-1152. Phosphorylation levels of Thr(38)-CPI-17 and Thr(696)/Thr(850)-MYPT1 were measured at different times during carbachol stimulation using site-specific antibodies. Thr(38)-CPI-17 phosphorylation increased concurrently with carbachol-stimulated force generation. This increase was reduced by inhibition of PKC during the entire contraction but was only reduced by ROCK inhibition during the sustained phase of contraction. MYPT1 showed high basal phosphorylation levels at both sites; however, only Thr(850) phosphorylation increased with carbachol stimulation; the increase was abolished by the inhibition of either ROCK or PKC. Our results suggest that during agonist stimulation, PKC regulates MLC phosphatase activity through phosphorylation of CPI-17. In contrast, ROCK phosphorylates both Thr(850)-MYPT1 and CPI-17, possibly through cross talk with a PKC pathway, but is only significant during the sustained phase of contraction. Last, our results demonstrate that there is a constitutively activate pool of ROCK that phosphorylates MYPT1 in the basal state, which may account for the high resting levels of MLC phosphorylation measured in rabbit bladder smooth muscle.

Src Family Kinases (SFK) Mediate Angiotensin II-Induced Myosin Light Chain Phosphorylation and Hypertension.

PubMed

Qin, Bo; Zhou, Junlan

2015-01-01

Angiotensin (Ang) II is the major bioactive peptide of the renin-angiotensin system (RAS); it contributes to the pathogenesis of hypertension by inducing vascular contraction and adverse remodeling, thus elevated peripheral resistance. Ang II also activates Src family kinases (SFK) in the vascular system, which has been implicated in cell proliferation and migration. However, the role of SFK in Ang II-induced hypertension is largely unknown. In this study, we found that administration of a SFK inhibitor SU6656 markedly lowered the level of systemic BP in Ang II-treated mice, which was associated with an attenuated phosphorylation of the smooth-muscle myosin-light-chain (MLC) in the mesenteric resistant arteries. In the cultured human coronary artery smooth muscle cells (SMCs), pretreatment with SU6656 blocked Ang II-induced MLC phosphorylation and contraction. These results for the first time demonstrate that SFK directly regulate vascular contractile machinery to influence BP. Thus our study provides an additional mechanistic link between Ang II and vasoconstriction via SFK-enhanced MLC phosphorylation in SMCs, and suggests that targeted inhibition of Src may provide a new therapeutic opportunity in the treatment of hypertension.

Asymmetric programming: a highly reliable metadata allocation strategy for MLC NAND flash memory-based sensor systems.

PubMed

Huang, Min; Liu, Zhaoqing; Qiao, Liyan

2014-10-10

While the NAND flash memory is widely used as the storage medium in modern sensor systems, the aggressive shrinking of process geometry and an increase in the number of bits stored in each memory cell will inevitably degrade the reliability of NAND flash memory. In particular, it's critical to enhance metadata reliability, which occupies only a small portion of the storage space, but maintains the critical information of the file system and the address translations of the storage system. Metadata damage will cause the system to crash or a large amount of data to be lost. This paper presents Asymmetric Programming, a highly reliable metadata allocation strategy for MLC NAND flash memory storage systems. Our technique exploits for the first time the property of the multi-page architecture of MLC NAND flash memory to improve the reliability of metadata. The basic idea is to keep metadata in most significant bit (MSB) pages which are more reliable than least significant bit (LSB) pages. Thus, we can achieve relatively low bit error rates for metadata. Based on this idea, we propose two strategies to optimize address mapping and garbage collection. We have implemented Asymmetric Programming on a real hardware platform. The experimental results show that Asymmetric Programming can achieve a reduction in the number of page errors of up to 99.05% with the baseline error correction scheme.

Asymmetric Programming: A Highly Reliable Metadata Allocation Strategy for MLC NAND Flash Memory-Based Sensor Systems

PubMed Central

Huang, Min; Liu, Zhaoqing; Qiao, Liyan

2014-01-01

While the NAND flash memory is widely used as the storage medium in modern sensor systems, the aggressive shrinking of process geometry and an increase in the number of bits stored in each memory cell will inevitably degrade the reliability of NAND flash memory. In particular, it's critical to enhance metadata reliability, which occupies only a small portion of the storage space, but maintains the critical information of the file system and the address translations of the storage system. Metadata damage will cause the system to crash or a large amount of data to be lost. This paper presents Asymmetric Programming, a highly reliable metadata allocation strategy for MLC NAND flash memory storage systems. Our technique exploits for the first time the property of the multi-page architecture of MLC NAND flash memory to improve the reliability of metadata. The basic idea is to keep metadata in most significant bit (MSB) pages which are more reliable than least significant bit (LSB) pages. Thus, we can achieve relatively low bit error rates for metadata. Based on this idea, we propose two strategies to optimize address mapping and garbage collection. We have implemented Asymmetric Programming on a real hardware platform. The experimental results show that Asymmetric Programming can achieve a reduction in the number of page errors of up to 99.05% with the baseline error correction scheme. PMID:25310473

CompactPCI/Linux Platform in FTU Slow Control System

NASA Astrophysics Data System (ADS)

Iannone, F.; Wang, L.; Centioli, C.; Panella, M.; Mazza, G.; Vitale, V.

2004-12-01

In large fusion experiments, such as tokamak devices, there is a common trend for slow control systems. Because of complexity of the plants, the so-called `Standard Model' (SM) in slow control has been adopted on several tokamak machines. This model is based on a three-level hierarchical control: 1) High-Level Control (HLC) with a supervisory function; 2) Medium-Level Control (MLC) to interface and concentrate I/O field equipments; 3) Low-Level Control (LLC) with hard real-time I/O function, often managed by PLCs. FTU control system designed with SM concepts has underwent several stages of developments in its fifteen years duration of runs. The latest evolution was inevitable, due to the obsolescence of the MLC CPUs, based on VME-MOTOROLA 68030 with OS9 operating system. A large amount of C code was developed for that platform to route the data flow from LLC, which is constituted by 24 Westinghouse Numalogic PC-700 PLCs with about 8000 field-points, to HLC, based on a commercial Object-Oriented Real-Time database on Alpha/CompaqTru64 platform. Therefore, we have to look for cost-effective solutions and finally a CompactPCI-Intel x86 platform with Linux operating system was chosen. A software porting has been done, taking into account the differences between OS9 and Linux operating system in terms of Inter/Network Processes Communications and I/O multi-ports serial driver. This paper describes the hardware/software architecture of the new MLC system, emphasizing the reliability and the low costs of the open source solutions. Moreover, a huge amount of software packages available in open source environment will assure a less painful maintenance, and will open the way to further improvements of the system itself.

In Vitro Reactivity of 3-M KC1-Solubilized Murine Histocompatibility (H-2) Antigens

DTIC Science & Technology

1974-01-01

experiment, varying concentra- mice were immunized with DBA/2 spleen tions of cells from day 5 BALB/c sensitized cells and subsequently skin grafted . Syn... skin grafts , spleen in MLC with mitomycin-C treated DBA/2 cells were removed and cultured with spleen cells. As seen in Table 4, increasing DBA/2...was solubilized antigens were assayed for levels produced by spleen cells from animals 5 of lymphotoxin (LT), it was seen that nor- days post skin graft sensitization

Maturation of the myogenic program is induced by postmitotic expression of insulin-like growth factor I.

PubMed

Musarò, A; Rosenthal, N

1999-04-01

The molecular mechanisms underlying myogenic induction by insulin-like growth factor I (IGF-I) are distinct from its proliferative effects on myoblasts. To determine the postmitotic role of IGF-I on muscle cell differentiation, we derived L6E9 muscle cell lines carrying a stably transfected rat IGF-I gene under the control of a myosin light chain (MLC) promoter-enhancer cassette. Expression of MLC-IGF-I exclusively in differentiated L6E9 myotubes, which express the embryonic form of myosin heavy chain (MyHC) and no endogenous IGF-I, resulted in pronounced myotube hypertrophy, accompanied by activation of the neonatal MyHC isoform. The hypertrophic myotubes dramatically increased expression of myogenin, muscle creatine kinase, beta-enolase, and IGF binding protein 5 and activated the myocyte enhancer factor 2C gene which is normally silent in this cell line. MLC-IGF-I induction in differentiated L6E9 cells also increased the expression of a transiently transfected LacZ reporter driven by the myogenin promoter, demonstrating activation of the differentiation program at the transcriptional level. Nuclear reorganization, accumulation of skeletal actin protein, and an increased expression of beta1D integrin were also observed. Inhibition of the phosphatidyl inositol (PI) 3-kinase intermediate in IGF-I-mediated signal transduction confirmed that the PI 3-kinase pathway is required only at early stages for IGF-I-mediated hypertrophy and neonatal MyHC induction in these cells. Expression of IGF-I in postmitotic muscle may therefore play an important role in the maturation of the myogenic program.

Lactobacillus farciminis treatment suppresses stress induced visceral hypersensitivity: a possible action through interaction with epithelial cell cytoskeleton contraction.

PubMed

Ait-Belgnaoui, A; Han, W; Lamine, F; Eutamene, H; Fioramonti, J; Bueno, L; Theodorou, V

2006-08-01

Stress induced increase in colonic paracellular permeability results from epithelial cell cytoskeleton contraction and is responsible for stress induced hypersensitivity to colorectal distension (CRD). The probiotic Lactobacillus farciminis releases spontaneously nitric oxide (NO) in the colonic lumen in vivo and exerts anti-inflammatory effects. This study aimed: (i) to evaluate the effects of L farciminis on stress induced hypersensitivity to CRD and increase in colonic paracellular permeability; and (ii) to ascertain whether these effects are NO mediated and related to changes in colonocyte myosin light chain phosphorylation (p-MLC). Female Wistar rats received either 10(11) CFU/day of L farciminis or saline orally over 15 days before partial restraint stress (PRS) or sham-PRS application. Visceral sensitivity to CRD and colonic paracellular permeability was assessed after PRS or sham-PRS. Haemoglobin was used as an NO scavenger. Western blotting for MLC kinase, MLC, and p-MLC were performed in colonic mucosa from L farciminis treated and control rats after PRS or sham-PRS. PRS significantly increased the number of spike bursts for CRD pressures of 30-60 mm Hg as well as colonic paracellular permeability. L farciminis treatment prevented both effects, while haemoglobin reversed the protective effects of L farciminis. p-MLC expression increased significantly from 15 to 45 minutes after PRS, and L farciminis treatment prevented this increase. L farciminis treatment prevents stress induced hypersensitivity, increase in colonic paracellular permeability, and colonocyte MLC phosphorylation. This antinociceptive effect occurs via inhibition of contraction of colonic epithelial cell cytoskeleton and the subsequent tight junction opening, and may also involve direct or indirect effects of NO produced by this probiotic.

Lactobacillus farciminis treatment suppresses stress induced visceral hypersensitivity: a possible action through interaction with epithelial cell cytoskeleton contraction

PubMed Central

Ait‐Belgnaoui, A; Han, W; Lamine, F; Eutamene, H; Fioramonti, J; Bueno, L; Theodorou, V

2006-01-01

Background Stress induced increase in colonic paracellular permeability results from epithelial cell cytoskeleton contraction and is responsible for stress induced hypersensitivity to colorectal distension (CRD). The probiotic Lactobacillus farciminis releases spontaneously nitric oxide (NO) in the colonic lumen in vivo and exerts anti‐inflammatory effects. This study aimed: (i) to evaluate the effects of L farciminis on stress induced hypersensitivity to CRD and increase in colonic paracellular permeability; and (ii) to ascertain whether these effects are NO mediated and related to changes in colonocyte myosin light chain phosphorylation (p‐MLC). Methods Female Wistar rats received either 1011 CFU/day of L farciminis or saline orally over 15 days before partial restraint stress (PRS) or sham‐PRS application. Visceral sensitivity to CRD and colonic paracellular permeability was assessed after PRS or sham‐PRS. Haemoglobin was used as an NO scavenger. Western blotting for MLC kinase, MLC, and p‐MLC were performed in colonic mucosa from L farciminis treated and control rats after PRS or sham‐PRS. Results PRS significantly increased the number of spike bursts for CRD pressures of 30–60 mm Hg as well as colonic paracellular permeability. L farciminis treatment prevented both effects, while haemoglobin reversed the protective effects of L farciminis. p‐MLC expression increased significantly from 15 to 45 minutes after PRS, and L farciminis treatment prevented this increase. Conclusion L farciminis treatment prevents stress induced hypersensitivity, increase in colonic paracellular permeability, and colonocyte MLC phosphorylation. This antinociceptive effect occurs via inhibition of contraction of colonic epithelial cell cytoskeleton and the subsequent tight junction opening, and may also involve direct or indirect effects of NO produced by this probiotic. PMID:16507583

Minimal-Level Cataloging: A Look at the Issues--A Symposium.

ERIC Educational Resources Information Center

Horny, Karen L.; And Others

1986-01-01

Six articles on pros and cons of minimal-level cataloging (MLC) highlight patron access and browsability, time and cost savings, network and bibliographic utility cooperation, standards, alternatives to MLC, levels of records, online catalogs, experimental cataloging program at University of Michigan, and experiences at Kent State University…

Development of an iterative reconstruction method to overcome 2D detector low resolution limitations in MLC leaf position error detection for 3D dose verification in IMRT.

PubMed

Visser, R; Godart, J; Wauben, D J L; Langendijk, J A; Van't Veld, A A; Korevaar, E W

2016-05-21

The objective of this study was to introduce a new iterative method to reconstruct multi leaf collimator (MLC) positions based on low resolution ionization detector array measurements and to evaluate its error detection performance. The iterative reconstruction method consists of a fluence model, a detector model and an optimizer. Expected detector response was calculated using a radiotherapy treatment plan in combination with the fluence model and detector model. MLC leaf positions were reconstructed by minimizing differences between expected and measured detector response. The iterative reconstruction method was evaluated for an Elekta SLi with 10.0 mm MLC leafs in combination with the COMPASS system and the MatriXX Evolution (IBA Dosimetry) detector with a spacing of 7.62 mm. The detector was positioned in such a way that each leaf pair of the MLC was aligned with one row of ionization chambers. Known leaf displacements were introduced in various field geometries ranging from  -10.0 mm to 10.0 mm. Error detection performance was tested for MLC leaf position dependency relative to the detector position, gantry angle dependency, monitor unit dependency, and for ten clinical intensity modulated radiotherapy (IMRT) treatment beams. For one clinical head and neck IMRT treatment beam, influence of the iterative reconstruction method on existing 3D dose reconstruction artifacts was evaluated. The described iterative reconstruction method was capable of individual MLC leaf position reconstruction with millimeter accuracy, independent of the relative detector position within the range of clinically applied MU's for IMRT. Dose reconstruction artifacts in a clinical IMRT treatment beam were considerably reduced as compared to the current dose verification procedure. The iterative reconstruction method allows high accuracy 3D dose verification by including actual MLC leaf positions reconstructed from low resolution 2D measurements.

Multileaf collimator performance monitoring and improvement using semiautomated quality control testing and statistical process control.

PubMed

Létourneau, Daniel; Wang, An; Amin, Md Nurul; Pearce, Jim; McNiven, Andrea; Keller, Harald; Norrlinger, Bernhard; Jaffray, David A

2014-12-01

High-quality radiation therapy using highly conformal dose distributions and image-guided techniques requires optimum machine delivery performance. In this work, a monitoring system for multileaf collimator (MLC) performance, integrating semiautomated MLC quality control (QC) tests and statistical process control tools, was developed. The MLC performance monitoring system was used for almost a year on two commercially available MLC models. Control charts were used to establish MLC performance and assess test frequency required to achieve a given level of performance. MLC-related interlocks and servicing events were recorded during the monitoring period and were investigated as indicators of MLC performance variations. The QC test developed as part of the MLC performance monitoring system uses 2D megavoltage images (acquired using an electronic portal imaging device) of 23 fields to determine the location of the leaves with respect to the radiation isocenter. The precision of the MLC performance monitoring QC test and the MLC itself was assessed by detecting the MLC leaf positions on 127 megavoltage images of a static field. After initial calibration, the MLC performance monitoring QC test was performed 3-4 times/week over a period of 10-11 months to monitor positional accuracy of individual leaves for two different MLC models. Analysis of test results was performed using individuals control charts per leaf with control limits computed based on the measurements as well as two sets of specifications of ± 0.5 and ± 1 mm. Out-of-specification and out-of-control leaves were automatically flagged by the monitoring system and reviewed monthly by physicists. MLC-related interlocks reported by the linear accelerator and servicing events were recorded to help identify potential causes of nonrandom MLC leaf positioning variations. The precision of the MLC performance monitoring QC test and the MLC itself was within ± 0.22 mm for most MLC leaves and the majority of the apparent leaf motion was attributed to beam spot displacements between irradiations. The MLC QC test was performed 193 and 162 times over the monitoring period for the studied units and recalibration had to be repeated up to three times on one of these units. For both units, rate of MLC interlocks was moderately associated with MLC servicing events. The strongest association with the MLC performance was observed between the MLC servicing events and the total number of out-of-control leaves. The average elapsed time for which the number of out-of-specification or out-of-control leaves was within a given performance threshold was computed and used to assess adequacy of MLC test frequency. A MLC performance monitoring system has been developed and implemented to acquire high-quality QC data at high frequency. This is enabled by the relatively short acquisition time for the images and automatic image analysis. The monitoring system was also used to record and track the rate of MLC-related interlocks and servicing events. MLC performances for two commercially available MLC models have been assessed and the results support monthly test frequency for widely accepted ± 1 mm specifications. Higher QC test frequency is however required to maintain tighter specification and in-control behavior.

Commissioning of the tongue-and-groove modelling in treatment planning systems: from static fields to VMAT treatments

NASA Astrophysics Data System (ADS)

Hernandez, Victor; Vera-Sánchez, Juan Antonio; Vieillevigne, Laure; Saez, Jordi

2017-08-01

Adequate modelling of the multi-leaf collimator (MLC) by treatment planning systems (TPS) is essential for accurate dose calculations in intensity-modulated radiation-therapy. For this reason modern TPSs incorporate MLC characteristics such as the leaf end curvature, MLC transmission and the tongue-and-groove. However, the modelling of the tongue-and-groove is often neglected during TPS commissioning and it is not known how accurate it is. This study evaluates the dosimetric consequences of the tongue-and-groove effect for two different MLC models using both film dosimetry and ionisation chambers. A set of comprehensive tests are presented that evaluate the ability of TPSs to accurately model this effect in (a) static fields, (b) sliding window beams and (c) VMAT arcs. The tests proposed are useful for the commissioning of TPSs and for the validation of major upgrades. With the ECLIPSE TPS, relevant differences were found between calculations and measurements for beams with dynamic MLCs in the presence of the TG effect, especially for the High Definition MLC, small gap sizes and the 1 mm calculation grid. For this combination, dose differences as high as 10% and 7% were obtained for dynamic MLC gaps of 5 mm and 10 mm, respectively. These differences indicate inadequate modelling of the tongue-and-groove effect, which might not be identified without the proposed tests. In particular, the TPS tended to underestimate the calculated dose, which may require tuning of other configuration parameters in the TPS (such as the dosimetric leaf gap) in order to maximise the agreement between calculations and measurements in clinical plans. In conclusion, a need for better modelling of the MLC by TPSs is demonstrated, one of the relevant aspects being the tongue-and-groove effect. This would improve the accuracy of TPS calculations, especially for plans using small MLC gaps, such as plans with small target volumes or high complexities. Improved modelling of the MLC would also reduce the need for tuning parameters in the TPS, facilitating a more comprehensive configuration and commissioning of TPSs.

Performance of a multi leaf collimator system for MR-guided radiation therapy.

PubMed

Cai, Bin; Li, Harold; Yang, Deshan; Rodriguez, Vivian; Curcuru, Austen; Wang, Yuhe; Wen, Jie; Kashani, Rojano; Mutic, Sasa; Green, Olga

2017-12-01

The purpose of this study was to investigate and characterize the performance of a Multi Leaf Collimator (MLC) designed for Cobalt-60 based MR-guided radiation therapy system in a 0.35 T magnetic field. The MLC design and unique assembly features in the ViewRay MRIdian system were first reviewed. The RF cage shielding of MLC motor and cables were evaluated using ACR phantoms with real-time imaging and quantified by signal-to-noise ratio. The dosimetric characterizations, including the leaf transmission, leaf penumbra, tongue-and-groove effect, were investigated using radiosensitive films. The output factor of MLC-defined fields was measured with ionization chambers for both symmetric fields from 2.1 × 2.1 cm 2 to 27.3 × 27.3 cm 2 and asymmetric fields from 10.5 × 10.5 cm 2 to 10.5 × 2.0 cm 2 . Multi leaf collimator (MLC) positional accuracy was assessed by delivering either a picket fence (PF) style pattern on radiochromic films with wire-jig phantom or double and triple-rectangular patterns on ArcCheck-MR (Sun Nuclear, Melbourne, FL, USA) with gamma analysis as the pass/fail indicator. Leaf speed tests were performed to assess the capability of full range leaf travel within manufacture's specifications. Multi leaf collimator plan delivery reproducibility was tested by repeatedly delivering both open fields and fields with irregular shaped segments over 1-month period. Comparable SNRs within 4% were observed for MLC moving and stationary plans on vendor-reconstructed images, and the direct k-space reconstructed images showed that the three SNRs are within 1%. The maximum leaf transmission for all three MLCs was less than 0.35% and the average leakage was 0.153 ± 0.006%, 0.151 ± 0.008%, and 0.159 ± 0.015% for head 1, 2, and 3, respectively. Both the leaf edge and leaf end penumbra showed comparable values within 0.05 cm, and the measured values are within 0.1 cm with TPS values. The leaf edge TG effect indicated 10% underdose and the leaf end TG showed a shifted dose distribution with 0.3 cm offset. The leaf positioning test showed a 0.2 cm accuracy in the PF style test, and a gamma passing rate above 96% was observed with a 3%/2 mm criteria when comparing the measured double/triple-rectangular pattern fluence with TPS calculated fluence. The average leaf speed when executing the test plan fell in a range from 1.86 to 1.95 cm/s. The measured and TPS calculated output factors were within 2% for squared fields and within 3% for rectangular fields. The reproducibility test showed the deviation of output factors were well within 2% for square fields and the gamma passing rate within 1.5% for fields with irregular segments. The Monte Carlo predicted output factors were within 2% compared to TPS values. 15 out of the 16 IMRT plans have gamma passing rate more than 98% compared to the TPS fluence with an average passing rate of 99.1 ± 0.6%. The MRIdian MLC has a good RF noise shielding design, low radiation leakage, good positioning accuracy, comparable TG effect, and can be modeled by an independent Monte Carlo calculation platform. © 2017 American Association of Physicists in Medicine.

SU-E-T-515: Field-In-Field Compensation Technique Using Multi-Leaf Collimator to Deliver Total Body Irradiation (TBI) Dose

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lakeman, T; Wang, IZ; Roswell Park Cancer Institute, Buffalo, NY

Purpose: Total body irradiation (TBI) uses large parallel-opposed radiation fields to suppress the patient's immune system and eradicate the residual cancer cells in preparation of recipient for bone marrow transplant. The manual placement of lead compensators has been used conventionally to compensate for the varying thickness through the entire body in large-field TBI. The goal of this study is to pursue utilizing the modern field-in-field (FIF) technique with the multi-leaf collimator (MLC) to more accurately and efficiently deliver dose to patients in need of TBI. Method: Treatment plans utilizing the FIF technique to deliver a total body dose were createdmore » retrospectively for patients for whom CT data had been previously acquired. Treatment fields include one pair of opposed open large fields (collimator=45°) with a specific weighting and a succession of smaller fields (collimator=90°) each with their own weighting. The smaller fields are shaped by moving MLC to block the sections of the patient which have already received close to 100% of the prescribed dose. The weighting factors for each of these fields were calculated using the attenuation coefficient of the initial lead compensators and the separation of the patient in different positions in the axial plane. Results: Dose-volume histograms (DVH) were calculated for evaluating the FIF compensation technique. The maximum body doses calculated from the DVH were reduced from the non-compensated 179.3% to 148.2% in the FIF plans, indicating a more uniform dose with the FIF compensation. All calculated monitor units were well within clinically acceptable limits and exceeded those of the original lead compensation plan by less than 50 MU (only ~1.1% increase). Conclusion: MLC FIF technique for TBI will not significantly increase the beam on time while it can substantially reduce the compensator setup time and the potential risk of errors in manually placing lead compensators.« less

Thrombin-induced phosphorylation of the regulatory light chain of myosin II in cultured bovine corneal endothelial cells.

PubMed

Satpathy, M; Gallagher, P; Lizotte-Waniewski, M; Srinivas, S P

2004-10-01

Phosphorylation of the regulatory light chain of myosin II (referred to as myosin light chain or MLC) leads to a loss of barrier integrity in cellular monolayers by an increase in the contractility of the cortical actin cytoskeleton. This effect has been examined in corneal endothelial (CE) cells. Experiments were performed using cultured bovine CE cells (BCEC). MLC phosphorylation was induced by a thrombin-mediated activation of the proteinase-activated receptor-1 (PAR-1). Expression of MLC kinase (MLCK), a Ca2+/calmodulin-dependent protein kinase that phosphorylates MLC at its Ser-19 and Thr-18 residues, was determined by RT-PCR and Western blotting. Expression of PAR-1, RhoA, and Rho kinase-1 (effector of RhoA) was ascertained by RT-PCR. MLC phosphorylation was assessed by urea-glycerol gel electrophoresis followed by immunoblotting. The effects of Rho kinase-1 and PKC were characterized by using their selective inhibitors, Y-27632 and chelerythrine, respectively. Reorganization of the cytoskeleton was evaluated by the phalloidin staining of actin. [Ca2+]i was measured using Fura-2. The barrier integrity was assayed as permeability of BCEC monolayers to horseradish peroxidase (HRP; 44 kDa). RT-PCR showed expression of MLCK, PAR-1, Rho kinase-1, and RhoA. Western blotting indicated expression of the non-muscle and smooth muscle isoforms of MLCK. Exposure to thrombin induced an increase in [Ca2+]i with the peak unaffected by an absence of extracellular Ca2+. Pre-exposure to thrombin (2 U ml(-1); 2 min) led to mono- and di-phosphorylation of MLC. Under both basal conditions and in the presence of thrombin, MLC phosphorylation was prevented by chelerythrine (10 microm) and Y-27632 (<25 microm). Thrombin led to inter-endothelial gaps secondary to the disruption of the cortical actin cytoskeleton, which under resting conditions was organized as a perijunctional actomyosin ring (PAMR). These responses were blocked by pre-treatment with Y-27632. Thrombin also increased permeability to HRP, which was abolished by pre-treatment with Y-27632. Thrombin induces MLC phosphorylation in BCEC. The consequent increase in the contractility of the actin cytoskeleton produces a centripetal force resulting in inter-endothelial gaps and a breakdown of barrier integrity. These responses are PKC- and Rho kinase-dependent. [Ca2+]i increase, as well as sensitivity of the thrombin response to PKC and Rho kinase inhibitors, are consistent with the expression of PAR-1 receptors in BCEC. Thrombin-induced hyperpermeability is a model to investigate barrier dysfunction induced by MLC phosphorylation.

SU-E-T-214: Intensity Modulated Proton Therapy (IMPT) Based On Passively Scattered Protons and Multi-Leaf Collimation: Prototype TPS and Dosimetry Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sanchez-Parcerisa, D; Carabe-Fernandez, A

2014-06-01

Purpose. Intensity-modulated proton therapy is usually implemented with multi-field optimization of pencil-beam scanning (PBS) proton fields. However, at the view of the experience with photon-IMRT, proton facilities equipped with double-scattering (DS) delivery and multi-leaf collimation (MLC) could produce highly conformal dose distributions (and possibly eliminate the need for patient-specific compensators) with a clever use of their MLC field shaping, provided that an optimal inverse TPS is developed. Methods. A prototype TPS was developed in MATLAB. The dose calculation process was based on a fluence-dose algorithm on an adaptive divergent grid. A database of dose kernels was precalculated in order tomore » allow for fast variations of the field range and modulation during optimization. The inverse planning process was based on the adaptive simulated annealing approach, with direct aperture optimization of the MLC leaves. A dosimetry study was performed on a phantom formed by three concentrical semicylinders separated by 5 mm, of which the inner-most and outer-most were regarded as organs at risk (OARs), and the middle one as the PTV. We chose a concave target (which is not treatable with conventional DS fields) to show the potential of our technique. The optimizer was configured to minimize the mean dose to the OARs while keeping a good coverage of the target. Results. The plan produced by the prototype TPS achieved a conformity index of 1.34, with the mean doses to the OARs below 78% of the prescribed dose. This Result is hardly achievable with traditional conformal DS technique with compensators, and it compares to what can be obtained with PBS. Conclusion. It is certainly feasible to produce IMPT fields with MLC passive scattering fields. With a fully developed treatment planning system, the produced plans can be superior to traditional DS plans in terms of plan conformity and dose to organs at risk.« less

SU-F-T-271: Comparing IMRT QA Pass Rates Before and After MLC Calibration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mazza, A; Perrin, D; Fontenot, J

Purpose: To compare IMRT QA pass rates before and after an in-house MLC leaf calibration procedure. Methods: The MLC leaves and backup jaws on four Elekta linear accelerators with MLCi2 heads were calibrated using the EPID-based RIT Hancock Test as the means for evaluation. The MLCs were considered to be successfully calibrated when they could pass the Hancock Test with criteria of 1 mm jaw position tolerance, and 1 mm leaf position tolerance. IMRT QA results were collected pre- and postcalibration and analyzed using gamma analysis with 3%/3mm DTA criteria. AAPM TG-119 test plans were also compared pre- and post-calibration,more » at both 2%/2mm DTA and 3%/3mm DTA. Results: A weighted average was performed on the results for all four linear accelerators. The pre-calibration IMRT QA pass rate was 98.3 ± 0.1%, compared with the post-calibration pass rate of 98.5 ± 0.1%. The TG-119 test plan results showed more of an improvement, particularly at the 2%/2mm criteria. The averaged results were 89.1% pre and 96.1% post for the C-shape plan, 94.8% pre and 97.1% post for the multi-target plan, 98.6% pre and 99.7% post for the prostate plan, 94.7% pre and 94.8% post for the head/neck plan. Conclusion: The patient QA results did not show statistically significant improvement at the 3%/3mm DTA criteria after the MLC calibration procedure. However, the TG-119 test cases did show significant improvement at the 2%/2mm level.« less

IL-4 inhibits the synthesis of IFN-gamma and induces the synthesis of IgE in human mixed lymphocyte cultures.

PubMed

Vercelli, D; Jabara, H H; Lauener, R P; Geha, R S

1990-01-15

The T cell-derived lymphokine IL-4 is essential for the induction of IgE synthesis by human lymphocytes. The IgE-inducing effect of IL-4 is antagonized by IFN-gamma. The secretion of IFN-gamma is vigorously triggered in MLC. Thus, IL-4-stimulated MLC represent a suitable model to characterize the functional antagonism between IL-4 and IFN-gamma. In this report, we show that rIL-4 consistently induced IgE synthesis when added to human primary MLC. IL-4-dependent IgE production required cognate T/B cell recognition, because it was inhibited by antibodies to CD3 and MHC class II (HlA-DR) Ag. A neutralizing anti-IFN-gamma mAb dramatically enhanced IL-4-dependent IgE synthesis by MLC, indicating that endogenous IFN-gamma is a major inhibitor of IgE production. More importantly, addition of rIL-4 markedly inhibited the release of IFN-gamma in supernatants of MLC and Con A-activated PBMC. The decrease in IFN-gamma protein was accompanied by a decreased expression of IFN-gamma mRNA transcripts. The downregulation of IFN-gamma by IL-4 is likely to play an important role in the IL-4-dependent induction of IgE synthesis.

IMRT sequencing for a six-bank multi-leaf system.

PubMed

Topolnjak, R; van der Heide, U A; Lagendijk, J J W

2005-05-07

In this study, we present a sequencer for delivering step-and-shoot IMRT using a six-bank multi-leaf system. Such a system was proposed earlier and combines a high-resolution field-shaping ability with a large field size. It consists of three layers of two opposing leaf banks with 1 cm leaves. The layers are rotated relative to each other at 60 degrees . A low-resolution mode of sequencing is achieved by using one layer of leaves as primary MLC, while the other two are used to improve back-up collimation. For high-resolution sequencing, an algorithm is presented that creates segments shaped by all six banks. Compared to a hypothetical mini-MLC with 0.4 cm leaves, a similar performance can be achieved, but a trade-off has to be made between accuracy and the number of segments.

Multileaf collimator performance monitoring and improvement using semiautomated quality control testing and statistical process control

DOE Office of Scientific and Technical Information (OSTI.GOV)

Létourneau, Daniel, E-mail: daniel.letourneau@rmp.uh.on.ca; McNiven, Andrea; Keller, Harald

2014-12-15

Purpose: High-quality radiation therapy using highly conformal dose distributions and image-guided techniques requires optimum machine delivery performance. In this work, a monitoring system for multileaf collimator (MLC) performance, integrating semiautomated MLC quality control (QC) tests and statistical process control tools, was developed. The MLC performance monitoring system was used for almost a year on two commercially available MLC models. Control charts were used to establish MLC performance and assess test frequency required to achieve a given level of performance. MLC-related interlocks and servicing events were recorded during the monitoring period and were investigated as indicators of MLC performance variations. Methods:more » The QC test developed as part of the MLC performance monitoring system uses 2D megavoltage images (acquired using an electronic portal imaging device) of 23 fields to determine the location of the leaves with respect to the radiation isocenter. The precision of the MLC performance monitoring QC test and the MLC itself was assessed by detecting the MLC leaf positions on 127 megavoltage images of a static field. After initial calibration, the MLC performance monitoring QC test was performed 3–4 times/week over a period of 10–11 months to monitor positional accuracy of individual leaves for two different MLC models. Analysis of test results was performed using individuals control charts per leaf with control limits computed based on the measurements as well as two sets of specifications of ±0.5 and ±1 mm. Out-of-specification and out-of-control leaves were automatically flagged by the monitoring system and reviewed monthly by physicists. MLC-related interlocks reported by the linear accelerator and servicing events were recorded to help identify potential causes of nonrandom MLC leaf positioning variations. Results: The precision of the MLC performance monitoring QC test and the MLC itself was within ±0.22 mm for most MLC leaves and the majority of the apparent leaf motion was attributed to beam spot displacements between irradiations. The MLC QC test was performed 193 and 162 times over the monitoring period for the studied units and recalibration had to be repeated up to three times on one of these units. For both units, rate of MLC interlocks was moderately associated with MLC servicing events. The strongest association with the MLC performance was observed between the MLC servicing events and the total number of out-of-control leaves. The average elapsed time for which the number of out-of-specification or out-of-control leaves was within a given performance threshold was computed and used to assess adequacy of MLC test frequency. Conclusions: A MLC performance monitoring system has been developed and implemented to acquire high-quality QC data at high frequency. This is enabled by the relatively short acquisition time for the images and automatic image analysis. The monitoring system was also used to record and track the rate of MLC-related interlocks and servicing events. MLC performances for two commercially available MLC models have been assessed and the results support monthly test frequency for widely accepted ±1 mm specifications. Higher QC test frequency is however required to maintain tighter specification and in-control behavior.« less

The national cholesterol education program diet vs a diet lower in carbohydrates and higher in protein and monounsaturated fat: a randomized trial.

PubMed

Aude, Y Wady; Agatston, Arthur S; Lopez-Jimenez, Francisco; Lieberman, Eric H; Marie Almon; Hansen, Melinda; Rojas, Gerardo; Lamas, Gervasio A; Hennekens, Charles H

2004-10-25

In the United States, obesity is a major clinical and public health problem causing diabetes, dyslipidemia, and hypertension, as well as increasing cardiovascular and total mortality. Dietary restrictions of calories and saturated fat are beneficial. However, it remains unclear whether replacement of saturated fat with carbohydrates (as in the US National Cholesterol Education Program [NCEP] diet) or protein and monounsaturated fat (as in our isocaloric modified low-carbohydrate [MLC] diet, which is lower in total carbohydrates but higher in protein, monounsaturated fat, and complex carbohydrates) is optimal. We randomized 60 participants (29 women and 31 men) to the NCEP or the MLC diet and evaluated them every 2 weeks for 12 weeks. They were aged 28 to 71 years (mean age, 44 years in the NCEP and 46 years in the MLC group). A total of 36% of participants from the NCEP group and 35% from the MLC group had a body mass index (calculated as weight in kilograms divided by the square of height in meters) greater than 27. The primary end point was weight loss, and secondary end points were blood lipid levels and waist-to-hip ratio. Weight loss was significantly greater in the MLC (13.6 lb) than in the NCEP group (7.5 lb), a difference of 6.1 lb (P = .02). There were no significant differences between the groups for total, low density, and high-density lipoprotein cholesterol, triglycerides, or the proportion of small, dense low-density lipoprotein particles. There were significantly favorable changes in all lipid levels within the MLC but not within the NCEP group. Waist-to-hip ratio was not significantly reduced between the groups (P = .27), but it significantly decreased within the MLC group (P = .009). Compared with the NCEP diet, the MLC diet, which is lower in total carbohydrates but higher in complex carbohydrates, protein, and monounsaturated fat, caused significantly greater weight loss over 12 weeks. There were no significant differences between the groups in blood lipid levels, but favorable changes were observed within the MLC diet group.

Differential Expression Levels of Integrin α6 Enable the Selective Identification and Isolation of Atrial and Ventricular Cardiomyocytes.

PubMed

Wiencierz, Anne Maria; Kernbach, Manuel; Ecklebe, Josephine; Monnerat, Gustavo; Tomiuk, Stefan; Raulf, Alexandra; Christalla, Peter; Malan, Daniela; Hesse, Michael; Bosio, Andreas; Fleischmann, Bernd K; Eckardt, Dominik

2015-01-01

Central questions such as cardiomyocyte subtype emergence during cardiogenesis or the availability of cardiomyocyte subtypes for cell replacement therapy require selective identification and purification of atrial and ventricular cardiomyocytes. However, current methodologies do not allow for a transgene-free selective isolation of atrial or ventricular cardiomyocytes due to the lack of subtype specific cell surface markers. In order to develop cell surface marker-based isolation procedures for cardiomyocyte subtypes, we performed an antibody-based screening on embryonic mouse hearts. Our data indicate that atrial and ventricular cardiomyocytes are characterized by differential expression of integrin α6 (ITGA6) throughout development and in the adult heart. We discovered that the expression level of this surface marker correlates with the intracellular subtype-specific expression of MLC-2a and MLC-2v on the single cell level and thereby enables the discrimination of cardiomyocyte subtypes by flow cytometry. Based on the differential expression of ITGA6 in atria and ventricles during cardiogenesis, we developed purification protocols for atrial and ventricular cardiomyocytes from mouse hearts. Atrial and ventricular identities of sorted cells were confirmed by expression profiling and patch clamp analysis. Here, we introduce a non-genetic, antibody-based approach to specifically isolate highly pure and viable atrial and ventricular cardiomyocytes from mouse hearts of various developmental stages. This will facilitate in-depth characterization of the individual cellular subsets and support translational research applications.

Differential Expression Levels of Integrin α6 Enable the Selective Identification and Isolation of Atrial and Ventricular Cardiomyocytes

PubMed Central

Wiencierz, Anne Maria; Kernbach, Manuel; Ecklebe, Josephine; Monnerat, Gustavo; Tomiuk, Stefan; Raulf, Alexandra; Christalla, Peter; Malan, Daniela; Hesse, Michael; Bosio, Andreas; Fleischmann, Bernd K.; Eckardt, Dominik

2015-01-01

Rationale Central questions such as cardiomyocyte subtype emergence during cardiogenesis or the availability of cardiomyocyte subtypes for cell replacement therapy require selective identification and purification of atrial and ventricular cardiomyocytes. However, current methodologies do not allow for a transgene-free selective isolation of atrial or ventricular cardiomyocytes due to the lack of subtype specific cell surface markers. Methods and Results In order to develop cell surface marker-based isolation procedures for cardiomyocyte subtypes, we performed an antibody-based screening on embryonic mouse hearts. Our data indicate that atrial and ventricular cardiomyocytes are characterized by differential expression of integrin α6 (ITGA6) throughout development and in the adult heart. We discovered that the expression level of this surface marker correlates with the intracellular subtype-specific expression of MLC-2a and MLC-2v on the single cell level and thereby enables the discrimination of cardiomyocyte subtypes by flow cytometry. Based on the differential expression of ITGA6 in atria and ventricles during cardiogenesis, we developed purification protocols for atrial and ventricular cardiomyocytes from mouse hearts. Atrial and ventricular identities of sorted cells were confirmed by expression profiling and patch clamp analysis. Conclusion Here, we introduce a non-genetic, antibody-based approach to specifically isolate highly pure and viable atrial and ventricular cardiomyocytes from mouse hearts of various developmental stages. This will facilitate in-depth characterization of the individual cellular subsets and support translational research applications. PMID:26618511

Airborne particulate matter in vitro exposure induces cytoskeleton remodeling through activation of the ROCK-MYPT1-MLC pathway in A549 epithelial lung cells.

PubMed

Chirino, Yolanda I; García-Cuellar, Claudia María; García-García, Carlos; Soto-Reyes, Ernesto; Osornio-Vargas, Álvaro Román; Herrera, Luis A; López-Saavedra, Alejandro; Miranda, Javier; Quintana-Belmares, Raúl; Pérez, Irma Rosas; Sánchez-Pérez, Yesennia

2017-04-15

Airborne particulate matter with an aerodynamic diameter ≤10μm (PM 10 ) is considered a risk factor for the development of lung cancer. Little is known about the cellular mechanisms by which PM 10 is associated with cancer, but there is evidence that its exposure can lead to an acquired invasive phenotype, apoptosis evasion, inflammasome activation, and cytoskeleton remodeling in lung epithelial cells. Cytoskeleton remodeling occurs through actin stress fiber formation, which is partially regulated through ROCK kinase activation, we aimed to investigate if this protein was activated in response to PM 10 exposure in A549 lung epithelial cells. Results showed that 10μg/cm 2 of PM 10 had no influence on cell viability but increased actin stress fibers, cytoplasmic ROCK expression, and phosphorylation of myosin phosphatase-targeting 1 (MYPT1) and myosin light chain (MLC) proteins, which are targeted by ROCK. The inhibition of ROCK prevented actin stress fiber formation and the phosphorylation of MYPT1 and MLC, suggesting that PM 10 activated the ROCK-MYPT1-MLC pathway in lung epithelial cells. The activation of ROCK1 has been involved in the acquisition of malignant phenotypes, and its induction by PM 10 exposure could contribute to the understanding of PM 10 as a risk factor for cancer development through the mechanisms associated with invasive phenotype. Copyright © 2017 Elsevier B.V. All rights reserved.

SU-E-T-784: Using MLC Log Files for Daily IMRT Delivery Verification

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stathakis, S; Defoor, D; Linden, P

2015-06-15

Purpose: To verify daily intensity modulated radiation therapy (IMRT) treatments using multi-leaf collimator (MLC) log files. Methods: The MLC log files from a NovalisTX Varian linear accelerator were used in this study. The MLC files were recorded daily for all patients undergoing IMRT or volumetric modulated arc therapy (VMAT). The first record of each patient was used as reference and all records for subsequent days were compared against the reference. An in house MATLAB software code was used for the comparisons. Each MLC log file was converted to a fluence map (FM) and a gamma index (γ) analysis was usedmore » for the evaluation of each daily delivery for every patient. The tolerance for the gamma index was set to 2% dose difference and 2mm distance to agreement while points with signal of 10% or lower of the maximum value were excluded from the comparisons. Results: The γ between each of the reference FMs and the consecutive daily fraction FMs had an average value of 99.1% (ranged from 98.2 to 100.0%). The FM images were reconstructed at various resolutions in order to study the effect of the resolution on the γ and at the same time reduce the time for processing the images. We found that the comparison of images with the highest resolution (768×1024) yielded on average a lower γ (99.1%) than the ones with low resolution (192×256) (γ 99.5%). Conclusion: We developed an in-house software that allows us to monitor the quality of daily IMRT and VMAT treatment deliveries using information from the MLC log files of the linear accelerator. The information can be analyzed and evaluated as early as after the completion of each daily treatment. Such tool can be valuable to assess the effect of MLC positioning on plan quality, especially in the context of adaptive radiotherapy.« less

SU-F-T-629: Effect of Multi-Leaf Collimator (MLC) Width On Plan Quality of Single-Isocenter VMAT Intracranial Stereotactic Radiosurgery for Multiple Metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kraus, J; Thomas, E; Wu, X

2016-06-15

Purpose: Single-isocenter VMAT has been shown able to create high quality plans for complex intracranial multiple metastasis SRS cases. Linacs capable of the technique are typically outfitted with an MLC that consists of a combination of 5 mm and 10 mm leaves (standard) or 2.5 mm and 5 mm leaves (high-definition). In this study, we test the hypothesis that thinner collimator leaves are associated with improved plan quality. Methods: Ten multiple metastasis cases were identified and planned for VMAT SRS using a 10 MV flattening filter free beam. Plans were created for a standard (std) and a high-definition (HD) MLC.more » Published values for leaf transmission factor and dosimetric leaf gap were utilized. All other parameters were invariant. Conformity (plan and individual target), moderate isodose spill (V50%), and low isodose spill (mean brain dose) were selected for analysis. Results: Compared to standard MLC, HD-MLC improved overall plan conformity (median: Paddick CI-HD = 0.83, Paddick CI-std = 0.79; p = 0.004 and median: RTOG CI-HD =1.18, RTOG CI-std =1.24; p = 0.01 ), improved individual lesion conformity (median: Paddick CI-HD,i =0.77, Paddick CI-std,i =0.72; p < 0.001 and median: RTOG CI-HD,i = 1.28, RTOG CI-std,i =1.35; p < 0.001), improved moderate isodose spill (median: V50%-HD = 37.0 cc, V50%-std = 45.7 cc; p = 0.002), and improved low dose spill (median: dmean-HD = 2.90 Gy, dmean-std = 3.19 Gy; p = 0.002). Conclusion: For the single-isocenter VMAT SRS of multiple metastasis plans examined, use of HD-MLC modestly improved conformity, moderate isodose, and low isodose spill compared to standard MLC. However, in all cases we were able to generate clinically acceptable plans with the standard MLC. More work is need to further quantify the difference in cases with higher numbers of small targets and to better understand any potential clinical significance. This research was supported in part by Varian Medical Systems.« less

Role of Rac1 in Escherichia coli K1 invasion of human brain microvascular endothelial cells.

PubMed

Rudrabhatla, Rajyalakshmi S; Selvaraj, Suresh K; Prasadarao, Nemani V

2006-02-01

Escherichia coli K1 invasion of human brain microvascular endothelial cells (HBMEC) requires the reorganization of host cytoskeleton at the sites of bacterial entry. Both actin and myosin constitute the cytoskeletal architecture. We have previously shown that myosin light chain (MLC) phosphorylation by MLC kinase is regulated during E. coli invasion by an upstream kinase, p21-activated kinase 1 (PAK1), which is an effector protein of Rac and Cdc42 GTPases, but not of RhoA. Here, we report that the binding of only Rac1 to PAK1 decreases in HBMEC upon infection with E. coli K1, which resulted in increased phosphorylation of MLC. Overexpression of a constitutively active (cAc) form of Rac1 in HBMEC blocked the E. coli invasion significantly, whereas overexpression of a dominant negative form had no effect. Increased PAK1 phosphorylation was observed in HBMEC expressing cAc-Rac1 with a concomitant reduction in the phosphorylation of MLC. Immunocytochemistry studies demonstrated that the inhibition of E. coli invasion into cAc-Rac1/HBMEC is due to lack of phospho-MLC recruitment to the sites of E. coli entry. Taken together the data suggest that E. coli modulates the binding of Rac1, but not Cdc42, to PAK1 during the invasion of HBMEC.

SU-F-T-230: A Simple Method to Assess Accuracy of Dynamic Wave Arc Irradiation Using An Electronic Portal Imaging Device and Log Files

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hirashima, H; Miyabe, Y; Yokota, K

2016-06-15

Purpose: The Dynamic Wave Arc (DWA) technique, where the multi-leaf collimator (MLC) and gantry/ring move simultaneously in a predefined non-coplanar trajectory, has been developed on the Vero4DRT. The aim of this study is to develop a simple method for quality assurance of DWA delivery using an electronic portal imaging device (EPID) measurements and log files analysis. Methods: The Vero4DRT has an EPID on the beam axis, the resolution of which is 0.18 mm/pixel at the isocenter plane. EPID images were acquired automatically. To verify the detection accuracy of the MLC position by EPID images, the MLC position with intentional errorsmore » was assessed. Tests were designed considering three factors: (1) accuracy of the MLC position (2) dose output consistency with variable dose rate (160–400 MU/min), gantry speed (2.4–6°/s), ring speed (0.5–2.5°/s), and (3) MLC speed (1.6–4.2 cm/s). All the patterns were delivered to the EPID and compared with those obtained with a stationary radiation beam with a 0° gantry angle. The irradiation log, including the MLC position and gantry/ring angle, were recorded simultaneously. To perform independent checks of the machine accuracy, the MLC position and gantry/ring angle position were assessed using log files. Results: 0.1 mm intentional error can be detected by the EPID, which is smaller than the EPID pixel size. The dose outputs with different conditions of the dose rate and gantry/ring speed and MLC speed showed good agreement, with a root mean square (RMS) error of 0.76%. The RMS error between the detected and recorded data were 0.1 mm for the MLC position, 0.12° for the gantry angle, and 0.07° for the ring angle. Conclusion: The MLC position and dose outputs in variable conditions during DWA irradiation can be easily detected using EPID measurements and log file analysis. The proposed method is useful for routine verification. This research is (partially) supported by the Practical Research for Innovative Cancer Control (15Ack0106151h0001) from Japan Agency for Medical Research and development, AMED. Authors Takashi Mizowaki and Masahiro Hiraoka have consultancy agreement with Mitsubishi Heavy Industries, Ltd., Japan.« less

Purification, Characterization and Analysis of the Allergenic Properties of Myosin Light Chain in Procambarus clarkia.

USDA-ARS?s Scientific Manuscript database

Myosin light chain (MLC) plays a vital role in cell and muscle functions and has been identified as an allergen in close species. In this study, MLC with the molecular mass of 18kDa was purified from crayfish (Procambarus clarkii) muscle fibrils. Its physicochemical characterization showed that the...

A post-transcriptional compensatory pathway in heterozygous ventricular myosin light chain 2-deficient mice results in lack of gene dosage effect during normal cardiac growth or hypertrophy.

PubMed

Minamisawa, S; Gu, Y; Ross, J; Chien, K R; Chen, J

1999-04-09

Our previous study of homozygous mutants of the ventricular specific isoform of myosin light chain 2 (mlc-2v) demonstrated that mlc-2v plays an essential role in murine heart development (Chen, J., Kubalak, S. W., Minamisawa, S., Price, R. L., Becker, K. D., Hickey, R., Ross, J., Jr., and Chien, K. R. (1998) J. Biol. Chem. 273, 1252-1256). As gene dosage of some myofibrillar proteins can affect muscle function, we have analyzed heterozygous mutants in depth. Ventricles of heterozygous mutants displayed a 50% reduction in mlc-2v mRNA, yet expressed normal levels of protein both under basal conditions and following induction of cardiac hypertrophy by aortic constriction. Heterozygous mutants exhibited cardiac function comparable to that of wild-type littermate controls both prior to and following aortic constriction. There were no significant differences in contractility and responses to calcium between wild-type and heterozygous unloaded cardiomyocytes. We conclude that heterozygous mutants show neither a molecular nor a physiological cardiac phenotype either at base line or following hypertrophic stimuli. These results suggest that post-transcriptional compensatory mechanisms play a major role in maintaining the level of MLC-2v protein in murine hearts. In addition, as our mlc-2v knockout mutants were created by a knock-in of Cre recombinase into the endogenous mlc-2v locus, this study demonstrates that heterozygous mlc-2v cre knock-in mice are appropriate for ventricular specific gene targeting.

The B2 Alternatively Spliced Isoform of Nonmuscle Myosin II-B Lacks Actin-activated MgATPase Activity and In Vitro Motility

PubMed Central

Kim, Kye-Young; Kawamoto, Sachiyo; Bao, Jianjun; Sellers, James R.; Adelstein, Robert S.

2008-01-01

We report the initial biochemical characterization of an alternatively spliced isoform of nonmuscle heavy meromyosin (HMM) II-B2 and compare it with HMM II-B0, the non-spliced isoform. HMM II-B2 is the HMM derivative of an alternatively spliced isoform of endogenous nonmuscle myosin (NM) II-B, which has 21-amino acids inserted into loop 2, near the actin-binding region. NM II-B2 is expressed in the Purkinje cells of the cerebellum as well as in other neuronal cells (Ma et al., Mol. Biol. Cell 15 (2006) 2138-2149). In contrast to any of the previously described isoforms of NM II (II-A, II-B0, II-B1, II-C0 and II-C1) or to smooth muscle myosin, the actin-activated MgATPase activity of HMM II-B2 is not significantly increased from a low, basal level by phosphorylation of the 20 kDa myosin light chain (MLC-20). Moreover, although HMM II-B2 can bind to actin in the absence of ATP and is released in its presence, it cannot propel actin in the sliding actin filament assay following MLC-20 phosphorylation. Unlike HMM II-B2, the actin-activated MgATPase activity of a chimeric HMM with the 21-amino acids II-B2 sequence inserted into the homologous location in the heavy chain of HMM II-C is increased following MLC-20 phosphorylation. This indicates that the effect of the II-B2 insert is myosin heavy chain specific. PMID:18060863

Different signaling pathways induced by alpha-CD3 monoclonal antibody versus alloantigen on the basis of differential ornithine sensitivity.

PubMed

Mehrotra nee Tandon, P; Lind, D S; Bear, H D; Susskind, B M

1992-08-01

Previously we reported that 10 mM ornithine (Orn) selectively inhibits the development of CD8+ CTL in MLC. Herein we show that induction by alpha-CD3 mAb of CD8+ killer cells which manifest antibody-redirected cytotoxicity (ARC) of FcR+ targets is not Orn sensitive. Orn resistance was independent of activation kinetics or alpha-CD3 mAb concentration. alpha-CD3 mAb added to the cytotoxicity assay did not reveal a cytolytic potential in CTL from an Orn-treated MLC when the target cells bore both the inducing alloantigen and FcR. Addition of alpha-CD3 mAb to MLC failed to overcome Orn inhibition of CTL and yet induced ARC activity in the same culture. Expression of mRNA for pore-forming proteins (PFP) and granzyme B was inhibited by Orn in CTL but not in ARC killer cells. Our results demonstrate differences in the T cell activation process stimulated by alloantigen or alpha-CD3 mAb.

Induction of specific immune unresponsiveness with purified mixed leukocyte culture-activated T lymphoblasts as autoimmunogen. II. An analysis of the effects measured at the cellular and serological levels

PubMed Central

1978-01-01

T lymphoblasts specific for foreign histocompatibility antigens and purified via mixed leukocyte culture (MLC) and 1 g velocity sedimentation procedures can be used as autoimmunogen to produce specific immunological unresponsiveness in adult animals. This unresponsiveness is positively correlated to the production of autoanti- idiotypic antibodies in the blast immunized animals and no evidence of coexisting alloimmunity was found. We consider this autoanti-idiotypic immunity to be the specific inducing agent of the immune tolerance. The blast immunization procedure will lead to selective reduction in T-cell reactivity against the relevant alloantigens as measured by MLC, cell- mediated lympholysis, or graft-versus-host assays. However, in individual animals, dichtomy in suppression between two T-cell assays could sometimes be observed indicating elimination of only a select group of idiotypic functionally distinct population of T cells in these blast-immunized animals. Attempts to abrogate already immune animals by the autoblast procedure were successful, in part suggesting the use of the present procedure when trying to induce in accelerated reversion of such immunity. PMID:75235

Mlc Is a Transcriptional Activator with a Key Role in Integrating Cyclic AMP Receptor Protein and Integration Host Factor Regulation of Leukotoxin RNA Synthesis in Aggregatibacter actinomycetemcomitans

PubMed Central

Childress, Catherine; Feuerbacher, Leigh A.; Phillips, Linda; Burgum, Alex

2013-01-01

Aggregatibacter actinomycetemcomitans, a periodontal pathogen, synthesizes leukotoxin (LtxA), a protein that helps the bacterium evade the host immune response. Transcription of the ltxA operon is induced during anaerobic growth. The cyclic AMP (cAMP) receptor protein (CRP) indirectly increases ltxA expression, but the intermediary regulator is unknown. Integration host factor (IHF) binds to and represses the leukotoxin promoter, but neither CRP nor IHF is responsible for the anaerobic induction of ltxA RNA synthesis. Thus, we have undertaken studies to identify other regulators of leukotoxin transcription and to demonstrate how these proteins work together to modulate leukotoxin synthesis. First, analyses of ltxA RNA expression from defined leukotoxin promoter mutations in the chromosome identify positions −69 to −35 as the key control region and indicate that an activator protein modulates leukotoxin transcription. We show that Mlc, which is a repressor in Escherichia coli, functions as a direct transcriptional activator in A. actinomycetemcomitans; an mlc deletion mutant reduces leukotoxin RNA synthesis, and recombinant Mlc protein binds specifically at the −68 to −40 region of the leukotoxin promoter. Furthermore, we show that CRP activates ltxA expression indirectly by increasing the levels of Mlc. Analyses of Δmlc, Δihf, and Δihf Δmlc strains demonstrate that Mlc can increase RNA polymerase (RNAP) activity directly and that IHF represses ltxA RNA synthesis mainly by blocking Mlc binding. Finally, a Δihf Δmlc mutant still induces ltxA during anaerobic growth, indicating that there are additional factors involved in leukotoxin transcriptional regulation. A model for the coordinated regulation of leukotoxin transcription is presented. PMID:23475968

SU-C-BRB-02: Symmetric and Asymmetric MLC Based Lung Shielding and Dose Optimization During Translating Bed TBI

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ahmed, S; Kakakhel, MB; Ahmed, SBS

2015-06-15

Purpose: The primary aim was to introduce a dose optimization method for translating bed total body irradiation technique that ensures lung shielding dynamically. Symmetric and asymmetric dynamic MLC apertures were employed for this purpose. Methods: The MLC aperture sizes were defined based on the radiological depth values along the divergent ray lines passing through the individual CT slices. Based on these RD values, asymmetrically shaped MLC apertures were defined every 9 mm of the phantom in superior-inferior direction. Individual MLC files were created with MATLAB™ and were imported into Eclipse™ treatment planning system for dose calculations. Lungs can be shieldedmore » to an optimum level by reducing the MLC aperture width over the lungs. The process was repeated with symmetrically shaped apertures. Results: Dose-volume histogram (DVH) analysis shows that the asymmetric MLC based technique provides better dose coverage to the body and optimum shielding of the lungs compared to symmetrically shaped beam apertures. Midline dose homogeneity is within ±3% with asymmetric MLC apertures whereas it remains within ±4.5% with symmetric ones (except head region where it drops down to −7%). The substantial over and under dosage of ±5% at tissue interfaces has been reduced to ±2% with asymmetric MLC technique. Lungs dose can be reduced to any desired limit. In this experiment lungs dose was reduced to 80% of the prescribed dose, as was desired. Conclusion: The novel asymmetric MLC based technique assures optimum shielding of OARs (e.g. lungs) and better 3-D dose homogeneity and body-dose coverage in comparison with the symmetric MLC aperture optimization. The authors acknowledge the financial and infrastructural support provided by Pakistan Institute of Engineering & Applied Sciences (PIEAS), Islamabad and Aga Khan University Hospital (AKUH), Karachi during the course of this research project. Authors have no conflict of interest with any national / international body for the presented work.« less

Minocycline Promotes Neurite Outgrowth of PC12 Cells Exposed to Oxygen-Glucose Deprivation and Reoxygenation Through Regulation of MLCP/MLC Signaling Pathways.

PubMed

Tao, Tao; Feng, Jin-Zhou; Xu, Guang-Hui; Fu, Jie; Li, Xiao-Gang; Qin, Xin-Yue

2017-04-01

Minocycline, a semi-synthetic second-generation derivative of tetracycline, has been reported to exert neuroprotective effects both in animal models and in clinic trials of neurological diseases. In the present study, we first investigated the protective effects of minocycline on oxygen-glucose deprivation and reoxygenation-induced impairment of neurite outgrowth and its potential mechanism in the neuronal cell line, PC12 cells. We found that minocycline significantly increased cell viability, promoted neurite outgrowth and enhanced the expression of growth-associated protein-43 (GAP-43) in PC12 cells exposed to oxygen-glucose deprivation/reoxygenation injury. In addition, immunoblots revealed that minocycline reversed the overexpression of phosphorylated myosin light chain (MLC) and the suppression of activated extracellular signal-regulated kinase 1/2 (ERK1/2) caused by oxygen-glucose deprivation/reoxygenation injury. Moreover, the minocycline-induced neurite outgrowth was significantly blocked by Calyculin A (1 nM), an inhibitor of myosin light chain phosphatase (MLCP), but not by an ERK1/2 inhibitor (U0126; 10 μM). These findings suggested that minocycline activated the MLCP/MLC signaling pathway in PC12 cells after oxygen-glucose deprivation/reoxygenation injury, which resulted in the promotion of neurite outgrowth.

Testing the methodology for dosimetry audit of heterogeneity corrections and small MLC-shaped fields: Results of IAEA multi-center studies

PubMed Central

Izewska, Joanna; Wesolowska, Paulina; Azangwe, Godfrey; Followill, David S.; Thwaites, David I.; Arib, Mehenna; Stefanic, Amalia; Viegas, Claudio; Suming, Luo; Ekendahl, Daniela; Bulski, Wojciech; Georg, Dietmar

2016-01-01

Abstract The International Atomic Energy Agency (IAEA) has a long tradition of supporting development of methodologies for national networks providing quality audits in radiotherapy. A series of co-ordinated research projects (CRPs) has been conducted by the IAEA since 1995 assisting national external audit groups developing national audit programs. The CRP ‘Development of Quality Audits for Radiotherapy Dosimetry for Complex Treatment Techniques’ was conducted in 2009–2012 as an extension of previously developed audit programs. Material and methods. The CRP work described in this paper focused on developing and testing two steps of dosimetry audit: verification of heterogeneity corrections, and treatment planning system (TPS) modeling of small MLC fields, which are important for the initial stages of complex radiation treatments, such as IMRT. The project involved development of a new solid slab phantom with heterogeneities containing special measurement inserts for thermoluminescent dosimeters (TLD) and radiochromic films. The phantom and the audit methodology has been developed at the IAEA and tested in multi-center studies involving the CRP participants. Results. The results of multi-center testing of methodology for two steps of dosimetry audit show that the design of audit procedures is adequate and the methodology is feasible for meeting the audit objectives. A total of 97% TLD results in heterogeneity situations obtained in the study were within 3% and all results within 5% agreement with the TPS predicted doses. In contrast, only 64% small beam profiles were within 3 mm agreement between the TPS calculated and film measured doses. Film dosimetry results have highlighted some limitations in TPS modeling of small beam profiles in the direction of MLC leave movements. Discussion. Through multi-center testing, any challenges or difficulties in the proposed audit methodology were identified, and the methodology improved. Using the experience of these studies, the participants could incorporate the auditing procedures in their national programs. PMID:26934916

Testing the methodology for dosimetry audit of heterogeneity corrections and small MLC-shaped fields: Results of IAEA multi-center studies.

PubMed

Izewska, Joanna; Wesolowska, Paulina; Azangwe, Godfrey; Followill, David S; Thwaites, David I; Arib, Mehenna; Stefanic, Amalia; Viegas, Claudio; Suming, Luo; Ekendahl, Daniela; Bulski, Wojciech; Georg, Dietmar

2016-07-01

The International Atomic Energy Agency (IAEA) has a long tradition of supporting development of methodologies for national networks providing quality audits in radiotherapy. A series of co-ordinated research projects (CRPs) has been conducted by the IAEA since 1995 assisting national external audit groups developing national audit programs. The CRP 'Development of Quality Audits for Radiotherapy Dosimetry for Complex Treatment Techniques' was conducted in 2009-2012 as an extension of previously developed audit programs. The CRP work described in this paper focused on developing and testing two steps of dosimetry audit: verification of heterogeneity corrections, and treatment planning system (TPS) modeling of small MLC fields, which are important for the initial stages of complex radiation treatments, such as IMRT. The project involved development of a new solid slab phantom with heterogeneities containing special measurement inserts for thermoluminescent dosimeters (TLD) and radiochromic films. The phantom and the audit methodology has been developed at the IAEA and tested in multi-center studies involving the CRP participants. The results of multi-center testing of methodology for two steps of dosimetry audit show that the design of audit procedures is adequate and the methodology is feasible for meeting the audit objectives. A total of 97% TLD results in heterogeneity situations obtained in the study were within 3% and all results within 5% agreement with the TPS predicted doses. In contrast, only 64% small beam profiles were within 3 mm agreement between the TPS calculated and film measured doses. Film dosimetry results have highlighted some limitations in TPS modeling of small beam profiles in the direction of MLC leave movements. Through multi-center testing, any challenges or difficulties in the proposed audit methodology were identified, and the methodology improved. Using the experience of these studies, the participants could incorporate the auditing procedures in their national programs.

SU-D-201-01: A Multi-Institutional Study Quantifying the Impact of Simulated Linear Accelerator VMAT Errors for Nasopharynx

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pogson, E; Liverpool and Macarthur Cancer Therapy Centres, Liverpool, NSW; Ingham Institute for Applied Medical Research, Sydney, NSW

Purpose: To quantify the impact of differing magnitudes of simulated linear accelerator errors on the dose to the target volume and organs at risk for nasopharynx VMAT. Methods: Ten nasopharynx cancer patients were retrospectively replanned twice with one full arc VMAT by two institutions. Treatment uncertainties (gantry angle and collimator in degrees, MLC field size and MLC shifts in mm) were introduced into these plans at increments of 5,2,1,−1,−2 and −5. This was completed using an in-house Python script within Pinnacle3 and analysed using 3DVH and MatLab. The mean and maximum dose were calculated for the Planning Target Volume (PTV1),more » parotids, brainstem, and spinal cord and then compared to the original baseline plan. The D1cc was also calculated for the spinal cord and brainstem. Patient average results were compared across institutions. Results: Introduced gantry angle errors had the smallest effect of dose, no tolerances were exceeded for one institution, and the second institutions VMAT plans were only exceeded for gantry angle of ±5° affecting different sided parotids by 14–18%. PTV1, brainstem and spinal cord tolerances were exceeded for collimator angles of ±5 degrees, MLC shifts and MLC field sizes of ±1 and beyond, at the first institution. At the second institution, sensitivity to errors was marginally higher for some errors including the collimator error producing doses exceeding tolerances above ±2 degrees, and marginally lower with tolerances exceeded above MLC shifts of ±2. The largest differences occur with MLC field sizes, with both institutions reporting exceeded tolerances, for all introduced errors (±1 and beyond). Conclusion: The plan robustness for VMAT nasopharynx plans has been demonstrated. Gantry errors have the least impact on patient doses, however MLC field sizes exceed tolerances even with relatively low introduced errors and also produce the largest errors. This was consistent across both departments. The authors acknowledge funding support from the NSW Cancer Council.« less

Rho-Rho kinase pathway in the actomyosin contraction and cell-matrix adhesion in immortalized human trabecular meshwork cells

PubMed Central

Ramachandran, C.; Patil, R.V.; Combrink, K.; Sharif, N.A.

2011-01-01

Purpose The outflow facility for aqueous humor across the trabecular meshwork (TM) is enhanced by agents that oppose the actomyosin contraction of its resident cells. Phosphorylation of MYPT1 (myosin light chain [MLC] phosphatase complex of Type 1) at Thr853 and Thr696 inhibits dephosphorylation of MLC, leading to an increase in actomyosin contraction. In this study, we examined the effects of Rho kinase (ROCK) inhibitors on the relative dephosphorylation of the two sites of MYPT1 using human TM cells (GTM3). Methods Dephosphorylation of MYPT1 at Thr853 and Thr696 was determined by western blot analysis following exposure to selective inhibitors of ROCK, namely Y-27632 and Y-39983. Consequent dephosphorylation of MLC and decreases in actomyosin contraction were assessed by western blot analysis and collagen gel contraction assay, respectively. Changes in the cell-matrix adhesion were measured in real time by electric cell-substrate impedance sensing and also assessed by staining for paxillin, vinculin, and focal adhesion kinase (FAK). Results Both ROCK inhibitors produced a concentration-dependent dephosphorylation at Thr853 and Thr696 of MYPT1 in adherent GTM3 cells. IC50 values for Y-39983 were 15 nM and 177 nM for dephosphorylation at Thr853 and Thr696, respectively. Corresponding values for Y-27632 were 658 nM and 2270 nM. Analysis of the same samples showed a decrease in MLC phosphorylation with IC50 values of 14 nM and 1065 nM for Y-39983 and Y-27632, respectively. Consistent with these changes, both inhibitors opposed contraction of collagen gels induced by TM cells. Exposure of cells to the inhibitors led to a decrease in the electrical cell-substrate resistance, with the effect of Y-39983 being more pronounced than Y-27632. Treatment with these ROCK inhibitors also showed a loss of stress fibers and a concomitant decrease in tyrosine phosphorylation of paxillin and FAK. Conclusions Y-39983 and Y-27632 oppose ROCK-dependent phosphorylation of MYPT1 predominantly at Thr853 with a corresponding decrease in MLC phosphorylation. A relatively low effect of both ROCK inhibitors at Thr696 suggests a role for other Ser/Thr kinases at this site. Y-39983 was several-fold more potent when compared with Y-27632 at inhibiting the phosphorylation of MYPT1 at either Thr853 or Thr696 commensurate with its greater potency at inhibiting the activity of human ROCK-I and ROCK-II enzymes. PMID:21850162

Front-signal-dependent accumulation of the RHOA inhibitor FAM65B at leading edges polarizes neutrophils

PubMed Central

Gao, Kun; Tang, Wenwen; Li, Yuan; Zhang, Pingzhao; Wang, Dejie; Yu, Long; Wang, Chenji; Wu, Dianqing

2015-01-01

ABSTRACT A hallmark of neutrophil polarization is the back localization of active RHOA and phosphorylated myosin light chain (pMLC, also known as MYL2). However, the mechanism for the polarization is not entirely clear. Here, we show that FAM65B, a newly identified RHOA inhibitor, is important for the polarization. When FAM65B is phosphorylated, it binds to 14-3-3 family proteins and becomes more stable. In neutrophils, chemoattractants stimulate FAM65B phosphorylation largely depending on the signals from the front of the cells that include those mediated by phospholipase Cβ (PLCβ) and phosphoinositide 3-kinase γ (PI3Kγ), leading to FAM65B accumulation at the leading edge. Concordantly, FAM65B deficiency in neutrophils resulted in an increase in RHOA activity and localization of pMLC to the front of cells, as well as defects in chemotaxis directionality and adhesion to endothelial cells under flow. These data together elucidate a mechanism for RHOA and pMLC polarization in stimulated neutrophils through direct inhibition of RHOA by FAM65B at the leading edge. PMID:25588844

Bridge Crossing Simulator

DTIC Science & Technology

2014-10-07

is counted as. Per the TDTC, a test bridge with longitudinal and/or lateral symmetry under non- eccentric loading can be considered as 1, 2, or 4...Level Run036 3 MLC70T (tracked) BA Run046 6 AB Run055 9 AB Run060 9 BA Run064 12 BA Run071 15 AB Run155 3 MLC96W ( wheeled ) AB...Run331 9 AB Run359 15 AB Run430 12 MLC96W ( wheeled ) BA Run434 12 AB Run447 3 BA Bank Condition: Side Slope, Even Strain Channels High

Thrombin-induced activation of RhoA in platelet shape change.

PubMed

Bodie, S L; Ford, I; Greaves, M; Nixon, G F

2001-09-14

Thrombin-induced activation of RhoA and its involvement in the regulation of myosin II light chain(20) phosphorylation (MLC-P) in alpha-toxin permeabilized platelets was investigated. Permeabilized platelets, expressing normal levels of P-selectin, displayed a Ca(2+)-dependent increase in shape change and MLC-P. Thrombin activated RhoA as measured by a rhotekin-binding assay within 30 s of stimulation under conditions of constant [Ca(2+)](i). Under the same conditions and timecourse, thrombin or GTPgammaS induced an increase in MLC-P and platelet shape change which was not dependent on an increase in [Ca(2+)](i). The thrombin- and GTPgammaS-induced MLC-P in constant [Ca(2+)](i) was inhibited by the addition of Y27632, a Rho-kinase inhibitor. This study directly demonstrates that thrombin can activate RhoA in platelets in a timecourse compatible with a role in increasing MLC-P and shape change (not involving an increase in [Ca(2+)](i)). This is also Rho-kinase-dependent. Copyright 2001 Academic Press.

SU-E-T-261: Plan Quality Assurance of VMAT Using Fluence Images Reconstituted From Log-Files

DOE Office of Scientific and Technical Information (OSTI.GOV)

Katsuta, Y; Shimizu, E; Matsunaga, K

2014-06-01

Purpose: A successful VMAT plan delivery includes precise modulations of dose rate, gantry rotational and multi-leaf collimator (MLC) shapes. One of the main problem in the plan quality assurance is dosimetric errors associated with leaf-positional errors are difficult to analyze because they vary with MU delivered and leaf number. In this study, we calculated integrated fluence error image (IFEI) from log-files and evaluated plan quality in the area of all and individual MLC leaves scanned. Methods: The log-file reported the expected and actual position for inner 20 MLC leaves and the dose fraction every 0.25 seconds during prostate VMAT onmore » Elekta Synergy. These data were imported to in-house software that developed to calculate expected and actual fluence images from the difference of opposing leaf trajectories and dose fraction at each time. The IFEI was obtained by adding all of the absolute value of the difference between expected and actual fluence images corresponding. Results: In the area all MLC leaves scanned in the IFEI, the average and root mean square (rms) were 2.5 and 3.6 MU, the area of errors below 10, 5 and 3 MU were 98.5, 86.7 and 68.1 %, the 95 % of area was covered with less than error of 7.1 MU. In the area individual MLC leaves scanned in the IFEI, the average and rms value were 2.1 – 3.0 and 3.1 – 4.0 MU, the area of errors below 10, 5 and 3 MU were 97.6 – 99.5, 81.7 – 89.5 and 51.2 – 72.8 %, the 95 % of area was covered with less than error of 6.6 – 8.2 MU. Conclusion: The analysis of the IFEI reconstituted from log-file was provided detailed information about the delivery in the area of all and individual MLC leaves scanned.« less

Apelin impairs myogenic response to induce diabetic nephropathy in mice.

PubMed

Zhang, Jia; Yin, Jiming; Wang, Yangjia; Li, Bin; Zeng, Xiangjun

2018-03-09

The cause of the invalid reaction of smooth muscle cells to mechanical stimulation that results in a dysfunctional myogenic response that mediates the disruption of renal blood flow (RBF) in patients with diabetes is debatable. The present study revealed that increased apelin concentration in serum of diabetic mice neutralized the myogenic response mediated by apelin receptor (APJ) and resulted in increased RBF, which promoted the progression of diabetic nephropathy. The results showed that apelin concentration, RBF, and albuminuria:creatinine ratio were all increased in kkAy mice, and increased RBF correlated positively with serum apelin both in C57 and diabetic mice. The increased RBF was accompanied by decreased phosphorylation of myosin light chain (MLC), β-arrestin, and increased endothelial NOS in glomeruli. Meanwhile, calcium, phosphorylation of MLC, and β-arrestin were decreased by high glucose and apelin treatment in cultured smooth muscle cells, as well. eNOS was increased by high glucose and increased by apelin in cultured endothelial cells (ECs). Knockdown of β-arrestin expression in smooth muscle cells cancelled phosphorylation of MLC induced by apelin. Therefore, apelin may induce the progression of diabetic nephropathy by counteracting the myogenic response in smooth muscle cells.-Zhang, J., Yin, J., Wang, Y., Li, B., Zeng, X. Apelin impairs myogenic response to induce diabetic nephropathy in mice.

Quantitative in vivo Analyses Reveal Calcium-dependent Phosphorylation Sites and Identifies a Novel Component of the Toxoplasma Invasion Motor Complex

PubMed Central

Nebl, Thomas; Prieto, Judith Helena; Kapp, Eugene; Smith, Brian J.; Williams, Melanie J.; Yates, John R.; Cowman, Alan F.; Tonkin, Christopher J.

2011-01-01

Apicomplexan parasites depend on the invasion of host cells for survival and proliferation. Calcium-dependent signaling pathways appear to be essential for micronemal release and gliding motility, yet the target of activated kinases remains largely unknown. We have characterized calcium-dependent phosphorylation events during Toxoplasma host cell invasion. Stimulation of live tachyzoites with Ca2+-mobilizing drugs leads to phosphorylation of numerous parasite proteins, as shown by differential 2-DE display of 32[P]-labeled protein extracts. Multi-dimensional Protein Identification Technology (MudPIT) identified ∼546 phosphorylation sites on over 300 Toxoplasma proteins, including 10 sites on the actomyosin invasion motor. Using a Stable Isotope of Amino Acids in Culture (SILAC)-based quantitative LC-MS/MS analyses we monitored changes in the abundance and phosphorylation of the invasion motor complex and defined Ca2+-dependent phosphorylation patterns on three of its components - GAP45, MLC1 and MyoA. Furthermore, calcium-dependent phosphorylation of six residues across GAP45, MLC1 and MyoA is correlated with invasion motor activity. By analyzing proteins that appear to associate more strongly with the invasion motor upon calcium stimulation we have also identified a novel 15-kDa Calmodulin-like protein that likely represents the MyoA Essential Light Chain of the Toxoplasma invasion motor. This suggests that invasion motor activity could be regulated not only by phosphorylation but also by the direct binding of calcium ions to this new component. PMID:21980283

SU-E-T-178: Clinical Feasibility of Multi-Leaf Collimator Based Dynamic Wedge

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jeong, C; Kwak, J; Ahn, S

2015-06-15

Purpose: A multi-leaf collimator (MLC) based dynamic wedge (MDW), which provide similar dose profile of physical wedge (PW) along x-jaw direction while significant monitor unit (MU) reduction, was developed and investigated for clinical use. Methods: A novel technique was used to create the wedge profile using MLC. A modification was applied to the DICOM-RT format file of the plan made with the PW to replace PW with MDW. The Varian enhanced dynamic wedge profile was used to produce MLC sequence, while the MU of the wedged field was recalculated using PW factor and fluence map. The profiles for all possiblemore » MDWs to substitute PWs were verified in 6/15 MV x-ray irradiations. New plans with MDWs were compared with the original plans in 5 rectal, 5 RT breast and 5 liver cases. Results: The wedge profile of the MDW fields were well matched with those of PWs inside the fields while less scatter than PW out of the fields. For plan comparisons of the clinical cases no significant dose discrepancy was observed between MDW plan and PW’s with the dose volume histograms. The maximum and mean doses in PTVs are agreed within 1.0%. The Result of OARs of MDW plans are slightly improved in the maximum doses (3.22 ∼ 150.4 cGy) and the mean doses (17.18 ∼ 85.52 cGy) on average for all cases while the prescribed doses are 45 Gy for rectal cases, 40 or 45 Gy for liver cases and 50 Gy for breast cases. The MUs of the fields which replace PW with MDW are reduced to 68% of those of PW. Conclusion: We developed a novel dynamic wedge technique with MLC that shows clinical advantage compared to PW.« less

Resistance controllability and variability improvement in a TaO{sub x}-based resistive memory for multilevel storage application

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prakash, A., E-mail: amitknp@postech.ac.kr, E-mail: amit.knp02@gmail.com, E-mail: hwanghs@postech.ac.kr; Song, J.; Hwang, H., E-mail: amitknp@postech.ac.kr, E-mail: amit.knp02@gmail.com, E-mail: hwanghs@postech.ac.kr

In order to obtain reliable multilevel cell (MLC) characteristics, resistance controllability between the different resistance levels is required especially in resistive random access memory (RRAM), which is prone to resistance variability mainly due to its intrinsic random nature of defect generation and filament formation. In this study, we have thoroughly investigated the multilevel resistance variability in a TaO{sub x}-based nanoscale (<30 nm) RRAM operated in MLC mode. It is found that the resistance variability not only depends on the conductive filament size but also is a strong function of oxygen vacancy concentration in it. Based on the gained insights through experimentalmore » observations and simulation, it is suggested that forming thinner but denser conductive filament may greatly improve the temporal resistance variability even at low operation current despite the inherent stochastic nature of resistance switching process.« less

Poster - Thur Eve - 10: Long term stability of VMAT quality assurance parameters using an EPID.

PubMed

Pekar, J; Diamond, K R

2012-07-01

The rapidly growing use of volumetric modulated arc therapy (VMAT) treatments in radiation therapy calls for a quantitative, automated, and reliable quality assurance (QA) procedure that can be used routinely in the clinical setting. In this work, we present a series VMAT QA procedures used to assess dynamic multi-leaf collimator (MLC) positional accuracy, variable dose-rate accuracy, and MLC leaf speed accuracy. The QA procedures were performed using amorphous silicon electronic portal imaging devices (EPID) to determine the long term stability of the measured parameters on two Varian linear accelerators. The measurements were repeated weekly on both linear accelerators for a period of three months and the EPID images were analyzed using custom Matlab software. The results of the picket fence tests indicate that MLC leaf positions can be identified to within 0.11 mm and 0.15 mm for static gantry delivery and VMAT delivery respectively. In addition, the dose-rate, gantry speed and MLC leaf speed tests both show very good stability over the measurement period. The measurements thus far, suggest that a number of the dosimetry tests may be suitable for quarterly QA for Varian iX and Trilogy linacs. However, additional measurements are required to confirm the frequency with which each test is required for safe and reliable VMAT delivery at our centre. © 2012 American Association of Physicists in Medicine.

SU-D-201-04: Evaluation of Elekta Agility MLC Performance Using Statistical Process Control

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meyers, SM; Balderson, MJ; Letourneau, D

2016-06-15

Purpose: to evaluate the performance and stability of the Elekta Agility MLC model using an automated quality control (QC) test in combination with statistical process control tools. Methods: Leaf positions were collected daily for 11 Elekta units over 5–19 months using the automated QC test, which analyzes 23 MV images to determine the location of MLC leaves relative to the radiation isocenter. The leaf positions are measured at 5 nominal positions, and images are acquired at collimator 0° and 180° to capture all MLC leaves in the field-of-view. Leaf positioning accuracy was assessed using individual and moving range control charts.more » Control limits were recomputed following MLC recalibration (occurred 1–2 times for 4 units). Specification levels of ±0.5, ±1 and ±1.5mm were tested. The mean and range of duration between out-of-control and out-of-specification events were determined. Results: Leaf position varied little over time, as confirmed by very tight individual control limits (mean ±0.19mm, range 0.09–0.44). Mean leaf position error was −0.03mm (range −0.89–0.83). Due to sporadic out-of-control events, the mean in-control duration was 3.3 days (range 1–23). Data stayed within ±1mm specification for 205 days on average (range 3–372) and within ±1.5mm for the entire date range. Measurements stayed within ±0.5mm for 1 day on average (range 0–17); however, our MLC leaves were not calibrated to this level of accuracy. Conclusion: The Elekta Agility MLC model was found to perform with high stability, as evidenced by the tight control limits. The in-specification durations support the current recommendation of monthly MLC QC tests with a ±1mm tolerance. Future work is on-going to determine if Agility performance can be optimized further using high-frequency QC test results to drive recalibration frequency. Factors that can affect leaf positioning accuracy, including beam spot motion, leaf gain calibration, drifting leaves, and image artifacts, are under investigation.« less

Inhibition of the AMP-activated protein kinase-α2 accentuates agonist-induced vascular smooth muscle contraction and high blood pressure in mice.

PubMed

Wang, Shuangxi; Liang, Bin; Viollet, Benoit; Zou, Ming-Hui

2011-05-01

The aim of the present study was to determine the effects and molecular mechanisms by which AMP-activated protein kinase (AMPK) regulates smooth muscle contraction and blood pressure in mice. In cultured human vascular smooth muscle cells, we observed that activation of AMPK by 5-aminoimidazole-4-carboxamide 1-β-d-ribofuranoside inhibited agonist-induced phosphorylation of myosin light chain (MLC) and myosin phosphatase targeting subunit 1 (MYPT1). Conversely, AMPK inhibition with pharmacological or genetic means potentiated agonist-induced the phosphorylation of MLC and MYPT1, whereas it inhibited both Ras homolog gene family member A and Rho-associated kinase activity. In addition, AMPK activation or Rho-associated kinase inhibition with Y27632 abolished agonist-induced phosphorylation of MLC and MYPT1. Gene silencing of p190-guanosine triphosphatase-activating protein abolished the effects of AMPK activation on MLC, MYPT1, and Ras homolog gene family member A in human smooth muscle cells. Ex vivo analyses revealed that agonist-induced contractions of the mesenteric artery and aortas were stronger in both AMPKα1(-/-) and AMPKα2(-/-) knockout mice than in wild-type mice. Inhibition of Rho-associated kinase with Y27632 normalized agonist-induced contractions of AMPKα1(-/-) and AMPKα2(-/-) vessels. AMPKα2(-/-) mice had higher blood pressure along with decreased serine phosphorylation of p190-guanosine triphosphatase-activating protein. Finally, inhibition of the Ras homolog gene family member A/Rho-associated kinase pathway with Y27632, which suppressed MYPT1 and MLC phosphorylation, lowered blood pressure in AMPKα2(-/-) mice. In conclusion, AMPK decreases vascular smooth muscle cell contractility by inhibiting p190-GTP-activating protein-dependent Ras homolog gene family member A activation, indicating that AMPK may be a new therapeutic target in lowering high blood pressure.

Validation of Dosimetric Leaf Gap (DLG) prior to its implementation in Treatment Planning System (TPS): TrueBeam™ millennium 120 leaf MLC.

PubMed

Shende, Ravindra; Patel, Ganesh

2017-01-01

Objective of present study is to determine optimum value of DLG and its validation prior to being incorporated in TPS for Varian TrueBeam™ millennium 120 leaves MLC. Partial transmission through the rounded leaf ends of the Multi Leaf Collimator (MLC) causes a conflict between the edges of the light field and radiation field. Parameter account for this partial transmission is called Dosimetric Leaf Gap (DLG). The complex high precession technique, such as Intensity Modulated Radiation Therapy (IMRT), entails the modeling of optimum value of DLG inside Eclipse Treatment Planning System (TPS) for precise dose calculation. Distinct synchronized uniformed extension of sweeping dynamic MLC leaf gap fields created by Varian MLC shaper software were use to determine DLG. DLG measurements performed with both 0.13 cc semi-flex ionization chamber and 2D-Array I-Matrix were used to validate the DLG; similarly, values of DLG from TPS were estimated from predicted dose. Similar mathematical approaches were employed to determine DLG from delivered and TPS predicted dose. DLG determined from delivered dose measured with both ionization chamber (DLG Ion ) and I-Matrix (DLG I-Matrix ) compared with DLG estimate from TPS predicted dose (DLG TPS ). Measurements were carried out for all available 6MV, 10MV, 15MV, 6MVFFF and 10MVFFF beam energies. Maximum and minimum DLG deviation between measured and TPS calculated DLG was found to be 0.2 mm and 0.1 mm, respectively. Both of the measured DLGs (DLG Ion and DLG I-Matrix ) were found to be in a very good agreement with estimated DLG from TPS (DLG TPS ). Proposed method proved to be helpful in verifying and validating the DLG value prior to its clinical implementation in TPS.

A novel method for dose distribution registration using fiducial marks made by a megavoltage beam in film dosimetry for intensity-modulated radiation therapy quality assurance.

PubMed

Nakayama, Shinichi; Monzen, Hajime; Oonishi, Yuuichi; Mizote, Rika; Iramina, Hiraku; Kaneshige, Souichirou; Mizowaki, Takashi

2015-06-01

Photographic film is widely used for the dose distribution verification of intensity-modulated radiation therapy (IMRT). However, analysis for verification of the results is subjective. We present a novel method for marking the isocenter using irradiation from a megavoltage (MV) beam transmitted through slits in a multi-leaf collimator (MLC). We evaluated the effect of the marking irradiation at 500 monitor units (MU) on the total transmission through the MLC using an ionization chamber and Radiochromic Film. Film dosimetry was performed for quality assurance (QA) of IMRT plans. Three methods of registration were used for each film: marking by irradiating with an MV beam through slits in the MLC (MLC-IC); marking with a fabricated phantom (Phantom-IC); and a subjective method based on isodose lines (Manual). Each method was subjected to local γ-analysis. The effect of the marking irradiation on the total transmission was 0.16%, as measured by a ionization chamber at a 10-cm depth in a solid phantom, while the inter-leaf transmission was 0.3%, determined from the film. The mean pass rates for each registration method agreed within ± 1% when the criteria used were a distance-to-agreement (DTA) of 3 mm and a dose difference (DD) of 3%. For DTA/DD criteria of 2mm/3%, the pass rates in the sagittal plane were 96.09 ± 0.631% (MLC-IC), 96.27 ± 0.399% (Phantom-IC), and 95.62 ± 0.988% (Manual). The present method is a versatile and useful method of improving the objectivity of film dosimetry for IMRT QA. Copyright © 2015 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

TU-FG-201-04: Computer Vision in Autonomous Quality Assurance of Linear Accelerators

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu, H; Jenkins, C; Yu, S

Purpose: Routine quality assurance (QA) of linear accelerators represents a critical and costly element of a radiation oncology center. Recently, a system was developed to autonomously perform routine quality assurance on linear accelerators. The purpose of this work is to extend this system and contribute computer vision techniques for obtaining quantitative measurements for a monthly multi-leaf collimator (MLC) QA test specified by TG-142, namely leaf position accuracy, and demonstrate extensibility for additional routines. Methods: Grayscale images of a picket fence delivery on a radioluminescent phosphor coated phantom are captured using a CMOS camera. Collected images are processed to correct formore » camera distortions, rotation and alignment, reduce noise, and enhance contrast. The location of each MLC leaf is determined through logistic fitting and a priori modeling based on knowledge of the delivered beams. Using the data collected and the criteria from TG-142, a decision is made on whether or not the leaf position accuracy of the MLC passes or fails. Results: The locations of all MLC leaf edges are found for three different picket fence images in a picket fence routine to 0.1mm/1pixel precision. The program to correct for image alignment and determination of leaf positions requires a runtime of 21– 25 seconds for a single picket, and 44 – 46 seconds for a group of three pickets on a standard workstation CPU, 2.2 GHz Intel Core i7. Conclusion: MLC leaf edges were successfully found using techniques in computer vision. With the addition of computer vision techniques to the previously described autonomous QA system, the system is able to quickly perform complete QA routines with minimal human contribution.« less

Development, physical properties and clinical applicability of a mechanical Multileaf Collimator for the use in Cobalt-60 radiotherapy

NASA Astrophysics Data System (ADS)

Langhans, Marco; Echner, Gernot; Runz, Armin; Baumann, Martin; Xu, Mark; Ueltzhöffer, Stefan; Häring, Peter; Schlegel, Wolfgang

2015-04-01

According to the Directory of Radiotherapy Centres (DIRAC) there are 2348 Cobalt-60 (Co-60) teletherapy units worldwide, most of them in low and middle income countries, compared to 11046 clinical accelerators. To improve teletherapy with Co-60, a mechanical Multi-Leaf Collimator (MLC) was developed, working with pneumatic pressure and thus independent of electricity supply. Instead of tungsten, brass was used as leaf material to make the mechanical MLC more affordable. The physical properties and clinical applicability of this mechanical MLC are presented here. The leakage strongly depends on the fieldsize of the therapy unit due to scatter effects. The maximum transmission through the leaves measured 2.5 cm from the end-to-end gap, within a field size of 20 cm × 30 cm defined by jaws of the therapy unit at 80 cm SAD, amounts 4.2%, normalized to an open 10 cm × 10 cm field, created by the mechanical MLC. Within a precollimated field size of 12.5 cm × 12.5 cm, the end-to-end leakage is 6.5% normalized to an open 10 cm × 10 cm field as well. This characteristic is clinically acceptable considering the criteria for non-IMRT MLCs of the International Electrotechnical Commission (IEC 60601-2-1). The penumbra for a 10 cm × 10 cm field was measured to be 9.14 mm in plane and 8.38 mm cross plane. The clinical applicability of the designed mechanical MLC was affirmed by measurements relating to all relevant clinical properties such as penumbra, leakage, output factors and field widths. Hence this novel device presents an apt way forward to make radiotherapy with conformal fields possible in low-infrastructure environments, using gantry based Co-60 therapy units.

Zinc supplementation augments TGF-β1-dependent regulatory T cell induction.

PubMed

Maywald, Martina; Meurer, Steffen K; Weiskirchen, Ralf; Rink, Lothar

2017-03-01

Regulatory T cells (Treg) play a pivotal role in immune regulation. For proper immune function, also trace elements such as zinc, and anti-inflammatory cytokines, including transforming growth factor beta 1 (TGF-β1) and interleukin (IL)-10 are indispensable. Hence, in this study the influence of TGF-β1, IL-10, and zinc supplementation on Treg cells differentiation was investigated. A synergistic effect of a combined zinc and TGF-β1 treatment on Foxp3 expression in peripheral blood mononuclear cells and mixed lymphocyte cultures (MLC) was found by performing Western blot analysis. Additionally, combined treatment causes elevated Smad 2/3 phosphorylation, which plays an important role in Foxp3 expression. This is due to a TGF-β1-mediated increase of intracellular-free zinc measured by zinc probes Fluozin3-AM and ZinPyr-1. Moreover, zinc as well as TGF-β1 treatment caused significantly reduced interferon (IFN)-γ secretion in MLC. Combined zinc and TGF-β1 treatment provoked an increased Treg cell induction due to a triggered intracellular zinc signal, which in association with an increased Smad 2/3 activation leads to a boosted Foxp3 expression and resulting in an ameliorated allogeneic reaction in MLC. Thus, zinc can be used as a favorable additive to elevate the induction of Treg cells in adverse immune reactions. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Dependence of cross-bridge kinetics on myosin light chain isoforms in rabbit and rat skeletal muscle fibres.

PubMed

Andruchov, Oleg; Andruchova, Olena; Wang, Yishu; Galler, Stefan

2006-02-15

Cross-bridge kinetics underlying stretch-induced force transients was studied in fibres with different myosin light chain (MLC) isoforms from skeletal muscles of rabbit and rat. The force transients were induced by stepwise stretches (< 0.3% of fibre length) applied on maximally Ca2+-activated skinned fibres. Fast fibre types IIB, IID (or IIX) and IIA and the slow fibre type I containing the myosin heavy chain isoforms MHC-IIb, MHC-IId (or MHC-IIx), MHC-IIa and MHC-I, respectively, were investigated. The MLC isoform content varied within fibre types. Fast fibre types contained the fast regulatory MLC isoform MLC2f and different proportions of the fast alkali MLC isoforms MLC1f and MLC3f. Type I fibres contained the slow regulatory MLC isoform MLC2s and the slow alkali MLC isoform MLC1s. Slow MLC isoforms were also present in several type IIA fibres. The kinetics of force transients differed by a factor of about 30 between fibre types (order from fastest to slowest kinetics: IIB > IID > IIA > I). The kinetics of the force transients was not dependent on the relative content of MLC1f and MLC3f. Type IIA fibres containing fast and slow MLC isoforms were about 1.2 times slower than type IIA fibres containing only fast MLC isoforms. We conclude that while the cross-bridge kinetics is mainly determined by the MHC isoforms present, it is affected by fast and slow MLC isoforms but not by the relative content of MLC1f and MLC3f. Thus, the physiological role of fast and slow MLC isoforms in type IIA fibres is a fine-tuning of the cross-bridge kinetics.

Effects of prostaglandin F2alpha and latanoprost on phosphoinositide turnover, myosin light chain phosphorylation and contraction in cat iris sphincter.

PubMed

Ansari, Habib R; Davis, Angela M; Kaddour-Djebbar, Ismail; Abdel-Latif, Ata A

2003-06-01

The effects of the ocular hypotensive agents prostaglandin F(2alpha) (PGF(2alpha)) and its analog latanoprost on intraocular pressure (IOP) in both animals and human have been investigated extensively in the last two decades. While there is general agreement that application of these PGs to the eye alters IOP by altering the aqueous humor outflow of the eye via the uveoscleral and trabecular meshwork pathways, the mechanism of action of these agents on IOP lowering remains unclear. There is evidence which suggests that myosin light kinase (MLC kinase) may be involved in the IOP-lowering effects of these agents. Thus, the purpose of the present work was to investigate in cat iris sphincter the effects of these PGs on the MLC kinase signaling pathway, inositol phosphates production, MLC phosphorylation and contraction, in order to gain more information about the mechanism through which these agents modulate smooth muscle function and lower IOP. [(3)H]myo-inositol phosphates production was measured by ion-exchange chromatography, MLC kinase activity was measured by incorporation of (32)Pi into MLC, and changes in muscle tension were recorded isometrically. PGF(2alpha) and latanoprost induced contraction in a concentration-dependent manner with EC(50) values of 18.6 and 29.9 nM, respectively, and increased inositol phosphates production in a concentration-dependent manner. At 1 microM, PGF(2alpha) and latanoprost increased inositol phosphates formation by 125 and 102% over basal, respectively. PGF(2alpha) and latanoprost increased MLC phosphorylation in a concentration- and time-dependent manner, at 1 microM and 5 min incubation, the PGs increased the MLC response by 181 and 176% over basal, respectively. In general, PGF(2alpha) was slightly more potent in inducing the biochemical and pharmacological responses. Wortmannin, ML-7 and ML-9, selective inhibitors of MLC kinase, inhibited significantly PGF(2alpha)- and latanoprost-induced MLC phosphorylation and contraction. These results demonstrate for the first time involvement of the MLC kinase pathway in the FP receptor function of this ocular tissue. Contraction-relaxation of smooth muscle alters the shape and stiffness of smooth muscle cells and MLC kinase, through myosin phosphorylation and dephosphorylation, has been shown to be involved in cytoskeletal remodeling, cytoskeletal alterations, and IOP lowering. In light of these reports and the findings presented here we suggest that alterations in the MLC kinase signaling pathway and its derived second messengers, which leads to changes in contraction-relaxation of the smooth muscles of the anterior segment, could facilitate aqueous humor outflow and thus contribute to the IOP-lowering effects of the FP-class PGs.

Co-regulation of the atrial natriuretic factor and cardiac myosin light chain-2 genes during alpha-adrenergic stimulation of neonatal rat ventricular cells. Identification of cis sequences within an embryonic and a constitutive contractile protein gene which mediate inducible expression.

PubMed

Knowlton, K U; Baracchini, E; Ross, R S; Harris, A N; Henderson, S A; Evans, S M; Glembotski, C C; Chien, K R

1991-04-25

To study the mechanisms which mediate the transcriptional activation of cardiac genes during alpha adrenergic stimulation, the present study examined the regulated expression of three cardiac genes, a ventricular embryonic gene (atrial natriuretic factor, ANF), a constitutively expressed contractile protein gene (cardiac MLC-2), and a cardiac sodium channel gene. alpha 1-Adrenergic stimulation activates the expression and release of ANF from neonatal ventricular cells. As assessed by RNase protection analyses, treatment with alpha-adrenergic agonists increases the steady-state levels of ANF mRNA by greater than 15-fold. However, a rat cardiac sodium channel gene mRNA is not induced, indicating that alpha-adrenergic stimulation does not lead to an increase in the expression of all cardiac genes. Studies employing a series of rat ANF luciferase and rat MLC-2 luciferase fusion genes identify 315- and 92-base pair cis regulatory sequences within an embryonic gene (ANF) and a constitutively expressed contractile protein gene (MLC-2), respectively, which mediate alpha-adrenergic-inducible gene expression. Transfection of various ANF luciferase reporters into neonatal rat ventricular cells demonstrated that upstream sequences which mediate tissue-specific expression (-3003 to -638) can be segregated from those responsible for inducibility. The lack of inducibility of a cardiac Na+ channel gene, and the segregation of ANF gene sequences which mediate cardiac specific from those which mediate inducible expression, provides further insight into the relationship between muscle-specific and inducible expression during cardiac myocyte hypertrophy. Based on these results, a testable model is proposed for the induction of embryonic cardiac genes and constitutively expressed contractile protein genes and the noninducibility of a subset of cardiac genes during alpha-adrenergic stimulation of neonatal rat ventricular cells.

Advanced error-prediction LDPC with temperature compensation for highly reliable SSDs

NASA Astrophysics Data System (ADS)

Tokutomi, Tsukasa; Tanakamaru, Shuhei; Iwasaki, Tomoko Ogura; Takeuchi, Ken

2015-09-01

To improve the reliability of NAND Flash memory based solid-state drives (SSDs), error-prediction LDPC (EP-LDPC) has been proposed for multi-level-cell (MLC) NAND Flash memory (Tanakamaru et al., 2012, 2013), which is effective for long retention times. However, EP-LDPC is not as effective for triple-level cell (TLC) NAND Flash memory, because TLC NAND Flash has higher error rates and is more sensitive to program-disturb error. Therefore, advanced error-prediction LDPC (AEP-LDPC) has been proposed for TLC NAND Flash memory (Tokutomi et al., 2014). AEP-LDPC can correct errors more accurately by precisely describing the error phenomena. In this paper, the effects of AEP-LDPC are investigated in a 2×nm TLC NAND Flash memory with temperature characterization. Compared with LDPC-with-BER-only, the SSD's data-retention time is increased by 3.4× and 9.5× at room-temperature (RT) and 85 °C, respectively. Similarly, the acceptable BER is increased by 1.8× and 2.3×, respectively. Moreover, AEP-LDPC can correct errors with pre-determined tables made at higher temperatures to shorten the measurement time before shipping. Furthermore, it is found that one table can cover behavior over a range of temperatures in AEP-LDPC. As a result, the total table size can be reduced to 777 kBytes, which makes this approach more practical.

Myosin light chain phosphorylation is critical for adaptation to cardiac stress.

PubMed

Warren, Sonisha A; Briggs, Laura E; Zeng, Huadong; Chuang, Joyce; Chang, Eileen I; Terada, Ryota; Li, Moyi; Swanson, Maurice S; Lecker, Stewart H; Willis, Monte S; Spinale, Francis G; Maupin-Furlowe, Julie; McMullen, Julie R; Moss, Richard L; Kasahara, Hideko

2012-11-27

Cardiac hypertrophy is a common response to circulatory or neurohumoral stressors as a mechanism to augment contractility. When the heart is under sustained stress, the hypertrophic response can evolve into decompensated heart failure, although the mechanism(s) underlying this transition remain largely unknown. Because phosphorylation of cardiac myosin light chain 2 (MLC2v), bound to myosin at the head-rod junction, facilitates actin-myosin interactions and enhances contractility, we hypothesized that phosphorylation of MLC2v plays a role in the adaptation of the heart to stress. We previously identified an enzyme that predominantly phosphorylates MLC2v in cardiomyocytes, cardiac myosin light-chain kinase (cMLCK), yet the role(s) played by cMLCK in regulating cardiac function in health and disease remain to be determined. We found that pressure overload induced by transaortic constriction in wild-type mice reduced phosphorylated MLC2v levels by ≈40% and cMLCK levels by ≈85%. To examine how a reduction in cMLCK and the corresponding reduction in phosphorylated MLC2v affect function, we generated Mylk3 gene-targeted mice and transgenic mice overexpressing cMLCK specifically in cardiomyocytes. Pressure overload led to severe heart failure in cMLCK knockout mice but not in mice with cMLCK overexpression in which cMLCK protein synthesis exceeded degradation. The reduction in cMLCK protein during pressure overload was attenuated by inhibition of ubiquitin-proteasome protein degradation systems. Our results suggest the novel idea that accelerated cMLCK protein turnover by the ubiquitin-proteasome system underlies the transition from compensated hypertrophy to decompensated heart failure as a result of reduced phosphorylation of MLC2v.

Disturb-Free Three-Dimensional Vertical Floating Gate NAND with Separated-Sidewall Control Gate

NASA Astrophysics Data System (ADS)

Seo, Moon-Sik; Endoh, Tetsuo

2012-02-01

Recently, the three-dimensional (3D) vertical floating gate (FG) type NAND cell arrays with the sidewall control gate (SCG) structure are receiving attention to overcome the reliability issues of charge trap (CT) type 3D NAND. In order to achieve the multilevel cell (MLC) operation for lower bit cost in 3D NAND, it is important to eliminate reliability issues, such as the Vth distribution with interference and disturbance problems and Vth shift with retention issues. In this paper, we intensively investigated the disturbance problems of the 3D vertical FG type NAND cell with separated-sidewall control gate (S-SCG) structure for the reliable MLC operation. Above all, we successfully demonstrate the fully suppressed disturbance problems, such as indirect programming of the unselected cells, hot electron injection of the edge cells and direct influence to the neighboring passing cells, by using the S-SCG with 30 nm pillar size.

Front-signal-dependent accumulation of the RHOA inhibitor FAM65B at leading edges polarizes neutrophils.

PubMed

Gao, Kun; Tang, Wenwen; Li, Yuan; Zhang, Pingzhao; Wang, Dejie; Yu, Long; Wang, Chenji; Wu, Dianqing

2015-03-01

A hallmark of neutrophil polarization is the back localization of active RHOA and phosphorylated myosin light chain (pMLC, also known as MYL2). However, the mechanism for the polarization is not entirely clear. Here, we show that FAM65B, a newly identified RHOA inhibitor, is important for the polarization. When FAM65B is phosphorylated, it binds to 14-3-3 family proteins and becomes more stable. In neutrophils, chemoattractants stimulate FAM65B phosphorylation largely depending on the signals from the front of the cells that include those mediated by phospholipase Cβ (PLCβ) and phosphoinositide 3-kinase γ (PI3Kγ), leading to FAM65B accumulation at the leading edge. Concordantly, FAM65B deficiency in neutrophils resulted in an increase in RHOA activity and localization of pMLC to the front of cells, as well as defects in chemotaxis directionality and adhesion to endothelial cells under flow. These data together elucidate a mechanism for RHOA and pMLC polarization in stimulated neutrophils through direct inhibition of RHOA by FAM65B at the leading edge. © 2015. Published by The Company of Biologists Ltd.

Postmitotic Expression of SOD1G93A Gene Affects the Identity of Myogenic Cells and Inhibits Myoblasts Differentiation

PubMed Central

Martini, Martina; Dobrowolny, Gabriella; Aucello, Michela; Musarò, Antonio

2015-01-01

To determine the role of mutant SOD1 gene (SOD1G93A) on muscle cell differentiation, we derived C2C12 muscle cell lines carrying a stably transfected SOD1G93A gene under the control of a myosin light chain (MLC) promoter-enhancer cassette. Expression of MLC/SOD1G93A in C2C12 cells resulted in dramatic inhibition of myoblast differentiation. Transfected SOD1G93A gene expression in postmitotic skeletal myocytes downregulated the expression of relevant markers of committed and differentiated myoblasts such as MyoD, Myogenin, MRF4, and the muscle specific miRNA expression. The inhibitory effects of SOD1G93A gene on myogenic program perturbed Akt/p70 and MAPK signaling pathways which promote differentiation cascade. Of note, the inhibition of the myogenic program, by transfected SOD1G93A gene expression, impinged also the identity of myogenic cells. Expression of MLC/SOD1G93A in C2C12 myogenic cells promoted a fibro-adipogenic progenitors (FAPs) phenotype, upregulating HDAC4 protein and preventing the myogenic commitment complex BAF60C-SWI/SNF. We thus identified potential molecular mediators of the inhibitory effects of SOD1G93A on myogenic program and disclosed potential signaling, activated by SOD1G93A, that affect the identity of the myogenic cell population. PMID:26491230

Postmitotic Expression of SOD1(G93A) Gene Affects the Identity of Myogenic Cells and Inhibits Myoblasts Differentiation.

PubMed

Martini, Martina; Dobrowolny, Gabriella; Aucello, Michela; Musarò, Antonio

2015-01-01

To determine the role of mutant SOD1 gene (SOD1(G93A)) on muscle cell differentiation, we derived C2C12 muscle cell lines carrying a stably transfected SOD1(G93A) gene under the control of a myosin light chain (MLC) promoter-enhancer cassette. Expression of MLC/SOD1(G93A) in C2C12 cells resulted in dramatic inhibition of myoblast differentiation. Transfected SOD1(G93A) gene expression in postmitotic skeletal myocytes downregulated the expression of relevant markers of committed and differentiated myoblasts such as MyoD, Myogenin, MRF4, and the muscle specific miRNA expression. The inhibitory effects of SOD1(G93A) gene on myogenic program perturbed Akt/p70 and MAPK signaling pathways which promote differentiation cascade. Of note, the inhibition of the myogenic program, by transfected SOD1(G93A) gene expression, impinged also the identity of myogenic cells. Expression of MLC/SOD1(G93A) in C2C12 myogenic cells promoted a fibro-adipogenic progenitors (FAPs) phenotype, upregulating HDAC4 protein and preventing the myogenic commitment complex BAF60C-SWI/SNF. We thus identified potential molecular mediators of the inhibitory effects of SOD1(G93A) on myogenic program and disclosed potential signaling, activated by SOD1(G93A), that affect the identity of the myogenic cell population.

PKCδ Regulates Force Signaling during VEGF/CXCL4 Induced Dissociation of Endothelial Tubes

PubMed Central

Jamison, Joshua; Wang, James H-C.; Wells, Alan

2014-01-01

Wound healing requires the vasculature to re-establish itself from the severed ends; endothelial cells within capillaries must detach from neighboring cells before they can migrate into the nascent wound bed to initiate angiogenesis. The dissociation of these endothelial capillaries is driven partially by platelets' release of growth factors and cytokines, particularly the chemokine CXCL4/platelet factor-4 (PF4) that increases cell-cell de-adherence. As this retraction is partly mediated by increased transcellular contractility, the protein kinase c-δ/myosin light chain-2 (PKCδ/MLC-2) signaling axis becomes a candidate mechanism to drive endothelial dissociation. We hypothesize that PKCδ activation induces contractility through MLC-2 to promote dissociation of endothelial cords after exposure to platelet-released CXCL4 and VEGF. To investigate this mechanism of contractility, endothelial cells were allowed to form cords following CXCL4 addition to perpetuate cord dissociation. In this study, CXCL4-induced dissociation was reduced by a VEGFR inhibitor (sunitinib malate) and/or PKCδ inhibition. During combined CXCL4+VEGF treatment, increased contractility mediated by MLC-2 that is dependent on PKCδ regulation. As cellular force is transmitted to focal adhesions, zyxin, a focal adhesion protein that is mechano-responsive, was upregulated after PKCδ inhibition. This study suggests that growth factor regulation of PKCδ may be involved in CXCL4-mediated dissociation of endothelial cords. PMID:24699667

PKCδ regulates force signaling during VEGF/CXCL4 induced dissociation of endothelial tubes.

PubMed

Jamison, Joshua; Wang, James H-C; Wells, Alan

2014-01-01

Wound healing requires the vasculature to re-establish itself from the severed ends; endothelial cells within capillaries must detach from neighboring cells before they can migrate into the nascent wound bed to initiate angiogenesis. The dissociation of these endothelial capillaries is driven partially by platelets' release of growth factors and cytokines, particularly the chemokine CXCL4/platelet factor-4 (PF4) that increases cell-cell de-adherence. As this retraction is partly mediated by increased transcellular contractility, the protein kinase c-δ/myosin light chain-2 (PKCδ/MLC-2) signaling axis becomes a candidate mechanism to drive endothelial dissociation. We hypothesize that PKCδ activation induces contractility through MLC-2 to promote dissociation of endothelial cords after exposure to platelet-released CXCL4 and VEGF. To investigate this mechanism of contractility, endothelial cells were allowed to form cords following CXCL4 addition to perpetuate cord dissociation. In this study, CXCL4-induced dissociation was reduced by a VEGFR inhibitor (sunitinib malate) and/or PKCδ inhibition. During combined CXCL4+VEGF treatment, increased contractility mediated by MLC-2 that is dependent on PKCδ regulation. As cellular force is transmitted to focal adhesions, zyxin, a focal adhesion protein that is mechano-responsive, was upregulated after PKCδ inhibition. This study suggests that growth factor regulation of PKCδ may be involved in CXCL4-mediated dissociation of endothelial cords.

Rho-associated kinase inhibitors promote the cardiac differentiation of embryonic and induced pluripotent stem cells.

PubMed

Cheng, Ya-Ting; Yeih, Dong-Feng; Liang, Shu-Man; Chien, Chia-Ying; Yu, Yen-Ling; Ko, Bor-Sheng; Jan, Yee-Jee; Kuo, Cheng-Chin; Sung, Li-Ying; Shyue, Song-Kun; Chen, Ming-Fong; Yet, Shaw-Fang; Wu, Kenneth K; Liou, Jun-Yang

2015-12-15

Rho-associated kinase (ROCK) plays an important role in maintaining embryonic stem (ES) cell pluripotency. To determine whether ROCK is involved in ES cell differentiation into cardiac and hematopoietic lineages, we evaluated the effect of ROCK inhibitors, Y-27632 and fasudil on murine ES and induced pluripotent stem (iPS) cell differentiation. Gene expression levels were determined by real-time PCR, Western blot analysis and immunofluorescent confocal microscopy. Cell transplantation of induced differentiated cells were assessed in vivo in a mouse model (three groups, n=8/group) of acute myocardial infarction (MI). The cell engraftment was examined by immunohistochemical staining and the outcome was analyzed by echocardiography. Cells were cultured in hematopoietic differentiation medium in the presence or absence of ROCK inhibitor and colony formation as well as markers of ES, hematopoietic stem cells (HSC) and cells of cardiac lineages were analyzed. ROCK inhibition resulted in a drastic change in colony morphology accompanied by loss of hematopoietic markers (GATA-1, CD41 and β-Major) and expressed markers of cardiac lineages (GATA-4, Isl-1, Tbx-5, Tbx-20, MLC-2a, MLC-2v, α-MHC, cTnI and cTnT) in murine ES and iPS cells. Fasudil-induced cardiac progenitor (Mesp-1 expressing) cells were infused into a murine MI model. They engrafted into the peri-infarct and infarct regions and preserved left ventricular function. These findings provide new insights into the signaling required for ES cell differentiation into hematopoietic as well as cardiac lineages and suggest that ROCK inhibitors are useful in directing iPS cell differentiation into cardiac progenitor cells for cell therapy of cardiovascular diseases. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

An experimental comparison of conventional two-bank and novel four-bank dynamic MLC tracking.

PubMed

Davies, G A; Clowes, P; McQuaid, D; Evans, P M; Webb, S; Poludniowski, G

2013-03-07

The AccuLeaf mMLC featuring four multileaf-collimator (MLC) banks has been used for the first time for an experimental comparison of conventional two-bank with novel four-bank dynamic MLC tracking of a two-dimensional sinusoidal respiratory motion. This comparison was performed for a square aperture, and for three conformal treatment apertures from clinical radiotherapy lung cancer patients. The system latency of this prototype tracking system was evaluated and found to be 1.0 s and the frequency at which MLC positions could be updated, 1 Hz, and therefore accurate MLC tracking of irregular patient motion would be difficult with the system in its current form. The MLC leaf velocity required for two-bank-MLC and four-bank-MLC tracking was evaluated for the apertures studied and a substantial decrease was found in the maximum MLC velocity required when four-banks were used for tracking rather than two. A dosimetric comparison of the two techniques was also performed and minimal difference was found between two-bank-MLC and four-bank-MLC tracking. The use of four MLC banks for dynamic MLC tracking is shown to be potentially advantageous for increasing the delivery efficiency compared with two-bank-MLC tracking where difficulties are encountered if large leaf shifts are required to track motion perpendicular to the direction of leaf travel.

Treatment planning systems for external whole brain radiation therapy: With and without MLC (multi leaf collimator) optimization

NASA Astrophysics Data System (ADS)

Budiyono, T.; Budi, W. S.; Hidayanto, E.

2016-03-01

Radiation therapy for brain malignancy is done by giving a dose of radiation to a whole volume of the brain (WBRT) followed by a booster at the primary tumor with more advanced techniques. Two external radiation fields given from the right and left side. Because the shape of the head, there will be an unavoidable hotspot radiation dose of greater than 107%. This study aims to optimize planning of radiation therapy using field in field multi-leaf collimator technique. A study of 15 WBRT samples with CT slices is done by adding some segments of radiation in each field of radiation and delivering appropriate dose weighting using a TPS precise plan Elekta R 2.15. Results showed that this optimization a more homogeneous radiation on CTV target volume, lower dose in healthy tissue, and reduced hotspots in CTV target volume. Comparison results of field in field multi segmented MLC technique with standard conventional technique for WBRT are: higher average minimum dose (77.25% ± 0:47%) vs (60% ± 3:35%); lower average maximum dose (110.27% ± 0.26%) vs (114.53% ± 1.56%); lower hotspot volume (5.71% vs 27.43%); and lower dose on eye lenses (right eye: 9.52% vs 18.20%); (left eye: 8.60% vs 16.53%).

Radio frequency noise from an MLC: a feasibility study of the use of an MLC for linac-MR systems.

PubMed

Lamey, M; Yun, J; Burke, B; Rathee, S; Fallone, B G

2010-02-21

Currently several groups are actively researching the integration of a megavoltage teletherapy unit with magnetic resonance (MR) imaging for real-time image-guided radiotherapy. The use of a multileaf collimator (MLC) for intensity-modulated radiotherapy for linac-MR units must be investigated. The MLC itself will likely reside in the fringe field of the MR and the motors will produce radio frequency (RF) noise. The RF noise power spectral density from a Varian 52-leaf MLC motor, a Varian Millennium MLC motor and a brushless fan motor has been measured as a function of the applied magnetic field using a near field probe set. For the Varian 52-leaf MLC system, the RF noise produced by 13 of 52 motors is studied as a function of distance from the MLC. Data are reported in the frequency range suitable for 0.2-1.5 T linac-MR systems. Below 40 MHz the Millennium MLC motor tested showed more noise than the Varian 52-leaf motor or the brushless fan motor. The brushless motor showed a small dependence on the applied magnetic field. Images of a phantom were taken by the prototype linac-MR system with the MLC placed in close proximity to the magnet. Several orientations of the MLC in both shielded and non-shielded configurations were studied. For the case of a non-shielded MLC and associated cables, the signal-to-noise ratio (SNR) was reduced when 13 of 52 MLC leaves were moved during imaging. When the MLC and associated cables were shielded, the measured SNR of the images with 13 MLC leaves moving was experimentally the same as the SNR of the stationary MLC image. When the MLC and cables are shielded, subtraction images acquired with and without MLC motion contains no systematic signal. This study illustrates that the small RF noise produced by functioning MLC motors can be effectively shielded to avoid SNR degradation. A functioning MLC can be incorporated into a linac-MR unit.

Radio frequency noise from an MLC: a feasibility study of the use of an MLC for linac-MR systems

PubMed Central

Lamey, M; Yun, J; Burke, B; Rathee, S; Fallone, B G

2010-01-01

Currently several groups are actively researching the integration of a megavoltage teletherapy unit with magnetic resonance (MR) imaging for real-time image-guided radiotherapy. The use of a multileaf collimator (MLC) for intensity-modulated radiotherapy for linac-MR units must be investigated. The MLC itself will likely reside in the fringe field of the MR and the motors will produce radio frequency (RF) noise. The RF noise power spectral density from a Varian 52-leaf MLC motor, a Varian Millennium MLC motor and a brushless fan motor has been measured as a function of the applied magnetic field using a near field probe set. For the Varian 52-leaf MLC system, the RF noise produced by 13 of 52 motors is studied as a function of distance from the MLC. Data are reported in the frequency range suitable for 0.2–1.5 T linac-MR systems. Below 40 MHz the Millennium MLC motor tested showed more noise than the Varian 52-leaf motor or the brushless fan motor. The brushless motor showed a small dependence on the applied magnetic field. Images of a phantom were taken by the prototype linac-MR system with the MLC placed in close proximity to the magnet. Several orientations of the MLC in both shielded and non-shielded configurations were studied. For the case of a non-shielded MLC and associated cables, the signal-to-noise ratio (SNR) was reduced when 13 of 52 MLC leaves were moved during imaging. When the MLC and associated cables were shielded, the measured SNR of the images with 13 MLC leaves moving was experimentally the same as the SNR of the stationary MLC image. When the MLC and cables are shielded, subtraction images acquired with and without MLC motion contains no systematic signal. This study illustrates that the small RF noise produced by functioning MLC motors can be effectively shielded to avoid SNR degradation. A functioning MLC can be incorporated into a linac-MR unit. PMID:20090187

Patient views through the keyhole: new perspectives on single-incision vs. multiport laparoscopic cholecystectomy

PubMed Central

Hey, Jennifer; Roberts, Keith John; Morris-Stiff, Gareth J; Toogood, Giles J

2012-01-01

Objectives Single-incision laparoscopic cholecystectomy (SILC) may be associated with less pain, shorter hospital stay and better cosmetic results than multiport laparoscopic cholecystectomy (MLC). Advocates suggest that patients prefer SILC, although research directly addressing the question of patient preferences is limited. This study aimed to assess patient preferences using currently available evidence. Methods Patients awaiting elective cholecystectomy were shown a series of postoperative images taken after SILC or MLC and asked which procedure this led them to prefer. This was repeated after patients had completed a questionnaire constructed using published objective data comparing patient-reported outcomes of SILC and MLC. Results The study was completed by 113 consecutive patients. After their initial viewing of the images, 16% of subjects preferred MLC. Younger age, lower body mass index and female sex were associated with choosing SILC. After completing the questionnaire, 88% of patients preferred MLC (P < 0.001). Patients ranked the level of risk for complications and postoperative pain above cosmetic results in determining their choice of procedure. Conclusions Patients' initial preference when presented with cosmetic appearance was for SILC. When contemporary outcome data were included, the majority chose MLC. This underlines the need to fully inform patients during the consent process and indicates that patient views of SILC may differ from the views of those introducing the technology. PMID:22404262

Brushed permanent magnet DC MLC motor operation in an external magnetic field.

PubMed

Yun, J; St Aubin, J; Rathee, S; Fallone, B G

2010-05-01

Linac-MR systems for real-time image-guided radiotherapy will utilize the multileaf collimators (MLCs) to perform conformal radiotherapy and tumor tracking. The MLCs would be exposed to the external fringe magnetic fields of the linac-MR hybrid systems. Therefore, an experimental investigation of the effect of an external magnetic field on the brushed permanent magnet DC motors used in some MLC systems was performed. The changes in motor speed and current were measured for varying external magnetic field strengths up to 2000 G generated by an EEV electromagnet. These changes in motor characteristics were measured for three orientations of the motor in the external magnetic field, mimicking changes in motor orientations due to installation and/or collimator rotations. In addition, the functionality of the associated magnetic motor encoder was tested. The tested motors are used with the Varian 120 leaf Millennium MLC (Maxon Motor half leaf and full leaf motors) and the Varian 52 leaf MKII MLC (MicroMo Electronics leaf motor) including a carriage motor (MicroMo Electronics). In most cases, the magnetic encoder of the motors failed prior to any damage to the gearbox or the permanent magnet motor itself. This sets an upper limit of the external magnetic field strength on the motor function. The measured limits of the external magnetic fields were found to vary by the motor type. The leaf motor used with a Varian 52 leaf MKII MLC system tolerated up to 450 +/- 10 G. The carriage motor tolerated up to 2000 +/- 10 G field. The motors used with the Varian 120 leaf Millennium MLC system were found to tolerate a maximum of 600 +/- 10 G. The current Varian MLC system motors can be used for real-time image-guided radiotherapy coupled to a linac-MR system, provided the fringe magnetic fields at their locations are below the determined tolerance levels. With the fringe magnetic fields of linac-MR systems expected to be larger than the tolerance levels determined, some form of magnetic shielding would be required.

Activation of Toll-like receptor 3 increases mouse aortic vascular smooth muscle cell contractility through ERK1/2 pathway.

PubMed

Hardigan, Trevor; Spitler, Kathryn; Matsumoto, Takayuki; Carrillo-Sepulveda, Maria Alicia

2015-11-01

Activation of Toll-like receptor 3 (TLR3), a pattern recognition receptor of the innate immune system, is associated with vascular complications. However, whether activation of TLR3 alters vascular contractility is unknown. We, therefore, hypothesized that TLR3 activation augments vascular contractility and activates vascular smooth muscle cell (VSMC) contractile apparatus proteins. Male mice were treated with polyinosinic-polycytidylic acid (Poly I:C group, 14 days), a TLR3 agonist; control mice received saline (vehicle, 14 days). At the end of protocol, blood pressure was measured by tail cuff method. Aortas were isolated and assessed for contractility experiments using a wire myograph. Aortic protein content was used to determine phosphorylated/total interferon regulatory factor 3 (IRF3), a downstream target of TLR3 signaling, and ERK1/2 using Western blot. We investigated the TLR3/IRF3/ERK1/2 signaling pathway and contractile-related proteins such as phosphorylated/total myosin light chain (MLC) and caldesmon (CaD) in aortic VSMC primary cultures. Poly I:C-treated mice exhibited (vs. vehicle-treated mice) (1) elevated systolic blood pressure. Moreover, Poly I:C treatment (2) enhanced aortic phenylephrine-induced maximum contraction, which was suppressed by PD98059 (ERK1/2 inhibitor), and (3) increased aortic levels of phosphorylated IRF3 and ERK1/2. Stimulation of mouse aortic VSMCs with Poly I:C resulted in increased phosphorylation of IRF3, ERK1/2, MLC, and CaD. Inhibition of ERK1/2 abolished Poly I:C-mediated phosphorylation of MLC and CaD. Our data provide functional evidence for the role of TLR3 in vascular contractile events, suggesting TLR3 as a potential new therapeutic target in vascular dysfunction and regulation of blood pressure.

Abnormal Activation of RhoA/ROCK-I Signaling in Junctional Zone Smooth Muscle Cells of Patients With Adenomyosis.

PubMed

Wang, S; Duan, H; Zhang, Y; Sun, F Q

2016-03-01

Adenomyosis (ADS) is a common estrogen-dependent gynecological disease with unknown etiology. The RhoA/Rho-kinase (ROCK) signaling pathway is involved in various cellular functions, including migration, proliferation, and smooth muscle contraction. Here we examined the potential role of this pathway in junctional zone (JZ) contraction in women with and without ADS. We demonstrated that in the normal JZ, RhoA and ROCK-I messenger RNA (mRNA) and protein expression was significantly higher in the proliferative phase of the menstrual cycle than in the secretory phase. Expression of RhoA and ROCK-I in the JZ from women with ADS was significantly higher than in the control women and showed no significant differences across the menstrual cycle. Treatment of JZ smooth muscle cells (JZSMCs) with estrogen at 0, 1, 10, or 100 nmol/L for 24 hours resulted in increased expression of RhoA, ROCK-I, and myosin light-chain (MLC) phosphorylation (p-MLC) in a dose-dependent manner. In parallel to its effects on p-MLC, estrogen-mediated, dose-dependent contraction responses in JZSMCs. Estrogen-mediated contraction in the ADS group was significantly higher than in the controls and also showed no significant differences across the menstrual cycle. These effects were suppressed in the presence of ICI 182780 or Y27632, supporting an estrogen receptor-dependent and RhoA activation-dependent mechanism. Our results indicate that the level of RhoA and ROCK-I increases in patients with ADS and the cyclic change is lost. Estrogen may affect uterine JZ contraction of ADS by enhancing RhoA/ ROCK-I signaling. © The Author(s) 2015.

Novel molecular insights into RhoA GTPase-induced resistance to aqueous humor outflow through the trabecular meshwork

PubMed Central

Zhang, Min; Maddala, Rupalatha; Rao, Ponugoti Vasantha

2008-01-01

Impaired drainage of aqueous humor through the trabecular meshwork (TM) culminating in increased intraocular pressure is a major risk factor for glaucoma, a leading cause of blindness worldwide. Regulation of aqueous humor drainage through the TM, however, is poorly understood. The role of RhoA GTPase-mediated actomyosin organization, cell adhesive interactions, and gene expression in regulation of aqueous humor outflow was investigated using adenoviral vector-driven expression of constitutively active mutant of RhoA (RhoAV14). Organ-cultured anterior segments from porcine eyes expressing RhoAV14 exhibited significant reduction of aqueous humor outflow. Cultured TM cells expressing RhoAV14 exhibited a pronounced contractile morphology, increased actin stress fibers, and focal adhesions and increased levels of phosphorylated myosin light chain (MLC), collagen IV, fibronectin, and laminin. cDNA microarray analysis of RNA extracted from RhoAV14-expressing human TM cells revealed a significant increase in the expression of genes encoding extracellular matrix (ECM) proteins, cytokines, integrins, cytoskeletal proteins, and signaling proteins. Conversely, various ECM proteins stimulated robust increases in phosphorylation of MLC, paxillin, and focal adhesion kinase and activated Rho GTPase and actin stress fiber formation in TM cells, indicating a potential regulatory feedback interaction between ECM-induced mechanical strain and Rho GTPase-induced isometric tension in TM cells. Collectively, these data demonstrate that sustained activation of Rho GTPase signaling in the aqueous humor outflow pathway increases resistance to aqueous humor outflow through the trabecular pathway by influencing the actomyosin assembly, cell adhesive interactions, and the expression of ECM proteins and cytokines in TM cells. PMID:18799648

The sensitivity of patient specific IMRT QC to systematic MLC leaf bank offset errors.

PubMed

Rangel, Alejandra; Palte, Gesa; Dunscombe, Peter

2010-07-01

Patient specific IMRT QC is performed routinely in many clinics as a safeguard against errors and inaccuracies which may be introduced during the complex planning, data transfer, and delivery phases of this type of treatment. The purpose of this work is to evaluate the feasibility of detecting systematic errors in MLC leaf bank position with patient specific checks. 9 head and neck (H&N) and 14 prostate IMRT beams were delivered using MLC files containing systematic offsets (+/- 1 mm in two banks, +/- 0.5 mm in two banks, and 1 mm in one bank of leaves). The beams were measured using both MAPCHECK (Sun Nuclear Corp., Melbourne, FL) and the aS1000 electronic portal imaging device (Varian Medical Systems, Palo Alto, CA). Comparisons with calculated fields, without offsets, were made using commonly adopted criteria including absolute dose (AD) difference, relative dose difference, distance to agreement (DTA), and the gamma index. The criteria most sensitive to systematic leaf bank offsets were the 3% AD, 3 mm DTA for MAPCHECK and the gamma index with 2% AD and 2 mm DTA for the EPID. The criterion based on the relative dose measurements was the least sensitive to MLC offsets. More highly modulated fields, i.e., H&N, showed greater changes in the percentage of passing points due to systematic MLC inaccuracy than prostate fields. None of the techniques or criteria tested is sufficiently sensitive, with the population of IMRT fields, to detect a systematic MLC offset at a clinically significant level on an individual field. Patient specific QC cannot, therefore, substitute for routine QC of the MLC itself.

Functional conservation between rodents and chicken of regulatory sequences driving skeletal muscle gene expression in transgenic chickens

PubMed Central

2010-01-01

Background Regulatory elements that control expression of specific genes during development have been shown in many cases to contain functionally-conserved modules that can be transferred between species and direct gene expression in a comparable developmental pattern. An example of such a module has been identified at the rat myosin light chain (MLC) 1/3 locus, which has been well characterised in transgenic mouse studies. This locus contains two promoters encoding two alternatively spliced isoforms of alkali myosin light chain. These promoters are differentially regulated during development through the activity of two enhancer elements. The MLC3 promoter alone has been shown to confer expression of a reporter gene in skeletal and cardiac muscle in transgenic mice and the addition of the downstream MLC enhancer increased expression levels in skeletal muscle. We asked whether this regulatory module, sufficient for striated muscle gene expression in the mouse, would drive expression in similar domains in the chicken. Results We have observed that a conserved downstream MLC enhancer is present in the chicken MLC locus. We found that the rat MLC1/3 regulatory elements were transcriptionally active in chick skeletal muscle primary cultures. We observed that a single copy lentiviral insert containing this regulatory cassette was able to drive expression of a lacZ reporter gene in the fast-fibres of skeletal muscle in chicken in three independent transgenic chicken lines in a pattern similar to the endogenous MLC locus. Reporter gene expression in cardiac muscle tissues was not observed for any of these lines. Conclusions From these results we conclude that skeletal expression from this regulatory module is conserved in a genomic context between rodents and chickens. This transgenic module will be useful in future investigations of muscle development in avian species. PMID:20184756

Dosimetric performance of the new high-definition multileaf collimator for intracranial stereotactic radiosurgery.

PubMed

Dhabaan, Anees; Elder, Eric; Schreibmann, Eduard; Crocker, Ian; Curran, Walter J; Oyesiku, Nelson M; Shu, Hui-Kuo; Fox, Tim

2010-06-21

The objective was to evaluate the performance of a high-definition multileaf collimator (MLC) of 2.5 mm leaf width (MLC2.5) and compare to standard 5 mm leaf width MLC (MLC5) for the treatment of intracranial lesions using dynamic conformal arcs (DCA) technique with a dedicated radiosurgery linear accelerator. Simulated cases of spherical targets were created to study solely the effect of target volume size on the performance of the two MLC systems independent of target shape complexity. In addition, 43 patients previously treated for intracranial lesions in our institution were retrospectively planned using DCA technique with MLC2.5 and MLC5 systems. The gross tumor volume ranged from 0.07 to 40.57 cm3 with an average volume of 5.9 cm3. All treatment parameters were kept the same for both MLC-based plans. The plan evaluation was performed using figures of merits (FOM) for a rapid and objective assessment on the quality of the two treatment plans for MLC2.5 and MLC5. The prescription isodose surface was selected as the greatest isodose surface covering >or= 95% of the target volume and delivering 95% of the prescription dose to 99% of target volume. A Conformity Index (CI) and conformity distance index (CDI) were used to quantifying the dose conformity to a target volume. To assess normal tissue sparing, a normal tissue difference (NTD) was defined as the difference between the volume of normal tissue receiving a certain dose utilizing MLC5 and the volume receiving the same dose using MLC2.5. The CI and normal tissue sparing for the simulated spherical targets were better with the MLC2.5 as compared to MLC5. For the clinical patients, the CI and CDI results indicated that the MLC2.5 provides better treatment conformity than MLC5 even at large target volumes. The CI's range was 1.15 to 2.44 with a median of 1.59 for MLC2.5 compared to 1.60-2.85 with a median of 1.71 for MLC5. Improved normal tissue sparing was also observed for MLC2.5 over MLC5, with the NTD always positive, indicating improvement, and ranging from 0.1 to 8.3 for normal tissue receiving 50% (NTV50), 70% (NTV70) and 90% (NTV90) of the prescription dose. The MLC2.5 has a dosimetric advantage over the MLC5 in Linac-based radiosurgery using DCA method for intracranial lesions, both in treatment conformity and normal tissue sparing when target shape complexity increases.

The β1 subunit of the Na,K-ATPase pump interacts with megalencephalic leucoencephalopathy with subcortical cysts protein 1 (MLC1) in brain astrocytes: new insights into MLC pathogenesis

PubMed Central

Brignone, Maria S.; Lanciotti, Angela; Macioce, Pompeo; Macchia, Gianfranco; Gaetani, Matteo; Aloisi, Francesca; Petrucci, Tamara C.; Ambrosini, Elena

2011-01-01

Megalencephalic leucoencephalopathy with subcortical cysts (MLC) is a rare congenital leucodystrophy caused by mutations in MLC1, a membrane protein of unknown function. MLC1 expression in astrocyte end-feet contacting blood vessels and meninges, along with brain swelling, fluid cysts and myelin vacuolation observed in MLC patients, suggests a possible role for MLC1 in the regulation of fluid and ion homeostasis and cellular volume changes. To identify MLC1 direct interactors and dissect the molecular pathways in which MLC1 is involved, we used NH2-MLC1 domain as a bait to screen a human brain library in a yeast two-hybrid assay. We identified the β1 subunit of the Na,K-ATPase pump as one of the interacting clones and confirmed it by pull-downs, co-fractionation assays and immunofluorescence stainings in human and rat astrocytes in vitro and in brain tissue. By performing ouabain-affinity chromatography on astrocyte and brain extracts, we isolated MLC1 and the whole Na,K-ATPase enzyme in a multiprotein complex that included Kir4.1, syntrophin and dystrobrevin. Because Na,K-ATPase is involved in intracellular osmotic control and volume regulation, we investigated the effect of hypo-osmotic stress on MLC1/Na,K-ATPase relationship in astrocytes. We found that hypo-osmotic conditions increased MLC1 membrane expression and favoured MLC1/Na,K-ATPase-β1 association. Moreover, hypo-osmosis induced astrocyte swelling and the reversible formation of endosome-derived vacuoles, where the two proteins co-localized. These data suggest that through its interaction with Na,K-ATPase, MLC1 is involved in the control of intracellular osmotic conditions and volume regulation in astrocytes, opening new perspectives for understanding the pathological mechanisms of MLC disease. PMID:20926452

Dosimetric comparison using different multileaf collimeters in intensity-modulated radiotherapy for upper thoracic esophageal cancer.

PubMed

Gong, Youling; Wang, Shichao; Zhou, Lin; Liu, Yongmei; Xu, Yong; Lu, You; Bai, Sen; Fu, Yuchuan; Xu, Qingfeng; Jiang, Qingfeng

2010-07-15

To study the impacts of multileaf collimators (MLC) width [standard MLC width of 10 mm (sMLC) and micro-MLC width of 4 mm (mMLC)] in the intensity-modulated radiotherapy (IMRT) planning for the upper thoracic esophageal cancer (UTEC). 10 patients with UTEC were retrospectively planned with the sMLC and the mMLC. The monitor unites (MUs) and dose volume histogram-based parameters [conformity index (CI) and homogeneous index (HI)] were compared between the IMRT plans with sMLC and with mMLC. The IMRT plans with the mMLC were more efficient (average MUs: 703.1 +/- 68.3) than plans with the sMLC (average MUs: 833.4 +/- 73.8) (p < 0.05). Also, compared to plans with the sMLC, the plans with the mMLC showed advantages in dose coverage of the planning gross tumor volume (Pgtv) (CI 0.706 +/- 0.056/HI 1.093 +/- 0.021) and the planning target volume (PTV) (CI 0.707 +/- 0.029/HI 1.315 +/- 0.013) (p < 0.05). In addition, the significant dose sparing in the D5 (3260.3 +/- 374.0 vs 3404.5 +/- 374.4)/gEUD (1815.1 +/- 281.7 vs 1849.2 +/- 297.6) of the spinal cord, the V10 (33.2 +/- 6.5 vs 34.0 +/- 6.7), V20 (16.0 +/- 4.6 vs 16.6 +/- 4.7), MLD (866.2 +/- 174.1 vs 887.9 +/- 172.1) and gEUD (938.6 +/- 175.2 vs 956.8 +/- 171.0) of the lungs were observed in the plans with the mMLC, respectively (p < 0.05). Comparing to the sMLC, the mMLC not only demonstrated higher efficiencies and more optimal target coverage, but also considerably improved the dose sparing of OARs in the IMRT planning for UTEC.

SU-E-T-627: Precision Modelling of the Leaf-Bank Rotation in Elekta’s Agility MLC: Is It Necessary?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vujicic, M; Belec, J; Heath, E

Purpose: To demonstrate the method used to determine the leaf bank rotation angle (LBROT) as a parameter for modeling the Elekta Agility multi-leaf collimator (MLC) for Monte Carlo simulations and to evaluate the clinical impact of LBROT. Methods: A detailed model of an Elekta Infinity linac including an Agility MLC was built using the EGSnrc/BEAMnrc Monte Carlo code. The Agility 160-leaf MLC is modelled using the MLCE component module which allows for leaf bank rotation using the parameter LBROT. A precise value of LBROT is obtained by comparing measured and simulated profiles of a specific field, which has leaves arrangedmore » in a repeated pattern such that one leaf is opened and the adjacent one is closed. Profile measurements from an Agility linac are taken with gafchromic film, and an ion chamber is used to set the absolute dose. The measurements are compared to Monte Carlo (MC) simulations and the LBROT is adjusted until a match is found. The clinical impact of LBROT is evaluated by observing how an MC dose calculation changes with LBROT. A clinical Stereotactic Body Radiation Treatment (SBRT) plan is calculated using BEAMnrc/DOSXYZnrc simulations with different input values for LBROT. Results: Using the method outlined above, the LBROT is determined to be 9±1 mrad. Differences as high as 4% are observed in a clinical SBRT plan between the extreme case (LBROT not modeled) and the nominal case. Conclusion: In small-field radiation therapy treatment planning, it is important to properly account for LBROT as an input parameter for MC dose calculations with the Agility MLC. More work is ongoing to elucidate the observed differences by determining the contributions from transmission dose, change in field size, and source occlusion, which are all dependent on LBROT. This work was supported by OCAIRO (Ontario Consortium of Adaptive Interventions in Radiation Oncology), funded by the Ontario Research Fund.« less

SU-G-JeP1-12: Head-To-Head Performance Characterization of Two Multileaf Collimator Tracking Algorithms for Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Caillet, V; Colvill, E; Royal North Shore Hospital, St Leonards, Sydney

2016-06-15

Purpose: Multi-leaf collimator (MLC) tracking is being clinically pioneered to continuously compensate for thoracic and abdominal motion during radiotherapy. The purpose of this work is to characterize the performance of two MLC tracking algorithms for cancer radiotherapy, based on a direct optimization and a piecewise leaf fitting approach respectively. Methods: To test the algorithms, both physical and in silico experiments were performed. Previously published high and low modulation VMAT plans for lung and prostate cancer cases were used along with eight patient-measured organ-specific trajectories. For both MLC tracking algorithm, the plans were run with their corresponding patient trajectories. The physicalmore » experiments were performed on a Trilogy Varian linac and a programmable phantom (HexaMotion platform). For each MLC tracking algorithm, plan and patient trajectory, the tracking accuracy was quantified as the difference in aperture area between ideal and fitted MLC. To compare algorithms, the average cumulative tracking error area for each experiment was calculated. The two-sample Kolmogorov-Smirnov (KS) test was used to evaluate the cumulative tracking errors between algorithms. Results: Comparison of tracking errors for the physical and in silico experiments showed minor differences between the two algorithms. The KS D-statistics for the physical experiments were below 0.05 denoting no significant differences between the two distributions pattern and the average error area (direct optimization/piecewise leaf-fitting) were comparable (66.64 cm2/65.65 cm2). For the in silico experiments, the KS D-statistics were below 0.05 and the average errors area were also equivalent (49.38 cm2/48.98 cm2). Conclusion: The comparison between the two leaf fittings algorithms demonstrated no significant differences in tracking errors, neither in a clinically realistic environment nor in silico. The similarities in the two independent algorithms give confidence in the use of either algorithm for clinical implementation.« less

SU-E-T-179: Clinical Impact of IMRT Failure Modes at Or Near TG-142 Tolerance Criteria Levels

DOE Office of Scientific and Technical Information (OSTI.GOV)

Faught, J Tonigan; Balter, P; Johnson, J

2015-06-15

Purpose: Quantitatively assess the clinical impact of 11 critical IMRT dose delivery failure modes. Methods: Eleven step-and-shoot IMRT failure modes (FMs) were introduced into twelve Pinnacle v9.8 treatment plans. One standard and one highly modulated plan on the IROC IMRT phantom and ten previous H&N patient treatment plans were used. FMs included physics components covered by basic QA near tolerance criteria levels (TG-142) such as beam energy, MLC positioning, and MLC modeling. Resultant DVHs were compared to those of failure-free plans and the severity of plan degradation was assessed considering PTV coverage and OAR and normal tissue tolerances and usedmore » for FMEA severity scoring. Six of these FMs were physically simulated and phantom irradiations performed. TLD and radiochromic film results are used for comparison to treatment planning studies. Results: Based on treatment planning studies, the largest clinical impact from the phantom cases was induced by 2 mm systematic MLC shift in one bank with the combination of a D95% target under dose near 16% and OAR overdose near 8%. Cord overdoses of 5%–11% occurred with gantry angle, collimator angle, couch angle, MLC leaf end modeling, and MLC transmission and leakage modeling FMs. PTV coverage and/or OAR sparing was compromised in all FMs introduced in phantom plans with the exception of CT number to electron density tables, MU linearity, and MLC tongue-and-groove modeling. Physical measurements did not entirely agree with treatment planning results. For example, symmetry errors resulted in the largest physically measured discrepancies of up to 3% in the PTVs while a maximum of 0.5% deviation was seen in the treatment planning studies. Patient treatment plan study results are under analysis. Conclusion: Even in the simplistic anatomy of the IROC phantom, some basic physics FMs, just outside of TG-142 tolerance criteria, appear to have the potential for large clinical implications.« less

Improving cardiovascular health of underserved populations in the community with Life's Simple 7.

PubMed

Murphy, Marcia Pencak; Coke, Lola; Staffileno, Beth A; Robinson, Janis D; Tillotson, Robin

2015-11-01

The purpose of this nurse practitioner (NP) led initiative was to improve the cardiovascular health of two underserved populations in the community using the American Heart Association (AHA) Life's Simple 7 and My Life Check (MLC) tools. Two inner city community sites were targeted: (a) a senior center servicing African American (AA) older adults, and (b) a residential facility servicing homeless women. Preprogram health data (blood pressure, cholesterol, blood glucose levels, body mass index, and health behaviors) were collected to calculate MLC scores. Postprogram health data were obtained on participants with the lowest MLC scores who completed the program. Eight older adults completed the program with a 37.1% increase in average MLC score (6.2 vs. 8.5). Ten women completed the program with a 9.3% decrease in average MLC score (4.3 vs. 3.9). Favorable benefits were observed in the AA older adults. In contrast, similar benefits were not observed in the women, which may be because of a constellation of social, environmental, biological, and mental health factors. NPs are prepared to target community-based settings to address the health of underserved populations. Engaging key stakeholders in the planning and implementation is essential for success. ©2015 American Association of Nurse Practitioners.

Transient up- and down-regulation of expression of myosin light chain 2 and myostatin mRNA mark the changes from stratified hyperplasia to muscle fiber hypertrophy in larvae of gilthead sea bream (Sparus aurata L.).

PubMed

Georgiou, Stella; Alami-Durante, Hélène; Power, Deborah M; Sarropoulou, Elena; Mamuris, Zissis; Moutou, Katerina A

2016-02-01

Hyperplasia and hypertrophy are the two mechanisms by which muscle develops and grows. We study these two mechanisms, during the early development of white muscle in Sparus aurata, by means of histology and the expression of structural and regulatory genes. A clear stage of stratified hyperplasia was identified early in the development of gilthead sea bream but ceased by 35 dph when hypertrophy took over. Mosaic recruitment of new white fibers began as soon as 60 dph. The genes mlc2a and mlc2b were expressed at various levels during the main phases of hyperplasia and hypertrophy. The genes myog and mlc2a were significantly up-regulated during the intensive stratified formation of new fibers and their expression was significantly correlated. Expression of mstn1 and igf1 increased at 35 dph, appeared to regulate the hyperplasia-to-hypertrophy transition, and may have stimulated the expression of mlc2a, mlc2b and col1a1 at the onset of mosaic hyperplasia. The up-regulation of mstn1 at transitional phases in muscle development indicates a dual regulatory role of myostatin in fish larval muscle growth.

Technology assessment of multileaf collimation: a North American users survey.

PubMed

Klein, E E; Tepper, J; Sontag, M; Franklin, M; Ling, C; Kubo, D

1999-06-01

The American Association of Physicists in Medicine (AAPM) initiated an Assessment of Technology Subcommittee (ATS) to help the radiotherapy community evaluate emerging technologies. The ATS decided to first address multileaf collimation (MLC) by means of a North American users survey. The survey attempted to address issues such as MLC utility, efficacy, cost-effectiveness, and customer satisfaction. The survey was designed with 38 questions, with cross-tabulation set up to decipher a particular clinic's perception of MLC. The surveys were coded according to MLC types, which were narrowed to four: Elekta, Siemens, Varian 52-leaf, and Varian 80-leaf. A 40% return rate was desired. A 44% (108 of 250) return was achieved. On an MLC machine, 76.5% of photon patients are being treated with MLC. The main reasons for not using MLC were stair stepping, field size limitation, and physician objection. The most common sites in which MLC is being used are lung, pelvis, and prostate. The least used sites are head & neck and mantle fields. Of the facilities, 31% claimed an increase in number of patients being treated since MLC was installed, and 44% claimed an increase in the number of fields. Though the staffing for block cutting has decreased, therapist staffing has not. However, 91% of the facilities claimed a decreased workload for the therapists, despite the increase in daily treated patients and fields. Of the facilities that justified MLC purchase for more daily patients, 63% are actually treating more patients. Only 26% of the facilities that justified an MLC purchase for intensity-modulated radiotherapy (IMRT) are currently using it for that purpose. The satisfaction rating (1 = low to 5 = high) for department groups averaged 4.0. Therapists ranked MLC as 4.6. Our survey shows that most users have successfully introduced MLC into the clinic as a block replacement. Most have found MLC to be cost-effective and efficient. The use of MLC for IMRT has progressed slower, but users anticipate escalated use.

The potential impact of multidimesional geriatric assessment in the social security system.

PubMed

Corbi, Graziamaria; Ambrosino, Immacolata; Massari, Marco; De Lucia, Onofrio; Simplicio, Sirio; Dragone, Michele; Paolisso, Giuseppe; Piccioni, Massimo; Ferrara, Nicola; Campobasso, Carlo Pietro

2018-01-12

To evaluate the efficacy of multidimensional geriatric assessment (MGA/CGA) in patients over 65 years old in predicting the release of the accompaniment allowance (AA) indemnity by a Local Medico-Legal Committee (MLC-NHS) and by the National Institute of Social Security Committee (MLC-INPS). In a longitudinal observational study, 200 Italian elder citizens requesting AA were first evaluated by MLC-NHS and later by MLC-INPS. Only MLC-INPS performed a MGA/CGA (including SPMSQ, Barthel Index, GDS-SF, and CIRS). This report was written according to the STROBE guidelines. The data analysis was performed on January 2016. The evaluation by the MLC-NHS and by the MLC-INPS was in agreement in 66% of cases. In the 28%, the AA benefit was recognized by the MLC-NHS, but not by the MLC-INPS. By the multivariate analysis, the best predictors of the AA release, by the MLC-NHS, were represented by gender and the Barthel Index score. The presence of carcinoma, the Barthel Index score, and the SPMQ score were the best predictors for the AA release by MLC-INPS. MGA/CGA could be useful in saving financial resources reducing the risk of incorrect indemnity release. It can improve the accuracy of the impairment assessment in social security system.

A method for photon beam Monte Carlo multileaf collimator particle transport

NASA Astrophysics Data System (ADS)

Siebers, Jeffrey V.; Keall, Paul J.; Kim, Jong Oh; Mohan, Radhe

2002-09-01

Monte Carlo (MC) algorithms are recognized as the most accurate methodology for patient dose assessment. For intensity-modulated radiation therapy (IMRT) delivered with dynamic multileaf collimators (DMLCs), accurate dose calculation, even with MC, is challenging. Accurate IMRT MC dose calculations require inclusion of the moving MLC in the MC simulation. Due to its complex geometry, full transport through the MLC can be time consuming. The aim of this work was to develop an MLC model for photon beam MC IMRT dose computations. The basis of the MC MLC model is that the complex MLC geometry can be separated into simple geometric regions, each of which readily lends itself to simplified radiation transport. For photons, only attenuation and first Compton scatter interactions are considered. The amount of attenuation material an individual particle encounters while traversing the entire MLC is determined by adding the individual amounts from each of the simplified geometric regions. Compton scatter is sampled based upon the total thickness traversed. Pair production and electron interactions (scattering and bremsstrahlung) within the MLC are ignored. The MLC model was tested for 6 MV and 18 MV photon beams by comparing it with measurements and MC simulations that incorporate the full physics and geometry for fields blocked by the MLC and with measurements for fields with the maximum possible tongue-and-groove and tongue-or-groove effects, for static test cases and for sliding windows of various widths. The MLC model predicts the field size dependence of the MLC leakage radiation within 0.1% of the open-field dose. The entrance dose and beam hardening behind a closed MLC are predicted within +/-1% or 1 mm. Dose undulations due to differences in inter- and intra-leaf leakage are also correctly predicted. The MC MLC model predicts leaf-edge tongue-and-groove dose effect within +/-1% or 1 mm for 95% of the points compared at 6 MV and 88% of the points compared at 18 MV. The dose through a static leaf tip is also predicted generally within +/-1% or 1 mm. Tests with sliding windows of various widths confirm the accuracy of the MLC model for dynamic delivery and indicate that accounting for a slight leaf position error (0.008 cm for our MLC) will improve the accuracy of the model. The MLC model developed is applicable to both dynamic MLC and segmental MLC IMRT beam delivery and will be useful for patient IMRT dose calculations, pre-treatment verification of IMRT delivery and IMRT portal dose transmission dosimetry.

Dynamic-MLC leaf control utilizing on-flight intensity calculations: a robust method for real-time IMRT delivery over moving rigid targets.

PubMed

McMahon, Ryan; Papiez, Lech; Rangaraj, Dharanipathy

2007-08-01

An algorithm is presented that allows for the control of multileaf collimation (MLC) leaves based entirely on real-time calculations of the intensity delivered over the target. The algorithm is capable of efficiently correcting generalized delivery errors without requiring the interruption of delivery (self-correcting trajectories), where a generalized delivery error represents anything that causes a discrepancy between the delivered and intended intensity profiles. The intensity actually delivered over the target is continually compared to its intended value. For each pair of leaves, these comparisons are used to guide the control of the following leaf and keep this discrepancy below a user-specified value. To demonstrate the basic principles of the algorithm, results of corrected delivery are shown for a leading leaf positional error during dynamic-MLC (DMLC) IMRT delivery over a rigid moving target. It is then shown that, with slight modifications, the algorithm can be used to track moving targets in real time. The primary results of this article indicate that the algorithm is capable of accurately delivering DMLC IMRT over a rigid moving target whose motion is (1) completely unknown prior to delivery and (2) not faster than the maximum MLC leaf velocity over extended periods of time. These capabilities are demonstrated for clinically derived intensity profiles and actual tumor motion data, including situations when the target moves in some instances faster than the maximum admissible MLC leaf velocity. The results show that using the algorithm while calculating the delivered intensity every 50 ms will provide a good level of accuracy when delivering IMRT over a rigid moving target translating along the direction of MLC leaf travel. When the maximum velocities of the MLC leaves and target were 4 and 4.2 cm/s, respectively, the resulting error in the two intensity profiles used was 0.1 +/- 3.1% and -0.5 +/- 2.8% relative to the maximum of the intensity profiles. For the same target motion, the error was shown to increase rapidly as (1) the maximum MLC leaf velocity was reduced below 75% of the maximum target velocity and (2) the system response time was increased.

Trastuzumab Alters the Expression of Genes Essential for Cardiac Function and Induces Ultrastructural Changes of Cardiomyocytes in Mice

PubMed Central

ElZarrad, M. Khair; Mukhopadhyay, Partha; Mohan, Nishant; Hao, Enkui; Dokmanovic, Milos; Hirsch, Dianne S.; Shen, Yi; Pacher, Pal; Wu, Wen Jin

2013-01-01

Treatment with trastuzumab, a humanized monoclonal antibody directed against the extracellular domain of Human Epidermal Growth Factor Receptor 2 (HER2), very successfully improves outcomes for women with HER2-positive breast cancer. However, trastuzumab treatment was recently linked to potentially irreversible serious cardiotoxicity, the mechanisms of which are largely elusive. This study reports that trastuzumab significantly alters the expression of myocardial genes essential for DNA repair, cardiac and mitochondrial functions, which is associated with impaired left ventricular performance in mice coupled with significant ultrastructural alterations in cardiomyocytes revealed by electron microscopy. Furthermore, trastuzumab treatment also promotes oxidative stress and apoptosis in myocardium of mice, and elevates serum levels of cardiac troponin-I (cTnI) and cardiac myosin light chain-1 (cMLC1). The elevated serum levels of cMLC1 in mice treated with trastuzumab highlights the potential that cMLC1 could be a useful biomarker for trastuzumab-induced cardiotoxicity. PMID:24255707

Calreticulin reveals a critical Ca2+ checkpoint in cardiac myofibrillogenesis

PubMed Central

Li, Jian; Pucéat, Michel; Perez-Terzic, Carmen; Mery, Annabelle; Nakamura, Kimitoshi; Michalak, Marek; Krause, Karl-Heinz; Jaconi, Marisa E.

2002-01-01

Calreticulin (crt) is an ubiquitously expressed and multifunctional Ca2+-binding protein that regulates diverse vital cell functions, including Ca2+ storage in the ER and protein folding. Calreticulin deficiency in mice is lethal in utero due to defects in heart development and function. Herein, we used crt − / − embryonic stem (ES) cells differentiated in vitro into cardiac cells to investigate the molecular mechanisms underlying heart failure of knockout embryos. After 8 d of differentiation, beating areas were prominent in ES-derived wild-type (wt) embryoid bodies (EBs), but not in ES-derived crt − / − EBs, despite normal expression levels of cardiac transcription factors. Crt − / − EBs exhibited a severe decrease in expression and a lack of phosphorylation of ventricular myosin light chain 2 (MLC2v), resulting in an impaired organization of myofibrils. Crt − / − phenotype could be recreated in wt cells by chelating extracellular or cytoplasmic Ca2+ with EGTA or BAPTA, or by inhibiting Ca2+/calmodulin-dependent kinases (CaMKs). An imposed ionomycin-triggered cystolic-free Ca2+ concentration ([Ca2+]c) elevation restored the expression, phosphorylation, and insertion of MLC2v into sarcomeric structures and in turn the myofibrillogenesis. The transcription factor myocyte enhancer factor C2 failed to accumulate into nuclei of crt − / − cardiac cells in the absence of ionomycin-triggered [Ca2+]c increase. We conclude that the absence of calreticulin interferes with myofibril formation. Most importantly, calreticulin deficiency revealed the importance of a Ca2+-dependent checkpoint critical for early events during cardiac myofibrillogenesis. PMID:12105184

Effects of stress fiber contractility on uniaxial stretch guiding mitosis orientation and stress fiber alignment.

PubMed

Zhao, Lei; Sang, Chen; Yang, Chun; Zhuang, Fengyuan

2011-09-02

It has been documented that mitosis orientation (MO) is guided by stress fibers (SFs), which are perpendicular to exogenous cyclic uniaxial stretch. However, the effect of mechanical forces on MO and the mechanism of stretch-induced SFs reorientation are not well elucidated to date. In the present study, we used murine 3T3 fibroblasts as a model, to investigate the effects of uniaxial stretch on SFO and MO utilizing custom-made stretch device. We found that cyclic uniaxial stretch induced both SFs and mitosis directions orienting perpendicularly to the stretch direction. The F-actin and myosin II blockages, which resulted in disoriented SFs and mitosis directions under uniaxial stretch, suggested a high correlation between SFO and MO. Y27632 (10 μM), ML7 (50 μM, or 75 μM), and blebbistatin (50 μM, or 75 μM) treatments resulted in SFO parallel to the principle stretch direction. Upon stimulating and inhibiting the phosphorylation of myosin light chain (p-MLC), we observed a monotonic proportion of SFO to the level of p-MLC. These results suggested that the level of cell contraction is crucial to the response of SFs, either perpendicular or parallel, to the external stretch. Showing the possible role of cell contractility in tuning SFO under external stretch, our experimental data are valuable to understand the predominant factor controlling SFO response to exogenous uniaxial stretch, and thus helpful for improving mechanical models. Copyright © 2011 Elsevier Ltd. All rights reserved.

3-Hydroxyflavone inhibits human osteosarcoma U2OS and 143B cells metastasis by affecting EMT and repressing u-PA/MMP-2 via FAK-Src to MEK/ERK and RhoA/MLC2 pathways and reduces 143B tumor growth in vivo.

PubMed

Lu, Ko-Hsiu; Chen, Pei-Ni; Hsieh, Yi-Hsien; Lin, Chin-Yin; Cheng, Fu-Yuan; Chiu, Peng-Chou; Chu, Shu-Chen; Hsieh, Yih-Shou

2016-11-01

Many natural flavonoids have cytostatic and apoptotic properties; however, we little know whether the effect of synthetic 3-hydroxyflavone on metastasis and tumor growth of human osteosarcoma. Here, we tested the hypothesis that 3-hydroxyflavone suppresses human osteosarcoma cells metastasis and tumor growth. 3-hydroxyflavone, up to 50 μM without cytotoxicity, inhibited U2OS and 143B cells motility, invasiveness and migration by reducing matrix metalloproteinase (MMP)-2 and urokinase-type plasminogen activator (u-PA) and also impaired cell adhesion to gelatin. 3-hydroxyflavone significantly reduced p-focal adhesion kinase (FAK) Tyr397, p-FAK Tyr925, p-steroid receptor coactivator (Src), p-mitogen/extracellular signal-regulated kinase (MEK)1/2, p-myosin light chain (MLC)2 Ser19, epithelial cell adhesion molecule, Ras homolog gene family (Rho)A and fibronectin expressions. 3-hydroxyflavone also affected the epithelial-mesenchymal transition (EMT) by down-regulating expressions of Vimentin and α-catenin with activation of the transcription factor Slug. In nude mice xenograft model and tail vein injection model showed that 3-hydroxyflavone reduced 143B tumor growth and lung metastasis. 3-hydroxyflavone possesses the anti-metastatic activity of U2OS and 143B cells by affecting EMT and repressing u-PA/MMP-2 via FAK-Src to MEK/ERK and RhoA/MLC2 pathways and suppresses 143B tumor growth in vivo. This may lead to clinical trials of osteosarcoma chemotherapy to confirm the promising result in the future. Copyright © 2016 Elsevier Ltd. All rights reserved.

Complexity metric based on fraction of penumbra dose - initial study

NASA Astrophysics Data System (ADS)

Bäck, A.; Nordström, F.; Gustafsson, M.; Götstedt, J.; Karlsson Hauer, A.

2017-05-01

Volumetric modulated arc therapy improve radiotherapy outcome for many patients compared to conventional three dimensional conformal radiotherapy but require a more extensive, most often measurement based, quality assurance. Multi leaf collimator (MLC) aperture-based complexity metrics have been suggested to be used to distinguish complex treatment plans unsuitable for treatment without time consuming measurements. This study introduce a spatially resolved complexity score that correlate to the fraction of penumbra dose and will give information on the spatial distribution and the clinical relevance of the calculated complexity. The complexity metric is described and an initial study on the correlation between the complexity score and the difference between measured and calculated dose for 30 MLC openings is presented. The result of an analysis of the complexity scores were found to correlate to differences between measurements and calculations with a Pearson’s r-value of 0.97.

The dosimetric impact of inversely optimized arc radiotherapy plan modulation for real-time dynamic MLC tracking delivery.

PubMed

Falk, Marianne; Larsson, Tobias; Keall, Paul; Chul Cho, Byung; Aznar, Marianne; Korreman, Stine; Poulsen, Per; Munck Af Rosenschold, Per

2012-03-01

Real-time dynamic multileaf collimator (MLC) tracking for management of intrafraction tumor motion can be challenging for highly modulated beams, as the leaves need to travel far to adjust for target motion perpendicular to the leaf travel direction. The plan modulation can be reduced by using a leaf position constraint (LPC) that reduces the difference in the position of adjacent MLC leaves in the plan. The purpose of this study was to investigate the impact of the LPC on the quality of inversely optimized arc radiotherapy plans and the effect of the MLC motion pattern on the dosimetric accuracy of MLC tracking delivery. Specifically, the possibility of predicting the accuracy of MLC tracking delivery based on the plan modulation was investigated. Inversely optimized arc radiotherapy plans were created on CT-data of three lung cancer patients. For each case, five plans with a single 358° arc were generated with LPC priorities of 0 (no LPC), 0.25, 0.5, 0.75, and 1 (highest possible LPC), respectively. All the plans had a prescribed dose of 2 Gy × 30, used 6 MV, a maximum dose rate of 600 MU/min and a collimator angle of 45° or 315°. To quantify the plan modulation, an average adjacent leaf distance (ALD) was calculated by averaging the mean adjacent leaf distance for each control point. The linear relationship between the plan quality [i.e., the calculated dose distributions and the number of monitor units (MU)] and the LPC was investigated, and the linear regression coefficient as well as a two tailed confidence level of 95% was used in the evaluation. The effect of the plan modulation on the performance of MLC tracking was tested by delivering the plans to a cylindrical diode array phantom moving with sinusoidal motion in the superior-inferior direction with a peak-to-peak displacement of 2 cm and a cycle time of 6 s. The delivery was adjusted to the target motion using MLC tracking, guided in real-time by an infrared optical system. The dosimetric results were evaluated using gamma index evaluation with static target measurements as reference. The plan quality parameters did not depend significantly on the LPC (p ≥ 0.066), whereas the ALD depended significantly on the LPC (p < 0.001). The gamma index failure rate depended significantly on the ALD, weighted to the percentage of the beam delivered in each control point of the plan (ALD(w)) when MLC tracking was used (p < 0.001), but not for delivery without MLC tracking (p ≥ 0.342). The gamma index failure rate with the criteria of 2% and 2 mm was decreased from > 33.9% without MLC tracking to <31.4% (LPC 0) and <2.2% (LPC 1) with MLC tracking. The results indicate that the dosimetric robustness of MLC tracking delivery of an inversely optimized arc radiotherapy plan can be improved by incorporating leaf position constraints in the objective function without otherwise affecting the plan quality. The dosimetric robustness may be estimated prior to delivery by evaluating the ALD(w) of the plan.

Micellar liquid chromatography

NASA Astrophysics Data System (ADS)

Basova, Elena M.; Ivanov, Vadim M.; Shpigun, Oleg A.

1999-12-01

Background and possibilities of practical applications of micellar liquid chromatography (MLC) are considered. Various retention models in MLC, the effects of the nature and concentration of surfactants and organic modifiers, pH, temperature and ionic strength on the MLC efficiency and selectivity are discussed. The advantages and limitations of MLC are demonstrated. The performance of MLC is critically evaluated in relationship to the reversed-phase HPLC and ion-pair chromatography. The potential of application of MLC for the analysis of pharmaceuticals including that in biological fluids and separation of inorganic anions, transition metal cations, metal chelates and heteropoly compounds is described. The bibliography includes 146 references.

Electromagnetic guided couch and multileaf collimator tracking on a TrueBeam accelerator

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hansen, Rune; Ravkilde, Thomas; Worm, Esben Schjødt

2016-05-15

Purpose: Couch and MLC tracking are two promising methods for real-time motion compensation during radiation therapy. So far, couch and MLC tracking experiments have mainly been performed by different research groups, and no direct comparison of couch and MLC tracking of volumetric modulated arc therapy (VMAT) plans has been published. The Varian TrueBeam 2.0 accelerator includes a prototype tracking system with selectable couch or MLC compensation. This study provides a direct comparison of the two tracking types with an otherwise identical setup. Methods: Several experiments were performed to characterize the geometric and dosimetric performance of electromagnetic guided couch and MLCmore » tracking on a TrueBeam accelerator equipped with a Millennium MLC. The tracking system latency was determined without motion prediction as the time lag between sinusoidal target motion and the compensating motion of the couch or MLC as recorded by continuous MV portal imaging. The geometric and dosimetric tracking accuracies were measured in tracking experiments with motion phantoms that reproduced four prostate and four lung tumor trajectories. The geometric tracking error in beam’s eye view was determined as the distance between an embedded gold marker and a circular MLC aperture in continuous MV images. The dosimetric tracking error was quantified as the measured 2%/2 mm gamma failure rate of a low and a high modulation VMAT plan delivered with the eight motion trajectories using a static dose distribution as reference. Results: The MLC tracking latency was approximately 146 ms for all sinusoidal period lengths while the couch tracking latency increased from 187 to 246 ms with decreasing period length due to limitations in the couch acceleration. The mean root-mean-square geometric error was 0.80 mm (couch tracking), 0.52 mm (MLC tracking), and 2.75 mm (no tracking) parallel to the MLC leaves and 0.66 mm (couch), 1.14 mm (MLC), and 2.41 mm (no tracking) perpendicular to the leaves. The motion-induced gamma failure rate was in mean 0.1% (couch tracking), 8.1% (MLC tracking), and 30.4% (no tracking) for prostate motion and 2.9% (couch), 2.4% (MLC), and 41.2% (no tracking) for lung tumor motion. The residual tracking errors were mainly caused by inadequate adaptation to fast lung tumor motion for couch tracking and to prostate motion perpendicular to the MLC leaves for MLC tracking. Conclusions: Couch and MLC tracking markedly improved the geometric and dosimetric accuracies of VMAT delivery. However, the two tracking types have different strengths and weaknesses. While couch tracking can correct perfectly for slowly moving targets such as the prostate, MLC tracking may have considerably larger dose errors for persistent target shift perpendicular to the MLC leaves. Advantages of MLC tracking include faster dynamics with better adaptation to fast moving targets, the avoidance of moving the patient, and the potential to track target rotations and deformations.« less

Is mini-laparoscopic cholecystectomy any better than the gold standard?: A comparative study.

PubMed

Shaikh, Haris R; Abbas, Asad; Aleem, Salik; Lakhani, Miqdad R

2017-01-01

Mini-laparoscopic cholecystectomy (MLC) has widened the horizons of modern laparoscopic surgery. Standard four port laparoscopic cholecystectomy (SLC), which has long been established as the "Gold Standard" for gall bladder diseases, is under reconsideration following the advent of further minimally-invasive procedures including MLC. Our study aims to provide a comparison between MLC and SLC and assesses whether MLC has any added benefits. Patients with symptomatic gall bladder disease undergoing MLC or SLC during the 2.5-month period were included in the study. Thirty-two patients underwent MLC while SLC was performed on 40 patients by the same surgeon. Data was collected prospectively and analysed retrospectively using a predesigned questionnaire. In our study, both the groups had similar age, body mass index (BMI) and gender distribution. No cases of MLC required insertion of additional ports. The mean operative time for MLC was 38.2 min (33-61 min), which is longer than SLC; but it was not statistically significant. There was no significant difference in mean operative blood loss, postoperative pain, analgesia requirement and mobilization. Patients who underwent MLC were able to return to normal activity earlier than patients undergoing SLC (P < 0.01). Our experience suggests that MLC can safely be used as an alternative to SLC. Compared to SLC, it has the added benefit of an early return to work along with excellent cosmetic results. Further large scale trials are required to prove any additional benefit of MLC.

Is mini-laparoscopic cholecystectomy any better than the gold standard?: A comparative study

PubMed Central

Shaikh, Haris R.; Abbas, Asad; Aleem, Salik; Lakhani, Miqdad R.

2017-01-01

BACKGROUND: Mini-laparoscopic cholecystectomy (MLC) has widened the horizons of modern laparoscopic surgery. Standard four port laparoscopic cholecystectomy (SLC), which has long been established as the “Gold Standard” for gall bladder diseases, is under reconsideration following the advent of further minimally-invasive procedures including MLC. Our study aims to provide a comparison between MLC and SLC and assesses whether MLC has any added benefits. MATERIALS AND METHODS: Patients with symptomatic gall bladder disease undergoing MLC or SLC during the 2.5-month period were included in the study. Thirty-two patients underwent MLC while SLC was performed on 40 patients by the same surgeon. Data was collected prospectively and analysed retrospectively using a predesigned questionnaire. RESULTS: In our study, both the groups had similar age, body mass index (BMI) and gender distribution. No cases of MLC required insertion of additional ports. The mean operative time for MLC was 38.2 min (33-61 min), which is longer than SLC; but it was not statistically significant. There was no significant difference in mean operative blood loss, postoperative pain, analgesia requirement and mobilization. Patients who underwent MLC were able to return to normal activity earlier than patients undergoing SLC (P < 0.01). CONCLUSION: Our experience suggests that MLC can safely be used as an alternative to SLC. Compared to SLC, it has the added benefit of an early return to work along with excellent cosmetic results. Further large scale trials are required to prove any additional benefit of MLC. PMID:27251827

Classification method, spectral diversity, band combination and accuracy assessment evaluation for urban feature detection

NASA Astrophysics Data System (ADS)

Erener, A.

2013-04-01

Automatic extraction of urban features from high resolution satellite images is one of the main applications in remote sensing. It is useful for wide scale applications, namely: urban planning, urban mapping, disaster management, GIS (geographic information systems) updating, and military target detection. One common approach to detecting urban features from high resolution images is to use automatic classification methods. This paper has four main objectives with respect to detecting buildings. The first objective is to compare the performance of the most notable supervised classification algorithms, including the maximum likelihood classifier (MLC) and the support vector machine (SVM). In this experiment the primary consideration is the impact of kernel configuration on the performance of the SVM. The second objective of the study is to explore the suitability of integrating additional bands, namely first principal component (1st PC) and the intensity image, for original data for multi classification approaches. The performance evaluation of classification results is done using two different accuracy assessment methods: pixel based and object based approaches, which reflect the third aim of the study. The objective here is to demonstrate the differences in the evaluation of accuracies of classification methods. Considering consistency, the same set of ground truth data which is produced by labeling the building boundaries in the GIS environment is used for accuracy assessment. Lastly, the fourth aim is to experimentally evaluate variation in the accuracy of classifiers for six different real situations in order to identify the impact of spatial and spectral diversity on results. The method is applied to Quickbird images for various urban complexity levels, extending from simple to complex urban patterns. The simple surface type includes a regular urban area with low density and systematic buildings with brick rooftops. The complex surface type involves almost all kinds of challenges, such as high dense build up areas, regions with bare soil, and small and large buildings with different rooftops, such as concrete, brick, and metal. Using the pixel based accuracy assessment it was shown that the percent building detection (PBD) and quality percent (QP) of the MLC and SVM depend on the complexity and texture variation of the region. Generally, PBD values range between 70% and 90% for the MLC and SVM, respectively. No substantial improvements were observed when the SVM and MLC classifications were developed by the addition of more variables, instead of the use of only four bands. In the evaluation of object based accuracy assessment, it was demonstrated that while MLC and SVM provide higher rates of correct detection, they also provide higher rates of false alarms.

Dosimetric comparison between cone/Iris-based and InCise MLC-based CyberKnife plans for single and multiple brain metastases.

PubMed

Jang, Si Young; Lalonde, Ron; Ozhasoglu, Cihat; Burton, Steven; Heron, Dwight; Huq, M Saiful

2016-09-08

We performed an evaluation of the CyberKnife InCise MLC by comparing plan qualities for single and multiple brain lesions generated using the first version of InCise MLC, fixed cone, and Iris collimators. We also investigated differences in delivery efficiency among the three collimators. Twenty-four patients with single or multiple brain mets treated previously in our clinic on a CyberKnife M6 using cone/Iris collimators were selected for this study. Treatment plans were generated for all lesions using the InCise MLC. Number of monitor units, delivery time, target coverage, conformity index, and dose falloff were compared between MLC- and clinical cone/Iris-based plans. Statistical analysis was performed using the non-parametric Wilcoxon-Mann-Whitney signed-rank test. The planning accuracy of the MLC-based plans was validated using chamber and film measurements. The InCise MLC-based plans achieved mean dose and target coverage comparable to the cone/Iris-based plans. Although the conformity indices of the MLC-based plans were slightly higher than those of the cone/Iris-based plans, beam delivery time for the MLC-based plans was shorter by 30% ~ 40%. For smaller targets or cases with OARs located close to or abutting target volumes, MLC-based plans provided inferior dose conformity compared to cone/Iris-based plans. The QA results of MLC-based plans were within 5% absolute dose difference with over 90% gamma passing rate using 2%/2 mm gamma criteria. The first version of InCise MLC could be a useful delivery modality, especially for clinical situations for which delivery time is a limiting factor or for multitarget cases. © 2016 The Authors.

Multileaf collimator characteristics and reliability requirements for IMRT Elekta system.

PubMed

Liu, Chihray; Simon, Thomas A; Fox, Christopher; Li, Jonathan; Palta, Jatinder R

2008-01-01

Understanding the characteristics of a multileaf collimator (MLC) system, modeling MLC in a treatment planning system, and maintaining the mechanical accuracy of the linear accelerator gantry head system are important factors in the safe implementation of an intensity-modulated radiotherapy program. We review the characteristics of an Elekta MLC system, discuss the necessary MLC modeling parameters for a treatment planning system, and provide a novel method to establish an MLC leaf position quality assurance program. To perform quality assurance on 40 pairs of individual MLC leaves is a time-consuming and difficult task. In this report, an effective routine MLC quality assurance method based on the field edge of a backup jaw as referenced in conjunction with a diode array as a radiation detector system is discussed. The sensitivity of this test for determining the relative leaf positions was observed to be better than 0.1 mm. The Elekta MLC leaf position accuracy measured with this system has been better than 0.3 mm.

SU-F-T-530: Characterization of a 60-Leaf Motorized MLC Designed for Cobalt-60 Units

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu, L; Smith, L; Ciresianu, A

2016-06-15

Purpose: In a continuing effort to improve conformal radiation therapy with Cobalt-60 units, a 60-leaf MLC was designed, manufactured, and released to market. This work describes the physics measurements taken to characterize the clinical performance of this MLC. Methods: A 60 leaf MLC was custom designed with tungsten leaves of 4.5 cm height, single focused, achieving field size of 30×30 cm^2 when mounted on a 100cm SAD Cobalt-60 unit. Leakage and output factor measurements were performed using a single ion chamber in a solid water phantom. Penumbra and surface dose were measured using scanning chambers and diodes in a watermore » phantom. Radiation-light coincidence measurements were performed using radiographic films. Results: With MLC mounted, measured penumbras at all depths are smaller than with jaws only. Surface doses were not significantly affected by the presence of MLC, and remained below values recommended by regulatory bodies. Light-radiation coincidences were found to be better than 3 mm for all field sizes. Leakage through the MLC was found to be strongly dependent on field size, increasing from 1.0 % for a 10×10 cm field to 2.0% for a 30×30 cm field. Such results meet the requirements of IEC 60601-2-11. The MLC was found to have significant influence on the output factor, when field size defined by MLC is significantly smaller than field size defined by jaws. Such effect is also observed on linear accelerators, but it is more pronounced on Cobalt-60 units. A 10×10 “diamond” MLC shape inside a 14×14 cm jaw showed output factor that is 5.7% higher than 10×10 cm field defined by matching MLC and jaws. Conclusion: The MLC offers clinically acceptable performance in penumbra, surface dose, and light-radiation coincidence. Several units of this MLC have recently been installed and used clinically. Validation of Cobalt-60 based IMRT with this MLC is ongoing. The authors are employees of Best Theratrnics Ltd.« less

Anti-Trichomonas vaginalis properties of the oil of Amomum tsao-ko and its major component, geraniol.

PubMed

Dai, Min; Peng, Cheng; Peng, Fu; Xie, Chengbin; Wang, Pinjia; Sun, Fenghui

2016-01-01

Trichomonosis, caused by the flagellate protozoan Trichomonas vaginalis, is the most common non-viral sexually transmitted disease (STD) and 5-nitroimidazole drugs are used for the treatment. However, a growing number of T. vaginalis isolates are resistant to these drugs, which make it becomes an urgent issue. The current study was designed to evaluate the anti-T. vaginalis activity of the essential oil from A. tsao-ko used in traditional Chinese medicine and as a spice and its main component, geraniol. The anti-T. vaginalis activities of A. tsao-ko essential oil and geraniol were evaluated by the minimum lethal concentration (MLC) and 50% inhibitory concentration (IC50) in vitro. The morphological changes of T. vaginalis were observed by transmission electron microscopy (TEM). Additionally, sub-MLC concentration treatment with sub-MLC A. tsao-ko essential oil and geraniol was also performed. This study shows that MLC/IC50 of A. tsao-ko essential oil was 44.97 µg/ml/22.49 µg/ml for T. vaginalis isolate Tv1, and 89.93 µg/ml/44.97 µg/ml for T. vaginalis isolate Tv2. Those of geraniol were 342.96 µg/ml/171.48 µg/ml, respectively. After A. tsao-ko essential oil or geraniol treatment, obvious similar morphological changes of T. vaginalis were observed by TEM: the nuclear membrane was damaged, nuclei were dissolved, and the chromatin was accumulated; in the cytoplasm, numerous vacuoles appeared, rough endoplasmic reticulum dilated, the number of ribosomes were reduced, organelles disintegrated, the cell membrane was partially damaged, with cytoplasmic leakage, and cell disintegration was observed. The action time did not increase the effect of A. tsao-ko essential oil or geraniol against T. vaginalis, as no significant difference was observed after sub-MLC concentration treatment for 1, 3, and 5 h with A. tsao-ko essential oil and geraniol. The study describes the first report on the activity and morphological changes of A. tsao-ko essential oil and geraniol against T. vaginalis. The results obtained herein presented new opportunities for antitrichomonal drugs.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Han, S; Ji, Y; Kim, K

Purpose: A diagnostics Multileaf Collimator (MLC) was designed for diagnostic radiography dose reduction. Monte Carlo simulation was used to evaluate efficiency of shielding material for producing leaves of Multileaf collimator. Material & Methods: The general radiography unit (Rex-650R, Listem, Korea) was modeling with Monte Carlo simulation (MCNPX, LANL, USA) and we used SRS-78 program to calculate the energy spectrum of tube voltage (80, 100, 120 kVp). The shielding materials was SKD 11 alloy tool steel that is composed of 1.6% carbon(C), 0.4% silicon (Si), 0.6% manganese (Mn), 5% chromium (Cr), 1% molybdenum (Mo), and vanadium (V). The density of itmore » was 7.89 g/m3. We simulated leafs diagnostic MLC using SKD 11 with general radiography unit. We calculated efficiency of diagnostic MLC using tally6 card of MCNPX depending on energy. Results: The diagnostic MLC consisted of 25 individual metal shielding leaves on both sides, with dimensions of 10 × 0.5 × 0.5 cm3. The leaves of MLC were controlled by motors positioned on both sides of the MLC. According to energy (tube voltage), the shielding efficiency of MLC in Monte Carlo simulation was 99% (80 kVp), 96% (100 kVp) and 93% (120 kVp). Conclusion: We certified efficiency of diagnostic MLC fabricated from SKD11 alloy tool steel. Based on the results, the diagnostic MLC was designed. We will make the diagnostic MLC for dose reduction of diagnostic radiography.« less

Ca2+-dependent rapid Ca2+ sensitization of contraction in arterial smooth muscle.

PubMed

Dimopoulos, George J; Semba, Shingo; Kitazawa, Kazuyo; Eto, Masumi; Kitazawa, Toshio

2007-01-05

Ca(2+) ion is a universal intracellular messenger that regulates numerous biological functions. In smooth muscle, Ca(2+) with calmodulin activates myosin light chain (MLC) kinase to initiate a rapid MLC phosphorylation and contraction. To test the hypothesis that regulation of MLC phosphatase is involved in the rapid development of MLC phosphorylation and contraction during Ca(2+) transient, we compared Ca(2+) signal, MLC phosphorylation, and 2 modes of inhibition of MLC phosphatase, phosphorylation of CPI-17 Thr38 and MYPT1 Thr853, during alpha(1) agonist-induced contraction with/without various inhibitors in intact rabbit femoral artery. Phenylephrine rapidly induced CPI-17 phosphorylation from a negligible amount to a peak value of 0.38+/-0.04 mol of Pi/mol within 7 seconds following stimulation, similar to the rapid time course of Ca(2+) rise and MLC phosphorylation. This rapid CPI-17 phosphorylation was dramatically inhibited by either blocking Ca(2+) release from the sarcoplasmic reticulum or by pretreatment with protein kinase C inhibitors, suggesting an involvement of Ca(2+)-dependent protein kinase C. This was followed by a slow Ca(2+)-independent and Rho-kinase/protein kinase C-dependent phosphorylation of CPI-17. In contrast, MYPT1 phosphorylation had only a slow component that increased from 0.29+/-0.09 at rest to the peak of 0.68+/-0.14 mol of Pi/mol at 1 minute, similar to the time course of contraction. Thus, there are 2 components of the Ca(2+) sensitization through inhibition of MLC phosphatase. Our results support the hypothesis that the initial rapid Ca(2+) rise induces a rapid inhibition of MLC phosphatase coincident with the Ca(2+)-induced MLC kinase activation to synergistically initiate a rapid MLC phosphorylation and contraction in arteries with abundant CPI-17 content.

MiRNA-335 suppresses neuroblastoma cell invasiveness by direct targeting of multiple genes from the non-canonical TGF-β signalling pathway

PubMed Central

Lynch, Jennifer; Fay, Joanna; Meehan, Maria; Bryan, Kenneth; Watters, Karen M.; Murphy, Derek M.; Stallings, Raymond L.

2012-01-01

Transforming growth factor-β (TGF-β) signaling regulates many diverse cellular activities through both canonical (SMAD-dependent) and non-canonical branches, which includes the mitogen-activated protein kinase (MAPK), Rho-like guanosine triphosphatase and phosphatidylinositol-3-kinase/AKT pathways. Here, we demonstrate that miR-335 directly targets and downregulates genes in the TGF-β non-canonical pathways, including the Rho-associated coiled-coil containing protein (ROCK1) and MAPK1, resulting in reduced phosphorylation of downstream pathway members. Specifically, inhibition of ROCK1 and MAPK1 reduces phosphorylation levels of the motor protein myosin light chain (MLC) leading to a significant inhibition of the invasive and migratory potential of neuroblastoma cells. Additionally, miR-335 targets the leucine-rich alpha-2-glycoprotein 1 (LRG1) messenger RNA, which similarly results in a significant reduction in the phosphorylation status of MLC and a decrease in neuroblastoma cell migration and invasion. Thus, we link LRG1 to the migratory machinery of the cell, altering its activity presumably by exerting its effect within the non-canonical TGF-β pathway. Moreover, we demonstrate that the MYCN transcription factor, whose coding sequence is highly amplified in a particularly clinically aggressive neuroblastoma tumor subtype, directly binds to a region immediately upstream of the miR-335 transcriptional start site, resulting in transcriptional repression. We conclude that MYCN contributes to neuroblastoma cell migration and invasion, by directly downregulating miR-335, resulting in the upregulation of the TGF-β signaling pathway members ROCK1, MAPK1 and putative member LRG1, which positively promote this process. Our results provide novel insight into the direct regulation of TGF-β non-canonical signaling by miR-335, which in turn is downregulated by MYCN. PMID:22382496

Pitfalls of tungsten multileaf collimator in proton beam therapy.

PubMed

Moskvin, Vadim; Cheng, Chee-Wai; Das, Indra J

2011-12-01

Particle beam therapy is associated with significant startup and operational cost. Multileaf collimator (MLC) provides an attractive option to improve the efficiency and reduce the treatment cost. A direct transfer of the MLC technology from external beam radiation therapy is intuitively straightforward to proton therapy. However, activation, neutron production, and the associated secondary cancer risk in proton beam should be an important consideration which is evaluated. Monte Carlo simulation with FLUKA particle transport code was applied in this study for a number of treatment models. The authors have performed a detailed study of the neutron generation, ambient dose equivalent [H∗(10)], and activation of a typical tungsten MLC and compared with those obtained from a brass aperture used in a typical proton therapy system. Brass aperture and tungsten MLC were modeled by absorber blocks in this study, representing worst-case scenario of a fully closed collimator. With a tungsten MLC, the secondary neutron dose to the patient is at least 1.5 times higher than that from a brass aperture. The H∗(10) from a tungsten MLC at 10 cm downstream is about 22.3 mSv/Gy delivered to water phantom by noncollimated 200 MeV beam of 20 cm diameter compared to 14 mSv/Gy for the brass aperture. For a 30-fraction treatment course, the activity per unit volume in brass aperture reaches 5.3 × 10⁴ Bq cm(-3) at the end of the last treatment. The activity in brass decreases by a factor of 380 after 24 h, additional 6.2 times after 40 days of cooling, and is reduced to background level after 1 yr. Initial activity in tungsten after 30 days of treating 30 patients per day is about 3.4 times higher than in brass that decreases only by a factor of 2 after 40 days and accumulates to 1.2 × 10⁶ Bq cm(-3) after a full year of operation. The daily utilization of the MLC leads to buildup of activity with time. The overall activity continues to increase due to (179)Ta with a half-life of 1.82 yr and thus require prolonged storage for activity cooling. The H∗(10) near the patient side of the tungsten block is about 100 μSv/h and is 27 times higher at the upstream side of the block. This would lead to an accumulated dose for therapists in a year that may exceed occupational maximum permissible dose (50 mSv/yr). The value of H∗(10) at the upstream surface of the tungsten block is about 220 times higher than that of the brass. MLC is an efficient way for beam shaping and overall cost reduction device in proton therapy. However, based on this study, tungsten seems to be not an optimal material for MLC in proton beam therapy. Usage of tungsten MLC in clinic may create unnecessary risks associated with the secondary neutrons and induced radioactivity for patients and staff depending on the patient load. A careful selection of material for manufacturing of an optimal MLC for proton therapy is thus desired.

TH-AB-202-03: A Novel Tool for Computing Deliverable Doses in Dynamic MLC Tracking Treatments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fast, M; Kamerling, C; Menten, M

2016-06-15

Purpose: In tracked dynamic multi-leaf collimator (MLC) treatments, segments are continuously adapted to the target centroid motion in beams-eye-view. On-the-fly segment adaptation, however, potentially induces dosimetric errors due to the finite MLC leaf width and non-rigid target motion. In this study, we outline a novel tool for computing the 4d dose of lung SBRT plans delivered with MLC tracking. Methods: The following automated workflow was developed: A) centroid tracking, where the initial segments are morphed to each 4dCT phase based on the beams-eye-view GTV shift (followed by a dose calculation on each phase); B) re-optimized tracking, in which all morphedmore » initial plans from (A) are further optimised (“warm-started”) in each 4dCT phase using the initial optimisation parameters but phase-specific volume definitions. Finally, both dose sets are accumulated to the reference phase using deformable image registration. Initial plans were generated according to the RTOG-1021 guideline (54Gy, 3-Fx, equidistant 9-beam IMRT) on the peak-exhale (reference) phase of a phase-binned 4dCT. Treatment planning and delivery simulations were performed in RayStation (research v4.6) using our in-house segment-morphing algorithm, which directly links to RayStation through a native C++ interface. Results: Computing the tracking plans and 4d dose distributions via the in-house interface takes 5 and 8 minutes respectively for centroid and re-optimized tracking. For a sample lung SBRT patient with 14mm peak-to-peak motion in sup-inf direction, mainly perpendicular leaf motion (0-collimator) resulted in small dose changes for PTV-D95 (−13cGy) and GTV-D98 (+18cGy) for the centroid tracking case compared to the initial plan. Modest reductions of OAR doses (e.g. spinal cord D2: −11cGy) were achieved in the idealized tracking case. Conclusion: This study presents an automated “1-click” workflow for computing deliverable MLC tracking doses in RayStation. Adding a non-deliverable re-optimized tracking scenario is expected to help quantify plan robustness for more challenging patients with anatomy deformations. We acknowledge support of the MLC tracking research from Elekta AB. MFF is supported by Cancer Research UK under Programme C33589/A19908. Research at ICR is also supported by Cancer Research UK under Programme C33589/A19727 and NHS funding to the NIHR Biomedical Research Centre at RMH and ICR.« less

SU-F-T-288: Impact of Trajectory Log Files for Clarkson-Based Independent Dose Verification of IMRT and VMAT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Takahashi, R; Kamima, T; Tachibana, H

2016-06-15

Purpose: To investigate the effect of the trajectory files from linear accelerator for Clarkson-based independent dose verification in IMRT and VMAT plans. Methods: A CT-based independent dose verification software (Simple MU Analysis: SMU, Triangle Products, Japan) with a Clarksonbased algorithm was modified to calculate dose using the trajectory log files. Eclipse with the three techniques of step and shoot (SS), sliding window (SW) and Rapid Arc (RA) was used as treatment planning system (TPS). In this study, clinically approved IMRT and VMAT plans for prostate and head and neck (HN) at two institutions were retrospectively analyzed to assess the dosemore » deviation between DICOM-RT plan (PL) and trajectory log file (TJ). An additional analysis was performed to evaluate MLC error detection capability of SMU when the trajectory log files was modified by adding systematic errors (0.2, 0.5, 1.0 mm) and random errors (5, 10, 30 mm) to actual MLC position. Results: The dose deviations for prostate and HN in the two sites were 0.0% and 0.0% in SS, 0.1±0.0%, 0.1±0.1% in SW and 0.6±0.5%, 0.7±0.9% in RA, respectively. The MLC error detection capability shows the plans for HN IMRT were the most sensitive and 0.2 mm of systematic error affected 0.7% dose deviation on average. Effect of the MLC random error did not affect dose error. Conclusion: The use of trajectory log files including actual information of MLC location, gantry angle, etc should be more effective for an independent verification. The tolerance level for the secondary check using the trajectory file may be similar to that of the verification using DICOM-RT plan file. From the view of the resolution of MLC positional error detection, the secondary check could detect the MLC position error corresponding to the treatment sites and techniques. This research is partially supported by Japan Agency for Medical Research and Development (AMED)« less

Interaction between src family kinases and rho-kinase in agonist-induced Ca2+-sensitization of rat pulmonary artery.

PubMed

Knock, Greg A; Shaifta, Yasin; Snetkov, Vladimir A; Vowles, Benjamin; Drndarski, Svetlana; Ward, Jeremy P T; Aaronson, Philip I

2008-02-01

We investigated the role of src family kinases (srcFK) in agonist-mediated Ca2+-sensitization in pulmonary artery and whether this involves interaction with the rho/rho-kinase pathway. Intra-pulmonary arteries (IPAs) and cultured pulmonary artery smooth muscle cells (PASMC) were obtained from rat. Expression of srcFK was determined at the mRNA and protein levels. Ca2+-sensitization was induced by prostaglandin F(2 alpha) (PGF(2 alpha)) in alpha-toxin-permeabilized IPAs. Phosphorylation of the regulatory subunit of myosin phosphatase (MYPT-1) and of myosin light-chain-20 (MLC20) and translocation of rho-kinase in response to PGF(2 alpha) were also determined. Nine srcFK were expressed at the mRNA level, including src, fyn, and yes, and PGF(2 alpha) enhanced phosphorylation of three srcFK proteins at tyr-416. In alpha-toxin-permeabilized IPAs, PGF(2 alpha) enhanced the Ca2+-induced contraction (pCa 6.9) approximately three-fold. This enhancement was inhibited by the srcFK blockers SU6656 and PP2 and by the rho-kinase inhibitor Y27632. Y27632, but not SU6656 or PP2, also inhibited the underlying pCa 6.9 contraction. PGF(2 alpha) enhanced phosphorylation of MYPT-1 at thr-697 and thr-855 and of MLC20 at ser-19. This enhancement, but not the underlying basal phosphorylation, was inhibited by SU6656. Y27632 suppressed both basal and PGF(2 alpha)-mediated phosphorylation. The effects of SU6656 and Y27632, on both contraction and MYPT-1 and MLC20 phosphorylation, were not additive. PGF(2 alpha) triggered translocation of rho-kinase in PASMC, and this was inhibited by SU6656. srcFK are activated by PGF(2 alpha) in the rat pulmonary artery and may contribute to Ca2+-sensitization and contraction via rho-kinase translocation and phosphorylation of MYPT-1.

Interaction between src family kinases and rho-kinase in agonist-induced Ca2+-sensitization of rat pulmonary artery

PubMed Central

Knock, Greg A.; Shaifta, Yasin; Snetkov, Vladimir A.; Vowles, Benjamin; Drndarski, Svetlana; Ward, Jeremy P.T.; Aaronson, Philip I.

2008-01-01

Abstract Aims We investigated the role of src family kinases (srcFK) in agonist-mediated Ca2+-sensitization in pulmonary artery and whether this involves interaction with the rho/rho-kinase pathway. Methods and results Intra-pulmonary arteries (IPAs) and cultured pulmonary artery smooth muscle cells (PASMC) were obtained from rat. Expression of srcFK was determined at the mRNA and protein levels. Ca2+-sensitization was induced by prostaglandin F2α (PGF2α) in α-toxin-permeabilized IPAs. Phosphorylation of the regulatory subunit of myosin phosphatase (MYPT-1) and of myosin light-chain-20 (MLC20) and translocation of rho-kinase in response to PGF2α were also determined. Nine srcFK were expressed at the mRNA level, including src, fyn, and yes, and PGF2α enhanced phosphorylation of three srcFK proteins at tyr-416. In α-toxin-permeabilized IPAs, PGF2α enhanced the Ca2+-induced contraction (pCa 6.9) approximately three-fold. This enhancement was inhibited by the srcFK blockers SU6656 and PP2 and by the rho-kinase inhibitor Y27632. Y27632, but not SU6656 or PP2, also inhibited the underlying pCa 6.9 contraction. PGF2α enhanced phosphorylation of MYPT-1 at thr-697 and thr-855 and of MLC20 at ser-19. This enhancement, but not the underlying basal phosphorylation, was inhibited by SU6656. Y27632 suppressed both basal and PGF2α-mediated phosphorylation. The effects of SU6656 and Y27632, on both contraction and MYPT-1 and MLC20 phosphorylation, were not additive. PGF2α triggered translocation of rho-kinase in PASMC, and this was inhibited by SU6656. Conclusions srcFK are activated by PGF2α in the rat pulmonary artery and may contribute to Ca2+-sensitization and contraction via rho-kinase translocation and phosphorylation of MYPT-1. PMID:18032393

Inhibitors of Rho kinase (ROCK) signaling revert the malignant phenotype of breast cancer cells in 3D context.

PubMed

Matsubara, Masahiro; Bissell, Mina J

2016-05-31

Loss of polarity and quiescence along with increased cellular invasiveness are associated with breast tumor progression. ROCK plays a central role in actin-cytoskeletal rearrangement. We used physiologically relevant 3D cultures of nonmalignant and cancer cells in gels made of laminin-rich extracellular matrix, to investigate ROCK function. Whereas expression levels of ROCK1 and ROCK2 were elevated in cancer cells compared to nonmalignant cells, this was not observed in 2D cultures. Malignant cells showed increased phosphorylation of MLC, corresponding to disorganized F-actin. Inhibition of ROCK signaling restored polarity, decreased disorganization of F-actin, and led to reduction of proliferation. Inhibition of ROCK also decreased EGFR and Integrinβ1 levels, and consequently suppressed activation of Akt, MAPK and FAK as well as GLUT3 and LDHA levels. Again, ROCK inhibition did not inhibit these molecules in 2D. A triple negative breast cancer cell line, which lacks E-cadherin, had high levels of ROCK but was less sensitive to ROCK inhibitors. Exogenous overexpression of E-cadherin, however, rendered these cells strikingly sensitive to ROCK inhibition. Our results add to the growing literature that demonstrate the importance of context and tissue architecture in determining not only regulation of normal and malignant phenotypes but also drug response.

Inhibitors of Rho kinase (ROCK) signaling revert the malignant phenotype of breast cancer cells in 3D context

PubMed Central

Matsubara, Masahiro; Bissell, Mina J.

2016-01-01

Loss of polarity and quiescence along with increased cellular invasiveness are associated with breast tumor progression. ROCK plays a central role in actin-cytoskeletal rearrangement. We used physiologically relevant 3D cultures of nonmalignant and cancer cells in gels made of laminin-rich extracellular matrix, to investigate ROCK function. Whereas expression levels of ROCK1 and ROCK2 were elevated in cancer cells compared to nonmalignant cells, this was not observed in 2D cultures. Malignant cells showed increased phosphorylation of MLC, corresponding to disorganized F-actin. Inhibition of ROCK signaling restored polarity, decreased disorganization of F-actin, and led to reduction of proliferation. Inhibition of ROCK also decreased EGFR and Integrinβ1 levels, and consequently suppressed activation of Akt, MAPK and FAK as well as GLUT3 and LDHA levels. Again, ROCK inhibition did not inhibit these molecules in 2D. A triple negative breast cancer cell line, which lacks E-cadherin, had high levels of ROCK but was less sensitive to ROCK inhibitors. Exogenous overexpression of E-cadherin, however, rendered these cells strikingly sensitive to ROCK inhibition. Our results add to the growing literature that demonstrate the importance of context and tissue architecture in determining not only regulation of normal and malignant phenotypes but also drug response. PMID:27203208

A quantitative method to the analysis of MLC leaf position and speed based on EPID and EBT3 film for dynamic IMRT treatment with different types of MLC.

PubMed

Li, Yinghui; Chen, Lixin; Zhu, Jinhan; Wang, Bin; Liu, Xiaowei

2017-07-01

A quantitative method based on the electronic portal imaging system (EPID) and film was developed for MLC position and speed testing; this method was used for three MLC types (Millennium, MLCi, and Agility MLC). To determine the leaf position, a picket fence designed by the dynamic (DMLC) model was used. The full-width half-maximum (FWHM) values of each gap measured by EPID and EBT3 were converted to the gap width using the FWHM versus nominal gap width relationship. The algorithm developed for the picket fence analysis was able to quantify the gap width, the distance between gaps, and each individual leaf position. To determine the leaf speed, a 0.5 × 20 cm 2 MLC-defined sliding gap was applied across a 14 × 20 cm 2 symmetry field. The linacs ran at a fixed-dose rate. The use of different monitor units (MUs) for this test led to different leaf speeds. The effect of leaf transmission was considered in a speed accuracy analysis. The difference between the EPID and film results for the MLC position is less than 0.1 mm. For the three MLC types, twice the standard deviation (2 SD) is provided; 0.2, 0.4, and 0.4 mm for gap widths of three MLC types, and 0.1, 0.2, and 0.2 mm for distances between gaps. The individual leaf positions deviate from the preset positions within 0.1 mm. The variations in the speed profiles for the EPID and EBT3 results are consistent, but the EPID results are slightly better than the film results. Different speeds were measured for each MLC type. For all three MLC types, speed errors increase with increasing speed. The analysis speeds deviate from the preset speeds within approximately 0.01 cm s -1 . This quantitative analysis of MLC position and speed provides an intuitive evaluation for MLC quality assurance (QA). © 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

SU-E-T-331: Dosimetric Impact of Multileaf Collimator Leaf Width On Stereotactic Radiosurgery (SRS) RapidArc Treatment Plans for Single and Multiple Brain Metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hossain, S; Keeling, V; Ahmad, S

Purpose: To determine the effects of multileaf collimator (MLC) leaf width on normal-brain-tissue doses and dose conformity of SRS RapidArc treatment plans for brain tumors. Methods: Ten patients with 24 intracranial tumors (seven with 1–2 and three with 4–6 lesions) were planned using RapidArc for both Varian Millennium 120 MLC (5 mm leaf width) and high definition (HD) MLC (2.5 mm leaf width). Between 2 and 8 arcs were used with two full coplanar arcs and the rest non-coplanar half arcs. 6 MV beams were used and plans were optimized with a high priority to the Normal Tissue Objective (tomore » achieve dose conformity and sharp dose fall-off) and normal brain tissue. Calculation was done using AAA on a 1 mm grid size. The prescription dose ranged from 14–22 Gy. Plans were normalized such that 99% of the target received the prescription dose. Identical beam geometries, optimizations, calculations, and normalizations were used for both plans. Paddick Conformity Index (PCI), V4, V8 and V12 Gy for normal brain tissue and Integral Dose were used for analysis. Results: In all cases, HD MLC plans performed better in sparing normal brain tissue, achieving a higher PCI with a lower Integral Dose. The average PCI for all 24 targets was 0.75±0.23 and 0.70±0.23 (p ≤0.0015) for HD MLC and Millennium MLC plans, respectively. The average ratio of normal brain doses for Millennium MLC to HD MLC plans was 1.30±0.16, 1.27±0.15, and 1.31±0.18 for the V4, V8, and V12, respectively. The differences in normal brain dose for all criteria were statistically significant with p-value < 0.02. On average Millennium MLC plans had a 16% higher integral dose than HD MLC plans. Conclusion: Significantly better dose conformity with reduced volume of normal brain tissue and integral dose was achieved with HD MLC plans compared to Millennium MLC plans.« less

SU-G-BRA-14: Dose in a Rigidly Moving Phantom with Jaw and MLC Compensation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chao, E; Lucas, D

Purpose: To validate dose calculation for a rigidly moving object with jaw motion and MLC shifts to compensate for the motion in a TomoTherapy™ treatment delivery. Methods: An off-line version of the TomoTherapy dose calculator was extended to perform dose calculations for rigidly moving objects. A variety of motion traces were added to treatment delivery plans, along with corresponding jaw compensation and MLC shift compensation profiles. Jaw compensation profiles were calculated by shifting the jaws such that the center of the treatment beam moved by an amount equal to the motion in the longitudinal direction. Similarly, MLC compensation profiles weremore » calculated by shifting the MLC leaves by an amount that most closely matched the motion in the transverse direction. The same jaw and MLC compensation profiles were used during simulated treatment deliveries on a TomoTherapy system, and film measurements were obtained in a rigidly moving phantom. Results: The off-line TomoTherapy dose calculator accurately predicted dose profiles for a rigidly moving phantom along with jaw motion and MLC shifts to compensate for the motion. Calculations matched film measurements to within 2%/1 mm. Jaw and MLC compensation substantially reduced the discrepancy between the delivered dose distribution and the calculated dose with no motion. For axial motion, the compensated dose matched the no-motion dose within 2%/1mm. For transverse motion, the dose matched within 2%/3mm (approximately half the width of an MLC leaf). Conclusion: The off-line TomoTherapy dose calculator accurately computes dose delivered to a rigidly moving object, and accurately models the impact of moving the jaws and shifting the MLC leaf patterns to compensate for the motion. Jaw tracking and MLC leaf shifting can effectively compensate for the dosimetric impact of motion during a TomoTherapy treatment delivery.« less

SU-F-T-650: The Comparison of Robotic Partial Breast Stereotactic Irradiation Using MLC Vs. Iris Cone

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ding, C; Timmerman, R; Jiang, S

Purpose: To evaluate the dosimetric impact on treatment planning for partial breast stereotactic irradiation using Cyberknife with MLC versus Iris Cone. Methods: Ten patients whom underwent lumpectomy for DCIS or stage I invasive non-lobular epithelial breast cancer were included in this study. All patients were previously treated on the Cyberknife using Iris cone with the prescription dose of 37.5Gy in 5 fractions covering at least 95% of PTV on our phase I SBRT 5 fraction partial breast irradiation trial. Retrospectively, treatment planning was performed and compared using the new Cyberknife M6 MLC system for each patient. Using the same contoursmore » and critical organ constraints for both MLC and Iris cone plans, the dose on target and critical organs were analyzed accordingly. Results: Dose to critical organs such as ipsilateral lung, contralateral lung, heart, skin, ipsilateral breast, and rib were analyzed, as well as conformity index and high dose spillage of the target area. In 9 of 10 patients, the MLC plans had less total ipsilateral breast volume encompassing the 50% prescription isodose (mean:22.3±8.2% MLC vs. 31.6±8.0 Iris, p=0.00014) .The MLC plans mean estimated treatment delivery time was significantly less than the Iris plans (51±3.9min vs. 56.2±9min, p=0.03) Both MLC and Iris cone plans were able to meet all dose constraints and there was no statistical difference between those dose constraints. Conclusion: Both MLC and Iris Cone can deliver conformal dose to a partial breast target and satisfy the dose constraints of critical organs. The new Cyberknife with MLC can deliver a more conformal dose in the lower dose region and spare more ipsilateral breast tissue to the 50% prescription isodose. The treatment time for partial breast SBRT plans was also reduced using MLC. Project receives research support from Accuray Inc.« less

Comparison of MLC error sensitivity of various commercial devices for VMAT pre-treatment quality assurance.

PubMed

Saito, Masahide; Sano, Naoki; Shibata, Yuki; Kuriyama, Kengo; Komiyama, Takafumi; Marino, Kan; Aoki, Shinichi; Ashizawa, Kazunari; Yoshizawa, Kazuya; Onishi, Hiroshi

2018-05-01

The purpose of this study was to compare the MLC error sensitivity of various measurement devices for VMAT pre-treatment quality assurance (QA). This study used four QA devices (Scandidos Delta4, PTW 2D-array, iRT systems IQM, and PTW Farmer chamber). Nine retrospective VMAT plans were used and nine MLC error plans were generated for all nine original VMAT plans. The IQM and Farmer chamber were evaluated using the cumulative signal difference between the baseline and error-induced measurements. In addition, to investigate the sensitivity of the Delta4 device and the 2D-array, global gamma analysis (1%/1, 2%/2, and 3%/3 mm), dose difference (1%, 2%, and 3%) were used between the baseline and error-induced measurements. Some deviations of the MLC error sensitivity for the evaluation metrics and MLC error ranges were observed. For the two ionization devices, the sensitivity of the IQM was significantly better than that of the Farmer chamber (P < 0.01) while both devices had good linearly correlation between the cumulative signal difference and the magnitude of MLC errors. The pass rates decreased as the magnitude of the MLC error increased for both Delta4 and 2D-array. However, the small MLC error for small aperture sizes, such as for lung SBRT, could not be detected using the loosest gamma criteria (3%/3 mm). Our results indicate that DD could be more useful than gamma analysis for daily MLC QA, and that a large-area ionization chamber has a greater advantage for detecting systematic MLC error because of the large sensitive volume, while the other devices could not detect this error for some cases with a small range of MLC error. © 2018 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

SU-E-T-479: IMRT Plan Recalculation in Patient Based On Dynalog Data and the Effect of a Single Failing MLC Motor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Morcos, M; Mitrou, E

2015-06-15

Purpose: Using Linac dynamic logs (Dynalogs) we evaluate the impact of a single failing MLC motor on the deliverability of an IMRT plan by assessing the recalculated dose volume histograms (DVHs) taking the delivered MLC positions and beam hold-offs into consideration. Methods: This is a retrospective study based on a deteriorating MLC motor (leaf 36B) which was observed to be failing via Dynalog analysis. To investigate further, Eclipse-importable MLC files were generated from Dynalogs to recalculate the actual delivered dose and to assess the clinical impact through DVHs. All deliveries were performed on a Varian 21EX linear accelerator equipped withmore » Millennium-120 MLC. The analysis of Dynalog files and subsequent conversion to Eclipse-importable MLC files were all performed by in-house programming in Python. Effects on plan DVH are presented in the following section on a particular brain-IMRT plan which was delivered with a failing MLC motor which was then replaced. Results: Global max dose increased by 13.5%, max dose to the brainstem PRV increased by 8.2%, max dose to the optic chiasm increased by 7.6%, max dose to optic nerve increased by 8.8% and the mean dose to the PTV increased by 7.9% when comparing the original plan to the fraction with the failing MLC motor. The reason the dose increased was due to the failure being on the B-bank which is the lagging side on a sliding window delivery, therefore any failures on this side will cause an over-irradiation as the B-bank leaves struggles to keep the window from growing. Conclusion: Our findings suggest that a single failing MLC motor may jeopardize the entire delivery. This may be due to the bad MLC motor drawing too much current causing all MLCs on the same bank to underperform. This hypothesis will be investigated in a future study.« less

TH-AB-BRA-01: A Novel Doubly-Focused Multileaf Collimator Design for MR-Guided Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, H; Mutic, S; Green, O

2016-06-15

Purpose: To describe the physical and dosimetric properties of a novel double-stack multileaf collimator (MLC). Methods: One of the compromises made in the MLC design has been to employ linear-motion singly-divergent shapes. Because the MLC leading edge moves linearly, it is rounded to provide a consistent, albeit compromised penumbra. The MLC employed in the new linac-based MR-IGRT unit is designed to be doubly focused in that each leaf moves in an arc centered at the source, and the sides of the leaves are machined such that they lie parallel to a line between the leaf edge and the source. Themore » curvature of the MLC keeps motors and encoders in lower magnetic field. However, high spatial-resolution leaves are difficult to manufacture to sufficiently tight tolerances and difficult to move due to restricted space on the gantry. Wider leaves alleviate this problem with less moving parts but the coarse resolution disallows treating very small lesions. This compromise has been overcome by splitting the MLC leaf bank into two sets, stacked one upon the other and offset half of a leaf width. The dosimetry has been simulated using Monte-Carlo and a 6 MV linac in a 0.35 T magnetic field. Results: The combined MLC leaf set has a spatial resolution of effectively half of the leaf width, 4mm here. The dosimetry resolution and conformality are consistent with 4mm wide MLC assisted by inverse fluence modulation. Also, because each leaf junction is backed up by the stacked leaf that lies over the junction, the problem of tongue-and-groove dosimetry has been greatly reduced. The novel MLC design allows the use of more powerful leaf motors than would be otherwise possible if a single MLC bank is employed. Conclusions: The stacked MLC will provide highly conformal dose distributions suitable for stereotactic radiation therapy of small lesions. The research was funded by ViewRay, Inc.« less

SU-E-T-501: Initial Orthovoltage Beam Profile Analysis of a Small Brass MLC

DOE Office of Scientific and Technical Information (OSTI.GOV)

Loughery, B; Snyder, M

2015-06-15

Purpose To create brass leaves for an orthovoltage MLC and take initial beam profile measurements. Methods The low-energy MLC was designed in previous work. Brass was chosen for its self-lubrication and low cost. Stock brass rectangles (30cm × 1.0cm × 0.5cm) were ordered with pre-cut gear rack along the topmost long edges. Leaf designs were translated into G-code, then cut with a Tormach CNC-1100 mill. Intense bowing was observed in the beam direction, which required straightening via an in-house jig. Straightened leaves were placed into MLC assembly and mounted to a 320 kVp orthovoltage tube. EDR2 film was irradiated inmore » four situations: MLC open so one edge was isocentric, and MLC open more than isocentric, completely closed MLC, and an open field shot with the MLC removed. The first two scans tested penumbra for our rectangular edges due to unfocused design. The final two scans tested transmission and interleaf leakage. All four experiments were set to 120 kVp and 10 mA for two minutes. Results Transmission and interleaf leakage were found to be zero. Interleaf leakage is faintly visible on film, but undetected by our film scanner despite high spatial resolution. Penumbra at isocenter was found to be 0.72mm, which matched the penumbras of true field edges. Penumbra off-isocenter was 1.1mm. Mechanically, leaves are moving smoothly once straightened. Conclusion Beam profiles through our brass MLC are acceptable. Leaves attenuate and move as designed. Looking forward, we intend to animate our MLC to deliver more complicated treatment plans.« less

Donor Cell Composition and Reactivity Predict Risk of Acute Graft-versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation.

PubMed

Sairafi, Darius; Stikvoort, Arwen; Gertow, Jens; Mattsson, Jonas; Uhlin, Michael

2016-01-01

Background . Graft-versus-host disease (GVHD) is a serious complication after allogeneic hematopoietic stem cell transplantation (HSCT). We designed a functional assay for assessment of individual risk for acute GVHD. Study Design and Methods . Blood samples were collected from patients and donors before HSCT. Two groups of seven patients each were selected, one in which individuals developed acute GVHD grades II-IV and one in which none showed any clinical signs of GVHD. Peripheral blood mononuclear cells (PBMCs) isolated from donors were incubated in mixed lymphocyte cultures (MLCs) with recipient PBMCs. The cells were characterized by flow cytometry before and after MLC. Results . Samples from donors in the GVHD group contained significantly lower frequencies of naïve γδ T-cells and T-cells expressing NK-cell markers CD56 and CD94. Donor samples in this group also exhibited lower frequencies of naïve CD95 + T-cells compared to controls. After MLC, there were dissimilarities in the CD4/CD8 T-cell ratio and frequency of CD69 + T-cells between the two patient groups, with the non-GVHD group showing higher frequencies of CD8 + and CD69 + T-cells. Conclusion . We conclude that a thorough flow cytometric analysis of donor cells for phenotype and allogeneic reactivity may be of value when assessing pretransplant risk for severe acute GVHD.

Effect of MLC leaf position, collimator rotation angle, and gantry rotation angle errors on intensity-modulated radiotherapy plans for nasopharyngeal carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bai, Sen; Li, Guangjun; Wang, Maojie

The purpose of this study was to investigate the effect of multileaf collimator (MLC) leaf position, collimator rotation angle, and accelerator gantry rotation angle errors on intensity-modulated radiotherapy plans for nasopharyngeal carcinoma. To compare dosimetric differences between the simulating plans and the clinical plans with evaluation parameters, 6 patients with nasopharyngeal carcinoma were selected for simulation of systematic and random MLC leaf position errors, collimator rotation angle errors, and accelerator gantry rotation angle errors. There was a high sensitivity to dose distribution for systematic MLC leaf position errors in response to field size. When the systematic MLC position errors weremore » 0.5, 1, and 2 mm, respectively, the maximum values of the mean dose deviation, observed in parotid glands, were 4.63%, 8.69%, and 18.32%, respectively. The dosimetric effect was comparatively small for systematic MLC shift errors. For random MLC errors up to 2 mm and collimator and gantry rotation angle errors up to 0.5°, the dosimetric effect was negligible. We suggest that quality control be regularly conducted for MLC leaves, so as to ensure that systematic MLC leaf position errors are within 0.5 mm. Because the dosimetric effect of 0.5° collimator and gantry rotation angle errors is negligible, it can be concluded that setting a proper threshold for allowed errors of collimator and gantry rotation angle may increase treatment efficacy and reduce treatment time.« less

Influence of fast and slow alkali myosin light chain isoforms on the kinetics of stretch-induced force transients of fast-twitch type IIA fibres of rat.

PubMed

Andruchov, Oleg; Galler, Stefan

2008-03-01

This study contributes to understand the physiological role of slow myosin light chain isoforms in fast-twitch type IIA fibres of skeletal muscle. These isoforms are often attached to the myosin necks of rat type IIA fibres, whereby the slow alkali myosin light chain isoform MLC1s is much more frequent and abundant than the slow regulatory myosin light chain isoform MLC2s. In the present study, single-skinned rat type IIA fibres were maximally Ca(2+) activated and subjected to stepwise stretches for causing a perturbation of myosin head pulling cycles. From the time course of the resulting force transients, myosin head kinetics was deduced. Fibres containing MLC1s exhibited slower kinetics independently of the presence or absence of MLC2s. At the maximal MLC1s concentration of about 75%, the slowing was about 40%. The slowing effect of MLC1s is possibly due to differences in the myosin heavy chain binding sites of the fast and slow alkali MLC isoforms, which changes the rigidity of the myosin neck. Compared with the impact of myosin heavy chain isoforms in various fast-twitch fibre types, the influence of MLC1s on myosin head kinetics of type IIA fibres is much smaller. In conclusion, the physiological role of fast and slow MLC isoforms in type IIA fibres is a fine-tuning of the myosin head kinetics.

Intensity-modulated radiation therapy (IMRT) with different combinations of treatment-planning systems and linacs: issues and how to detect them.

PubMed

Dobler, Barbara; Lorenz, Friedlieb; Wertz, Hansjörg; Polednik, Martin; Wolff, Dirk; Steil, Volker; Lohr, Frank; Wenz, Frederik

2006-08-01

To compare different combinations of intensity-modulated radiation therapy (IMRT) system components with regard to quality assurance (QA), especially robustness against malfunctions and dosimetry. Three different treatment-planning systems (TPS), two types of linacs and three multileaf collimator (MLC) types were compared: commissioning procedures were performed for the combination of the TPS Corvus 5.0 (Nomos) and KonRad v2.1.3 (Siemens OCS) with the linacs KD2 (Siemens) and Synergy (Elekta). For PrecisePLAN 2.03 (Elekta) measurements were performed for Elekta Synergy only. As record and verify (R&V) system Multi-Access v7 (IMPAC) was used. The use of the serial tomotherapy system Peacock (Nomos) was investigated in combination with the Siemens KD2 linac. In the comparison of calculated to measured dose, problems were encountered for the combination of KonRad and Elekta MLC as well as for the Peacock system. Multi-Access failed to assign the collimator angle correctly for plans with multiple collimator angles per beam. Communication problems of Multi-Access with both linacs were observed, resulting in incorrect recording of the treatment. All reported issues were addressed by the manufacturers. For the commissioning of IMRT systems, the whole chain from the TPS to the linac has to be investigated. Components that passed the commissioning in another clinical environment can have severe malfunctions when used in a new environment. Therefore, not only single components but the whole chain from planning to delivery has to be evaluated in commissioning and checked regularly for QA.

Land use/land cover mapping using multi-scale texture processing of high resolution data

NASA Astrophysics Data System (ADS)

Wong, S. N.; Sarker, M. L. R.

2014-02-01

Land use/land cover (LULC) maps are useful for many purposes, and for a long time remote sensing techniques have been used for LULC mapping using different types of data and image processing techniques. In this research, high resolution satellite data from IKONOS was used to perform land use/land cover mapping in Johor Bahru city and adjacent areas (Malaysia). Spatial image processing was carried out using the six texture algorithms (mean, variance, contrast, homogeneity, entropy, and GLDV angular second moment) with five difference window sizes (from 3×3 to 11×11). Three different classifiers i.e. Maximum Likelihood Classifier (MLC), Artificial Neural Network (ANN) and Supported Vector Machine (SVM) were used to classify the texture parameters of different spectral bands individually and all bands together using the same training and validation samples. Results indicated that texture parameters of all bands together generally showed a better performance (overall accuracy = 90.10%) for land LULC mapping, however, single spectral band could only achieve an overall accuracy of 72.67%. This research also found an improvement of the overall accuracy (OA) using single-texture multi-scales approach (OA = 89.10%) and single-scale multi-textures approach (OA = 90.10%) compared with all original bands (OA = 84.02%) because of the complementary information from different bands and different texture algorithms. On the other hand, all of the three different classifiers have showed high accuracy when using different texture approaches, but SVM generally showed higher accuracy (90.10%) compared to MLC (89.10%) and ANN (89.67%) especially for the complex classes such as urban and road.

Coordinate changes of myosin light and heavy chain isoforms during forced fiber type transitions in rabbit muscle.

PubMed

Leeuw, T; Pette, D

1996-01-01

Skeletal muscle fibers are versatile entities, capable of changing their phenotype in response to altered functional demands. In the present study, fast-to-slow fiber type transitions were induced in rabbit tibialis anterior (fA) muscles by chronic low-frequency stimulation (CLFS). The time course of changes in relative protein concentrations of fast and slow myosin light chain (MLC) isoforms and changes in their relative synthesis rates by in vivo labeling with [35S]methionine were followed during stimulation periods of up to 60 days. Generally, relative synthesis rates and protein concentrations changed in parallel; i.e., fast isoforms decreased and slow isoforms increased. MLC3f, however, which turns over at a higher rate than the other light chains, exhibited a conspicuous discrepancy between a markedly reduced relative synthesis but only a moderate decrease in protein amount during the initial 2 weeks of CLFS. Apparently, MLC3f is regulated independent of MLC1f, with protein degradation playing an important role in its regulation. The exchange of fast MLC isoforms with their slow counterparts seemed to correspond to the ultimate fast-to-slow (MHCIIa-->MHCI) transition at the MHC level. However, due to an earlier onset of the fast-to-slow transition of the regulatory light chain and the delayed fast-to-slow exchange of the alkali light chains, a spectrum of hybrid isomyosins composed of fast and slow light and heavy chains must have existed transiently in transforming fibers. Such hybrid isomyosins appeared to be restricted to MHCIIa- and MHCI-based combinations. In conclusion, fiber type specific programs that normally coordinate the expression of myofibrillar protein isoforms seem to be maintained during fiber type transitions. Possible differences in post-transcriptional regulation may result in the transient accumulation of atypical combinations of fast and slow MLC and MHC isoforms, giving rise to the appearance of hybrid fibers under the conditions of forced fiber type conversion.

Impact of the MLC on the MRI field distortion of a prototype MRI-linac

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kolling, Stefan; Keall, Paul; Oborn, Brad

2013-12-15

Purpose: To cope with intrafraction tumor motion, integrated MRI-linac systems for real-time image guidance are currently under development. The multileaf collimator (MLC) is a key component in every state-of-the-art radiotherapy treatment system, allowing for accurate field shaping and tumor tracking. This work quantifies the magnetic impact of a widely used MLC on the MRI field homogeneity for such a modality.Methods: The finite element method was employed to model a MRI-linac assembly comprised of a 1.0 T split-bore MRI magnet and the key ferromagnetic components of a Varian Millennium 120 MLC, namely, the leaves and motors. Full 3D magnetic field maps ofmore » the system were generated. From these field maps, the peak-to-peak distortion within the MRI imaging volume was evaluated over a 30 cm diameter sphere volume (DSV) around the isocenter and compared to a maximum preshim inhomogeneity of 300 μT. Five parametric studies were performed: (1) The source-to-isocenter distance (SID) was varied from 100 to 200 cm, to span the range of a compact system to that with lower magnetic coupling. (2) The MLC model was changed from leaves only to leaves with motors, to determine the contribution to the total distortion caused by MLC leaves and motors separately. (3) The system was configured in the inline or perpendicular orientation, i.e., the linac treatment beam was oriented parallel or perpendicular to the magnetic field direction. (4) The treatment field size was varied from 0 × 0 to 20×20 cm{sup 2}, to span the range of clinical treatment fields. (5) The coil currents were scaled linearly to produce magnetic field strengths B{sub 0} of 0.5, 1.0, and 1.5 T, to estimate how the MLC impact changes with B{sub 0}.Results: (1) The MLC-induced MRI field distortion fell continuously with increasing SID. (2) MLC leaves and motors were found to contribute to the distortion in approximately equal measure. (3) Due to faster falloff of the fringe field, the field distortion was generally smaller in the perpendicular beam orientation. The peak-to-peak DSV distortion was below 300 μT at SID≥130 cm (perpendicular) and SID≥140 cm (inline) for the 1.0 T design. (4) The simulation of different treatment fields was identified to cause dynamic changes in the field distribution. However, the estimated residual distortion was below 1.2 mm geometric distortion at SID≥120 cm (perpendicular) and SID≥130 cm (inline) for a 10 mT/m frequency-encoding gradient. (5) Due to magnetic saturation of the MLC materials, the field distortion remained constant at B{sub 0}>1.0 T.Conclusions: This work shows that the MRI field distortions caused by the MLC cannot be ignored and must be thoroughly investigated for any MRI-linac system. The numeric distortion values obtained for our 1.0 T magnet may vary for other magnet designs with substantially different fringe fields, however the concept of modest increases in the SID to reduce the distortion to a shimmable level is generally applicable.« less

Aspects of cooling tower biocides and protozoa

DOE Office of Scientific and Technical Information (OSTI.GOV)

Berk, S.G.; Ashburn, R.J.; Ting, R.S.

1998-12-31

Previous work has shown that certain cooling tower amoebae and ciliated protozoa are resistant to several cooling tower biocides, even at the manufacturer`s recommended dosages. For the present study, an Acunthumoeba species was isolated from a cooling tower in Australia. Suspensions of the trophozoites (feeding stages) were exposed to isothiazolones. Cysts were tested separately. The minimum lethal concentration (MLC) for trophozoites was between 31-62 ppm of the biocide product, which is slightly less than the MLC for an amoebae species from the United States; and cyst forms were twofold more resistant than those of the US species, with a MLCmore » of 62,500 ppm. A ciliate and an amoeba species were also exposed to bromochlorodimethylhydantoin. The MLC for the ciliate species was 1 ppm of the biocide product, and the MLC was 30--40 ppm for the amoeba trophozoites. Since amoebae can expel vesicles containing live Legionella, experiments were conducted to determine whether exposure of Acunthamoebu polyphugu to biocides influenced release of such potentially infectious particles. Vesicle release was not inhibited by any of the three biocides: quaternary ammonium compounds (QACs), isothiazolones, and a thiocarbamate compound. These results suggest that amoebae from various sources are resistant to recommended levels of biocides, and the amoebae may continue to release potentially infectious vesicles in the presence of biocides.« less

Combining MLC and SVM Classifiers for Learning Based Decision Making: Analysis and Evaluations

PubMed Central

Zhang, Yi; Ren, Jinchang; Jiang, Jianmin

2015-01-01

Maximum likelihood classifier (MLC) and support vector machines (SVM) are two commonly used approaches in machine learning. MLC is based on Bayesian theory in estimating parameters of a probabilistic model, whilst SVM is an optimization based nonparametric method in this context. Recently, it is found that SVM in some cases is equivalent to MLC in probabilistically modeling the learning process. In this paper, MLC and SVM are combined in learning and classification, which helps to yield probabilistic output for SVM and facilitate soft decision making. In total four groups of data are used for evaluations, covering sonar, vehicle, breast cancer, and DNA sequences. The data samples are characterized in terms of Gaussian/non-Gaussian distributed and balanced/unbalanced samples which are then further used for performance assessment in comparing the SVM and the combined SVM-MLC classifier. Interesting results are reported to indicate how the combined classifier may work under various conditions. PMID:26089862

Combining MLC and SVM Classifiers for Learning Based Decision Making: Analysis and Evaluations.

PubMed

Zhang, Yi; Ren, Jinchang; Jiang, Jianmin

2015-01-01

Maximum likelihood classifier (MLC) and support vector machines (SVM) are two commonly used approaches in machine learning. MLC is based on Bayesian theory in estimating parameters of a probabilistic model, whilst SVM is an optimization based nonparametric method in this context. Recently, it is found that SVM in some cases is equivalent to MLC in probabilistically modeling the learning process. In this paper, MLC and SVM are combined in learning and classification, which helps to yield probabilistic output for SVM and facilitate soft decision making. In total four groups of data are used for evaluations, covering sonar, vehicle, breast cancer, and DNA sequences. The data samples are characterized in terms of Gaussian/non-Gaussian distributed and balanced/unbalanced samples which are then further used for performance assessment in comparing the SVM and the combined SVM-MLC classifier. Interesting results are reported to indicate how the combined classifier may work under various conditions.

Emerging Role of Angiotensin Type 2 Receptor (AT2R)/Akt/NO Pathway in Vascular Smooth Muscle Cell in the Hyperthyroidism

PubMed Central

Carrillo-Sepúlveda, Maria Alícia; Ceravolo, Graziela S.; Furstenau, Cristina R.; Monteiro, Priscilla de Souza; Bruno-Fortes, Zuleica; Carvalho, Maria Helena; Laurindo, Francisco R.; Tostes, Rita C.; Webb, R. Clinton; Barreto-Chaves, Maria Luiza M.

2013-01-01

Hyperthyroidism is characterized by increased vascular relaxation and decreased vascular contraction and is associated with augmented levels of triiodothyronine (T3) that contribute to the diminished systemic vascular resistance found in this condition. T3 leads to augmented NO production via PI3K/Akt signaling pathway, which in turn causes vascular smooth muscle cell (VSMC) relaxation; however, the underlying mechanisms involved remain largely unknown. Evidence from human and animal studies demonstrates that the renin-angiotensin system (RAS) plays a crucial role in vascular function and also mediates some of cardiovascular effects found during hyperthyroidism. Thus, in this study, we hypothesized that type 2 angiotensin II receptor (AT2R), a key component of RAS vasodilatory actions, mediates T3 induced-decreased vascular contraction. Marked induction of AT2R expression was observed in aortas from T3-induced hyperthyroid rats (Hyper). These vessels showed decreased protein levels of the contractile apparatus: α-actin, calponin and phosphorylated myosin light chain (p-MLC). Vascular reactivity studies showed that denuded aortic rings from Hyper rats exhibited decreased maximal contractile response to angiotensin II (AngII), which was attenuated in aortic rings pre-incubated with an AT2R blocker. Further study showed that cultured VSMC stimulated with T3 (0.1 µmol/L) for 24 hours had increased AT2R gene and protein expression. Augmented NO levels and decreased p-MLC levels were found in VSMC stimulated with T3, both of which were reversed by a PI3K/Akt inhibitor and AT2R blocker. These findings indicate for the first time that the AT2R/Akt/NO pathway contributes to decreased contractile responses in rat aorta, promoted by T3, and this mechanism is independent from the endothelium. PMID:23637941

HIV induces production of IL-18 from intestinal epithelial cells that increases intestinal permeability and microbial translocation

PubMed Central

Allam, Ossama; Samarani, Suzanne; Mehraj, Vikram; Jenabian, Mohammad-Ali; Tremblay, Cecile; Routy, Jean-Pierre; Amre, Devendra

2018-01-01

Interleukin-18 (IL-18) is a pleiotropic cytokine of the IL-1 family with multiple context dependent functions. We and others have shown that HIV infection is accompanied by increased circulating levels of IL-18 along with decreased levels of its antagonist, Interleukin-18 Binding Protein (IL-18BP). The infection is also accompanied by intestinal inflammation and decreased intestinal integrity as measured by intestinal permeability, regeneration and repair. However, little is known concerning the relation between high level of IL-18 associated with the viral infection and intestinal permeability. Here we demonstrate that HIV treatment increases production of IL-18 and decreases that of IL-18BP production in human intestinal epithelial cell (IEC) lines. IL-18 causes apoptosis of the IEC by activating caspase-1 and caspase-3. It induces epithelial barrier hyperpermeability by decreasing and disrupting both tight and adherens junction proteins, occludin, claudin 2 and beta-catenin. Disorganization of F-actin was also observed in the IEC that were exposed to the cytokine. Moreover IL-18 decreases transepithelial electrical resistance (TEER) in Caco-2 and increases permeability in HT29 monolayers. The cells’ treatment with IL-18 causes an increase in the expression of phosphorylated myosin II regulatory light-chain (p-MLC) and myosin light-chain kinase (MLCK), and a decrease in phosphorylated Signal Transducer and Activator of Transcription (p-STAT)-5. This increase in p-MLC is suppressed by a Rho-kinase (ROCK)-specific inhibitor. Interestingly, the levels of the cytokine correlate with those of LPS in the circulation in three different categories of HIV infected patients (HAART-naïve and HAART-treated HIV-infected individuals, and Elite controls) as well as in healthy controls. Collectively, these results suggest that the HIV-induced IL-18 plays a role in increased intestinal permeability and microbial translocation observed in HIV-infected individuals. PMID:29601578

SU-E-T-247: Multi-Leaf Collimator Model Adjustments Improve Small Field Dosimetry in VMAT Plans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Young, L; Yang, F

2014-06-01

Purpose: The Elekta beam modulator linac employs a 4-mm micro multileaf collimator (MLC) backed by a fixed jaw. Out-of-field dose discrepancies between treatment planning system (TPS) calculations and output water phantom measurements are caused by the 1-mm leaf gap required for all moving MLCs in a VMAT arc. In this study, MLC parameters are optimized to improve TPS out-of-field dose approximations. Methods: Static 2.4 cm square fields were created with a 1-mm leaf gap for MLCs that would normally park behind the jaw. Doses in the open field and leaf gap were measured with an A16 micro ion chamber andmore » EDR2 film for comparison with corresponding point doses in the Pinnacle TPS. The MLC offset table and tip radius were adjusted until TPS point doses agreed with photon measurements. Improvements to the beam models were tested using static arcs consisting of square fields ranging from 1.6 to 14.0 cm, with 45° collimator rotation, and 1-mm leaf gap to replicate VMAT conditions. Gamma values for the 3-mm distance, 3% dose difference criteria were evaluated using standard QA procedures with a cylindrical detector array. Results: The best agreement in point doses within the leaf gap and open field was achieved by offsetting the default rounded leaf end table by 0.1 cm and adjusting the leaf tip radius to 13 cm. Improvements in TPS models for 6 and 10 MV photon beams were more significant for smaller field sizes 3.6 cm or less where the initial gamma factors progressively increased as field size decreased, i.e. for a 1.6cm field size, the Gamma increased from 56.1% to 98.8%. Conclusion: The MLC optimization techniques developed will achieve greater dosimetric accuracy in small field VMAT treatment plans for fixed jaw linear accelerators. Accurate predictions of dose to organs at risk may reduce adverse effects of radiotherapy.« less

Commissioning and quality assurance for VMAT delivery systems: An efficient time-resolved system using real-time EPID imaging.

PubMed

Zwan, Benjamin J; Barnes, Michael P; Hindmarsh, Jonathan; Lim, Seng B; Lovelock, Dale M; Fuangrod, Todsaporn; O'Connor, Daryl J; Keall, Paul J; Greer, Peter B

2017-08-01

An ideal commissioning and quality assurance (QA) program for Volumetric Modulated Arc Therapy (VMAT) delivery systems should assess the performance of each individual dynamic component as a function of gantry angle. Procedures within such a program should also be time-efficient, independent of the delivery system and be sensitive to all types of errors. The purpose of this work is to develop a system for automated time-resolved commissioning and QA of VMAT control systems which meets these criteria. The procedures developed within this work rely solely on images obtained, using an electronic portal imaging device (EPID) without the presence of a phantom. During the delivery of specially designed VMAT test plans, EPID frames were acquired at 9.5 Hz, using a frame grabber. The set of test plans was developed to individually assess the performance of the dose delivery and multileaf collimator (MLC) control systems under varying levels of delivery complexities. An in-house software tool was developed to automatically extract features from the EPID images and evaluate the following characteristics as a function of gantry angle: dose delivery accuracy, dose rate constancy, beam profile constancy, gantry speed constancy, dynamic MLC positioning accuracy, MLC speed and acceleration constancy, and synchronization between gantry angle, MLC positioning and dose rate. Machine log files were also acquired during each delivery and subsequently compared to information extracted from EPID image frames. The largest difference between measured and planned dose at any gantry angle was 0.8% which correlated with rapid changes in dose rate and gantry speed. For all other test plans, the dose delivered was within 0.25% of the planned dose for all gantry angles. Profile constancy was not found to vary with gantry angle for tests where gantry speed and dose rate were constant, however, for tests with varying dose rate and gantry speed, segments with lower dose rate and higher gantry speed exhibited less profile stability. MLC positional accuracy was not observed to be dependent on the degree of interdigitation. MLC speed was measured for each individual leaf and slower leaf speeds were shown to be compensated for by lower dose rates. The test procedures were found to be sensitive to 1 mm systematic MLC errors, 1 mm random MLC errors, 0.4 mm MLC gap errors and synchronization errors between the MLC, dose rate and gantry angle controls systems of 1°. In general, parameters measured by both EPID and log files agreed with the plan, however, a greater average departure from the plan was evidenced by the EPID measurements. QA test plans and analysis methods have been developed to assess the performance of each dynamic component of VMAT deliveries individually and as a function of gantry angle. This methodology relies solely on time-resolved EPID imaging without the presence of a phantom and has been shown to be sensitive to a range of delivery errors. The procedures developed in this work are both comprehensive and time-efficient and can be used for streamlined commissioning and QA of VMAT delivery systems. © 2017 American Association of Physicists in Medicine.

[Overexpression of LaeA enhances mevastatin production and reduces sporulation of Penicillium citrinum].

PubMed

Zheng, Yueliang; Cao, Shuang; Huang, Yuqi; Liao, Guojian; Hu, Changhua

2014-12-04

To study the regulation of laeA overexpression on mevastatin production and sporulation in Penicillium citrinum. We cloned the laeA gene from Penicillium citrinum and constructed the vector pGiHTGi-laeA. The plasmid pGiHTGi-laeA was transformed in Penicillium citrinum by agrobacterium tumefaciens-mediated transformation. Positive transformants were detected by cloning the hygromycin gene. The mevastatin production of the wild type and OE:: laeA was compared by HPLC. The conidia number was counted by blood counting chamber. The biosynthetic gene cluster expression quantity of mevastatin in the wild type and OE: :laeA were analyzed by qRT-PCR. We constructed the plasmid pGiHTGi-laeA, and screened the positive transformants that overexpress the laeA in Penicillium citrinum. With the overexpression of laeA, the mevastatin production was increased from (0.69 ± 0.12) mg/g to (4.02 ± 0.50) mg/g dry cell weight. Compared to the wild type strain, the laeA expression quantity in the OE :: laeA strain increased 29%, and the mlcB expression increased 72%, the mlcR expression increased 153%. Moreover, the overexpression of laeA would decrease the conidia number. Overexpression of LaeA enhances mevastatin production and reduces sporulation of Penicillium citrinum, with increases expression of pathway-regulator mlcR, and biosynthetic gene MlcR. These results could guide global regulatory mechanism of mevastatin biosynthesis and the exploitation of high-production strain.

Evaluation of the Radiation Susceptibility of a 3D NAND Flash Memory

NASA Technical Reports Server (NTRS)

Chen, Dakai; Wilcox, Edward; Ladbury, Raymond; Seidleck, Christina; Kim, Hak; Phan, Anthony; LaBel, Kenneth

2017-01-01

We evaluated the heavy ion and proton-induced single-event effects (SEE) for a 3D NAND flash. The 3D NAND showed similar single-event upset (SEU) sensitivity to a planar NAND of similar density and performance in the multiple-cell level (MLC) storage mode. However, the single-level-cell (SLC) storage mode of the 3D NAND showed significantly reduced SEU susceptibility. Additionally, the 3D NAND showed less MBU susceptibility than the planar NAND, with reduced number of upset bits per byte and reduced cross sections overall. However, the 3D architecture exhibited angular sensitivities for both base and face angles, reflecting the anisotropic nature of the SEU vulnerability in space. Furthermore, the SEU cross section decreased with increasing fluence for both the 3D NAND and the latest generation planar NAND, indicating a variable upset rate for a space mission. These unique characteristics introduce complexity to traditional ground irradiation test procedures.

Induction of alloantigen-specific hyporesponsiveness in human T lymphocytes by blocking interaction of CD28 with its natural ligand B7/BB1

PubMed Central

1993-01-01

The specificity of T lymphocyte activation is determined by engagement of the T cell receptor (TCR) by peptide/major histocompatibility complexes expressed on the antigen-presenting cell (APC). Lacking costimulation by accessory molecules on the APC, T cell proliferation does not occur and unresponsiveness to subsequent antigenic stimulus is induced. The B7/BB1 receptor on APCs binds CD28 and CTLA-4 on T cells, and provides a costimulus for T cell proliferation. Here, we show that prolonged, specific T cell hyporesponsiveness to antigenic restimulation is achieved by blocking the interaction between CD28 and B7/BB1 in human mixed leukocyte culture (MLC). Secondary T cell proliferative responses to specific alloantigen were inhibited by addition to the primary culture of monovalent Fab fragments of anti- CD28 monoclonal antibody (mAb) 9.3, which block interaction of CD28 with B7/BB1 without activating T cells. Hypo-responsiveness was also induced in MLC by CTLA4Ig, a chimeric immunoglobulin fusion protein incorporating the extracellular domain of CTLA-4 with high binding avidity for B7/BB1. Cells previously primed could also be made hyporesponsive, if exposed to alloantigen in the presence of CTLA4Ig. Maximal hyporesponsiveness was achieved in MLC after 2 d of incubation with CTLA4Ig, and was maintained for at least 27 d after removal of CTLA4Ig. Accumulation of interleukin 2 (IL-2) and interferon gamma but not IL-4 mRNA was blocked by CTLA4Ig in T cells stimulated by alloantigen. Antigen-specific responses could be restored by addition of exogenous IL-2 at the time of the secondary stimulation. Addition to primary cultures of the intact bivalent anti-CD28 mAb 9.3, or B7/BB1+ transfected CHO cells or exogenous IL-2, abrogated induction of hyporesponsiveness by CTLA4Ig. These data indicate that interaction of CD28 with B7/BB1 during TCR engagement with antigen is required to maintain T cell competence and that blocking such interaction can result in a state of T cell hyporesponsiveness. PMID:7678111

SU-E-T-293: Simplifying Assumption for Determining Sc and Sp

DOE Office of Scientific and Technical Information (OSTI.GOV)

King, R; Cheung, A; Anderson, R

Purpose: Scp(mlc,jaw) is a two-dimensional function of collimator field size and effective field size. Conventionally, Scp(mlc,jaw) is treated as separable into components Sc(jaw) and Sp(mlc). Scp(mlc=jaw) is measured in phantom and Sc(jaw) is measured in air with Sp=Scp/Sc. Ideally, Sc and Sp would be able to predict measured values of Scp(mlc,jaw) for all combinations of mlc and jaw. However, ideal Sc and Sp functions do not exist and a measured two-dimensional Scp dataset cannot be decomposed into a unique pair of one-dimensional functions.If the output functions Sc(jaw) and Sp(mlc) were equal to each other and thus each equal to Scp(mlc=jaw){supmore » 0.5}, this condition would lead to a simpler measurement process by eliminating the need for in-air measurements. Without the distorting effect of the buildup-cap, small-field measurement would be limited only by the dimensions of the detector and would thus be improved by this simplification of the output functions. The goal of the present study is to evaluate an assumption that Sc=Sp. Methods: For a 6 MV x-ray beam, Sc and Sp were determined both by the conventional method and as Scp(mlc=jaw){sup 0.5}. Square field benchmark values of Scp(mlc,jaw) were then measured across the range from 2×2 to 29×29. Both Sc and Sp functions were then evaluated as to their ability to predict these measurements. Results: Both methods produced qualitatively similar results with <4% error for all cases and >3% error in 1 case. The conventional method produced 2 cases with >2% error, while the squareroot method produced only 1 such case. Conclusion: Though it would need to be validated for any specific beam to which it might be applied, under the conditions studied, the simplifying assumption that Sc = Sp is justified.« less

SU-E-T-347: Effect of MLC Leaf Position Inaccuracy On Dose Distribution for Spinal SBRT with Different Energies and Dose Rates

DOE Office of Scientific and Technical Information (OSTI.GOV)

You, T; Dang, J; Dai, C

2015-06-15

Purpose: To evaluate dosimetric impact of spinal SBRT when MLC leaf positions deviate from planning positions for different energies and doserates. Methods and Materials: 18 localized spinal metastases patients were selected for SBRT using IMRT planning with 9 posterior beams delivered at gantry angles ranging between 100°–260°. A modern linear accelerator(Varian Turebeam STX with HDMLC 2.5 mm thick leaf at isocenter) IMRT plans were generated using both 6X and 6X-FFF(Flattening filter free) beams with a nominal prescription dose of 6 Gy/fraction to PTV. Doserates ranging from 200–600 MU/min for 6X and 400–1400 MU/min for 6X-FFF, with 200 increments were examined.more » A fixed amount(0.3, 0.5, 1, and 2 mm) of MLC-leaf position deviation was simulated to each plan under following conditions: 1)only along X1 collimator; 2)with increments at both X1 and X2 collimator directions;3)with reductions at both X1 and X2 collimator directions. Dose was recalculated for each modified plans. Both original and modified plans were delivered using Turebeam STX machine and measured using both portal dosimetry and a 3D dosimeter(Delta4 of ScandiDos). Each field’s Result were compared using following three parameters: the 95% iso-dose level Conformal Index(95%CI), the spinal cord maximum dose(SCDmax), and the planned target volume(PTV) mean dose. Results: Dosimetric impacts on the 95%CI, SCDmax and the PTV mean dose are: 1)negligible if MLC-leaf position deviation only along a single collimator direction ≥1.0 mm,2)substantial if MLC-leaf position increment along both collimator directions ≥0.3 mm(95% CI decreases while SCDmax and PTV mean-dose increase), 3)substantial if MLC-leaf position reduction along both collimator directions ≥0.3 mm(95% CI first increases and then decreases while SCDmax and PTV mean-dose decrease). Different energies and doserates demonstrated comparable dosimetric impacts. Conclusion: Substantial dose deviations could happen for spinal SBRT using IMRT plan with HD-MLC if leaf position deviation ≥0.3 mm. The effects of different energy and doserate are negligible.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Riis, Hans L.; Zimmermann, Sune J.; Hjelm-Hansen, Mogens

Purpose: The delivery of high quality stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT) treatments to the patient requires knowledge of the position of the isocenter to submillimeter accuracy. To meet the requirements the deviation between the radiation and mechanical isocenters must be less than 1 mm. The use of add-on micromultileaf collimators ({mu}MLCs) in SRS and SRT is an additional challenge to the anticipated high-level geometric and dosimetric accuracy of the treatment. The aim of this work was to quantify the gantry excursions during rotation with and without an add-on {mu}MLC attached to the gantry head. In addition, the shiftmore » in the position of the isocenter and its correlation to the kV beam center of the cone-beam CT system was included in the study. Methods: The quantification of the gantry rotational performance was done using a pointer supported by an in-house made rigid holder attached to the gantry head of the accelerator. The pointer positions were measured using a digital theodolite. To quantify the effect of an {mu}MLC of 50 kg, the measurements were repeated with the {mu}MLC attached to the gantry head. The displacement of the isocenter due to an add-on {mu}MLC of 50 kg was also investigated. In case of the pointer measurement the {mu}MLC was simulated by weights attached to the gantry head. A method of least squares was applied to determine the position and displacement of the mechanical isocenter. Additionally, the displacement of the radiation isocenter was measured using a ball-bearing phantom and the electronic portal image device system. These measurements were based on 8 MV photon beams irradiated onto the ball from the four cardinal angles and two opposed collimator angles. The measurements and analysis of the data were carried out automatically using software delivered by the manufacturer. Results: The displacement of the mechanical isocenter caused by a 50 kg heavy {mu}MLC was found to be (-0.01 {+-} 0.05, -0.10 {+-} 0.03, -0.26 {+-} 0.05) mm in lateral, longitudinal, and vertical direction, respectively. Similarly, the displacement of the radiation isocenter was found to be (0.00 {+-} 0.03, -0.08 {+-} 0.06, -0.32 {+-} 0.02) mm. Good agreement was found between the displacement of the two isocenters. A displacement of the kV cone-beam CT beam center due to the attached weight of 50 kg could not be detected. Conclusions: General characteristics of the gantry arm excursions and displacements caused by an add-on {mu}MLC have been reported. A 50 kg heavy add-on {mu}MLC results in a isocenter displacement downward of 0.26-0.32 mm. The authors recommend that the beam center of the kV cone-beam CT image system should be matched to the isocenter related to the weight of the {mu}MLC. Consequently, the imperfections in isocenter localizations are transferred to the conventional radiotherapy where the clinical consequences of uncertainties in the submillimeter regime are negligible.« less

The first clinical implementation of electromagnetic transponder-guided MLC tracking.

PubMed

Keall, Paul J; Colvill, Emma; O'Brien, Ricky; Ng, Jin Aun; Poulsen, Per Rugaard; Eade, Thomas; Kneebone, Andrew; Booth, Jeremy T

2014-02-01

We report on the clinical process, quality assurance, and geometric and dosimetric results of the first clinical implementation of electromagnetic transponder-guided MLC tracking which occurred on 28 November 2013 at the Northern Sydney Cancer Centre. An electromagnetic transponder-based positioning system (Calypso) was modified to send the target position output to in-house-developed MLC tracking code, which adjusts the leaf positions to optimally align the treatment beam with the real-time target position. Clinical process and quality assurance procedures were developed and performed. The first clinical implementation of electromagnetic transponder-guided MLC tracking was for a prostate cancer patient being treated with dual-arc VMAT (RapidArc). For the first fraction of the first patient treatment of electromagnetic transponder-guided MLC tracking we recorded the in-room time and transponder positions, and performed dose reconstruction to estimate the delivered dose and also the dose received had MLC tracking not been used. The total in-room time was 21 min with 2 min of beam delivery. No additional time was needed for MLC tracking and there were no beam holds. The average prostate position from the initial setup was 1.2 mm, mostly an anterior shift. Dose reconstruction analysis of the delivered dose with MLC tracking showed similar isodose and target dose volume histograms to the planned treatment and a 4.6% increase in the fractional rectal V60. Dose reconstruction without motion compensation showed a 30% increase in the fractional rectal V60 from that planned, even for the small motion. The real-time beam-target correction method, electromagnetic transponder-guided MLC tracking, has been translated to the clinic. This achievement represents a milestone in improving geometric and dosimetric accuracy, and by inference treatment outcomes, in cancer radiotherapy.

The first clinical implementation of electromagnetic transponder-guided MLC tracking

PubMed Central

Keall, Paul J.; Colvill, Emma; O’Brien, Ricky; Ng, Jin Aun; Poulsen, Per Rugaard; Eade, Thomas; Kneebone, Andrew; Booth, Jeremy T.

2014-01-01

Purpose: We report on the clinical process, quality assurance, and geometric and dosimetric results of the first clinical implementation of electromagnetic transponder-guided MLC tracking which occurred on 28 November 2013 at the Northern Sydney Cancer Centre. Methods: An electromagnetic transponder-based positioning system (Calypso) was modified to send the target position output to in-house-developed MLC tracking code, which adjusts the leaf positions to optimally align the treatment beam with the real-time target position. Clinical process and quality assurance procedures were developed and performed. The first clinical implementation of electromagnetic transponder-guided MLC tracking was for a prostate cancer patient being treated with dual-arc VMAT (RapidArc). For the first fraction of the first patient treatment of electromagnetic transponder-guided MLC tracking we recorded the in-room time and transponder positions, and performed dose reconstruction to estimate the delivered dose and also the dose received had MLC tracking not been used. Results: The total in-room time was 21 min with 2 min of beam delivery. No additional time was needed for MLC tracking and there were no beam holds. The average prostate position from the initial setup was 1.2 mm, mostly an anterior shift. Dose reconstruction analysis of the delivered dose with MLC tracking showed similar isodose and target dose volume histograms to the planned treatment and a 4.6% increase in the fractional rectal V60. Dose reconstruction without motion compensation showed a 30% increase in the fractional rectal V60 from that planned, even for the small motion. Conclusions: The real-time beam-target correction method, electromagnetic transponder-guided MLC tracking, has been translated to the clinic. This achievement represents a milestone in improving geometric and dosimetric accuracy, and by inference treatment outcomes, in cancer radiotherapy. PMID:24506591

SU-E-T-430: Modeling MLC Leaf End in 2D for Sliding Window IMRT and Arc Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liang, X; Zhu, T

2014-06-01

Purpose: To develop a 2D geometric model for MLC accounting for leaf end dose leakage for dynamic IMRT and Rapidarc therapy. Methods: Leaf-end dose leakage is one of the problems for MLC dose calculation and modeling. Dosimetric leaf gap used to model the MLC and to count for leakage in dose calculation, but may not be accurate for smaller leaf gaps. We propose another geometric modeling method to compensate for the MLC round-shape leaf ends dose leakage, and improve the accuracy of dose calculation and dose verification. A triangular function is used to geometrically model the MLC leaf end leakagemore » in the leaf motion direction, and a step function is used in the perpendicular direction. Dose measurements with different leaf gap, different window width, and different window height were conducted, and the results were used to fit the analytical model to get the model parameters. Results: Analytical models have been obtained for stop-and-shoot and dynamic modes for MLC motion. Parameters a=0.4, lw'=5.0 mm for 6X and a=0.54, lw'=4.1 mm for 15x were obtained from the fitting process. The proposed MLC leaf end model improves the dose profile at the two ends of the sliding window opening. This improvement is especially significant for smaller sliding window openings, which are commonly used for highly modulated IMRT plans and arc therapy plans. Conclusion: This work models the MLC round leaf end shape and movement pattern for IMRT dose calculation. The theory, as well as the results in this work provides a useful tool for photon beam IMRT dose calculation and verification.« less

Development and evaluation of aperture-based complexity metrics using film and EPID measurements of static MLC openings

DOE Office of Scientific and Technical Information (OSTI.GOV)

Götstedt, Julia; Karlsson Hauer, Anna; Bäck, Anna, E-mail: anna.back@vgregion.se

Purpose: Complexity metrics have been suggested as a complement to measurement-based quality assurance for intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT). However, these metrics have not yet been sufficiently validated. This study develops and evaluates new aperture-based complexity metrics in the context of static multileaf collimator (MLC) openings and compares them to previously published metrics. Methods: This study develops the converted aperture metric and the edge area metric. The converted aperture metric is based on small and irregular parts within the MLC opening that are quantified as measured distances between MLC leaves. The edge area metricmore » is based on the relative size of the region around the edges defined by the MLC. Another metric suggested in this study is the circumference/area ratio. Earlier defined aperture-based complexity metrics—the modulation complexity score, the edge metric, the ratio monitor units (MU)/Gy, the aperture area, and the aperture irregularity—are compared to the newly proposed metrics. A set of small and irregular static MLC openings are created which simulate individual IMRT/VMAT control points of various complexities. These are measured with both an amorphous silicon electronic portal imaging device and EBT3 film. The differences between calculated and measured dose distributions are evaluated using a pixel-by-pixel comparison with two global dose difference criteria of 3% and 5%. The extent of the dose differences, expressed in terms of pass rate, is used as a measure of the complexity of the MLC openings and used for the evaluation of the metrics compared in this study. The different complexity scores are calculated for each created static MLC opening. The correlation between the calculated complexity scores and the extent of the dose differences (pass rate) are analyzed in scatter plots and using Pearson’s r-values. Results: The complexity scores calculated by the edge area metric, converted aperture metric, circumference/area ratio, edge metric, and MU/Gy ratio show good linear correlation to the complexity of the MLC openings, expressed as the 5% dose difference pass rate, with Pearson’s r-values of −0.94, −0.88, −0.84, −0.89, and −0.82, respectively. The overall trends for the 3% and 5% dose difference evaluations are similar. Conclusions: New complexity metrics are developed. The calculated scores correlate to the complexity of the created static MLC openings. The complexity of the MLC opening is dependent on the penumbra region relative to the area of the opening. The aperture-based complexity metrics that combined either the distances between the MLC leaves or the MLC opening circumference with the aperture area show the best correlation with the complexity of the static MLC openings.« less

Antimicrobial Activity and Biocompatibility of the Psidium cattleianum Extracts for Endodontic Purposes.

PubMed

Massunari, Loiane; Novais, Renata Zoccal; Oliveira, Márcio Teixeira; Valentim, Diego; Dezan Junior, Eloi; Duque, Cristiane

2017-01-01

Psidium cattleianum (PC) has been displaying inhibitory effect against a variety of microorganisms, but this effect has not yet been tested against endodontic pathogens. The aim of this study was to evaluate the antimicrobial activity and biocompatibility of the aqueous (PCAE) and hydroethanolic (PCHE) extracts from Psidium cattleianum (PC) leaves. Minimum inhibitory concentration (MIC) and minimum lethal concentration (MLC) were determined using the microdilution broth method in order to analyze the antimicrobial effect against Enterococcus faecalis, Pseudomonas aeruginosa, Actinomyces israelii and Candida albicans in planktonic conditions. Biofilm assays were conducted only with the extracts that were able to determine the MLC for microorganisms in planktonic conditions. Immediate and late tissue reactions against PC extracts were evaluated using edemogenic test and histological analysis of subcutaneous implants in Wistar rats. The results showed that the MIC and MLC values ranged between 0.25 and 4 mg/mL. The MLC obtained for PCHE inhibited 100% growth of all the tested strains, except for C. albicans. PCAE had the same effect for E. faecalis and P. aeruginosa. Both PC extracts were able to eliminate E. faecalis biofilms and only the PCHE eliminated P. aeruginosa biofilms. The positive controls inhibited the growth of all tested strains in MIC and MLC essays, but no CHX tested concentrations were able to eliminate A. israelii biofilm. PCAE caused a discrete increase in the edema over time, while PCHE caused a higher initial edema, which decreased progressively. Both PCAE and PCHE extracts were biocompatible, but PCHE showed better results with slight levels of inflammation at 28 days. In conclusion, PCHE was biocompatible and presented better antimicrobial effect against important pathogens associated with persistent endodontic infections.

Myosin Light Chain Kinase Mediates Intestinal Barrier Disruption following Burn Injury

PubMed Central

Chen, Chuanli; Wang, Pei; Su, Qin; Wang, Shiliang; Wang, Fengjun

2012-01-01

Background Severe burn injury results in the loss of intestinal barrier function, however, the underlying mechanism remains unclear. Myosin light chain (MLC) phosphorylation mediated by MLC kinase (MLCK) is critical to the pathophysiological regulation of intestinal barrier function. We hypothesized that the MLCK-dependent MLC phosphorylation mediates the regulation of intestinal barrier function following burn injury, and that MLCK inhibition attenuates the burn-induced intestinal barrier disfunction. Methodology/Principal Findings Male balb/c mice were assigned randomly to either sham burn (control) or 30% total body surface area (TBSA) full thickness burn without or with intraperitoneal injection of ML-9 (2 mg/kg), an MLCK inhibitor. In vivo intestinal permeability to fluorescein isothiocyanate (FITC)-dextran was measured. Intestinal mucosa injury was assessed histologically. Tight junction proteins ZO-1, occludin and claudin-1 was analyzed by immunofluorescent assay. Expression of MLCK and phosphorylated MLC in ileal mucosa was assessed by Western blot. Intestinal permeability was increased significantly after burn injury, which was accompanied by mucosa injury, tight junction protein alterations, and increase of both MLCK and MLC phosphorylation. Treatment with ML-9 attenuated the burn-caused increase of intestinal permeability, mucosa injury, tight junction protein alterations, and decreased MLC phosphorylation, but not MLCK expression. Conclusions/Significance The MLCK-dependent MLC phosphorylation mediates intestinal epithelial barrier dysfunction after severe burn injury. It is suggested that MLCK-dependent MLC phosphorylation may be a critical target for the therapeutic treatment of intestinal epithelial barrier disruption after severe burn injury. PMID:22529961

Electromagnetic-Guided MLC Tracking Radiation Therapy for Prostate Cancer Patients: Prospective Clinical Trial Results.

PubMed

Keall, Paul J; Colvill, Emma; O'Brien, Ricky; Caillet, Vincent; Eade, Thomas; Kneebone, Andrew; Hruby, George; Poulsen, Per R; Zwan, Benjamin; Greer, Peter B; Booth, Jeremy

2018-06-01

To report on the primary and secondary outcomes of a prospective clinical trial of electromagnetic-guided multileaf collimator (MLC) tracking radiation therapy for prostate cancer. Twenty-eight men with prostate cancer were treated with electromagnetic-guided MLC tracking with volumetric modulated arc therapy. A total of 858 fractions were delivered, with the dose per fraction ranging from 2 to 13.75 Gy. The primary outcome was feasibility, with success determined if >95% of fractions were successfully delivered. The secondary outcomes were (1) the improvement in beam-target geometric alignment, (2) the improvement in dosimetric coverage of the prostate and avoidance of critical structures, and (3) no acute grade ≥3 genitourinary or gastrointestinal toxicity. All 858 planned fractions were successfully delivered with MLC tracking, demonstrating the primary outcome of feasibility (P < .001). MLC tracking improved the beam-target geometric alignment from 1.4 to 0.90 mm (root-mean-square error). MLC tracking improved the dosimetric coverage of the prostate and reduced the daily variation in dose to critical structures. No acute grade ≥3 genitourinary or gastrointestinal toxicity was observed. Electromagnetic-guided MLC tracking radiation therapy for prostate cancer is feasible. The patients received improved geometric targeting and delivered dose distributions that were closer to those planned than they would have received without electromagnetic-guided MLC tracking. No significant acute toxicity was observed. Copyright © 2018 Elsevier Inc. All rights reserved.

Poster — Thur Eve — 56: Design of Quality Assurance Methodology for VMAT system on Agility System equipped with CVDR

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thind, K; Tolakanahalli, R

2014-08-15

The aim of this study was to analyze the feasibility of designing comprehensive QA plans using iComCAT for Elekta machines equipped with Agility multileaf collimator and continuously variable dose rate. Test plans with varying MLC speed, gantry speed, and dose rate were created and delivered in a controlled manner. A strip test was designed with three 1 cm MLC positions and delivered using dynamic, StepNShoot and VMAT techniques. Plans were also designed to test error in MLC position with various gantry speeds and various MLC speeds. The delivery fluence was captured using the electronic portal-imaging device. Gantry speed was foundmore » to be within tolerance as per the Canadian standards. MLC positioning errors at higher MLC speed with gravity effects does add more than 2 mm discrepancy. More tests need to be performed to evaluate MLC performance using independent measurement systems. The treatment planning system with end-to-end testing necessary for commissioning was also investigated and found to have >95% passing rates within 3%/3mm gamma criteria. Future studies involve performing off-axis gantry starshot pattern and repeating the tests on three matched Elekta linear accelerators.« less

Spatial variation of dosimetric leaf gap and its impact on dose delivery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kumaraswamy, Lalith K., E-mail: Lalith.Kumaraswamy@roswellpark.org; Schmitt, Jonathan D.; Bailey, Daniel W.

Purpose: During dose calculation, the Eclipse treatment planning system (TPS) retracts the multileaf collimator (MLC) leaf positions by half of the dosimetric leaf gap (DLG) value (measured at central axis) for all leaf positions in a dynamic MLC plan to accurately model the rounded leaf ends. The aim of this study is to map the variation of DLG along the travel path of each MLC leaf pair and quantify how this variation impacts delivered dose. Methods: 6 MV DLG values were measured for all MLC leaf pairs in increments of 1.0 cm (from the line intersecting the CAX and perpendicularmore » to MLC motion) to 13.0 cm off axis distance at dmax. The measurements were performed on two Varian linear accelerators, both employing the Millennium 120-leaf MLCs. The measurements were performed at several locations in the beam with both a Sun Nuclear MapCHECK device and a PTW pinpoint ion chamber. Results: The measured DLGs for the middle 40 MLC leaf pairs (each 0.5 cm width) at positions along a line through the CAX and perpendicular to MLC leaf travel direction were very similar, varying maximally by only 0.2 mm. The outer 20 MLC leaf pairs (each 1.0 cm width) have much lower DLG values, about 0.3–0.5 mm lower than the central MLC leaf pair, at their respective central line position. Overall, the mean and the maximum variation between the 0.5 cm width leaves and the 1.0 cm width leaf pairs are 0.32 and 0.65 mm, respectively. Conclusions: The spatial variation in DLG is caused by the variation of intraleaf transmission through MLC leaves. Fluences centered on the CAX would not be affected since DLG does not vary; but any fluences residing significantly off axis with narrow sweeping leaves may exhibit significant dose differences. This is due to the fact that there are differences in DLG between the true DLG exhibited by the 1.0 cm width outer leaves and the constant DLG value utilized by the TPS for dose calculation. Since there are large differences in DLG between the 0.5 cm width leaf pairs and 1.0 cm width leaf pairs, there is a need to correct the TPS plans, especially those with high modulation (narrow dynamic MLC gap), with 2D variation of DLG.« less

Effect of MLC leaf width on treatment adaptation and accuracy for concurrent irradiation of prostate and pelvic lymph nodes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shang Qingyang; Qi Peng; Ferjani, Samah

2013-06-15

Purpose: The aim of the study was to evaluate the impact of multileaf collimator (MLC) leaf width on treatment adaptation and delivery accuracy for concurrent treatment of the prostate and pelvic lymph nodes with intensity modulated radiation therapy (IMRT). Methods: Seventy-five kilovoltage cone beam CTs (KV-CBCT) from six patients were included for this retrospective study. For each patient, three different IMRT plans were created based on a planning CT using three different MLC leaf widths of 2.5, 5, and 10 mm, respectively. For each CBCT, the prostate displacement was determined by a dual image registration. Adaptive plans were created bymore » shifting selected MLC leaf pairs to compensate for daily prostate movements. To evaluate the impact of MLC leaf width on the adaptive plan for each daily CBCT, three MLC shifted plans were created using three different leaf widths of MLCs (a total of 225 adaptive treatment plans). Selective dosimetric endpoints for the tumor volumes and organs at risk (OARs) were evaluated for these adaptive plans. Using the planning CT from a selected patient, MLC shifted plans for three hypothetical longitudinal shifts of 2, 4, and 8 mm were delivered on the three linear accelerators to test the deliverability of the shifted plans and to compare the dose accuracy of the shifted plans with the original IMRT plans. Results: Adaptive plans from 2.5 and 5 mm MLCs had inadequate dose coverage to the prostate (D99 < 97%, or D{sub mean} < 99% of the planned dose) in 6%-8% of the fractions, while adaptive plans from 10 mm MLC led to inadequate dose coverage to the prostate in 25.3% of the fractions. The average V{sub 56Gy} of the prostate over the six patients was improved by 6.4% (1.6%-32.7%) and 5.8% (1.5%-35.7%) with adaptive plans from 2.5 and 5 mm MLCs, respectively, when compared with adaptive plans from 10 mm MLC. Pelvic lymph nodes were well covered for all MLC adaptive plans, as small differences were observed for D99, D{sub mean}, and V{sub 50.4Gy}. Similar OAR sparing could be achieved for the bladder and rectum with all three MLCs for treatment adaptation. The MLC shifted plans can be accurately delivered on all three linear accelerators with accuracy similar to their original IMRT plans, where gamma (3%/3 mm) passing rates were 99.6%, 93.0%, and 92.1% for 2.5, 5, and 10 mm MLCs, respectively. The percentages of pixels with dose differences between the measurement and calculation being less than 3% of the maximum dose were 85.9%, 82.5%, and 70.5% for the original IMRT plans from the three MLCs, respectively. Conclusions: Dosimetric advantages associated with smaller MLC leaves were observed in terms of the coverage to the prostate, when the treatment was adapted to account for daily prostate movement for concurrent irradiation of the prostate and pelvic lymph nodes. The benefit of switching the MLC from 10 to 5 mm was significant (p Much-Less-Than 0.01); however, switching the MLC from 5 to 2.5 mm would not gain significant (p= 0.15) improvement. IMRT plans with smaller MLC leaf widths achieved more accurate dose delivery.« less

Comparision of beam data requirements for MLC commissioning on a TPS

NASA Astrophysics Data System (ADS)

Solaiappan, Gopi; Singaravelu, Ganesan; Prakasarao, Aruna; Supe, Sanjay S.

2008-01-01

The treatment planning system (TPS) has become a key element in the radiotherapy process with the introduction of computer tomography (CT) based 3D conformal treatment planning. Commissioning of a MLC on a TPS either for conformal radiotherapy or intensity modulated radiation therapy (IMRT) requires beam data to be generated on a linear accelerator. Most of the TPS require these beam data to be generated with routine collimator jaws. However some TPS demand the data to be provided for MLC shaped fields. This prompted us to investigate whether beam data with jaws differ than that with MLC and whether the jaw based beam data would suffice for the commissioning of a MLC on a TPS. Beam data like percentage depth dose (PDD), cross beam profiles and output factors was acquired for jaws and MLC defined square fields for 6, 10 and 23 MV photon beams. Percentage depth dose and cross beam profiles were acquired with a radiation field analyzer RFA-200, CC13-S ion chambers with active volume of 0.13 cm3 and OmniPro-Accept software from Scanditronix-Wellhofer. A Medtec-TG51 water tank with Max-4000 electrometer and 0.6 cc PTW ionization chamber and a mini phantom from Standard Imaging was utilized for output measurements for millennium-120 MLC (Varian Medical Systems) and SRS diode detector (Scanditronix-Wellhofer) of 0.6 mm diameter of active area and 0.3 mm of active volume thickness for micro-MLC (BrainLab). The difference in PDD in the build-up region for millennium MLC was ±1.0% for 6 MV photons. For 10 MV photons the PDD difference was within ±4.0%. The difference in PDD for 23 MV photons ranged from 0% to 40.0%. PDD difference from build-up depth to about 28 cm was within ±1.0%. Difference in PDD crossed ±1.0% at 30 cm depth for 6 MV photons. The difference in PDD in the build-up region for mMLC was ±8.0% for 6 MV photons. For the smallest field size studied with micro-MLC i.e. 0.6 × 0.6 cm2 difference in PDD was more than ±1.0% in the build-up region and beyond a depth of 8.0 cm. The profiles for jaws and MLC agreed within the umbra region. However in the penumbra region small differences in doses were observed. The collimator scatter factor (Sc), phantom scatter factor (Sp) and output factor values for MLC were different that those for jaws. The differences in beam characteristics could have implication for intensity modulated radiation therapy and stereotactic radiosurgery in terms of dose in the build up region, exit dose, dose to the planning target volume (PTV) and organ at risk (OAR). Impact of these dosimetric differences between jaw and MLC needs to be further studied in terms of dose volume histograms for PTV and OAR and its further impact on tumor control probability (TCP) and normal tissue complication probability (NTCP).

Ten Novel Mutations in Chinese Patients with Megalencephalic Leukoencephalopathy with Subcortical Cysts and a Long-Term Follow-Up Research

PubMed Central

Cao, Binbin; Yan, Huifang; Guo, Mangmang; Xie, Han; Wu, Ye; Gu, Qiang; Xiao, Jiangxi; Shang, Jing; Yang, Yanling; Xiong, Hui; Niu, Zhengping; Wu, Xiru; Jiang, Yuwu; Wang, Jingmin

2016-01-01

Objective Megalencephalic leukoencephalopathy with subcortical cysts (MLC, OMIM 604004) is a rare neurological deterioration disease. We aimed to clarify clinical and genetic features of Chinese MLC patients. Methods Clinical information and peripheral venous blood of 20 patients and their families were collected, Sanger-sequencing and Multiple Ligation-dependent Probe Amplification were performed to make genetic analysis. Splicing-site mutation was confirmed with RT-PCR. UPD was detected by haplotype analysis. Follow-up study was performed through telephone for 27 patients. Results Out of 20 patients, macrocephaly, classic MRI features, motor development delay and cognitive impairment were detected in 20(100%), 20(100%), 17(85%) and 4(20%) patients, respectively. 20(100%) were clinically diagnosed with MLC. 19(95%) were genetically diagnosed with 10 novel mutations in MLC1, MLC1 and GlialCAM mutations were identified in 15 and 4 patients, respectively. Deletion mutation from exon4 to exon9 and a homozygous point mutation due to maternal UPD of chromosome22 in MLC1 were found firstly. c.598-2A>C in MLC1 leads to the skip of exon8. c.772-1G>C in MLC1 accounting for 15.5%(9/58) alleles in Chinese patients might be a founder or a hot-spot mutation. Out of 27 patients in the follow-up study, head circumference was ranged from 56cm to 61cm in patients older than 5yeas old, with a median of 57cm. Motor development delay and cognitive impairment were detected in 22(81.5%) and 5(18.5%) patients, respectively. Motor and cognitive deterioration was found in 5 (18.5%) and 2 patients (7.4%), respectively. Improvements and MRI recovery were first found in Chinese patients. Rate of seizures (45.5%), transient motor retrogress (45.5%) and unconsciousness (13.6%) after head trauma was much higher than that after fever (18.2%, 9.1%, 0%, respectively). Significance It’s a clinical and genetic analysis and a follow-up study for largest sample of Chinese MLC patients, identifying 10 novel mutations, expanding mutation spectrums and discovering clinical features of Chinese MLC patients. PMID:27322623

Real-time tracking of respiratory-induced tumor motion by dose-rate regulation

NASA Astrophysics Data System (ADS)

Han-Oh, Yeonju Sarah

We have developed a novel real-time tumor-tracking technology, called Dose-Rate-Regulated Tracking (DRRT), to compensate for tumor motion caused by breathing. Unlike other previously proposed tumor-tracking methods, this new method uses a preprogrammed dynamic multileaf collimator (MLC) sequence in combination with real-time dose-rate control. This new scheme circumvents the technical challenge in MLC-based tumor tracking, that is to control the MLC motion in real time, based on real-time detected tumor motion. The preprogrammed MLC sequence describes the movement of the tumor, as a function of breathing phase, amplitude, or tidal volume. The irregularity of tumor motion during treatment is handled by real-time regulation of the dose rate, which effectively speeds up or slows down the delivery of radiation as needed. This method is based on the fact that all of the parameters in dynamic radiation delivery, including MLC motion, are enslaved to the cumulative dose, which, in turn, can be accelerated or decelerated by varying the dose rate. Because commercially available MLC systems do not allow the MLC delivery sequence to be modified in real time based on the patient's breathing signal, previously proposed tumor-tracking techniques using a MLC cannot be readily implemented in the clinic today. By using a preprogrammed MLC sequence to handle the required motion, the task for real-time control is greatly simplified. We have developed and tested the pre- programmed MLC sequence and the dose-rate regulation algorithm using lung-cancer patients breathing signals. It has been shown that DRRT can track the tumor with an accuracy of less than 2 mm for a latency of the DRRT system of less than 0.35 s. We also have evaluated the usefulness of guided breathing for DRRT. Since DRRT by its very nature can compensate for breathing-period changes, guided breathing was shown to be unnecessary for real-time tracking when using DRRT. Finally, DRRT uses the existing dose-rate control system that is provided for current linear accelerators. Therefore, DRRT can be achieved with minimal modification of existing technology, and this can shorten substantially the time necessary to establish DRRT in clinical practice.

Multileaf Collimator Tracking Improves Dose Delivery for Prostate Cancer Radiation Therapy: Results of the First Clinical Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Colvill, Emma; Northern Sydney Cancer Centre, Royal North Shore Hospital, St. Leonards, NSW; Booth, Jeremy T.

2015-08-01

Purpose: To test the hypothesis that multileaf collimator (MLC) tracking improves the consistency between the planned and delivered dose compared with the dose without MLC tracking, in the setting of a prostate cancer volumetric modulated arc therapy trial. Methods and Materials: Multileaf collimator tracking was implemented for 15 patients in a prostate cancer radiation therapy trial; in total, 513 treatment fractions were delivered. During each treatment fraction, the prostate trajectory and treatment MLC positions were collected. These data were used as input for dose reconstruction (multiple isocenter shift method) to calculate the treated dose (with MLC tracking) and the dose thatmore » would have been delivered had MLC tracking not been applied (without MLC tracking). The percentage difference from planned for target and normal tissue dose-volume points were calculated. The hypothesis was tested for each dose-volume value via analysis of variance using the F test. Results: Of the 513 fractions delivered, 475 (93%) were suitable for analysis. The mean difference and standard deviation between the planned and treated MLC tracking doses and the planned and without-MLC tracking doses for all 475 fractions were, respectively, PTV D{sub 99%} −0.8% ± 1.1% versus −2.1% ± 2.7%; CTV D{sub 99%} −0.6% ± 0.8% versus −0.6% ± 1.1%; rectum V{sub 65%} 1.6% ± 7.9% versus −1.2% ± 18%; and bladder V{sub 65%} 0.5% ± 4.4% versus −0.0% ± 9.2% (P<.001 for all dose-volume results). Conclusion: This study shows that MLC tracking improves the consistency between the planned and delivered doses compared with the modeled doses without MLC tracking. The implications of this finding are potentially improved patient outcomes, as well as more reliable dose-volume data for radiobiological parameter determination.« less

A novel mechanism for the Ca(2+)-sensitizing effect of protein kinase C on vascular smooth muscle: inhibition of myosin light chain phosphatase

PubMed Central

1994-01-01

Mechanisms of Ca2+ sensitization of both myosin light chain (MLC) phosphorylation and force development by protein kinase C (PKC) were studied in permeabilized tonic smooth muscle obtained from the rabbit femoral artery. For comparison, the Ca2+ sensitizing effect of guanosine 5'-O-(gamma-thiotriphosphate) (GTP gamma S) was examined, which had been previously shown to inhibit MLC phosphatase in phasic vascular smooth muscle. We now report that PKC activators (phorbol esters, short chain synthetic diacylglycerols and a diacylglycerol kinase inhibitor) and GTP gamma S significantly increase both MLC phosphorylation and force development at constant [Ca2+]. Major phosphorylation site occurring in the presence of phorbol-12,13- dibutyrate (PDBu) or GTP gamma S at constant [Ca2+] is the same serine residue (Ser-19) as that phosphorylated by MLC kinase in response to increased Ca2+ concentrations. In an ATP- and Ca(2+)-free solution containing 1-(5-chloronaphthalene-1-sulfonyl)-1H-hexahydro-1,4- diazepine (ML-9), to avoid the kinase activity, both PDBu and GTP gamma S significantly decreased the rate of MLC dephosphorylation to half its control value. However, PDBu inhibited the relaxation rate more than did GTP gamma S. In the presence of microcystin-LR to inhibit the phosphatase activity, neither PDBu nor GTP gamma S affected MLC phosphorylation and force development. These results indicate that PKC, like activation of GTP binding protein, increases Ca2+ sensitivity of both MLC phosphorylation and force production through inhibition of MLC phosphatase. PMID:7807049

YAP is essential for mechanical force production and epithelial cell proliferation during lung branching morphogenesis

PubMed Central

Lin, Chuwen; Yao, Erica; Zhang, Kuan; Jiang, Xuan; Croll, Stacey; Thompson-Peer, Katherine; Chuang, Pao-Tien

2017-01-01

Branching morphogenesis is a fundamental program for tissue patterning. We show that active YAP, a key mediator of Hippo signaling, is distributed throughout the murine lung epithelium and loss of epithelial YAP severely disrupts branching. Failure to branch is restricted to regions where YAP activity is removed. This suggests that YAP controls local epithelial cell properties. In support of this model, mechanical force production is compromised and cell proliferation is reduced in Yap mutant lungs. We propose that defective force generation and insufficient epithelial cell number underlie the branching defects. Through genomic analysis, we also uncovered a feedback control of pMLC levels, which is critical for mechanical force production, likely through the direct induction of multiple regulators by YAP. Our work provides a molecular pathway that could control epithelial cell properties required for proper morphogenetic movement and pattern formation. DOI: http://dx.doi.org/10.7554/eLife.21130.001 PMID:28323616

SU-F-T-586: Pre-Treatment QA of InCise2 MLC Plans On a Cyberknife-M6 Using the Delta4 System in SBRT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schmidhalter, D; Henzen, D; Malthaner, M

Purpose: Performing pre-treatment quality assurance (QA) with the Delta4 system (ScandiDos Inc., Madison, WI) is well established for linac-based radiotherapy. This is not true when using a Cyberknife (Accuray Inc., Sunnyvale, CA) where, typically film-based QA is applied. The goal of this work was to test the feasibility to use the Delta4 system for pre-treatment QA for stereotactic body radiation therapy (SBRT) using a Cyberknife-M6 equipped with the InCise2 multileaf collimator (MLC). Methods: In order to perform measurements without accelerator pulse signal, the Tomotherapy option within the Delta4 software was used. Absolute calibration of the Delta4 phantom was performed usingmore » a 10×10 cm{sup 2} field shaped by the InCise2 MLC of the Cyberknife-M6. Five fiducials were attached to the Delta4 phantom in order to be able to track the phantom before and during measurements. For eight SBRT treatment plans (two liver, two prostate, one lung, three bone metastases) additional verification plans were recalculated on the Delta4 phantom using MultiPlan. Dicom data was exported from MultiPlan and was adapted in order to be compatible with the Delta4 software. The measured and calculated dose distributions were compared using the gamma analysis of the Delta4 system. Results: All eight SBRT plans were successfully measured with the aid of the Delta4 system. In the mean, 98.0±1.9%, 95.8±4.1% and 88.40±11.4% of measured dose points passed the gamma analysis using a global dose deviation criterion of 3% (100% corresponds to the dose maximum) and a distance-to-agreement criterion of 3 mm, 2 mm and 1 mm, respectively, and a threshold of 20%. Conclusion: Pre-treatment QA of SBRT plans using the Delta4 system on a Cyberknife-M6 is feasible. Measured dose distributions of SBRT plans showed clinically acceptable agreement with the corresponding calculated dose distributions.« less

The Mathematics and Computer Science Learning Center (MLC).

ERIC Educational Resources Information Center

Abraham, Solomon T.

The Mathematics and Computer Science Learning Center (MLC) was established in the Department of Mathematics at North Carolina Central University during the fall semester of the 1982-83 academic year. The initial operations of the MLC were supported by grants to the University from the Burroughs-Wellcome Company and the Kenan Charitable Trust Fund.…

76 FR 4375 - In the Matter of Certain MLC Flash Memory Devices and Products Containing Same; Notice of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-25

... INTERNATIONAL TRADE COMMISSION [Investigation No. 337-TA-683] In the Matter of Certain MLC Flash Memory Devices and Products Containing Same; Notice of Commission Determination Not To Review an Initial... the United States after importation of certain MLC flash memory devices and products containing same...

Quality assurance for online adapted treatment plans: Benchmarking and delivery monitoring simulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Taoran, E-mail: taoran.li.duke@gmail.com; Wu, Qiuwen; Yang, Yun

Purpose: An important challenge facing online adaptive radiation therapy is the development of feasible and efficient quality assurance (QA). This project aimed to validate the deliverability of online adapted plans and develop a proof-of-concept online delivery monitoring system for online adaptive radiation therapy QA. Methods: The first part of this project benchmarked automatically online adapted prostate treatment plans using traditional portal dosimetry IMRT QA. The portal dosimetry QA results of online adapted plans were compared to original (unadapted) plans as well as randomly selected prostate IMRT plans from our clinic. In the second part, an online delivery monitoring system wasmore » designed and validated via a simulated treatment with intentional multileaf collimator (MLC) errors. This system was based on inputs from the dynamic machine information (DMI), which continuously reports actual MLC positions and machine monitor units (MUs) at intervals of 50 ms or less during delivery. Based on the DMI, the system performed two levels of monitoring/verification during the delivery: (1) dynamic monitoring of cumulative fluence errors resulting from leaf position deviations and visualization using fluence error maps (FEMs); and (2) verification of MLC positions against the treatment plan for potential errors in MLC motion and data transfer at each control point. Validation of the online delivery monitoring system was performed by introducing intentional systematic MLC errors (ranging from 0.5 to 2 mm) to the DMI files for both leaf banks. These DMI files were analyzed by the proposed system to evaluate the system’s performance in quantifying errors and revealing the source of errors, as well as to understand patterns in the FEMs. In addition, FEMs from 210 actual prostate IMRT beams were analyzed using the proposed system to further validate its ability to catch and identify errors, as well as establish error magnitude baselines for prostate IMRT delivery. Results: Online adapted plans were found to have similar delivery accuracy in comparison to clinical IMRT plans when validated with portal dosimetry IMRT QA. FEMs for the simulated deliveries with intentional MLC errors exhibited distinct patterns for different MLC error magnitudes and directions, indicating that the proposed delivery monitoring system is highly specific in detecting the source of errors. Implementing the proposed QA system for online adapted plans revealed excellent delivery accuracy: over 99% of leaf position differences were within 0.5 mm, and >99% of pixels in the FEMs had fluence errors within 0.5 MU. Patterns present in the FEMs and MLC control point analysis for actual patient cases agreed with the error pattern analysis results, further validating the system’s ability to reveal and differentiate MLC deviations. Calculation of the fluence map based on the DMI was performed within 2 ms after receiving each DMI input. Conclusions: The proposed online delivery monitoring system requires minimal additional resources and time commitment to the current clinical workflow while still maintaining high sensitivity to leaf position errors and specificity to error types. The presented online delivery monitoring system therefore represents a promising QA system candidate for online adaptive radiation therapy.« less

Quality assurance for online adapted treatment plans: benchmarking and delivery monitoring simulation.

PubMed

Li, Taoran; Wu, Qiuwen; Yang, Yun; Rodrigues, Anna; Yin, Fang-Fang; Jackie Wu, Q

2015-01-01

An important challenge facing online adaptive radiation therapy is the development of feasible and efficient quality assurance (QA). This project aimed to validate the deliverability of online adapted plans and develop a proof-of-concept online delivery monitoring system for online adaptive radiation therapy QA. The first part of this project benchmarked automatically online adapted prostate treatment plans using traditional portal dosimetry IMRT QA. The portal dosimetry QA results of online adapted plans were compared to original (unadapted) plans as well as randomly selected prostate IMRT plans from our clinic. In the second part, an online delivery monitoring system was designed and validated via a simulated treatment with intentional multileaf collimator (MLC) errors. This system was based on inputs from the dynamic machine information (DMI), which continuously reports actual MLC positions and machine monitor units (MUs) at intervals of 50 ms or less during delivery. Based on the DMI, the system performed two levels of monitoring/verification during the delivery: (1) dynamic monitoring of cumulative fluence errors resulting from leaf position deviations and visualization using fluence error maps (FEMs); and (2) verification of MLC positions against the treatment plan for potential errors in MLC motion and data transfer at each control point. Validation of the online delivery monitoring system was performed by introducing intentional systematic MLC errors (ranging from 0.5 to 2 mm) to the DMI files for both leaf banks. These DMI files were analyzed by the proposed system to evaluate the system's performance in quantifying errors and revealing the source of errors, as well as to understand patterns in the FEMs. In addition, FEMs from 210 actual prostate IMRT beams were analyzed using the proposed system to further validate its ability to catch and identify errors, as well as establish error magnitude baselines for prostate IMRT delivery. Online adapted plans were found to have similar delivery accuracy in comparison to clinical IMRT plans when validated with portal dosimetry IMRT QA. FEMs for the simulated deliveries with intentional MLC errors exhibited distinct patterns for different MLC error magnitudes and directions, indicating that the proposed delivery monitoring system is highly specific in detecting the source of errors. Implementing the proposed QA system for online adapted plans revealed excellent delivery accuracy: over 99% of leaf position differences were within 0.5 mm, and >99% of pixels in the FEMs had fluence errors within 0.5 MU. Patterns present in the FEMs and MLC control point analysis for actual patient cases agreed with the error pattern analysis results, further validating the system's ability to reveal and differentiate MLC deviations. Calculation of the fluence map based on the DMI was performed within 2 ms after receiving each DMI input. The proposed online delivery monitoring system requires minimal additional resources and time commitment to the current clinical workflow while still maintaining high sensitivity to leaf position errors and specificity to error types. The presented online delivery monitoring system therefore represents a promising QA system candidate for online adaptive radiation therapy.

SU-F-BRE-16: VMAT Commissioning and Quality Assurance (QA) of An Elekta Synergy-STM Linac Using ICOM Test HarnessTM

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nguyen, A; Ironwood CRC, Phoenix, AZ; Rajaguru, P

2014-06-15

Purpose: To establish a set of tests based on the iCOM software that can be used to commission and perform periodic QA of VMAT delivery on the Elekta Synergy-S, commonly known as the Beam Modulator (BM). Methods: iCOM is used to create and deliver customized treatment fields to characterize the system in terms of 1) MLC positioning accuracy under static and dynamic delivery with full gantry rotation, 2) MLC positioning with known errors, 3) Maximum dose rate, 4) Maximum MLC speed, 5) Maximum gantry speed, 6) Synchronization: gantry speed versus dose rate, and 7) Synchronization: MLC speed versus dose rate.more » The resulting images were captured on the iView GT and exported in DICOM format to Dosimetry Check™ system for visual and quantitative analysis. For the initial commissioning phase, the system tests described should be supplemented with extensive patient QAs covering all clinically relevant treatment sites. Results: The system performance test suite showed that on our Synergy-S, MLC positioning was accurate under both static and dynamic deliveries. Intentional errors of 1 mm were also easily identified on both static and dynamic picket fence tests. Maximum dose rate was verified with stop watch to be consistently between 475-480 MU/min. Maximum gantry speed and MLC speed were 5.5 degree/s and 2.5 cm/s respectively. After accounting for beam flatness, both synchronization tests, gantry versus dose rate and MLC speed versus dose rate, were successful as the fields were uniform across the strips and there were no obvious cold/hot spots. Conclusion: VMAT commissioning and quality assurance should include machine characterization tests in addition to patient QAs. Elekta iCOM is a valuable tool for the design of customized VMAT field with specific MU, MLC leaf positions, dose rate, and indirect control of MLC and gantry speed at each of its control points.« less

SU-F-T-429: Craniospinal Irradiation by VMAT Technique: Impact of FFF Beam and High Resolution MLC On Plan Quality

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ganesh, T; Sarkar, B; Munshi, A

2016-06-15

Purpose: Objective of this study was to evaluate the impact of using flattening filter free (FFF) beam with 0.5 cm multileaf collimator (MLC) leaves over conventional flattened beam with 1 cm leaf width MLC on the treatment plan quality in cranio-spinal irradiation (CSI). Methods: For five medulloblastoma cases (3 males and 2 females), who were previously treated by volumetric modulated arc therapy (VMAT) technique using conventional flattened beam shaped by 1 cm width MLC leaves, four test plans were generated and compared against the delivered plan. These retrospective plans consisted of four different combinations of flattened and FFF beams frommore » Elekta’s Agility treatment head with 0.5 cm width MLC leaves. Sparing of organs at risks (OAR) in terms of dose to 5%, 50%, 75% and 90% volumes, mean and maximum dose were evaluated. Results: All plans satisfied the planning objective of covering 95% of PTV by at least 95% of prescription dose. Marginal variation of dose spillage was observed between different VMAT plans at very low dose range (1–5 Gy). Variation in dose statistics for PTVs and OARs were within 1% or 1 Gy. Amongst the five plans, the plan with flattened beam with 1 cm MLC had the highest number of MUs, 2.13 times higher than the plan with Agility MLC with FFF beam that had the least number of MUs. No statistically significant difference (p≥0.05) was observed between the reference plan and the retrospectively generated plans in terms of PTV coverage, cold spot, hot spot and organ at risk doses. Conclusion: In the treatment of CSI cases by VMAT technique, FFF beams and/or finer width MLC did not exhibit advantage over the flattened beams or wider MLC in terms of plan quality except for reduction in MUs.« less

SU-F-T-366: Dosimetric Parameters Enhancement of 120-Leaf Millennium MLC Using EGSnrc and IAEA Phase-Space Data

DOE Office of Scientific and Technical Information (OSTI.GOV)

Haddad, K; Alopoor, H

Purpose: Recently, the multileaf collimators (MLC) have become an important part of any LINAC collimation systems because they reduce the treatment planning time and improves the conformity. Important factors that affects the MLCs collimation performance are leaves material composition and their thickness. In this study, we investigate the main dosimetric parameters of 120-leaf Millennium MLC including dose in the buildup point, physical penumbra as well as average and end leaf leakages. Effects of the leaves geometry and density on these parameters are evaluated Methods: From EGSnrc Monte Carlo code, BEAMnrc and DOSXYZnrc modules are used to evaluate the dosimetric parametersmore » of a water phantom exposed to a Varian xi for 100cm SSD. Using IAEA phasespace data just above MLC (Z=46cm) and BEAMnrc, for the modified 120-leaf Millennium MLC a new phase space data at Z=52cm is produces. The MLC is modified both in leaf thickness and material composition. EGSgui code generates 521ICRU library for tungsten alloys. DOSXYZnrc with the new phase space evaluates the dose distribution in a water phantom of 60×60×20 cm3 with voxel size of 4×4×2 mm3. Using DOSXYZnrc dose distributions for open beam and closed beam as well as the leakages definition, end leakage, average leakage and physical penumbra are evaluated. Results: A new MLC with improved dosimetric parameters is proposed. The physical penumbra for proposed MLC is 4.7mm compared to 5.16 mm for Millennium. Average leakage in our design is reduced to 1.16% compared to 1.73% for Millennium, the end leaf leakage suggested design is also reduced to 4.86% compared to 7.26% of Millennium. Conclusion: The results show that the proposed MLC with enhanced dosimetric parameters could improve the conformity of treatment planning.« less

Measurement and Monte Carlo simulation for energy- and intensity-modulated electron radiotherapy delivered by a computer-controlled electron multileaf collimator.

PubMed

Jin, Lihui; Eldib, Ahmed; Li, Jinsheng; Emam, Ismail; Fan, Jiajin; Wang, Lu; Ma, C-M

2014-01-06

The dosimetric advantage of modulated electron radiotherapy (MERT) has been explored by many investigators and is considered to be an advanced radiation therapy technique in the utilization of electrons. A computer-controlled electron multileaf collimator (MLC) prototype, newly designed to be added onto a Varian linac to deliver MERT, was investigated both experimentally and by Monte Carlo simulations. Four different electron energies, 6, 9, 12, and 15 MeV, were employed for this investigation. To ensure that this device was capable of delivering the electron beams properly, measurements were performed to examine the electron MLC (eMLC) leaf leakage and to determine the appropriate jaw positioning for an eMLC-shaped field in order to eliminate a secondary radiation peak that could otherwise appear outside of an intended radiation field in the case of inappropriate jaw positioning due to insufficient radiation blockage from the jaws. Phase space data were obtained by Monte Carlo (MC) simulation and recorded at the plane just above the jaws for each of the energies (6, 9, 12, and 15 MeV). As an input source, phase space data were used in MC dose calculations for various sizes of the eMLC shaped field (10 × 10 cm2, 3.4 × 3.4 cm2, and 2 × 2 cm2) with respect to a water phantom at source-to-surface distance (SSD) = 94 cm, while the jaws, eMLC leaves, and some accessories associated with the eMLC assembly as well were modeled as modifiers in the calculations. The calculated results were then compared with measurements from a water scanning system. The results showed that jaw settings with 5 mm margins beyond the field shaped by the eMLC were appropriate to eliminate the secondary radiation peak while not widening the beam penumbra; the eMLC leaf leakage measurements ranged from 0.3% to 1.8% for different energies based on in-phantom measurements, which should be quite acceptable for MERT. Comparisons between MC dose calculations and measurements showed agreement within 1%/1 mm based on percentage depth doses (PDDs) and off-axis dose profiles for a range of field sizes for each of the electron energies. Our current work has demonstrated that the eMLC and other relevant components in the linac were correctly modeled and simulated via our in-house MC codes, and the eMLC is capable of accurately delivering electron beams for various eMLC-shaped field sizes with appropriate jaw settings. In the next stage, patient-specific verification with a full MERT plan should be performed.

On the suitability of Elekta’s Agility 160 MLC for tracked radiation delivery: closed-loop machine performance

NASA Astrophysics Data System (ADS)

Glitzner, M.; Crijns, S. P. M.; de Senneville, B. Denis; Lagendijk, J. J. W.; Raaymakers, B. W.

2015-03-01

For motion adaptive radiotherapy, dynamic multileaf collimator tracking can be employed to reduce treatment margins by steering the beam according to the organ motion. The Elekta Agility 160 MLC has hitherto not been evaluated for its tracking suitability. Both dosimetric performance and latency are key figures and need to be assessed generically, independent of the used motion sensor. In this paper, we propose the use of harmonic functions directly fed to the MLC to determine its latency during continuous motion. Furthermore, a control variable is extracted from a camera system and fed to the MLC. Using this setup, film dosimetry and subsequent γ statistics are performed, evaluating the response when tracking (MRI)-based physiologic motion in a closed-loop. The delay attributed to the MLC itself was shown to be a minor contributor to the overall feedback chain as compared to the impact of imaging components such as MRI sequences. Delay showed a linear phase behaviour of the MLC employed in continuously dynamic applications, which enables a general MLC-characterization. Using the exemplary feedback chain, dosimetry showed a vast increase in pass rate employing γ statistics. In this early stage, the tracking performance of the Agility using the test bench yielded promising results, making the technique eligible for translation to tracking using clinical imaging modalities.

Fetal bovine serum enables cardiac differentiation of human embryonic stem cells.

PubMed

Bettiol, Esther; Sartiani, Laura; Chicha, Laurie; Krause, Karl Heinz; Cerbai, Elisabetta; Jaconi, Marisa E

2007-10-01

During development, cardiac commitment within the mesoderm requires endoderm-secreted factors. Differentiation of embryonic stem cells into the three germ layers in vitro recapitulates developmental processes and can be influenced by supplements added to culture medium. Hence, we investigated the effect of fetal bovine serum (FBS) and KnockOut serum replacement (SR) on germ layers specification and cardiac differentiation of H1 human embryonic stem cells (hESC) within embryoid bodies (EB). At the time of EB formation, FBS triggered an increased apoptosis. As assessed by quantitative PCR on 4-, 10-, and 20-day-old EB, FBS promoted a faster down-regulation of pluripotency marker Oct4 and an increased expression of endodermal (Sox17, alpha-fetoprotein, AFP) and mesodermal genes (Brachyury, CSX). While neuronal and hematopoietic differentiation occurred in both supplements, spontaneously beating cardiomyocytes were only observed in FBS. Action potential (AP) morphology of hESC-derived cardiomyocytes indicated that ventricular cells were present only after 2 months of culture. However, quantification of myosin light chain 2 ventricular (mlc2v)-positive areas revealed that mlc2v-expressing cardiomyocytes could be detected already after 2 weeks of differentiation, but not in all beating clusters. In conclusion, FBS enabled cardiac differentiation of hESC, likely in an endodermal-dependent pathway. Among cardiac cells, ventricular cardiomyocytes differentiated over time, but not as the predominant cardiac cell subtype.

SU-F-T-313: Clinical Results of a New Customer Acceptance Test for Elekta VMAT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rusk, B; Fontenot, J

Purpose: To report the results of a customer acceptance test (CAT) for VMAT treatments for two matched Elekta linear accelerators. Methods: The CAT tests were performed on two clinically matched Elekta linear accelerators equipped with a 160-leaf MLC. Functional tests included performance checks of the control system during dynamic movements of the diaphragms, MLC, and gantry. Dosimetric tests included MLC picket fence tests at static and variable dose rates and a diaphragm alignment test, all performed using the on-board EPID. Additionally, beam symmetry during arc delivery was measured at the four cardinal angles for high and low dose rate modesmore » using a 2D detector array. Results of the dosimetric tests were analyzed using the VMAT CAT analysis tool. Results: Linear accelerator 1 (LN1) met all stated CAT tolerances. Linear accelerator 2 (LN2) passed the geometric, beam symmetry, and MLC position error tests but failed the relative dose average test for the diaphragm abutment and all three picket fence fields. Though peak doses in the abutment regions were consistent, the average dose was below the stated tolerance corresponding to a leaf junction that was too narrow. Despite this, no significant differences in patient specific VMAT quality assurance measured were observed between the accelerators and both passed monthly MLC quality assurance performed with the Hancock test. Conclusion: Results from the CAT showed LN2 with relative dose averages in the abutment regions of the diaphragm and MLC tests outside the tolerances resulting from differences in leaf gap distances. Tolerances of the dose average tests from the CAT may be small enough to detect MLC errors which do not significantly affect patient QA or the routine MLC tests.« less

Automatic online adaptive radiation therapy techniques for targets with significant shape change: a feasibility study.

PubMed

Court, Laurence E; Tishler, Roy B; Petit, Joshua; Cormack, Robert; Chin, Lee

2006-05-21

This work looks at the feasibility of an online adaptive radiation therapy concept that would detect the daily position and shape of the patient, and would then correct the daily treatment to account for any changes compared with planning position. In particular, it looks at the possibility of developing algorithms to correct for large complicated shape change. For co-planar beams, the dose in an axial plane is approximately associated with the positions of a single multi-leaf collimator (MLC) pair. We start with a primary plan, and automatically generate several secondary plans with gantry angles offset by regular increments. MLC sequences for each plan are calculated keeping monitor units (MUs) and number of segments constant for a given beam (fluences are different). Bulk registration (3D) of planning and daily CT images gives global shifts. Slice-by-slice (2D) registration gives local shifts and rotations about the longitudinal axis for each axial slice. The daily MLC sequence is then created for each axial slice/MLC leaf pair combination, by taking the MLC positions from the pre-calculated plan with the nearest rotation, and shifting using a beam's-eye-view calculation to account for local linear shifts. A planning study was carried out using two head and neck region MR images of a healthy volunteer which were contoured to simulate a base-of-tongue treatment: one with the head straight (used to simulate the planning image) and the other with the head tilted to the left (the daily image). Head and neck treatment was chosen to evaluate this technique because of its challenging nature, with varying internal and external contours, and multiple degrees of freedom. Shape change was significant: on a slice-by-slice basis, local rotations in the daily image varied from 2 to 31 degrees, and local shifts ranged from -0.2 to 0.5 cm and -0.4 to 0.0 cm in right-left and posterior-anterior directions, respectively. The adapted treatment gave reasonable target coverage (100%, 90% and 80% of the base-of-tongue, left nodes and right nodes, respectively, receiving the daily prescription dose), and kept the daily cord dose below the limit used in the original plan (65%, equivalent to 46 Gy over 35 fractions). Most of the loss of coverage was due to one shoulder being raised more superior relative to the other shoulder compared with the plan. This type of skew-like motion is not accounted for by the proposed ART technique. In conclusion, this technique has potential to correct for fairly extreme daily changes in patient setup, but some control of the daily position would still be necessary. Importantly, it was possible to combine treatments from different plans (MLC sequences) to correct for position and shape change.

Mini-laparoscopic cholecystectomy in children under 10 years of age with sickle cell disease.

PubMed

Seleem, Mohamed I; Al-Hashemy, Ahmed M; Meshref, Sahar S

2005-07-01

Cholelithiasis is very common in patients with sickle cell disease (SCD) and is responsible for recurrent attacks of abdominal pain. The ideal management, especially for children, remains controversial. The purpose of the present study was to evaluate the safety and outcome of mini-laparoscopic cholecystectomy (MLC) in young children under age of 10 years with SCD. A prospective study was carried out of 75 children with SCD under 10 years of age with recurrent abdominal pains seen between August 2001 and March 2004 at Armed Forces Hospital, Khamis Mushayt, Saudi Arabia, who were screened for cholelithiasis. Twelve (16%) of the 75 children were found to have gallstones. The mean age was 7.8 years (range 4-9 years). All 12 children underwent MLC. Anaemia was corrected preoperatively in all the patients. Operative time, intraoperative complications, hospital stay, and postoperative recurrent abdominal pain were recorded. The mean operating time was 46.5 min (range: 35-65 min). Intraoperative cholangiogram failed in two children due to narrow cystic ducts. The mean hospital stay was 2.1 days (range: 2-4 days). No patient required intra-abdominal drain. The mean follow-up period was 13.4 months (range: 4-24 months). The only postoperative complication was deep jaundice 1 month postoperatively due to cholestasis, and this responded to medical treatment. None of the children had recurrent abdominal pain after MLC. Mini-laparoscopic cholecystectomy is a safe surgical procedure for the management of cholelithiasis in children with SCD and leads to improvement in the quality of life by decreasing the frequency of recurrent abdominal pain.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Caillet, V; Colvill, E; Royal North Shore Hospital, Sydney, NSW

Purpose: The objective of this study was to investigate the dosimetric benefits of multi-leaf collimator (MLC) tracking for lung SABR treatments in end-to-end clinically realistic planning and delivery scenarios. Methods: The clinical benefits of MLC tracking were assessed using previously delivered treatment plans and physical experiments. The 10 most recent single lesion lung SABR patients were re-planned following a 4D-GTV-based real-time adaptive protocol (PTV defined as the end-of-exhalation GTV plus 5.0 mm margins). The plans were delivered on a Trilogy Varian linac. Electromagnetic transponders (Calypso, Varian Medical Systems, USA) were embedded into a programmable moving phantom (HexaMotion platform) tracked withmore » the Varian Calypso system. For each physical experiment, the MLC positions were collected and used as input for dose reconstruction. For both planned and physical experiments, the OAR dose metrics from the conventional and real-time adaptive SABR plans (Mean Lung Dose (MLD), V20 for lung, and near-maximum dose (D2%) for spine and heart) were statistically compared. The Wilcoxon test was used to compare plan and physical experiment dose metrics. Results: While maintaining target coverage, percentage reductions in dose metrics to the OARs were observed for both planned and physical experiments. Comparing the two plans showed MLD percentage reduction (MLDr) of 25.4% (absolute differences of 1.41 Gy) and 28.9% (1.29%) for the V20r. D2% percentage reduction for spine and heart were respectively 27.9% (0.3 Gy) and 20.2% (0.3 Gy). For the physical experiments, MLDr was 23.9% (1.3 Gy), and V20r 37.4% (1.6%). D2% reduction for spine and heart were respectively 27.3% (0.3 Gy) and 19.6% (0.3 Gy). For both plans and physical experiments, significant OAR dose differences (p<0.05) were found between the conventional SABR and real-time adaptive plans. Conclusion: Application of MLC tracking for lung SABR patients has the potential to reduce the dose to OARs during radiation therapy.« less

Mainland Chinese Students at an Elite Hong Kong University: Habitus-Field Disjuncture in a Transborder Context

ERIC Educational Resources Information Center

Xu, Cora Lingling

2017-01-01

Drawing on in-depth interview data from 31 mainland Chinese (MLC) students in a Hong Kong university, this article conceptualises MLC and Hong Kong higher education as two dissonant but interrelated subfields of the Chinese higher education field. The article argues that these MLC students' habitus, one that possesses rich economic, social and…

SU-E-J-67: Evaluation of Adaptive MLC Morphing for Online Correction of Prostate Cancer Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sandhu, R; Qin, A; Yan, D

Purpose: Online adaptive MLC morphing is desirable over translational couch shifts to accommodate target position as well as anatomic changes. A reliable method of adaptive MLC segment to target during prostate cancer IMRT treatment is proposed and evaluated by comparison with daily online-image guidance (IGRT) correction and online-IMRT planning. Methods: The MLC adaptive algorithm involves following steps; move the MLC segments according to target translational shifts, and then morph the segment shape to maintain the spatial relationship between the planning-target contour and MLC segment. Efficacy of this method was evaluated retrospectively using daily-CBCT images on seven prostate patients treated withmore » seven-beam IMRT treatment to deliver 64Gy in 20 fractions. Daily modification was simulated with three approaches; daily-IGRT correction based on implanted radio-markers, adaptive MLC morphing, and online-IMRT planning, with no-residual variation. The selected dosimetric endpoints and nEUD (normalized equivalent uniform dose to online-IMRT planning) of each organ of interest were determined for evaluation and comparison. Results: For target(prostate), bladder and rectal-wall, the mean±sd of nEUD were 97.6%+3.2%, 103.9%±4.9% and 97.4%±1.1% for daily-IGRT correction; and 100.2%+0.2%, 108.9%±5.1% and 99.8%±1.2% for adaptive MLC morphing, respectively. For daily-IGRT correction, adaptive MLC morphing and online-IMRT planning, target D99 was <95% of the prescription dose in 30%, 0% and 0% of 140 fractions, respectively. For the rectal-wall, D5 exceeded 105% of the planned-D5 in 2.8%, 11.4% and 0% of 140 fractions, respectively. For the bladder, Dmax exceeded 105% of the planned-D5 in 2.8%, 5.6% and 0% of 140 fractions, respectively. D30 of bladder and rectal-wall were well within the planned-D30 for all three approaches. Conclusion: The proposed method of adaptive MLC morphing can be beneficial for the prostate patient population with large deformation and rotation. It is superior to the daily-IGRT correction, and comparable to the online-IMRT planning for dose to the target and rectal-wall.« less

The microwell control of embryoid body size in order to regulate cardiac differentiation of human embryonic stem cells.

PubMed

Mohr, Jeffrey C; Zhang, Jianhua; Azarin, Samira M; Soerens, Andrew G; de Pablo, Juan J; Thomson, James A; Lyons, Gary E; Palecek, Sean P; Kamp, Timothy J

2010-03-01

The differentiation of human embryonic stem cells (hESCs) into cardiomyocytes (CMs) using embryoid bodies (EBs) is relatively inefficient and highly variable. Formation of EBs using standard enzymatic disaggregation techniques results in a wide range of sizes and geometries of EBs. Use of a 3-D cuboidal microwell system to culture hESCs in colonies of defined dimensions, 100-500 microm in lateral dimensions and 120 microm in depth, enabled formation of more uniform-sized EBs. The 300 microm microwells produced highest percentage of contracting EBs, but flow cytometry for myosin light chain 2A (MLC2a) expressing cells revealed a similar percentage (approximately 3%) of cardiomyocytes formed in EBs from 100 microm to 300 microm microwells. These data, and immunolabeling with anti-MF20 and MLC2a, suggest that the smaller EBs are less likely to form contracting EBs, but those contracting EBs are relatively enriched in cardiomyocytes compared to larger EB sizes where CMs make up a proportionately smaller fraction of the total cells. We conclude that microwell-engineered EB size regulates cardiogenesis and can be used for more efficient and reproducible formation of hESC-CMs needed for research and therapeutic applications. (c) 2009 Elsevier Ltd. All rights reserved.

Treatment plan comparison between helical tomotherapy and MLC-based IMRT using radiobiological measures

NASA Astrophysics Data System (ADS)

Mavroidis, Panayiotis; Costa Ferreira, Brigida; Shi, Chengyu; Lind, Bengt K.; Papanikolaou, Nikos

2007-07-01

The rapid implementation of advanced treatment planning and delivery technologies for radiation therapy has brought new challenges in evaluating the most effective treatment modality. Intensity-modulated radiotherapy (IMRT) using multi-leaf collimators (MLC) and helical tomotherapy (HT) are becoming popular modes of treatment delivery and their application and effectiveness continues to be investigated. Presently, there are several treatment planning systems (TPS) that can generate and optimize IMRT plans based on user-defined objective functions for the internal target volume (ITV) and organs at risk (OAR). However, the radiobiological parameters of the different tumours and normal tissues are typically not taken into account during dose prescription and optimization of a treatment plan or during plan evaluation. The suitability of a treatment plan is typically decided based on dosimetric criteria such as dose-volume histograms (DVH), maximum, minimum, mean and standard deviation of the dose distribution. For a more comprehensive treatment plan evaluation, the biologically effective uniform dose ({\\bar{\\bar{D}}}) is applied together with the complication-free tumour control probability (P+). Its utilization is demonstrated using three clinical cases that were planned with two different forms of IMRT. In this study, three different cancer types at different anatomical sites were investigated: head and neck, lung and prostate cancers. For each cancer type, a linac MLC-based step-and-shoot IMRT plan and a HT plan were developed. The MLC-based IMRT treatment plans were developed on the Philips treatment-planning platform, using the Pinnacle 7.6 software release. For the tomotherapy HiArt plans, the dedicated tomotherapy treatment planning station was used, running version 2.1.2. By using {\\bar{\\bar{D}}} as the common prescription point of the treatment plans and plotting the tissue response probabilities versus {\\bar{\\bar{D}}} for a range of prescription doses, a number of plan trials can be compared based on radiobiological measures. The applied plan evaluation method shows that in the head and neck cancer case the HT treatment gives better results than MLC-based IMRT in terms of expected clinical outcome (P+ of 62.2% and 46.0%, {\\bar{\\bar{D}}} to the ITV of 72.3 Gy and 70.7 Gy, respectively). In the lung cancer and prostate cancer cases, the MLC-based IMRT plans are better over the clinically useful dose prescription range. For the lung cancer case, the HT and MLC-based IMRT plans give a P+ of 66.9% and 72.9%, {\\bar{\\bar{D}}} to the ITV of 64.0 Gy and 66.9 Gy, respectively. Similarly, for the prostate cancer case, the two radiation modalities give a P+ of 68.7% and 72.2%, {\\bar{\\bar{D}}} to the ITV of 86.0 Gy and 85.9 Gy, respectively. If a higher risk of complications (higher than 5%) could be allowed, the complication-free tumour control could increase by over 40%, 2% and 30% compared to the initial dose prescription for the three cancer cases, respectively. Both MLC-based IMRT and HT can encompass the often-large ITV required while they minimize the volume of the organs at risk receiving high doses. Radiobiological evaluation of treatment plans may provide an improved correlation of the delivered treatment with the clinical outcome by taking into account the dose-response characteristics of the irradiated targets and normal tissues. There may exist clinical cases, which may look dosimetrically similar but in radiobiological terms may be quite different. In such situations, traditional dose-based evaluation tools can be complemented by the use of P_ +{-}{\\bar{\\bar{D}}} diagrams to effectively evaluate and compare treatment plans.

A clinically observed discrepancy between image-based and log-based MLC positions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Neal, Brian, E-mail: bpn2p@virginia.edu; Ahmed, Mahmoud; Kathuria, Kunal

2016-06-15

Purpose: To present a clinical case in which real-time intratreatment imaging identified an multileaf collimator (MLC) leaf to be consistently deviating from its programmed and logged position by >1 mm. Methods: An EPID-based exit-fluence dosimetry system designed to prevent gross delivery errors was used to capture cine during treatment images. The author serendipitously visually identified a suspected MLC leaf displacement that was not otherwise detected. The leaf position as recorded on the EPID images was measured and log-files were analyzed for the treatment in question, the prior day’s treatment, and for daily MLC test patterns acquired on those treatment days.more » Additional standard test patterns were used to quantify the leaf position. Results: Whereas the log-file reported no difference between planned and recorded positions, image-based measurements showed the leaf to be 1.3 ± 0.1 mm medial from the planned position. This offset was confirmed with the test pattern irradiations. Conclusions: It has been clinically observed that log-file derived leaf positions can differ from their actual position by >1 mm, and therefore cannot be considered to be the actual leaf positions. This cautions the use of log-based methods for MLC or patient quality assurance without independent confirmation of log integrity. Frequent verification of MLC positions through independent means is a necessary precondition to trust log-file records. Intratreatment EPID imaging provides a method to capture departures from MLC planned positions.« less

The first patient treatment of electromagnetic-guided real time adaptive radiotherapy using MLC tracking for lung SABR.

PubMed

Booth, Jeremy T; Caillet, Vincent; Hardcastle, Nicholas; O'Brien, Ricky; Szymura, Kathryn; Crasta, Charlene; Harris, Benjamin; Haddad, Carol; Eade, Thomas; Keall, Paul J

2016-10-01

Real time adaptive radiotherapy that enables smaller irradiated volumes may reduce pulmonary toxicity. We report on the first patient treatment of electromagnetic-guided real time adaptive radiotherapy delivered with MLC tracking for lung stereotactic ablative body radiotherapy. A clinical trial was developed to investigate the safety and feasibility of MLC tracking in lung. The first patient was an 80-year old man with a single left lower lobe lung metastasis to be treated with SABR to 48Gy in 4 fractions. In-house software was integrated with a standard linear accelerator to adapt the treatment beam shape and position based on electromagnetic transponders implanted in the lung. MLC tracking plans were compared against standard ITV-based treatment planning. MLC tracking plan delivery was reconstructed in the patient to confirm safe delivery. Real time adaptive radiotherapy delivered with MLC tracking compared to standard ITV-based planning reduced the PTV by 41% (18.7-11cm 3 ) and the mean lung dose by 30% (202-140cGy), V20 by 35% (2.6-1.5%) and V5 by 9% (8.9-8%). An emerging technology, MLC tracking, has been translated into the clinic and used to treat lung SABR patients for the first time. This milestone represents an important first step for clinical real-time adaptive radiotherapy that could reduce pulmonary toxicity in lung radiotherapy. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Role of RhoA and its effectors ROCK and mDia1 in the modulation of deformation-induced FAK, ERK, p38, and MLC motogenic signals in human Caco-2 intestinal epithelial cells

PubMed Central

Chaturvedi, Lakshmi S.; Marsh, Harold M.

2011-01-01

Repetitive deformation enhances intestinal epithelial migration across tissue fibronectin. We evaluated the contribution of RhoA and its effectors Rho-associated kinase (ROK/ROCK) and mammalian diaphanous formins (mDia1) to deformation-induced intestinal epithelial motility across fibronectin and the responsible focal adhesion kinase (FAK), extracellular signal-regulated kinase (ERK), p38, and myosin light chain (MLC) signaling. We reduced RhoA, ROCK1, ROCK2, and mDia1 by smart-pool double-stranded short-interfering RNAs (siRNA) and pharmacologically inhibited RhoA, ROCK, and FAK in human Caco-2 intestinal epithelial monolayers on fibronectin-coated membranes subjected to 10% repetitive deformation at 10 cycles/min. Migration was measured by wound closure. Stimulation of migration by deformation was prevented by exoenzyme C3, Y27632, or selective RhoA, ROCK1, and ROCK2 or mDia1 siRNAs. RhoA, ROCK inhibition, or RhoA, ROCK1, ROCK2, mDia1, and FAK reduction by siRNA blocked deformation-induced nuclear ERK phosphorylation without preventing ERK phosphorylation in the cytoplasmic protein fraction. Furthermore, RhoA, ROCK inhibition or RhoA, ROCK1, ROCK2, and mDia1 reduction by siRNA also blocked strain-induced FAK-Tyr925, p38, and MLC phosphorylation. These results suggest that RhoA, ROCK, mDia1, FAK, ERK, p38, and MLC all mediate the stimulation of intestinal epithelial migration by repetitive deformation. This pathway may be an important target for interventions to promote mechanotransduced mucosal healing during inflammation. PMID:21849669

Heavy Ion and Proton-Induced Single Event Upset Characteristics of a 3D NAND Flash Memory

NASA Technical Reports Server (NTRS)

Chen, Dakai; Wilcox, Edward; Ladbury, Raymond; Seidleck, Christina; Kim, Hak; Phan, Anthony; Label, Kenneth

2017-01-01

We evaluated the effects of heavy ion and proton irradiation for a 3D NAND flash. The 3D NAND showed similar single-event upset (SEU) sensitivity to a planar NAND of identical density in the multiple-cell level (MLC) storage mode. The 3D NAND showed significantly reduced SEU susceptibility in single-level-cell (SLC) storage mode. Additionally, the 3D NAND showed less multiple-bit upset susceptibility than the planar NAND, with fewer number of upset bits per byte and smaller cross sections overall. However, the 3D architecture exhibited angular sensitivities for both base and face angles, reflecting the anisotropic nature of the SEU vulnerability in space. Furthermore, the SEU cross section decreased with increasing fluence for both the 3D NAND and the Micron 16 nm planar NAND, which suggests that typical heavy ion test fluences will underestimate the upset rate during a space mission. These unique characteristics introduce complexity to traditional ground irradiation test procedures.

In vitro immunomodulatory effects of herbal products.

PubMed

Wilasrusmee, Chumpon; Siddiqui, Josephine; Bruch, David; Wilasrusmee, Skuntala; Kittur, Smita; Kittur, Dilip S

2002-10-01

Immunosuppressive drugs have been developed from natural products such as soil and fungi, which are also the sources of some commonly used herbal products. However, the effect of herbal products on immune response has not been investigated. Because these products can affect the host immune system they can induce either rejection or tolerance after a transplant procedure. To investigate the effects of ten commonly used herbal products on transplant-related immune function we performed in vitro lymphocyte proliferation tests using phytohemagglutinin, mixed lymphocyte culture (MLC) assay, and interleukin (IL)-2 and IL-10 production from MLC. Dong quai, ginseng, and milk thistle had nonspecific immunostimulatory effects on lymphocyte proliferation, whereas ginger and green tea had immunosuppressive effects. Dong quai and milk thistle increased alloresponsiveness in MLC, whereas ginger and tea decreased these responses. The immunostimulatory effects of dong quai and milk thistle were consistently seen in both cell-mediated immune response and nonspecific lymphoproliferation, whereas that of ginseng was not. The immunosuppressive effect of green tea and ginger were mediated through a decrease in IL-2 production, but the immunostimulatory effects of dong quai and milk thistle were not. We conclude that green tea, dong quai, ginseng, milk thistle, and ginger have effects on in vitro immune assays that may be relevant in transplantation in humans.

Dose-to-water conversion for the backscatter-shielded EPID: A frame-based method to correct for EPID energy response to MLC transmitted radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zwan, Benjamin J., E-mail: benjamin.zwan@uon.edu.au; O’Connor, Daryl J.; King, Brian W.

2014-08-15

Purpose: To develop a frame-by-frame correction for the energy response of amorphous silicon electronic portal imaging devices (a-Si EPIDs) to radiation that has transmitted through the multileaf collimator (MLC) and to integrate this correction into the backscatter shielded EPID (BSS-EPID) dose-to-water conversion model. Methods: Individual EPID frames were acquired using a Varian frame grabber and iTools acquisition software then processed using in-house software developed inMATLAB. For each EPID image frame, the region below the MLC leaves was identified and all pixels in this region were multiplied by a factor of 1.3 to correct for the under-response of the imager tomore » MLC transmitted radiation. The corrected frames were then summed to form a corrected integrated EPID image. This correction was implemented as an initial step in the BSS-EPID dose-to-water conversion model which was then used to compute dose planes in a water phantom for 35 IMRT fields. The calculated dose planes, with and without the proposed MLC transmission correction, were compared to measurements in solid water using a two-dimensional diode array. Results: It was observed that the integration of the MLC transmission correction into the BSS-EPID dose model improved agreement between modeled and measured dose planes. In particular, the MLC correction produced higher pass rates for almost all Head and Neck fields tested, yielding an average pass rate of 99.8% for 2%/2 mm criteria. A two-sample independentt-test and fisher F-test were used to show that the MLC transmission correction resulted in a statistically significant reduction in the mean and the standard deviation of the gamma values, respectively, to give a more accurate and consistent dose-to-water conversion. Conclusions: The frame-by-frame MLC transmission response correction was shown to improve the accuracy and reduce the variability of the BSS-EPID dose-to-water conversion model. The correction may be applied as a preprocessing step in any pretreatment portal dosimetry calculation and has been shown to be beneficial for highly modulated IMRT fields.« less

Ulcerative colitis: ultrastructure of interstitial cells in myenteric plexus.

PubMed

Rumessen, J J; Vanderwinden, J-M; Horn, T

2010-10-01

Interstitial cells of Cajal (ICC) are key regulatory cells in the gut. In the colon of patients with severe ulcerative colitis (UC), myenteric ICC had myoid ultrastructural features and were in close contact with nerve terminals. In all patients as opposed to controls, some ICC profiles showed degenerative changes, such as lipid droplets and irregular vacuoles. Nerve terminals often appeared swollen and empty. Glial cells, muscle cells, and fibroblast-like cells (FLC) showed no alterations. FLC enclosed macrophages (MLC), which were in close contact with naked axon terminals. The organization and cytological changes may be of pathophysiological significance in patients with UC.

Leaf-level to Canopy Exchange of NOx and Ozone in a Forest at the University of Michigan Biological Station

NASA Astrophysics Data System (ADS)

Wang, W.; Ganzeveld, L.; Helmig, D.; Hueber, J.; Rossabi, S.; Vogel, C. S.

2017-12-01

During the month-long PROPHET-AMOS campaign in July, 2016 we investigated NOx and ozone dynamics at the University of Michigan AmeriFlux Tower (US-UMB tower) and the PROPHET Tower research sites at the University of Michigan Biological Station (UMBS), using a multi-pronged experimental approach. The two sites are within 100 m of each other, located in a mixed forest on the northern lower peninsula of Michigan, USA. In a previous study, it was found that invoking a leaf-level compensation point for NOx uptake and emission provided better agreement between observed and model-simulated in- and above-canopy NOx concentrations in this forest. To further examine the role of foliar exchange relative to other in-canopy sources and sinks of NOx, we conducted detailed vertical gradient measurements of NOx and ozone at ten heights from the forest floor to above the canopy, along with micrometeorological conditions at the AmeriFlux Tower. In parallel, to investigate the leaf-level exchanges of NOx and ozone, we carried out branch enclosure experiments near the PROPHET tower on the dominant tree species of this forest. We combine these observations with micrometeorological data from the AmeriFlux Tower to constrain simulations with the Multi-Layer Canopy Chemical Exchange Model (MLC-CHEM) for investigation of sources, sinks, and dynamics that determine NOx concentrations, vertical gradients, and fluxes in this forest. We will compare our results with previous studies and other observations during the PHOPHET-AMOS campaign.

Monte Carlo modeling and simulations of the High Definition (HD120) micro MLC and validation against measurements for a 6 MV beam

DOE Office of Scientific and Technical Information (OSTI.GOV)

Borges, C.; Zarza-Moreno, M.; Heath, E.

2012-01-15

Purpose: The most recent Varian micro multileaf collimator (MLC), the High Definition (HD120) MLC, was modeled using the BEAMNRC Monte Carlo code. This model was incorporated into a Varian medical linear accelerator, for a 6 MV beam, in static and dynamic mode. The model was validated by comparing simulated profiles with measurements. Methods: The Varian Trilogy (2300C/D) accelerator model was accurately implemented using the state-of-the-art Monte Carlo simulation program BEAMNRC and validated against off-axis and depth dose profiles measured using ionization chambers, by adjusting the energy and the full width at half maximum (FWHM) of the initial electron beam. Themore » HD120 MLC was modeled by developing a new BEAMNRC component module (CM), designated HDMLC, adapting the available DYNVMLC CM and incorporating the specific characteristics of this new micro MLC. The leaf dimensions were provided by the manufacturer. The geometry was visualized by tracing particles through the CM and recording their position when a leaf boundary is crossed. The leaf material density and abutting air gap between leaves were adjusted in order to obtain a good agreement between the simulated leakage profiles and EBT2 film measurements performed in a solid water phantom. To validate the HDMLC implementation, additional MLC static patterns were also simulated and compared to additional measurements. Furthermore, the ability to simulate dynamic MLC fields was implemented in the HDMLC CM. The simulation results of these fields were compared with EBT2 film measurements performed in a solid water phantom. Results: Overall, the discrepancies, with and without MLC, between the opened field simulations and the measurements using ionization chambers in a water phantom, for the off-axis profiles are below 2% and in depth-dose profiles are below 2% after the maximum dose depth and below 4% in the build-up region. On the conditions of these simulations, this tungsten-based MLC has a density of 18.7 g cm{sup -3} and an overall leakage of about 1.1 {+-} 0.03%. The discrepancies between the film measured and simulated closed and blocked fields are below 2% and 8%, respectively. Other measurements were performed for alternated leaf patterns and the agreement is satisfactory (to within 4%). The dynamic mode for this MLC was implemented and the discrepancies between film measurements and simulations are within 4%. Conclusions: The Varian Trilogy (2300 C/D) linear accelerator including the HD120 MLC was successfully modeled and simulated using the Monte Carlo BEAMNRC code by developing an independent CM, the HDMLC CM, either in static and dynamic modes.« less

Analysis of Neutron Production in Passively Scattered Ion-Beam Therapy.

PubMed

Heo, Seunguk; Yoo, Seunghoon; Song, Yongkeun; Kim, Eunho; Shin, Jaeik; Han, Soorim; Jung, Wongyun; Nam, Sanghee; Lee, Rena; Lee, Kitae; Cho, Sungho

2017-07-01

A new treatment facility for heavy ion therapy since 2010 was constructed. In the broad beam, a range shifter, ridge filter and multi leaf collimator (MLC) for the generation of the spread-out Bragg peak is used. In this case, secondary neutrons produced by the interactions of the ion field with beam-modifying devices (e.g. double-scattering system, beam shaping collimators and range compensators) are very important for patient safety. Therefore, these components must be carefully examined in the context of secondary neutron yield and associated secondary cancer risk. In this article, Monte Carlo simulation has been carried out with the FLUktuierende KAskade particle transport code, the fluence and distribution of neutron generation and the neutron dose equivalent from the broad beam components are compared using carbon and proton beams. As a result, it is confirmed that the yield of neutron production using a carbon beam from all components of the broad beam was higher than using a proton beam. The ambient dose by neutrons per heavy ion and proton ion from the MLC surface was 0.12-0.18 and 0.0067-0.0087 pSv, respectively, which shows that heavy ions generate more neutrons than protons. However, ambient dose per treatment 2 Gy, which means physical dose during treatment by ion beam, is higher than carbon beam because proton therapy needs more beam flux to make 2-Gy prescription dose. Therefore, the neutron production from the MLC, which is closed to the patient, is a very important parameter for patient safety. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Biotransfer, bioaccumulation and effects of herbivore dietary Co, Cu, Ni, and Zn on growth and development of the insect predator Podisus maculiventris (Say).

PubMed

Cheruiyot, Dorothy J; Boyd, Robert S; Coudron, Thomas A; Cobine, Paul A

2013-06-01

Increased metal availability in the environment can be detrimental for the growth and development of all organisms in a food web. In part, this toxicity is due to biotransfer or bioaccumulation of metals between trophic levels. We evaluated the survival, growth, and development of a generalist Hemipteran predator (Podisus maculiventris) when fed herbivorous prey (Spodoptera exigua) reared on artificial diet amended with Cu, Zn, Ni, and Co. Predator nymphs were fed S. exigua larvae raised on diet amended with sublethal (Minimum Sublethal Concentration or MSC) or lethal (Minimum Lethal Concentration or MLC) concentrations of each metal, as well as control diet. We determined if metals were biotransferred or bioaccumulated from the diet to herbivore and predator, as well as if predator growth or survival was affected by herbivore diet. Podisus maculiventris fed herbivores raised on MLC levels of both Cu and Zn took significantly longer to mature to adults, whereas their overall survival was not affected by prey diet metal concentration for any metal. Adult weights were significantly reduced for predators raised on herbivores reared on diets amended with the MLC of Cu and Zn. Copper and Zn were bioaccumulated from diet to herbivore and from herbivore to predator, whereas Ni was biotransferred (although concentrations decreased as trophic level increased). The pattern for Co was more complex, with biotransfer the main outcome. Our results show that availability of metals in a food web can affect growth and development of a hemipteran predator, and that metals are transferred between trophic levels, with metal-specific biotransfer and bioaccumulation outcomes.

Poster - 53: Improving inter-linac DMLC IMRT dose precision by fine tuning of MLC leaf calibration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nakonechny, Keith; Tran, Muoi; Sasaki, David

Purpose: To develop a method to improve the inter-linac precision of DMLC IMRT dosimetry. Methods: The distance between opposing MLC leaf banks (“gap size”) can be finely tuned on Varian linacs. The dosimetric effect due to small deviations from the nominal gap size (“gap error”) was studied by introducing known errors for several DMLC sliding gap sizes, and for clinical plans based on the TG119 test cases. The plans were delivered on a single Varian linac and the relationship between gap error and the corresponding change in dose was measured. The plans were also delivered on eight Varian 2100 seriesmore » linacs (at two institutions) in order to quantify the inter-linac variation in dose before and after fine tuning the MLC calibration. Results: The measured dose differences for each field agreed well with the predictions of LoSasso et al. Using the default MLC calibration, the variation in the physical MLC gap size was determined to be less than 0.4 mm between all linacs studied. The dose difference between the linacs with the largest and smallest physical gap was up to 5.4% (spinal cord region of the head and neck TG119 test case). This difference was reduced to 2.5% after fine tuning the MLC gap calibration. Conclusions: The inter-linac dose precision for DMLC IMRT on Varian linacs can be improved using a simple modification of the MLC calibration procedure that involves fine adjustment of the nominal gap size.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Otageri, P; Grant, E; Maricle, S

Purpose: To evaluate the effects of MLC modeling after commissioning the Varian TrueBeam LINAC in Pinnacle version 9.2. Methods: Stepand-shoot IMRT QAs were investigated when we observed our measured absolute dose results using ion chamber (Capintec PR-05P) were uncharacteristically low; about 4–5% compared to doses calculated by Pinnacle{sup 3} (Phillips, Madison, WI). This problem was predominant for large and highly modulated head and neck (HN) treatments. Intuitively we knew this had to be related to shortcomings in the MLC modeling in Pinnacle. Using film QA we were able to iteratively adjust the MLC parameters. We confirmed results by re-testing fivemore » failed IMRT QA patients; and ion chamber measurements were verified in Quasar anthropomorphic phantom. Results: After commissioning the LINAC in Pinnacle version 9.2, the MLC transmission for 6X, 10X and 15X were 2.0%, 1.7% and 2.0%, respectively, and additional Interleaf leakage for all three energies was 0.5%. These parameters were obtained from profiles scanned with an Edge detector (Sun Nuclear, Melbourne, FL) during machine commissioning. A Verification testing with radiographic EDR2 film (Kodak, Rochester, NY) measurement was performed by creating a closed MLC leaf pattern and analyzing using RIT software (RIT, Colorado Springs, CO). This reduced MLC transmission for 6X, 10X and 15X to 0.7%, 0.9% and 0.9%, respectively; while increasing additional Interleaf leakage for all three energies to 1.0%. Conclusion: Radiographic film measurements were used to correct MLC transmission values for step and shoot IMRT fields used in Pinnacle version 9.2. After adjusting the MLC parameters to correlate with the film QA, there was still very good agreement between the Pinnacle model and commissioning data. Using the same QA methodology, we were also able to improve the beam models for the Varian C-series linacs, Novalis-Tx, and TrueBeam M-120 linacs.« less

SU-E-T-195: Gantry Angle Dependency of MLC Leaf Position Error

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ju, S; Hong, C; Kim, M

Purpose: The aim of this study was to investigate the gantry angle dependency of the multileaf collimator (MLC) leaf position error. Methods: An automatic MLC quality assurance system (AutoMLCQA) was developed to evaluate the gantry angle dependency of the MLC leaf position error using an electronic portal imaging device (EPID). To eliminate the EPID position error due to gantry rotation, we designed a reference maker (RM) that could be inserted into the wedge mount. After setting up the EPID, a reference image was taken of the RM using an open field. Next, an EPID-based picket-fence test (PFT) was performed withoutmore » the RM. These procedures were repeated at every 45° intervals of the gantry angle. A total of eight reference images and PFT image sets were analyzed using in-house software. The average MLC leaf position error was calculated at five pickets (-10, -5, 0, 5, and 10 cm) in accordance with general PFT guidelines using in-house software. This test was carried out for four linear accelerators. Results: The average MLC leaf position errors were within the set criterion of <1 mm (actual errors ranged from -0.7 to 0.8 mm) for all gantry angles, but significant gantry angle dependency was observed in all machines. The error was smaller at a gantry angle of 0° but increased toward the positive direction with gantry angle increments in the clockwise direction. The error reached a maximum value at a gantry angle of 90° and then gradually decreased until 180°. In the counter-clockwise rotation of the gantry, the same pattern of error was observed but the error increased in the negative direction. Conclusion: The AutoMLCQA system was useful to evaluate the MLC leaf position error for various gantry angles without the EPID position error. The Gantry angle dependency should be considered during MLC leaf position error analysis.« less

Investigation of the feasibility of a simple method for verifying the motion of a binary multileaf collimator synchronized with the rotation of the gantry for helical tomotherapy

PubMed Central

Uematsu, Masahiro; Ito, Makiko; Hama, Yukihiro; Inomata, Takayuki; Fujii, Masahiro; Nishio, Teiji; Nakamura, Naoki; Nakagawa, Keiichi

2012-01-01

In this paper, we suggest a new method for verifying the motion of a binary multileaf collimator (MLC) in helical tomotherapy. For this we used a combination of a cylindrical scintillator and a general‐purpose camcorder. The camcorder records the light from the scintillator following photon irradiation, which we use to track the motion of the binary MLC. The purpose of this study is to demonstrate the feasibility of this method as a binary MLC quality assurance (QA) tool. First, the verification was performed using a simple binary MLC pattern with a constant leaf open time; secondly, verification using the binary MLC pattern used in a clinical setting was also performed. Sinograms of simple binary MLC patterns, in which leaves that were open were detected as “open” from the measured light, define the sensitivity which, in this case, was 1.000. On the other hand, the specificity, which gives the fraction of closed leaves detected as “closed”, was 0.919. The leaf open error identified by our method was −1.3±7.5%. The 68.6% of observed leaves were performed within ± 3% relative error. The leaf open error was expressed by the relative errors calculated on the sinogram. In the clinical binary MLC pattern, the sensitivity and specificity were 0.994 and 0.997, respectively. The measurement could be performed with −3.4±8.0% leaf open error. The 77.5% of observed leaves were performed within ± 3% relative error. With this method, we can easily verify the motion of the binary MLC, and the measurement unit developed was found to be an effective QA tool. PACS numbers: 87.56.Fc, 87.56.nk PMID:22231222

SU-E-T-144: Effective Analysis of VMAT QA Generated Trajectory Log Files for Medical Accelerator Predictive Maintenance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Able, CM; Baydush, AH; Nguyen, C

Purpose: To determine the effectiveness of SPC analysis for a model predictive maintenance process that uses accelerator generated parameter and performance data contained in trajectory log files. Methods: Each trajectory file is decoded and a total of 131 axes positions are recorded (collimator jaw position, gantry angle, each MLC, etc.). This raw data is processed and either axis positions are extracted at critical points during the delivery or positional change over time is used to determine axis velocity. The focus of our analysis is the accuracy, reproducibility and fidelity of each axis. A reference positional trace of the gantry andmore » each MLC is used as a motion baseline for cross correlation (CC) analysis. A total of 494 parameters (482 MLC related) were analyzed using Individual and Moving Range (I/MR) charts. The chart limits were calculated using a hybrid technique that included the use of the standard 3σ limits and parameter/system specifications. Synthetic errors/changes were introduced to determine the initial effectiveness of I/MR charts in detecting relevant changes in operating parameters. The magnitude of the synthetic errors/changes was based on: TG-142 and published analysis of VMAT delivery accuracy. Results: All errors introduced were detected. Synthetic positional errors of 2mm for collimator jaw and MLC carriage exceeded the chart limits. Gantry speed and each MLC speed are analyzed at two different points in the delivery. Simulated Gantry speed error (0.2 deg/sec) and MLC speed error (0.1 cm/sec) exceeded the speed chart limits. Gantry position error of 0.2 deg was detected by the CC maximum value charts. The MLC position error of 0.1 cm was detected by the CC maximum value location charts for every MLC. Conclusion: SPC I/MR evaluation of trajectory log file parameters may be effective in providing an early warning of performance degradation or component failure for medical accelerator systems.« less

SU-F-T-372: Surface and Peripheral Dose in Compensator-Based FFF Beam IMRT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, D; Feygelman, V; Moros, E

2016-06-15

Purpose: Flattening filter free (FFF) beams produce higher dose rates. Combined with compensator IMRT techniques, the dose delivery for each beam can be much shorter compared to the flattened beam MLC-based or compensator-based IMRT. This ‘snap shot’ IMRT delivery is beneficial to patients for tumor motion management. Due to softer energy, surface doses in FFF beam treatment are usually higher than those from flattened beams. Because of less scattering due to no flattening filter, peripheral doses are usually lower in FFF beam treatment. However, in compensator-based IMRT using FFF beams, the compensator is in the beam pathway. Does it introducemore » beam hardening effects and scattering such that the surface dose is lower and peripheral dose is higher compared to FFF beam MLC-based IMRT? Methods: This study applied Monte Carlo techniques to investigate the surface and peripheral doses in compensator-based IMRT using FFF beams and compared it to the MLC-based IMRT using FFF beams and flattened beams. Besides various thicknesses of copper slabs to simulate various thicknesses of compensators, a simple cone-shaped compensator was simulated to mimic a clinical application. The dose distribution in water phantom by the cone-shaped compensator was then simulated by multiple MLC defined FFF and flattened beams with various openings. After normalized to Dmax, the surface and peripheral dose was compared between the FFF beam compensator-based IMRT and FFF/flattened beam MLC-based IMRT. Results: The surface dose at the central 0.5mm depth was close between the compensator and 6FFF MLC dose distributions, and about 8% (of Dmax) higher than the flattened 6MV MLC dose. At 8cm off axis at dmax, the peripheral dose between the 6FFF and flattened 6MV MLC demonstrated similar doses, while the compensator dose was about 1% higher. Conclusion: Compensator does not reduce the surface doses but slightly increases the peripheral doses due to scatter inside compensator.« less

SU-E-T-122: Dosimetric Comparison Between Cone, HDMLC and MicroMLC for the Treatment of Trigeminal Neuralgia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vacca, N; Caussa, L; Filipuzzi, M

2014-06-01

Purpose: The purpose of this work was to evaluate the dosimetric characteristics of three collimation systems, 5mm circular cone (Brainlab) and square fields of 5mm with HDMLC (Varian) and microMLC Moduleaf, Siemens) for trigeminal neuralgia treatment. Methods: A TPS Iplan v4.5 BrainLAB was used to do treatment plans for each collimations system in a square solid water phantom with isocenter at 5cm depth. Single field and treatment plan including 11 arcs with fix field and 100° gantry range was made for each collimation systems. EBT3 films were positioned at isocenter in a coronal plane to measured dose distribution for allmore » geometries. Films were digitized with a Vidar DosimetryPro Red scanner with a resolution of 89dpi and RIT113v6.1 software was used for analysis. Penumbra region (80%–20%), FWHM and dose percentage at 5mm and 10mm from CAX were determined. All profiles were normalized at CAX. Results: For single beam the penumbra (FWHM) was 1.5mm (5.3mm) for the cone, 1.9mm (5.5mm) for HDMLC and 1.8mm (5.4mm) for the microMLC. Dose percentage at 5mm was 6.9% for cone, 12.5% for HDMLC and 8.7% for the microMLC. For treatment plan the penumbra (FWHM) was 2.58mm (5.47mm) for the cone, 2.8mm (5.84mm) for HDMLC and 2.58mm (6.09mm) for the microMLC. Dose perecentage at 5mm was 13.1% for cone, 16.1% for HDMLC, 15.2% for the microMLC. Conclusion: The cone has a dose falloff larger than the microMLC and HDMLC, by its reduced penumbra, this translates into better protection of surrounding healthy tissue, however, the microMLC and HDMLC have similar accuracy to cone.« less

Electron beam collimation with a photon MLC for standard electron treatments

NASA Astrophysics Data System (ADS)

Mueller, S.; Fix, M. K.; Henzen, D.; Frei, D.; Frauchiger, D.; Loessl, K.; Stampanoni, M. F. M.; Manser, P.

2018-01-01

Standard electron treatments are currently still performed using standard or molded patient-specific cut-outs placed in the electron applicator. Replacing cut-outs and electron applicators with a photon multileaf collimator (pMLC) for electron beam collimation would make standard electron treatments more efficient and would facilitate advanced treatment techniques like modulated electron radiotherapy (MERT) and mixed beam radiotherapy (MBRT). In this work, a multiple source Monte Carlo beam model for pMLC shaped electron beams commissioned at a source-to-surface distance (SSD) of 70 cm is extended for SSDs of up to 100 cm and validated for several Varian treatment units with field sizes typically used for standard electron treatments. Measurements and dose calculations agree generally within 3% of the maximal dose or 2 mm distance to agreement. To evaluate the dosimetric consequences of using pMLC collimated electron beams for standard electron treatments, pMLC-based and cut-out-based treatment plans are created for a left and a right breast boost, a sternum, a testis and a parotid gland case. The treatment plans consist of a single electron field, either alone (1E) or in combination with two 3D conformal tangential photon fields (1E2X). For each case, a pMLC plan with similar treatment plan quality in terms of dose homogeneity to the target and absolute mean dose values to the organs at risk (OARs) compared to a cut-out plan is found. The absolute mean dose to an OAR is slightly increased for pMLC-based compared to cut-out-based 1E plans if the OAR is located laterally close to the target with respect to beam direction, or if a 6 MeV electron beam is used at an extended SSD. In conclusion, treatment plans using cut-out collimation can be replaced by plans of similar treatment plan quality using pMLC collimation with accurately calculated dose distributions.

Modeling of a multileaf collimator

NASA Astrophysics Data System (ADS)

Kim, Siyong

A comprehensive physics model of a multileaf collimator (MLC) field for treatment planning was developed. Specifically, an MLC user interface module that includes a geometric optimization tool and a general method of in- air output factor calculation were developed. An automatic tool for optimization of MLC conformation is needed to realize the potential benefits of MLC. It is also necessary that a radiation therapy treatment planning (RTTP) system is capable of modeling MLC completely. An MLC geometric optimization and user interface module was developed. The planning time has been reduced significantly by incorporating the MLC module into the main RTTP system, Radiation Oncology Computer System (ROCS). The dosimetric parameter that has the most profound effect on the accuracy of the dose delivered with an MLC is the change in the in-air output factor that occurs with field shaping. It has been reported that the conventional method of calculating an in-air output factor cannot be used for MLC shaped fields accurately. Therefore, it is necessary to develop algorithms that allow accurate calculation of the in-air output factor. A generalized solution for an in-air output factor calculation was developed. Three major contributors of scatter to the in-air output-flattening filter, wedge, and tertiary collimator-were considered separately. By virtue of a field mapping method, in which a source plane field determined by detector's eye view is mapped into a detector plane field, no additional dosimetric data acquisition other than the standard data set for a range of square fields is required for the calculation of head scatter. Comparisons of in-air output factors between calculated and measured values show a good agreement for both open and wedge fields. For rectangular fields, a simple equivalent square formula was derived based on the configuration of a linear accelerator treatment head. This method predicts in-air output to within 1% accuracy. A two-effective-source algorithm was developed to account for the effect of source to detector distance on in-air output for wedge fields. Two effective sources, one for head scatter and the other for wedge scatter, were dealt with independently. Calculations provided less than 1% difference of in-air output factors from measurements. This approach offers the best comprehensive accuracy in radiation delivery with field shapes defined using MLC. This generalized model works equally well with fields shaped by any type of tertiary collimator and have the necessary framework to extend its application to intensity modulated radiation therapy.

Simple suspension culture system of human iPS cells maintaining their pluripotency for cardiac cell sheet engineering.

PubMed

Haraguchi, Yuji; Matsuura, Katsuhisa; Shimizu, Tatsuya; Yamato, Masayuki; Okano, Teruo

2015-12-01

In this study, a simple three-dimensional (3D) suspension culture method for the expansion and cardiac differentiation of human induced pluripotent stem cells (hiPSCs) is reported. The culture methods were easily adapted from two-dimensional (2D) to 3D culture without any additional manipulations. When hiPSCs were directly applied to 3D culture from 2D in a single-cell suspension, only a few aggregated cells were observed. However, after 3 days, culture of the small hiPSC aggregates in a spinner flask at the optimal agitation rate created aggregates which were capable of cell passages from the single-cell suspension. Cell numbers increased to approximately 10-fold after 12 days of culture. The undifferentiated state of expanded hiPSCs was confirmed by flow cytometry, immunocytochemistry and quantitative RT-PCR, and the hiPSCs differentiated into three germ layers. When the hiPSCs were subsequently cultured in a flask using cardiac differentiation medium, expression of cardiac cell-specific genes and beating cardiomyocytes were observed. Furthermore, the culture of hiPSCs on Matrigel-coated dishes with serum-free medium containing activin A, BMP4 and FGF-2 enabled it to generate robust spontaneous beating cardiomyocytes and these cells expressed several cardiac cell-related genes, including HCN4, MLC-2a and MLC-2v. This suggests that the expanded hiPSCs might maintain the potential to differentiate into several types of cardiomyocytes, including pacemakers. Moreover, when cardiac cell sheets were fabricated using differentiated cardiomyocytes, they beat spontaneously and synchronously, indicating electrically communicative tissue. This simple culture system might enable the generation of sufficient amounts of beating cardiomyocytes for use in cardiac regenerative medicine and tissue engineering. Copyright © 2013 John Wiley & Sons, Ltd.

Use of plan quality degradation to evaluate tradeoffs in delivery efficiency and clinical plan metrics arising from IMRT optimizer and sequencer compromises

PubMed Central

Wilkie, Joel R.; Matuszak, Martha M.; Feng, Mary; Moran, Jean M.; Fraass, Benedick A.

2013-01-01

Purpose: Plan degradation resulting from compromises made to enhance delivery efficiency is an important consideration for intensity modulated radiation therapy (IMRT) treatment plans. IMRT optimization and/or multileaf collimator (MLC) sequencing schemes can be modified to generate more efficient treatment delivery, but the effect those modifications have on plan quality is often difficult to quantify. In this work, the authors present a method for quantitative assessment of overall plan quality degradation due to tradeoffs between delivery efficiency and treatment plan quality, illustrated using comparisons between plans developed allowing different numbers of intensity levels in IMRT optimization and/or MLC sequencing for static segmental MLC IMRT plans. Methods: A plan quality degradation method to evaluate delivery efficiency and plan quality tradeoffs was developed and used to assess planning for 14 prostate and 12 head and neck patients treated with static IMRT. Plan quality was evaluated using a physician's predetermined “quality degradation” factors for relevant clinical plan metrics associated with the plan optimization strategy. Delivery efficiency and plan quality were assessed for a range of optimization and sequencing limitations. The “optimal” (baseline) plan for each case was derived using a clinical cost function with an unlimited number of intensity levels. These plans were sequenced with a clinical MLC leaf sequencer which uses >100 segments, assuring delivered intensities to be within 1% of the optimized intensity pattern. Each patient's optimal plan was also sequenced limiting the number of intensity levels (20, 10, and 5), and then separately optimized with these same numbers of intensity levels. Delivery time was measured for all plans, and direct evaluation of the tradeoffs between delivery time and plan degradation was performed. Results: When considering tradeoffs, the optimal number of intensity levels depends on the treatment site and on the stage in the process at which the levels are limited. The cost of improved delivery efficiency, in terms of plan quality degradation, increased as the number of intensity levels in the sequencer or optimizer decreased. The degradation was more substantial for the head and neck cases relative to the prostate cases, particularly when fewer than 20 intensity levels were used. Plan quality degradation was less severe when the number of intensity levels was limited in the optimizer rather than the sequencer. Conclusions: Analysis of plan quality degradation allows for a quantitative assessment of the compromises in clinical plan quality as delivery efficiency is improved, in order to determine the optimal delivery settings. The technique is based on physician-determined quality degradation factors and can be extended to other clinical situations where investigation of various tradeoffs is warranted. PMID:23822412

TM 4: Beam through the Main Linac Cryomodule

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bartnik, A.

2017-06-14

On May 15th 2017, the CBETA project reached the major funding milestone, “Beam through the MLC.” For this test, the team had to successfully accelerate the electron beam to 6 MeV in the Injector Cryomodule (ICM), and then to a final energy of 12 MeV in the Main Linac Cryomodule (MLC). The MLC contains six superconducting accelerating cavities; for this initial test only a single cavity was powered.

Zinc supplementation induces CD4+CD25+Foxp3+ antigen-specific regulatory T cells and suppresses IFN-γ production by upregulation of Foxp3 and KLF-10 and downregulation of IRF-1.

PubMed

Maywald, Martina; Rink, Lothar

2017-08-01

The essential trace element zinc plays a fundamental role in immune function and regulation since its deficiency is associated with autoimmunity, allergies, and transplant rejection. Thus, we investigated the influence of zinc supplementation on the Th1-driven alloreaction in mixed lymphocyte cultures (MLC), on generation of antigen-specific T cells, and analyzed underlying molecular mechanisms. Cell proliferation and pro-inflammatory cytokine production were monitored by [ 3 H]-thymidine proliferation assay and ELISA, respectively. Analysis of surface and intracellular T cell marker was performed by flow cytometry. Western blotting and mRNA analysis were used for Foxp3, KLF-10, and IRF-1 expression. Zinc supplementation on antigen-specific T cells in physiological doses (50 µM) provokes a significant amelioration of cell proliferation and pro-inflammatory cytokine production after reactivation compared to untreated controls. Zinc administration on MLC results in an increased induction and stabilization of CD4 + CD25 + Foxp3 + and CD4 + CD25 + CTLA-4 + T cells (p < 0.05). The effect is based on zinc-induced upregulation of Foxp3 and KLF-10 and downregulation of IRF-1. However, in resting lymphocytes zinc increases IRF-1. In summary, zinc is capable of ameliorating the allogeneic immune reaction by enhancement of antigen-specific iTreg cells due to modulation of essential molecular targets: Foxp3, KLF-10, and IRF-1. Thus, zinc can be seen as an auspicious tool for inducing tolerance in adverse immune reactions.

SU-F-T-527: A Novel Dynamic Multileaf Collimator Leaf-Sequencing Algorithm in Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jing, J; Lin, H; Chow, J

Purpose: A novel leaf-sequencing algorithm is developed for generating arbitrary beam intensity profiles in discrete levels using dynamic multileaf collimator (MLC). The efficiency of this dynamic MLC leaf-sequencing method was evaluated using external beam treatment plans delivered by intensity modulated radiation therapy technique. Methods: To qualify and validate this algorithm, integral test for the beam segment of MLC generated by the CORVUS treatment planning system was performed with clinical intensity map experiments. The treatment plans were optimized and the fluence maps for all photon beams were determined. This algorithm started with the algebraic expression for the area under the beammore » profile. The coefficients in the expression can be transformed into the specifications for the leaf-setting sequence. The leaf optimization procedure was then applied and analyzed for clinical relevant intensity profiles in cancer treatment. Results: The macrophysical effect of this method can be described by volumetric plan evaluation tools such as dose-volume histograms (DVHs). The DVH results are in good agreement compared to those from the CORVUS treatment planning system. Conclusion: We developed a dynamic MLC method to examine the stability of leaf speed including effects of acceleration and deceleration of leaf motion in order to make sure the stability of leaf speed did not affect the intensity profile generated. It was found that the mechanical requirements were better satisfied using this method. The Project is sponsored by the Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry.« less

Chemical composition and antifungal activity of the essential oils of Lavandula viridis L'Her.

PubMed

Zuzarte, Mónica; Gonçalves, Maria José; Cavaleiro, Carlos; Canhoto, Jorge; Vale-Silva, Luís; Silva, Maria João; Pinto, Eugénia; Salgueiro, Lígia

2011-05-01

In the present work we report for what we believe to be the first time the antifungal activity and mechanism of action of the essential oils of Lavandula viridis from Portugal. The essential oils were isolated by hydrodistillation and analysed by GC and GC/MS. The MIC and the minimal lethal concentration (MLC) of the essential oil and its major compounds were determined against several pathogenic fungi. The influence of subinhibitory concentrations of the essential oil on the dimorphic transition in Candida albicans was also studied, as well as propidium iodide and FUN-1 staining of Candida albicans cells by flow cytometry following short treatments with the essential oil. The oils were characterized by a high content of oxygen-containing monoterpenes, with 1,8-cineole being the main constituent. Monoterpene hydrocarbons were present at lower concentrations. According to the determined MIC and MLC values, the dermatophytes and Cryptococcus neoformans were the most sensitive fungi (MIC and MLC values ranging from 0.32 to 0.64 µl ml⁻¹), followed by Candida species (at 0.64-2.5 µl ml⁻¹). For most of these strains, MICs were equivalent to MLCs, indicating a fungicidal effect of the essential oil. The oil was further shown to completely inhibit filamentation in Candida albicans at concentrations well below the respective MICs (as low as MIC/16). Flow cytometry results suggested a mechanism of action ultimately leading to cytoplasmic membrane disruption and cell death. Our results show that L. viridis essential oils may be useful in the clinical treatment of fungal diseases, particularly dermatophytosis and candidosis, although clinical trials are required to evaluate the practical relevance of our in vitro research.

Substance P activates both contractile and inflammatory pathways in lymphatics through the neurokinin receptors NK1R and NK3R

PubMed Central

Chakraborty, Sanjukta; Nepiyushchikh, Zhanna; Davis, Michael J.; Zawieja, David C.; Muthuchamy, Mariappan

2010-01-01

Objective The aim of this study was to elucidate the molecular signaling mechanisms by which substance P (SP) modulates lymphatic muscle contraction and to determine whether SP stimulates both contractile as well as inflammatory pathways in the lymphatics. Methods A rat mesenteric lymphatic muscle cell culture model (RMLMCs) and known specific pharmacological inhibitors were utilized to delineate SP mediated signaling pathways in lymphatics. Results We detected expression of neurokinin receptor 1 (NK1R) and neurokinin receptor 3 (NK3R) in RMLMCs. SP stimulation increased phosphorylation of myosin light chain 20 (MLC20) as well as p38 mitogen associated protein kinase (p38-MAPK) and extracellular signal regulated kinase (ERK1/2) indicating activation of both a contractile and a pro-inflammatory MAPK pathway. Pharmacological inhibition of both NK1R and NK3R significantly affected the downstream SP signaling. We further examined whether there was any crosstalk between the two pathways upon SP stimulation. Inhibition of ERK1/2 decreased levels of p-MLC20 after SP activation, in a PKC dependent manner, indicating a potential crosstalk between these two pathways. Conclusions These data provide the first evidence that SP mediated crosstalk between pro-inflammatory and contractile signaling mechanisms exists in the lymphatic system and may be an important bridge between lymphatic function modulation and inflammation. PMID:21166923

Raf-1 kinase regulates smooth muscle contraction in the rat mesenteric arteries.

PubMed

Sathishkumar, Kunju; Yallampalli, Uma; Elkins, Rebekah; Yallampalli, Chandra

2010-01-01

We investigated the potential role of Raf-1 kinase in mesenteric arterial contraction. Inhibitors of Raf-1 kinase, GW5074, L779450 and ZM 336372 reversed phenylephrine (PE)-induced mesenteric vascular contraction. Studies in vivo in rats showed that GW5074 inhibited PE-induced increase in mean arterial pressure in adult female Sprague-Dawley rats. Isometric tension studies in mesenteric arteries of rats showed that GW5074 did not change the KCl-evoked contraction but significantly inhibited the contractions to PE, 5-HT, U46619, endothelin 1, angiotensin II and phorbol 12, 13-dibutyrate (PDBu). In mesenteric vascular smooth muscle cells (VSMCs), PE stimulated increase in Raf-1 phosphorylation which was inhibited by GW5074. Measurement of [Ca(2+)](i) with Fura-2 showed that GW5074-mediated inhibition of PE-induced contraction was not associated with decreases in [Ca(2+)](i). VSMCs treated with PE exhibited higher levels of the contractile proteins, p-MYPT1 and p-MLC(20), which was inhibited by GW5074. Similarly, PDBu induced increases in phosphorylation of Raf-1, MLC(20) and MYPT1 and this was inhibited by GW5074. However, GW5074 did not have any significant effect on PE/PDBu-induced MEK/ERK activation. The results indicate that Raf-1 kinase plays an important role in the regulation of vascular contractility through regulation of calcium sensitization.

Fluence field modulated CT on a clinical TomoTherapy radiation therapy machine

NASA Astrophysics Data System (ADS)

Szczykutowicz, Timothy P.; Hermus, James

2015-03-01

Purpose: The multi-leaf collimator (MLC) assembly present on TomoTherapy (Accuray, Madison WI) radiation therapy (RT) and mega voltage CT machines is well suited to perform fluence field modulated CT (FFMCT). In addition, there is a demand in the RT environment for FFMCT imaging techniques, specifically volume of interest (VOI) imaging. Methods: A clinical TomoTherapy machine was programmed to deliver 30% imaging dose outside predefined VOIs. Four different size ROIs were placed at varying distances from isocenter. Projections intersecting the VOI received "full dose" while those not intersecting the VOI received 30% of the dose (i.e. the incident fluence for non VOI projections was 30% of the incident fluence for projections intersecting the VOI). Additional scans without fluence field modulation were acquired at "full" and 30% dose. The noise (pixel standard deviation) was measured inside the VOI region and compared between the three scans. Results: The VOI-FFMCT technique produced an image noise 1.09, 1.05, 1.05, and 1.21 times higher than the "full dose" scan for ROI sizes of 10 cm, 13 cm, 10 cm, and 6 cm respectively within the VOI region. Conclusions: Noise levels can be almost unchanged within clinically relevant VOIs sizes for RT applications while the integral imaging dose to the patient can be decreased, and/or the image quality in RT can be dramatically increased with no change in dose relative to non-FFMCT RT imaging. The ability to shift dose away from regions unimportant for clinical evaluation in order to improve image quality or reduce imaging dose has been demonstrated. This paper demonstrates that FFMCT can be performed using the MLC on a clinical TomoTherapy machine for the first time.

Evaluation of MLC leaf transmission on IMRT treatment plan quality of patients with advanced lung cancer.

PubMed

Chen, Jiayun; Fu, Guishan; Li, Minghui; Song, Yixin; Dai, Jianrong; Miao, Junjie; Liu, Zhiqiang; Li, Yexiong

2017-12-14

The purpose of this paper was to evaluate the impact of leaf treatment of multileaf collimator (MLC) in plan quality of intensity-modulated radiotherapy (IMRT) of patients with advanced lung cancer. Five MLCs with different leaf transmissions (0.01%, 0.5%, 1.2%, 1.8%, and 3%) were configured for an accelerator in a treatment planning system. Correspondingly, 5 treatment plans with the same optimization setting were created and evaluated quantitatively for each patient (11 patients total) who was diagnosed with advanced lung cancer. All of the 5 plans for each patient met the dose requirement for the planning treatment volumes (PTVs) and had similar target dose homogeneity and conformity. On average, the doses to selected organs were as follows: (1) V 5 , V 20 , and the mean dose of total lung; (2) the maximum and mean dose to spinal cord planning organ-at-risk volume (PRV); and (3) V 30 and V 40 of heart, decreased slightly when MLC transmission was decreased, but with no statistical differences. There is a clear grouping of plans having total quality score (S D ) value, which is used to evaluate plan quality: (1) more than 1 (patient nos. 1 to 3, 5, and 8), and more than 2.5 (patient no. 6); (2) less than 1 (patient nos. 7 and 10); (3) around 1 (patient nos. 4, 9, and 11). As MLC transmission increased, overall S D values increased as well and plan dose requirement was harder to meet. The clinical requirements were violated increasingly as MLC transmission became large. Total S D with and without normal tissue (NT) showed similar results, with no statistically significant differences. Therefore, decrease of MLC transmission did have minimum impact on plan, and it improved target coverage and reduced normal tissue radiation slightly, with no statistical significance. Plan quality could not be significantly improved by MLC transmission reduction. However, lower MLC transmission may have advantages on lung sparing to low- and intermediate-dose exposure. Besides conventional fraction, hyperfraction, or stereotactic body radiotherapy (SBRT), the reduction on lung sparing is still essential because it is highly relevant to radiation pneumonitis (RP). It has potential to diminish incidence of RP and improve patient's quality of life after irradiation with lowered MLC transmission. Copyright © 2017 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

SU-G-BRB-10: New Generation of High Frame-Rate and High Spatial-Resolution EPID QA System for Full-Body MLC-Based Robotic Radiosurgery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Han, B; Xing, L; Wang, L

Purpose: To systematically investigate an ultra-high spatial-resolution amorphous silicon flat-panel electronic portal imaging device (EPID) for MLC-based full-body robotic radiosurgery geometric and dosimetric quality assurance (QA). Methods: The high frame-rate and ultra-high spatial resolution EPID is an outstanding detector for measuring profiles, MLC-shaped radiosurgery field aperture verification, and small field dosimetry. A Monte Carlo based technique with a robotic linac specific response and calibration is developed to convert a raw EPID-measured image of a radiosurgery field into water-based dose distribution. The technique is applied to measure output factors and profiles for 6MV MLC-defined radiosurgery fields with various sizes ranging frommore » 7.6mm×7.7mm to 100mm×100.1mm and the results are compared with the radiosurgery diode scan measurements in water tank. The EPID measured field sizes and the penumbra regions are analyzed to evaluate the MLC positioning accuracy. Results: For all MLC fields, the EPID measured output factors of MLC-shaped fields are in good agreement with the diode measurements. The mean output difference between the EPID and diode measurement is 0.05±0.87%. The max difference is −1.33% for 7.6mm×7.7mm field. The MLC field size derived from the EPID measurements are in good agreement comparing to the diode scan result. For crossline field sizes, the mean difference is −0.17mm±0.14mm with a maximum of −0.35mm for the 30.8mm×30.8mm field. For inline field sizes, the mean difference is +0.08mm±0.18mm with a maximum of +0.45mm for the 100mm×100.1mm field. The high resolution EPID is able to measure the whole radiation field, without the need to align the detector center perfectly at field center as diode or ion chamber measurement. The setup time is greatly reduced so that the whole process is possible for machine and patient-specific QA. Conclusion: The high spatial-resolution EPID is proved to be an accurate and efficient tool for QA of MLC-equipped robotic radiosurgery system.« less

SU-F-T-469: A Clinically Observed Discrepancy Between Image-Based and Log- Based MLC Position

DOE Office of Scientific and Technical Information (OSTI.GOV)

Neal, B; Ahmed, M; Siebers, J

2016-06-15

Purpose: To present a clinical case which challenges the base assumption of log-file based QA, by showing that the actual position of a MLC leaf can suddenly deviate from its programmed and logged position by >1 mm as observed with real-time imaging. Methods: An EPID-based exit-fluence dosimetry system designed to prevent gross delivery errors was used in cine mode to capture portal images during treatment. Visual monitoring identified an anomalous MLC leaf pair gap not otherwise detected by the automatic position verification. The position of the erred leaf was measured on EPID images and log files were analyzed for themore » treatment in question, the prior day’s treatment, and for daily MLC test patterns acquired on those treatment days. Additional standard test patterns were used to quantify the leaf position. Results: Whereas the log file reported no difference between planned and recorded positions, image-based measurements showed the leaf to be 1.3±0.1 mm medial from the planned position. This offset was confirmed with the test pattern irradiations. Conclusion: It has been clinically observed that log-file derived leaf positions can differ from their actual positions by >1 mm, and therefore cannot be considered to be the actual leaf positions. This cautions the use of log-based methods for MLC or patient quality assurance without independent confirmation of log integrity. Frequent verification of MLC positions through independent means is a necessary precondition to trusting log file records. Intra-treatment EPID imaging provides a method to capture departures from MLC planned positions. Work was supported in part by Varian Medical Systems.« less

The Effects of Lactobacillus acidophilus on the Intestinal Smooth Muscle Contraction through PKC/MLCK/MLC Signaling Pathway in TBI Mouse Model

PubMed Central

Fang, Huan; Zhu, Lina; Gao, Ning; Zhu, Jingci

2015-01-01

Clinical studies have shown that probiotics influence gastrointestinal motility. However, the molecular mechanisms by which probiotic Lactobacillus modulates intestinal motility in traumatic brain injury (TBI) mouse model have not been explored. In the present study, we provided evidence showing that treatment of TBI mice with Lactobacillus acidophilus significantly improved the terminal ileum villus morphology, restored the impaired interstitial cells of Cajal (ICC) and the disrupted ICC networks after TBI, and prevented TBI-mediated inhibition of contractile activity in intestinal smooth muscle. Mechanistically, the decreased concentration of MLCK, phospho-MLC20 and phospho-MYPT1 and increased concentration of MLCP and PKC were observed after TBI, and these events mediated by TBI were efficiently prevented by Lactobacillus acidophilus application. These findings may provide a novel mechanistic basis for the application of Lactobacillus acidophilus in the treatment of TBI. PMID:26030918

The Effects of Lactobacillus acidophilus on the Intestinal Smooth Muscle Contraction through PKC/MLCK/MLC Signaling Pathway in TBI Mouse Model.

PubMed

Sun, Bo; Hu, Chen; Fang, Huan; Zhu, Lina; Gao, Ning; Zhu, Jingci

2015-01-01

Clinical studies have shown that probiotics influence gastrointestinal motility. However, the molecular mechanisms by which probiotic Lactobacillus modulates intestinal motility in traumatic brain injury (TBI) mouse model have not been explored. In the present study, we provided evidence showing that treatment of TBI mice with Lactobacillus acidophilus significantly improved the terminal ileum villus morphology, restored the impaired interstitial cells of Cajal (ICC) and the disrupted ICC networks after TBI, and prevented TBI-mediated inhibition of contractile activity in intestinal smooth muscle. Mechanistically, the decreased concentration of MLCK, phospho-MLC20 and phospho-MYPT1 and increased concentration of MLCP and PKC were observed after TBI, and these events mediated by TBI were efficiently prevented by Lactobacillus acidophilus application. These findings may provide a novel mechanistic basis for the application of Lactobacillus acidophilus in the treatment of TBI.

Multi-angle backscatter classification and sub-bottom profiling for improved seafloor characterization

NASA Astrophysics Data System (ADS)

Alevizos, Evangelos; Snellen, Mirjam; Simons, Dick; Siemes, Kerstin; Greinert, Jens

2018-06-01

This study applies three classification methods exploiting the angular dependence of acoustic seafloor backscatter along with high resolution sub-bottom profiling for seafloor sediment characterization in the Eckernförde Bay, Baltic Sea Germany. This area is well suited for acoustic backscatter studies due to its shallowness, its smooth bathymetry and the presence of a wide range of sediment types. Backscatter data were acquired using a Seabeam1180 (180 kHz) multibeam echosounder and sub-bottom profiler data were recorded using a SES-2000 parametric sonar transmitting 6 and 12 kHz. The high density of seafloor soundings allowed extracting backscatter layers for five beam angles over a large part of the surveyed area. A Bayesian probability method was employed for sediment classification based on the backscatter variability at a single incidence angle, whereas Maximum Likelihood Classification (MLC) and Principal Components Analysis (PCA) were applied to the multi-angle layers. The Bayesian approach was used for identifying the optimum number of acoustic classes because cluster validation is carried out prior to class assignment and class outputs are ordinal categorical values. The method is based on the principle that backscatter values from a single incidence angle express a normal distribution for a particular sediment type. The resulting Bayesian classes were well correlated to median grain sizes and the percentage of coarse material. The MLC method uses angular response information from five layers of training areas extracted from the Bayesian classification map. The subsequent PCA analysis is based on the transformation of these five layers into two principal components that comprise most of the data variability. These principal components were clustered in five classes after running an external cluster validation test. In general both methods MLC and PCA, separated the various sediment types effectively, showing good agreement (kappa >0.7) with the Bayesian approach which also correlates well with ground truth data (r2 > 0.7). In addition, sub-bottom data were used in conjunction with the Bayesian classification results to characterize acoustic classes with respect to their geological and stratigraphic interpretation. The joined interpretation of seafloor and sub-seafloor data sets proved to be an efficient approach for a better understanding of seafloor backscatter patchiness and to discriminate acoustically similar classes in different geological/bathymetric settings.

Fast regional readout CMOS Image Sensor for dynamic MLC tracking

NASA Astrophysics Data System (ADS)

Zin, H.; Harris, E.; Osmond, J.; Evans, P.

2014-03-01

Advanced radiotherapy techniques such as volumetric modulated arc therapy (VMAT) require verification of the complex beam delivery including tracking of multileaf collimators (MLC) and monitoring the dose rate. This work explores the feasibility of a prototype Complementary metal-oxide semiconductor Image Sensor (CIS) for tracking these complex treatments by utilising fast, region of interest (ROI) read out functionality. An automatic edge tracking algorithm was used to locate the MLC leaves edges moving at various speeds (from a moving triangle field shape) and imaged with various sensor frame rates. The CIS demonstrates successful edge detection of the dynamic MLC motion within accuracy of 1.0 mm. This demonstrates the feasibility of the sensor to verify treatment delivery involving dynamic MLC up to ~400 frames per second (equivalent to the linac pulse rate), which is superior to any current techniques such as using electronic portal imaging devices (EPID). CIS provides the basis to an essential real-time verification tool, useful in accessing accurate delivery of complex high energy radiation to the tumour and ultimately to achieve better cure rates for cancer patients.

Multi-scale heat and mass transfer modelling of cell and tissue cryopreservation

PubMed Central

Xu, Feng; Moon, Sangjun; Zhang, Xiaohui; Shao, Lei; Song, Young Seok; Demirci, Utkan

2010-01-01

Cells and tissues undergo complex physical processes during cryopreservation. Understanding the underlying physical phenomena is critical to improve current cryopreservation methods and to develop new techniques. Here, we describe multi-scale approaches for modelling cell and tissue cryopreservation including heat transfer at macroscale level, crystallization, cell volume change and mass transport across cell membranes at microscale level. These multi-scale approaches allow us to study cell and tissue cryopreservation. PMID:20047939

Measurement and Monte Carlo simulation for energy‐ and intensity‐modulated electron radiotherapy delivered by a computer‐controlled electron multileaf collimator

PubMed Central

Eldib, Ahmed; Li, Jinsheng; Emam, Ismail; Fan, Jiajin; Wang, Lu; Ma, C‐M

2014-01-01

The dosimetric advantage of modulated electron radiotherapy (MERT) has been explored by many investigators and is considered to be an advanced radiation therapy technique in the utilization of electrons. A computer‐controlled electron multileaf collimator (MLC) prototype, newly designed to be added onto a Varian linac to deliver MERT, was investigated both experimentally and by Monte Carlo simulations. Four different electron energies, 6, 9, 12, and 15 MeV, were employed for this investigation. To ensure that this device was capable of delivering the electron beams properly, measurements were performed to examine the electron MLC (eMLC) leaf leakage and to determine the appropriate jaw positioning for an eMLC‐shaped field in order to eliminate a secondary radiation peak that could otherwise appear outside of an intended radiation field in the case of inappropriate jaw positioning due to insufficient radiation blockage from the jaws. Phase space data were obtained by Monte Carlo (MC) simulation and recorded at the plane just above the jaws for each of the energies (6, 9, 12, and 15 MeV). As an input source, phase space data were used in MC dose calculations for various sizes of the eMLC shaped field (10×10 cm2, 3.4×3.4 cm2, and 2×2 cm2) with respect to a water phantom at source‐to‐surface distance (SSD)=94cm, while the jaws, eMLC leaves, and some accessories associated with the eMLC assembly as well were modeled as modifiers in the calculations. The calculated results were then compared with measurements from a water scanning system. The results showed that jaw settings with 5 mm margins beyond the field shaped by the eMLC were appropriate to eliminate the secondary radiation peak while not widening the beam penumbra; the eMLC leaf leakage measurements ranged from 0.3% to 1.8% for different energies based on in‐phantom measurements, which should be quite acceptable for MERT. Comparisons between MC dose calculations and measurements showed agreement within 1%/1mm based on percentage depth doses (PDDs) and off‐axis dose profiles for a range of field sizes for each of the electron energies. Our current work has demonstrated that the eMLC and other relevant components in the linac were correctly modeled and simulated via our in‐house MC codes, and the eMLC is capable of accurately delivering electron beams for various eMLC‐shaped field sizes with appropriate jaw settings. In the next stage, patient‐specific verification with a full MERT plan should be performed. PACS number: 87.55.ne PMID:24423848

33 CFR 1.07-90 - Criminal penalties.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Commandant is required, the Area, Maintenance & Logistics Command (MLC), and District Commanders are..., 121 to 126 inclusive). (c) The Area, MLC, or District Commander will identify the laws or regulations...

33 CFR 1.07-90 - Criminal penalties.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Commandant is required, the Area, Maintenance & Logistics Command (MLC), and District Commanders are..., 121 to 126 inclusive). (c) The Area, MLC, or District Commander will identify the laws or regulations...

33 CFR 1.07-90 - Criminal penalties.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Commandant is required, the Area, Maintenance & Logistics Command (MLC), and District Commanders are..., 121 to 126 inclusive). (c) The Area, MLC, or District Commander will identify the laws or regulations...

33 CFR 1.07-90 - Criminal penalties.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Commandant is required, the Area, Maintenance & Logistics Command (MLC), and District Commanders are..., 121 to 126 inclusive). (c) The Area, MLC, or District Commander will identify the laws or regulations...

33 CFR 1.07-90 - Criminal penalties.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Commandant is required, the Area, Maintenance & Logistics Command (MLC), and District Commanders are..., 121 to 126 inclusive). (c) The Area, MLC, or District Commander will identify the laws or regulations...

Micro-Laser Range Finder Development: Using the Monolithic Approach

DTIC Science & Technology

1999-02-01

components can be joined together, optically aligned to form the laser cavity and then sliced to produce MLC modules . This batch process can greatly reduce...the overall fabrication costs of the µLRF system. The MLC module is ultra-compact. Its overall size is approximately 56 mm (L) x 3 mm (W) x 3 mm (H) as...MLC module is placed on a laser pallet for stiffness, mechanical stability. The laser pallet size is selected as part of the integration design

SU-G-JeP2-03: Automatic Quantification of MLC Positional Accuracy in An MRI Guided Radiotherapy System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, X; Studenski, M; Yang, F

Purpose: MRI-guided-radiotherapy (MRIGRT) systems lack many features of traditional Linac based RT systems and specialized tests need to be developed to evaluate MLC performance. This work describes automatic tools for the analysis of positional accuracy of an MLC equipped MRIGRT system. Methods: This MLC analysis tool was developed for the MRIdian™ RT system which has three Co-60 equipped treatment heads each with a double focused MLC containing 30 leaf pairs, leaf thickness is 1.05cm defined at isocenter (SAD 105 cm). For MLC positional analysis a picket fence test was performed using a 25.4cm × 25.4cm Gafchromic™ RTQA2 film placed betweenmore » 5cm solidwater and a 30cm × 30cm × 1cm jigwire phantom with seven embedded parallel metal strips 4cm apart. A plan was generated to deliver 2Gy per field and seven 23.1cm × 2cm fields centered over each wire in the phantom. For each leaf pair the center of the radiation profile was determined by fitting the horizontal profile with a Gaussian model and determining the center of the FWHM. This was compared with the metal strip location to determine any deviation. The following metrics were used to evaluate the deviations per gantry angle including maximum, minimum, mean, Kurtosis, and skewness. Results: The identified maximum/mean leaf deviations are, 1.32/0.55 mm for gantry 0°, 1.59/0.76 mm for gantry 90°, and 1.19/0.39 mm for gantry 270°. The percentage of leaf deviation less than 1mm are 90.0% at 0°, 74.6% at 90°, and 97.0% at 270°. Kurtosis/skewness of the leaf deviation are 2.41/0.14 at 0°, 2.53/0.23 at 90°, 3.33/0.83 at 270°, respectively. Conclusion: This work presents an automatic tool for evaluation of the MLC position accuracy of the MRIdian™ radiotherapy system which can be used to benchmark the performance of the MLC system for each treatment head and track the results longitudinally.« less

Characteristics and performance of the first commercial multileaf collimator for a robotic radiosurgery system

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fürweger, Christoph, E-mail: christoph.fuerweger@cyber-knife.net; Prins, Paulette; Coskan, Harun

Purpose: The “InCise™ multileaf-collimator (MLC)” is the first commercial MLC to be mounted on a robotic SRS/SBRT platform (CyberKnife). The authors assessed characteristics and performance of this novel device in a preclinical five months test period. Methods: Commissioning beam data were acquired with unshielded diodes. EBT3 radiochromic films were employed for measurement of transmission, leaf/bank position accuracy (garden fence) before and after exercising the MLC, for end-to-end testing and further characterization of the beam. The robot workspace with MLC was assessed analytically by transformation to an Euler geometry (“plane,” “gantry,” and “collimator” angles) and by measuring pointing accuracy at eachmore » node. Stability over time was evaluated in picket fence and adapted Winston–Lutz tests (AQA). Results: Beam penumbrae (80%–20%, with 100% = 2 × dose at inflection point for field sizes ≥ 50 × 50 mm{sup 2}) were 2.2–3.7 mm for square fields in reference condition (source-axis-distance 800 mm, depth 15 mm) and depended on field size and off-axis position. Transmission and leakage did not exceed 0.5%. Accessible clinical workspace with MLC covered non-coplanar gantry angles of [−113°; +112°] and collimator angles of [−100°; +107°], with an average robot pointing accuracy of 0.12 ± 0.09 mm. For vertical beams, garden fence tests exhibited an average leaf positioning error of ≤0.2 mm, which increased by 0.25 and 0.30 mm (banks X1 and X2) with leaves traveling parallel to gravity. After execution of a leaf motion stress routine, garden fence tests showed slightly increased jaggedness and allowed to identify one malfunctioning leaf motor. Total system accuracy with MLC was 0.38 ± 0.05 mm in nine end-to-end tests. Picket fence and AQA tests displayed stable results over the test period. Conclusions: The InCise™ MLC for CyberKnife showed high accuracy and adequate characteristics for SRS/SBRT applications. MLC performance after exercise demands specific quality assurance measures.« less

Characteristics and performance of the first commercial multileaf collimator for a robotic radiosurgery system.

PubMed

Fürweger, Christoph; Prins, Paulette; Coskan, Harun; Heijmen, Ben J M

2016-05-01

The "InCise™ multileaf-collimator (MLC)" is the first commercial MLC to be mounted on a robotic SRS/SBRT platform (CyberKnife). The authors assessed characteristics and performance of this novel device in a preclinical five months test period. Commissioning beam data were acquired with unshielded diodes. EBT3 radiochromic films were employed for measurement of transmission, leaf/bank position accuracy (garden fence) before and after exercising the MLC, for end-to-end testing and further characterization of the beam. The robot workspace with MLC was assessed analytically by transformation to an Euler geometry ("plane," "gantry," and "collimator" angles) and by measuring pointing accuracy at each node. Stability over time was evaluated in picket fence and adapted Winston-Lutz tests (AQA). Beam penumbrae (80%-20%, with 100% = 2 × dose at inflection point for field sizes ≥ 50 × 50 mm(2)) were 2.2-3.7 mm for square fields in reference condition (source-axis-distance 800 mm, depth 15 mm) and depended on field size and off-axis position. Transmission and leakage did not exceed 0.5%. Accessible clinical workspace with MLC covered non-coplanar gantry angles of [-113°; +112°] and collimator angles of [-100°; +107°], with an average robot pointing accuracy of 0.12 ± 0.09 mm. For vertical beams, garden fence tests exhibited an average leaf positioning error of ≤0.2 mm, which increased by 0.25 and 0.30 mm (banks X1 and X2) with leaves traveling parallel to gravity. After execution of a leaf motion stress routine, garden fence tests showed slightly increased jaggedness and allowed to identify one malfunctioning leaf motor. Total system accuracy with MLC was 0.38 ± 0.05 mm in nine end-to-end tests. Picket fence and AQA tests displayed stable results over the test period. The InCise™ MLC for CyberKnife showed high accuracy and adequate characteristics for SRS/SBRT applications. MLC performance after exercise demands specific quality assurance measures.

Evaluation of Video Image Analysis (VIA) technology to predict meat yield of sheep carcasses on-line under UK abattoir conditions.

PubMed

Rius-Vilarrasa, E; Bünger, L; Maltin, C; Matthews, K R; Roehe, R

2009-05-01

The Meat and Livestock Commission's (MLC) EUROP classification based scheme and Video Image Analysis (VIA) system were compared in their ability to predict weights of primal carcass joints. A total of 443 commercial lamb carcasses under 12 months of age and mixed gender were selected by their cold carcass weight (CCW), conformation and fat scores. Lamb carcasses were classified for conformation and fatness, scanned by the VIA system and dissected into primal joints of leg, chump, loin, breast and shoulder. After adjustment for CCW, the estimation of primal joints using MLC EUROP scores showed high coefficients of determination (R(2)) in the range of 0.82-0.99. The use of VIA always resulted in equal or higher R(2). The precision measured as root mean square error (RMSE) was 27% (leg), 13% (chump), 1% (loin), 11% (breast), 5% (shoulders) and 13% (total primals) higher using VIA than MLC carcass information. Adjustment for slaughter day and gender effects indicated that estimations of primal joints using MLC EUROP scores were more sensitive to these factors than using VIA. This was consistent with an increase in stability of the prediction model of 28%, 11%, 2%, 12%, 6% and 14% for leg, chump, loin, breast and shoulder and total primals, respectively, using VIA compared to MLC EUROP scores. Consequently, VIA was capable of improving the prediction of primal meat yields compared to the current MLC EUROP carcass classification scheme used in the UK abattoirs.

Patient SWAP-200 personality dimensions and FFM traits: Do they predict therapist responses?

PubMed

Tanzilli, Annalisa; Lingiardi, Vittorio; Hilsenroth, Mark

2018-05-01

The main aim of this study was to examine the relationship between therapists' emotional responses and patients' personality evaluated by 3 dimensional diagnostic approaches empirically derived from the Shedler-Westen Assessment Procedure-200 (SWAP-200; Westen & Shedler, 1999a, 1999b): Two of these rely on the 5-factor model (FFM) domains, that were assessed with different SWAP-200 FFM versions developed by Shedler and Westen (SW-FFM scales; 2004) and McCrae, Löckenhoff, and Costa (MLC-FFM scales; 2005); the third approach is based on a multifaceted model of personality syndromes (SWAP personality dimension scales; see Shedler & Westen, 2004). A national sample of psychiatrists and psychologists (N = 166) of various theoretical orientations completed the Therapist Response Questionnaire (TRQ; Zittel Conklin & Westen, 2003) to identify patterns of therapist response, and the SWAP-200 to assess personality regarding a patient currently in their care. The findings showed good levels of construct validity between the SW-FFM and MLC-FFM scales, with the exception of the Openness trait. Moreover, specific SW-FFM and MLC-FFM scales were significantly associated with distinct SWAP personality dimension scales according in a conceptually meaningful nomological network. Although there were significant, theoretically coherent, and systematic relationships between therapists' responses and patients' personality features, overall the contribution of the SW-FFM and MLC-FFM traits in predicting therapists' responses was less sizable than the SWAP personality dimensions. These results seem to confirm the diagnostic and therapeutic value of countertransference as an essential tool in understanding psychological traits/dimensions that underlie the patients' psychopathology, both from within and outside of the FFM. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Methods for quantitative measurement of tooth wear using the area and volume of virtual model cusps.

PubMed

Kim, Soo-Hyun; Park, Young-Seok; Kim, Min-Kyoung; Kim, Sulhee; Lee, Seung-Pyo

2018-04-01

Clinicians must examine tooth wear to make a proper diagnosis. However, qualitative methods of measuring tooth wear have many disadvantages. Therefore, this study aimed to develop and evaluate quantitative parameters using the cusp area and volume of virtual dental models. The subjects of this study were the same virtual models that were used in our former study. The same age group classification and new tooth wear index (NTWI) scoring system were also reused. A virtual occlusal plane was generated with the highest cusp points and lowered vertically from 0.2 to 0.8 mm to create offset planes. The area and volume of each cusp was then measured and added together. In addition to the former analysis, the differential features of each cusp were analyzed. The scores of the new parameters differentiated the age and NTWI groups better than those analyzed in the former study. The Spearman ρ coefficients between the total area and the area of each cusp also showed higher scores at the levels of 0.6 mm (0.6A) and 0.8A. The mesiolingual cusp (MLC) showed a statistically significant difference ( P <0.01) from the other cusps in the paired t -test. Additionally, the MLC exhibited the highest percentage of change at 0.6A in some age and NTWI groups. Regarding the age groups, the MLC showed the highest score in groups 1 and 2. For the NTWI groups, the MLC was not significantly different in groups 3 and 4. These results support the proposal that the lingual cusp exhibits rapid wear because it serves as a functional cusp. Although this study has limitations due to its cross-sectional nature, it suggests better quantitative parameters and analytical tools for the characteristics of cusp wear.

Comparison of secondary neutron dose in proton therapy resulting from the use of a tungsten alloy MLC or a brass collimator system.

PubMed

Diffenderfer, Eric S; Ainsley, Christopher G; Kirk, Maura L; McDonough, James E; Maughan, Richard L

2011-11-01

To apply the dual ionization chamber method for mixed radiation fields to an accurate comparison of the secondary neutron dose arising from the use of a tungsten alloy multileaf collimator (MLC) as opposed to a brass collimator system for defining the shape of a therapeutic proton field. Hydrogenous and nonhydrogenous ionization chambers were constructed with large volumes to enable measurements of absorbed doses below 10(-4) Gy in mixed radiation fields using the dual ionization chamber method for mixed-field dosimetry. Neutron dose measurements were made with a nominal 230 MeV proton beam incident on a closed tungsten alloy MLC and a solid brass block. The chambers were cross-calibrated against a (60)Co-calibrated Farmer chamber in water using a 6 MV x-ray beam and Monte Carlo simulations were performed to account for variations in ionization chamber response due to differences in secondary neutron energy spectra. The neutron and combined proton plus γ-ray absorbed doses are shown to be nearly equivalent downstream from either a closed tungsten alloy MLC or a solid brass block. At 10 cm downstream from the distal edge of the collimating material the neutron dose from the closed MLC was (5.3 ± 0.4) × 10(- 5) Gy/Gy. The neutron dose with brass was (6.4 ± 0.7) × 10(- 5) Gy/Gy. Further from the secondary neutron source, at 50 cm, the neutron doses remain close for both the MLC and brass block at (6.9 ± 0.6) × 10(- 6) Gy/Gy and (6.3 ± 0.7) × 10(- 6) Gy/Gy, respectively. The dual ionization chamber method is suitable for measuring secondary neutron doses resulting from proton irradiation. The results of measurements downstream from a closed tungsten alloy MLC and a brass block indicate that, even in an overly pessimistic worst-case scenario, secondary neutron production in a tungsten alloy MLC leads to absorbed doses that are nearly equivalent to those seen from brass collimators. Therefore, the choice of tungsten alloy in constructing the leaves of a proton MLC is appropriate, and does not lead to a substantial increase in the secondary neutron dose to the patient compared to that generated in a brass collimator.

Mechanical Fault Diagnosis of High Voltage Circuit Breakers Based on Variational Mode Decomposition and Multi-Layer Classifier.

PubMed

Huang, Nantian; Chen, Huaijin; Cai, Guowei; Fang, Lihua; Wang, Yuqiang

2016-11-10

Mechanical fault diagnosis of high-voltage circuit breakers (HVCBs) based on vibration signal analysis is one of the most significant issues in improving the reliability and reducing the outage cost for power systems. The limitation of training samples and types of machine faults in HVCBs causes the existing mechanical fault diagnostic methods to recognize new types of machine faults easily without training samples as either a normal condition or a wrong fault type. A new mechanical fault diagnosis method for HVCBs based on variational mode decomposition (VMD) and multi-layer classifier (MLC) is proposed to improve the accuracy of fault diagnosis. First, HVCB vibration signals during operation are measured using an acceleration sensor. Second, a VMD algorithm is used to decompose the vibration signals into several intrinsic mode functions (IMFs). The IMF matrix is divided into submatrices to compute the local singular values (LSV). The maximum singular values of each submatrix are selected as the feature vectors for fault diagnosis. Finally, a MLC composed of two one-class support vector machines (OCSVMs) and a support vector machine (SVM) is constructed to identify the fault type. Two layers of independent OCSVM are adopted to distinguish normal or fault conditions with known or unknown fault types, respectively. On this basis, SVM recognizes the specific fault type. Real diagnostic experiments are conducted with a real SF₆ HVCB with normal and fault states. Three different faults (i.e., jam fault of the iron core, looseness of the base screw, and poor lubrication of the connecting lever) are simulated in a field experiment on a real HVCB to test the feasibility of the proposed method. Results show that the classification accuracy of the new method is superior to other traditional methods.

Mechanical Fault Diagnosis of High Voltage Circuit Breakers Based on Variational Mode Decomposition and Multi-Layer Classifier

PubMed Central

Huang, Nantian; Chen, Huaijin; Cai, Guowei; Fang, Lihua; Wang, Yuqiang

2016-01-01

Mechanical fault diagnosis of high-voltage circuit breakers (HVCBs) based on vibration signal analysis is one of the most significant issues in improving the reliability and reducing the outage cost for power systems. The limitation of training samples and types of machine faults in HVCBs causes the existing mechanical fault diagnostic methods to recognize new types of machine faults easily without training samples as either a normal condition or a wrong fault type. A new mechanical fault diagnosis method for HVCBs based on variational mode decomposition (VMD) and multi-layer classifier (MLC) is proposed to improve the accuracy of fault diagnosis. First, HVCB vibration signals during operation are measured using an acceleration sensor. Second, a VMD algorithm is used to decompose the vibration signals into several intrinsic mode functions (IMFs). The IMF matrix is divided into submatrices to compute the local singular values (LSV). The maximum singular values of each submatrix are selected as the feature vectors for fault diagnosis. Finally, a MLC composed of two one-class support vector machines (OCSVMs) and a support vector machine (SVM) is constructed to identify the fault type. Two layers of independent OCSVM are adopted to distinguish normal or fault conditions with known or unknown fault types, respectively. On this basis, SVM recognizes the specific fault type. Real diagnostic experiments are conducted with a real SF6 HVCB with normal and fault states. Three different faults (i.e., jam fault of the iron core, looseness of the base screw, and poor lubrication of the connecting lever) are simulated in a field experiment on a real HVCB to test the feasibility of the proposed method. Results show that the classification accuracy of the new method is superior to other traditional methods. PMID:27834902

Cytokines affecting CD4+T regulatory cells in transplant tolerance. II. Interferon gamma (IFN-γ) promotes survival of alloantigen-specific CD4+T regulatory cells.

PubMed

Nomura, Masaru; Hodgkinson, Suzanne J; Tran, Giang T; Verma, Nirupama D; Robinson, Catherine; Plain, Karren M; Boyd, Rochelle; Hall, Bruce M

2017-06-01

CD4 + T cells that transfer alloantigen-specific transplant tolerance are short lived in culture unless stimulated with specific-donor alloantigen and lymphocyte derived cytokines. Here, we examined if IFN-γ maintained survival of tolerance transferring CD4 + T cells. Alloantigen-specific transplant tolerance was induced in DA rats with heterotopic adult PVG heart allografts by a short course of immunosuppression and these grafts functioned for >100days with no further immunosuppression. In previous studies, we found the CD4 + T cells from tolerant rats that transfer tolerance to an irradiated DA host grafted with a PVG heart, lose their tolerance transferring ability after 3days of culture, either with or without donor alloantigen, and effect rejection of specific-donor grafts. If cultures with specific-donor alloantigen are supplemented by supernatant from ConA activated lymphocytes the tolerance transferring cells survive, suggesting these cells depend on cytokines for their survival. In this study, we found addition of rIFN-γ to MLC with specific-donor alloantigen maintained the capacity of tolerant CD4 + T cells to transfer alloantigen-specific tolerance and their ability to suppress PVG allograft rejection mediated by co-administered naïve CD4 + T cells. IFN-γ suppressed the in vitro proliferation of tolerant CD4 + T cells. Tolerant CD4 + CD25 + T cells did not proliferate in MLC to PVG stimulator cells with no cytokine added, but did when IFN-γ was present. IFN-γ did not alter proliferation of tolerant CD4 + CD25 + T cells to third-party Lewis. Tolerant CD4 + CD25 + T cells' expression of IFN-γ receptor (IFNGR) was maintained in culture when IFN-γ was present. This study suggested that IFN-γ maintained tolerance mediating alloantigen-specific CD4 + CD25 + T cells. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Technical Note: A novel leaf sequencing optimization algorithm which considers previous underdose and overdose events for MLC tracking radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wisotzky, Eric, E-mail: eric.wisotzky@charite.de, E-mail: eric.wisotzky@ipk.fraunhofer.de; O’Brien, Ricky; Keall, Paul J., E-mail: paul.keall@sydney.edu.au

2016-01-15

Purpose: Multileaf collimator (MLC) tracking radiotherapy is complex as the beam pattern needs to be modified due to the planned intensity modulation as well as the real-time target motion. The target motion cannot be planned; therefore, the modified beam pattern differs from the original plan and the MLC sequence needs to be recomputed online. Current MLC tracking algorithms use a greedy heuristic in that they optimize for a given time, but ignore past errors. To overcome this problem, the authors have developed and improved an algorithm that minimizes large underdose and overdose regions. Additionally, previous underdose and overdose events aremore » taken into account to avoid regions with high quantity of dose events. Methods: The authors improved the existing MLC motion control algorithm by introducing a cumulative underdose/overdose map. This map represents the actual projection of the planned tumor shape and logs occurring dose events at each specific regions. These events have an impact on the dose cost calculation and reduce recurrence of dose events at each region. The authors studied the improvement of the new temporal optimization algorithm in terms of the L1-norm minimization of the sum of overdose and underdose compared to not accounting for previous dose events. For evaluation, the authors simulated the delivery of 5 conformal and 14 intensity-modulated radiotherapy (IMRT)-plans with 7 3D patient measured tumor motion traces. Results: Simulations with conformal shapes showed an improvement of L1-norm up to 8.5% after 100 MLC modification steps. Experiments showed comparable improvements with the same type of treatment plans. Conclusions: A novel leaf sequencing optimization algorithm which considers previous dose events for MLC tracking radiotherapy has been developed and investigated. Reductions in underdose/overdose are observed for conformal and IMRT delivery.« less

Sci-Fri PM: Radiation Therapy, Planning, Imaging, and Special Techniques - 02: Feasibility of using multileaf collimation for stereotactic radiosurgery of arteriovenous malformation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Young; Ruschin, Mark

SRS using linac and cones offers steep dose fall-off but a tradeoff exists between conformality and treatment time, which depends on the number of isocentres. Purpose of this study is to quantify planning metrics between cones- and MLC-based SRS for arteriovenous malformation(AVM). Seven AVM cases treated with cones were re-planned with MLC on Pinnacle treatment planning system. Planning target volume(PTV) was created with 1mm uniform margin to the AVM to account for MLC positional variation. Clinically-planned prescription dose(15–25Gy) was used. Four plans were generated per case:non-coplanar VMAT(ncV), single-arc VMAT(saV), non-coplanar IMRT(ncI), non-coplanar conformal(ncC). Plans were compared for conformity(CI), heterogeneity(HI) andmore » gradient(GI) indices and brain doses. Estimated treatment times and monitor units(MU) were compared. Cone-based plans required 2–6 isocentres. Though CI-RTOG was similar for plans(median=0.98), CI-Paddick was most favourable for ncV(median=0.86) and worst for cones(0.54). HI for MLC plans(median=1.19–1.27) were lower than cone-based plans(1.43). GI was similar for all plans. For 2/7 ncC had brainstem maximum dose>16.7Gy and therefore were clinically unacceptable. Brain V12Gy,V10Gy,V2Gy were lowest in the cones plan. ncV brain V12Gy,V10Gy,V2Gy were lowest of all MLC-based plans studied. Treatment MUs were similar for MLC-based plans and up to 70% lower than clinically delivered plans. ncV showed best conformality in this study. Of the MLC-based plans, ncV also showed lowest normal tissue dose with reasonable treatment time.« less

Multiple Leader Candidate and Competitive Position Allocation for Robust Formation against Member Robot Faults

PubMed Central

Kwon, Ji-Wook; Kim, Jin Hyo; Seo, Jiwon

2015-01-01

This paper proposes a Multiple Leader Candidate (MLC) structure and a Competitive Position Allocation (CPA) algorithm which can be applicable for various applications including environmental sensing. Unlike previous formation structures such as virtual-leader and actual-leader structures with position allocation including a rigid allocation and an optimization based allocation, the formation employing the proposed MLC structure and CPA algorithm is robust against the fault (or disappearance) of the member robots and reduces the entire cost. In the MLC structure, a leader of the entire system is chosen among leader candidate robots. The CPA algorithm is the decentralized position allocation algorithm that assigns the robots to the vertex of the formation via the competition of the adjacent robots. The numerical simulations and experimental results are included to show the feasibility and the performance of the multiple robot system employing the proposed MLC structure and the CPA algorithm. PMID:25954956

Endothelial disruptive proinflammatory effects of nicotine and e-cigarette vapor exposures.

PubMed

Schweitzer, Kelly S; Chen, Steven X; Law, Sarah; Van Demark, Mary; Poirier, Christophe; Justice, Matthew J; Hubbard, Walter C; Kim, Elena S; Lai, Xianyin; Wang, Mu; Kranz, William D; Carroll, Clinton J; Ray, Bruce D; Bittman, Robert; Goodpaster, John; Petrache, Irina

2015-07-15

The increased use of inhaled nicotine via e-cigarettes has unknown risks to lung health. Having previously shown that cigarette smoke (CS) extract disrupts the lung microvasculature barrier function by endothelial cell activation and cytoskeletal rearrangement, we investigated the contribution of nicotine in CS or e-cigarettes (e-Cig) to lung endothelial injury. Primary lung microvascular endothelial cells were exposed to nicotine, e-Cig solution, or condensed e-Cig vapor (1-20 mM nicotine) or to nicotine-free CS extract or e-Cig solutions. Compared with nicotine-containing extract, nicotine free-CS extract (10-20%) caused significantly less endothelial permeability as measured with electric cell-substrate impedance sensing. Nicotine exposures triggered dose-dependent loss of endothelial barrier in cultured cell monolayers and rapidly increased lung inflammation and oxidative stress in mice. The endothelial barrier disruptive effects were associated with increased intracellular ceramides, p38 MAPK activation, and myosin light chain (MLC) phosphorylation, and was critically mediated by Rho-activated kinase via inhibition of MLC-phosphatase unit MYPT1. Although nicotine at sufficient concentrations to cause endothelial barrier loss did not trigger cell necrosis, it markedly inhibited cell proliferation. Augmentation of sphingosine-1-phosphate (S1P) signaling via S1P1 improved both endothelial cell proliferation and barrier function during nicotine exposures. Nicotine-independent effects of e-Cig solutions were noted, which may be attributable to acrolein, detected along with propylene glycol, glycerol, and nicotine by NMR, mass spectrometry, and gas chromatography, in both e-Cig solutions and vapor. These results suggest that soluble components of e-Cig, including nicotine, cause dose-dependent loss of lung endothelial barrier function, which is associated with oxidative stress and brisk inflammation.

VMAT testing for an Elekta accelerator

PubMed Central

Sweeney, Larry E.; Marshall, Edward I.; Mahendra, Saikanth

2012-01-01

Volumetric‐modulated arc therapy (VMAT) has been shown to be able to deliver plans equivalent to intensity‐modulated radiation therapy (IMRT) in a fraction of the treatment time. This improvement is important for patient immobilization/ localization compliance due to comfort and treatment duration, as well as patient throughput. Previous authors have suggested commissioning methods for this modality. Here, we extend the methods reported for the Varian RapidArc system (which tested individual system components) to the Elekta linear accelerator, using custom files built using the Elekta iComCAT software. We also extend the method reported for VMAT commissioning of the Elekta accelerator by verifying maximum values of parameters (gantry speed, multileaf collimator (MLC) speed, and backup jaw speed), investigating: 1) beam profiles as a function of dose rate during an arc, 2) over/under dosing due to MLC reversals, and 3) over/under dosing at changing dose rate junctions. Equations for construction of the iComCAT files are given. Results indicate that the beam profile for lower dose rates varies less than 3% from that of the maximum dose rate, with no difference during an arc. The gantry, MLC, and backup jaw maximum speed are internally consistent. The monitor unit chamber is stable over the MUs and gantry movement conditions expected. MLC movement and position during VMAT delivery are within IMRT tolerances. Dose rate, gantry speed, and MLC speed are accurately controlled. Over/under dosing at junctions of MLC reversals or dose rate changes are within clinical acceptability. PACS numbers: 87.55.de, 87.55.Qr, 87.56.bd PMID:22402389

Quantitative measurement of MLC leaf displacements using an electronic portal image device

NASA Astrophysics Data System (ADS)

Yang, Yong; Xing, Lei

2004-04-01

The success of an IMRT treatment relies on the positioning accuracy of the MLC (multileaf collimator) leaves for both step-and-shoot and dynamic deliveries. In practice, however, there exists no effective and quantitative means for routine MLC QA and this has become one of the bottleneck problems in IMRT implementation. In this work we present an electronic portal image device (EPID) based method for fast and accurate measurement of MLC leaf positions at arbitrary locations within the 40 cm × 40 cm radiation field. The new technique utilizes the fact that the integral signal in a small region of interest (ROI) is a sensitive and reliable indicator of the leaf displacement. In this approach, the integral signal at a ROI was expressed as a weighted sum of the contributions from the displacements of the leaf above the point and the adjacent leaves. The weighting factors or linear coefficients of the system equations were determined by fitting the integral signal data for a group of pre-designed MLC leaf sequences to the known leaf displacements that were intentionally introduced during the creation of the leaf sequences. Once the calibration is done, the system can be used for routine MLC leaf positioning QA to detect possible leaf errors. A series of tests was carried out to examine the functionality and accuracy of the technique. Our results show that the proposed technique is potentially superior to the conventional edge-detecting approach in two aspects: (i) it deals with the problem in a systematic approach and allows us to take into account the influence of the adjacent MLC leaves effectively; and (ii) it may improve the signal-to-noise ratio and is thus capable of quantitatively measuring extremely small leaf positional displacements. Our results indicate that the technique can detect a leaf positional error as small as 0.1 mm at an arbitrary point within the field in the absence of EPID set-up error and 0.3 mm when the uncertainty is considered. Given its simplicity, efficiency and accuracy, we believe that the technique is ideally suitable for routine MLC leaf positioning QA. This work was presented at the 45th Annual Meeting of American Society of Therapeutic Radiology and Oncology (ASTRO), Salt Lake City, UT, 2003. A US Patent is pending (application no. 10/197,232).

Determination of MLC model parameters for Monaco using commercial diode arrays.

PubMed

Kinsella, Paul; Shields, Laura; McCavana, Patrick; McClean, Brendan; Langan, Brian

2016-07-08

Multileaf collimators (MLCs) need to be characterized accurately in treatment planning systems to facilitate accurate intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT). The aim of this study was to examine the use of MapCHECK 2 and ArcCHECK diode arrays for optimizing MLC parameters in Monaco X-ray voxel Monte Carlo (XVMC) dose calculation algorithm. A series of radiation test beams designed to evaluate MLC model parameters were delivered to MapCHECK 2, ArcCHECK, and EBT3 Gafchromic film for comparison. Initial comparison of the calculated and ArcCHECK-measured dose distributions revealed it was unclear how to change the MLC parameters to gain agreement. This ambiguity arose due to an insufficient sampling of the test field dose distributions and unexpected discrepancies in the open parts of some test fields. Consequently, the XVMC MLC parameters were optimized based on MapCHECK 2 measurements. Gafchromic EBT3 film was used to verify the accuracy of MapCHECK 2 measured dose distributions. It was found that adjustment of the MLC parameters from their default values resulted in improved global gamma analysis pass rates for MapCHECK 2 measurements versus calculated dose. The lowest pass rate of any MLC-modulated test beam improved from 68.5% to 93.5% with 3% and 2 mm gamma criteria. Given the close agreement of the optimized model to both MapCHECK 2 and film, the optimized model was used as a benchmark to highlight the relatively large discrepancies in some of the test field dose distributions found with ArcCHECK. Comparison between the optimized model-calculated dose and ArcCHECK-measured dose resulted in global gamma pass rates which ranged from 70.0%-97.9% for gamma criteria of 3% and 2 mm. The simple square fields yielded high pass rates. The lower gamma pass rates were attributed to the ArcCHECK overestimating the dose in-field for the rectangular test fields whose long axis was parallel to the long axis of the ArcCHECK. Considering ArcCHECK measurement issues and the lower gamma pass rates for the MLC-modulated test beams, it was concluded that MapCHECK 2 was a more suitable detector than ArcCHECK for the optimization process. © 2016 The Authors

SU-F-T-481: Physics Evaluation of a Newly Released InCise™ Multileaf Collimator for CyberKnife M6™ System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, L; Chin, E; Lo, A

2016-06-15

Purpose: This work reports the results of the physics evaluation of a newly released InCise™2 Multileaf Collimator (MLC) installed in our institution. Methods: Beam property data was measured with unshielded diode and EBT2 films. The measurements included MLC leaf transmission, beam profiles, output factors and tissue-phantom ratios. MLC performance was evaluated for one month after commissioning. Weekly Garden Fence tests were performed for leaf / bank positioning in standard (A/P) and clinically relevant non-standard positions, before and after MLC driving exercises of 10+ minutes. Daily Picket Fence test and AQA test, End-to-End tests and dosimetric quality assurance were performed tomore » evaluate the overall system performance. Results: All measurements including beam energy, flatness and symmetry, were within manufacture specifications. Leaf transmission was 0.4% <0.5% specification. The values of output factors ranged from 0.825 (7.6 mm × 7.5 mm) to 1.026 (115.0 mm × 100.1 mm). Average beam penumbra at 10 cm depth ranged from 2.7mm/2.7mm(7.6 mm × 7.5 mm) to 6.0 mm/6.2mm(84.6 mm × 84.7 mm). Slight penumbra difference (<10% from average penumbra for fields >20 mm) was observed in the direction perpendicular to leaf motion due to the tilting of the leaf housing. Mean leaf position offsets was −0.08±0.07mm and −0.13 ± 0.08 for X1 and X2 leaf banks in 13 Garden Fence tests. No significant difference on average leaf positioning offsets was observed between different leaf orientations and before/after MLC driving exercises. Six End-to-End tests showed 0.43±0.23mm overall targeting accuracy. Picket-Fence and AQA showed stable performance of MLC during the test period. Dosimetric point dose measurements for test cases agreed with calculation within 3%. All film measurements on relative dose had Gamma (2%, 2mm) passing rate of >95%. Conclusion: The Incise™2 MLC for CyberKnife M6™ was proven to be accurate and reliable, and it is currently in clinical use. Stanford was one of the physics evaluation sites for the newly released InCise 2 MLC for Accuray Inc.« less

Intestinal infection with Giardia spp. reduces epithelial barrier function in a myosin light chain kinase-dependent fashion.

PubMed

Scott, Kevin G-E; Meddings, Jonathon B; Kirk, David R; Lees-Miller, Susan P; Buret, André G

2002-10-01

Giardiasis causes malabsorptive diarrhea, and symptoms can be present in the absence of any significant morphologic injury to the intestinal mucosa. The effects of giardiasis on epithelial permeability in vivo remain unknown, and the role of T cells and myosin light chain kinase (MLCK) in altered intestinal barrier function is unclear. This study was conducted to determine whether Giardia spp. alters intestinal permeability in vivo, to assess whether these abnormalities are dependent on T cells, and to assess the role of MLCK in altered epithelial barrier function. Immunocompetent and isogenic athymic mice were inoculated with axenic Giardia muris trophozoites or sterile vehicle (control), then assessed for trophozoite colonization and gastrointestinal permeability. Mechanistic studies using nontransformed human duodenal epithelial monolayers (SCBN) determined the effects of Giardia on myosin light chain (MLC) phosphorylation, transepithelial fluorescein isothiocyanate-dextran fluxes, cytoskeletal F-actin, tight junctional zonula occludens-1 (ZO-1), and MLCK. Giardia infection caused a significant increase in small intestinal, but not gastric or colonic, permeability that correlated with trophozoite colonization in both immunocompetent and athymic mice. In vitro, Giardia increased permeability and phosphorylation of MLC and reorganized F-actin and ZO-1. These alterations were abolished with an MLCK inhibitor. Disruption of small intestinal barrier function is T cell independent, disappears on parasite clearance, and correlates with reorganization of cytoskeletal F-actin and tight junctional ZO-1 in an MLCK-dependent fashion.

Impact of jamming on collective cell migration

NASA Astrophysics Data System (ADS)

Nnetu, Kenechukwu David; Knorr, Melanie; Pawlizak, Steve; Fuhs, Thomas; Zink, Mareike; KäS, Josef A.

2012-02-01

Multi-cellular migration plays an important role in physiological processes such as embryogenesis, cancer metastasis and tissue repair. During migration, single cells undergo cycles of extension, adhesion and retraction resulting in morphological changes. In a confluent monolayer, there are inter-cellular interactions and crowding, however, the impact of these interactions on the dynamics and elasticity of the monolayer at the multi-cellular and single cell level is not well understood. Here we study the dynamics of a confluent epithelial monolayer by simultaneously measuring cell motion at the multi-cellular and single cell level for various cell densities and tensile elasticity. At the multi-cellular level, the system exhibited spatial kinetic transitions from isotropic to anisotropic migration on long times and the velocity of the monolayer decreased with increasing cell density. Moreover, the dynamics was spatially and temporally heterogeneous. Interestingly, the dynamics was also heterogeneous in wound-healing assays and the correlation length was fitted by compressed exponential. On the single cell scale, we observed transient caging effects with increasing cage rearrangement times as the system age due to an increase in density. Also, the density dependent elastic modulus of the monolayer scaled as a weak power law. Together, these findings suggest that caging effects at the single cell level initiates a slow and heterogeneous dynamics at the multi-cellular level which is similar to the glassy dynamics of deformable colloidal systems.

Two distinct roles of mitogen-activated protein kinases in platelets and a novel Rac1-MAPK–dependent integrin outside-in retractile signaling pathway

PubMed Central

Flevaris, Panagiotis; Li, Zhenyu; Zhang, Guoying; Zheng, Yi; Liu, Junling

2009-01-01

Mitogen-activated protein kinases (MAPK), p38, and extracellular stimuli-responsive kinase (ERK), are acutely but transiently activated in platelets by platelet agonists, and the agonist-induced platelet MAPK activation is inhibited by ligand binding to the integrin αIIbβ3. Here we show that, although the activation of MAPK, as indicated by MAPK phosphorylation, is initially inhibited after ligand binding to integrin αIIbβ3, integrin outside-insignaling results in a late but sustained activation of MAPKs in platelets. Furthermore, we show that the early agonist-induced MAPK activation and the late integrin-mediated MAPK activation play distinct roles in different stages of platelet activation. Agonist-induced MAPK activation primarily plays an important role in stimulating secretion of platelet granules, while integrin-mediated MAPK activation is important in facilitating clot retraction. The stimulatory role of MAPK in clot retraction is mediated by stimulating myosin light chain (MLC) phosphorylation. Importantly, integrin-dependent MAPK activation, MAPK-dependent MLC phosphorylation, and clot retraction are inhibited by a Rac1 inhibitor and in Rac1 knockout platelets, indicating that integrin-induced activation of MAPK and MLC and subsequent clot retraction is Rac1-dependent. Thus, our results reveal 2 different activation mechanisms of MAPKs that are involved in distinct aspects of platelet function and a novel Rac1-MAPK–dependent cell retractile signaling pathway. PMID:18957688

SU-E-T-35: A General Fill Factor Definition Serving to Characterise the MLC Misalignment Detection Capabilities of Two-Dimensional Detector Arrays

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stelljes, T.S.; Looe, H.K.; Poppe, B.

Purpose: To present a general definition of the fill factor realistically characterizing the “field coverage”, i.e. the MLC misalignment detection capabilities of a detector array. Methods: According to Gago-Arias et al.{sup 1} the fill factor of a 2D array is defined as the ratio of the area enclosed by the FWHM of the fluence response function KM(x) of a single detector and its cell area defined by the detector spacing. More generally - accounting also for the possible overlap between FWHM’s of neighboured detectors - the fill factor is here defined as that fraction of the sum of the detectormore » cell areas in which a defined MLC misalignment is detectable when the induced percentage signal changes exceed a detection threshold d. Ideally the generalized fill factor may reach 100 %. With user code EGS-chamber and a 2 MeV photon slit beam 0.25 mm wide, both types of the fill factor were calculated for an array with total cell area 100 cm{sup 2} for chamber widths 1–9 mm, using =1mm, d=5%. Results: For single chamber width 5 mm, fill factors were 0.49 (FWHM) and 0.61 (generalized). For chamber width 2 mm the FWHM fill factor was 0.13 whereas the generalized fill factor was 0.32. For chamber widths above 7 mm, the FWHM fill factor exceeds unity, and the general fill factor is exactly 1.00. Conclusions: An updated fill factor definition is introduced which, as a generalization of the FWHM-based definition, more closely estimates the performance of small array chambers and gives a realistic value in the case of overlapping sensitive areas of neighboured chambers. References:{sup 1}A. Gago-Arias, L. Brualla-Gonzalez, D.M. Gonzalez-Castano, F. Gomez, M.S. Garcia, V.L. Vega, J.M. Sueiro, J. Pardo-Montero, “Evaluation of chamber response function influence on IMRT verification using 2D commercial detector arrays,” Phys. Med. Biol. 57, 2005–2020 (2012)« less

The effect of iron on metronidazole activity against Trichomonas vaginalis in vitro.

PubMed

Elwakil, Hala Salah; Tawfik, Rania Ayman; Alam-Eldin, Yosra Hussein; Nassar, Doaa Ashraf

2017-11-01

Metronidazole is administered in an inactive form then activated to its cytotoxic form within the hydrogenosome of trichomonads. Two hydrogenosomal proteins, pyruvate ferredoxin oxidoreductase (PFOR) and ferredoxin, play a critical role in the reductive activation of metronidazole. The expression of these proteins and other hydrogenosomal proteins are likewise positively regulated by iron. In the present study, the effect of iron on minimal lethal concentration (MLC) of metronidazole on in vitro cultured Trichomonas vaginalis(T. vaginalis) isolates was investigated. Interestingly, Addition of Ferrous ammonium sulphate (FAS) to T. vaginalis culture led to decrease in the MLC of metronidazole. On using aerobic assay, MLC of metronidazole on untreated T. vaginalis of both isolates was 12.5 μg/ml that decreased to 0.38 μg/ml on FAS treated trichomonads. Also anaerobic assay revealed that MLC on untreated parasites was 3.12 μg/ml that decreased to 0.097 μg/ml and 0.19 μg/ml for isolate 1 and isolate 2 respectively after iron addition. It was concluded that, addition of iron to in vitro cultured T. vaginalis decreases metronidazole MLC that was detected by both aerobic and anaerobic assays. Copyright © 2017 Elsevier Inc. All rights reserved.

SU-C-BRB-04: Characteristics and Performance Evaluation of the First Commercial MLC for a Robotic Delivery System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fuerweger, C; European Cyberknife Center Munich, Munich, DE; Prins, P

Purpose: To assess characteristics and performance of the “Incise™” MLC (41 leaf pairs, 2.5mm width, FFF linac) mounted on the robotic SRS/SBRT platform “CyberKnife M6™” in a pre-clinical 5 months (11/2014–03/2015) test period. Methods: Beam properties were measured with unshielded diodes and EBT3 film. The CyberKnife workspace for MLC was analyzed by transforming robot node coordinates (cranial / body paths) into Euler geometry. Bayouth tests for leaf / bank position accuracy were performed in standard (A/P) and clinically relevant non-standard positions, before and after exercising the MLC for 10+ minutes. Total system and delivery accuracy were assessed in End-to-End testsmore » and dosimetric verification of exemplary plans. Stability over time was evaluated in Picket-Fence-and adapted Winston-Lutz-tests (AQA) for different collimator angles. Results: Penumbrae (80–20%, with 100%=2*dose at inflection point; SAD 80cm; 10cm depth) parallel / perpendicular to leaf motion were 2.87/2.64mm for the smallest (0×76×0.75cm{sup 2}) and 5.34/4.94mm for the largest (9.76×9.75cm{sup 2}) square field. MLC circular field penumbrae exceeded fixed cones by 10–20% (e.g. 60mm: 4.0 vs. 3.6mm; 20mm: 3.6 vs. 2.9mm). Interleaf leakage was <0.5%. Clinically accessible workspace with MLC covered (non-coplanar) gantry angles of [-113°;+112°] (cranial) and [-108°;+102°] (body), and collimator angles of [-100°;+107°] (cranial) and [-91°;+100°] (body). Average leaf position offsets were ≤0.2mm in 14 standard A/P Bayouth tests and ≤0.6mm in 8 non-standard direction tests. Pre-test MLC exercise increased jaggedness (range ±0.3mm vs. ±0.5mm) and allowed to identify one malfunctioning leaf motor. Total system accuracy with MLC was 0.39±0.06mm in 6 End-to-End tests. Picket-Fence and AQA showed no adverse trends during the test period. Conclusion: The Incise™ MLC for CyberKnife M6™ displayed high accuracy and mechanical stability over the test period. The specific CyberKnife geometry and performance after exercise demand dedicated QA measures. This work is in part funded by a research grant from Accuray Inc, Sunnyvale, USA. Erasmus MC Cancer Institute also has research collaborations with Elekta AB, Stockholm, Sweden. C Fuerweger has previously received speaker honoraria from Accuray Inc, Sunnyvale, USA.« less

SU-E-T-424: Dosimetric Verification of Modulated Electron Radiation Therapy Delivered Using An Electron Specific Multileaf Collimator for Treatment of Scalp Cases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eldib, A; Al-Azhar University Cairo; Jin, L

2014-06-01

Purpose: Modulated electron radiotherapy (MERT) has the potential to achieve better treatment outcome for shallow tumors such as those of breast and scalp. In a separate study with scalp lesions, MERT was compared to volumetric modulated arc therapy. Our results showed a reduction in the dose reaching the brain with MERT. However dose calculation accuracy and delivery efficiency challenges remain. Thus in the current study we proceed to add more cases to demonstrate MERT beneficial outcome and its delivery accuracy using an electron specific multileaf collimator (eMLC). Methods: We have used the MCBEAM code for treatment head simulation and formore » generating phase space files to be used as radiation source input for our Monte Carlo based treatment planning system (MC TPS). MCPLAN code is used for calculation of patient specific dose deposition coefficient and for final MERT plan dose calculation. An in-house developed optimization code is used for the optimization process. MERT plans were generated for real patients and head and neck phantom. Film was used for dosimetric verification. The film was cut following the contour of the curved phantom surface and then sealed with black masking tape. In the measurement, the sealed film packet was sandwiched between two adjacent slabs of the head and neck phantom. The measured 2D dose distribution was then compared with calculations. Results: The eMLC allows effective treatment of scalps with multi-lesions spreading around the patient head, which was usually difficult to plan or very time consuming with conventional applicators. MERT continues to show better reduction in the brain dose. The dosimetric measurements showed slight discrepancy, which was attributed to the film setup. Conclusion: MERT can improve treatment plan quality for patients with scalp cancers. Our in-house MC TPS is capable of performing treatment planning and accurate dose calculation for MERT using the eMLC.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hussain, A

Purpose: Novel linac machines, TrueBeam (TB) and Elekta Versa have updated head designing and software control system, include flattening-filter-free (FFF) photon and electron beams. Later on FFF beams were also introduced on C-Series machines. In this work FFF beams for same energy 6MV but from different machine versions were studied with reference to beam data parameters. Methods: The 6MV-FFF percent depth doses, profile symmetry and flatness, dose rate tables, and multi-leaf collimator (MLC) transmission factors were measured during commissioning process of both C-series and Truebeam machines. The scanning and dosimetric data for 6MV-FFF beam from Truebeam and C-Series linacs wasmore » compared. A correlation of 6MV-FFF beam from Elekta Versa with that of Varian linacs was also found. Results: The scanning files were plotted for both qualitative and quantitative analysis. The dosimetric leaf gap (DLG) for C-Series 6MV-FFF beam is 1.1 mm. Published values for Truebeam dosimetric leaf gap is 1.16 mm. 6MV MLC transmission factor varies between 1.3 % and 1.4 % in two separate measurements and measured DLG values vary between 1.32 mm and 1.33 mm on C-Series machine. MLC transmission factor from C-Series machine varies between 1.5 % and 1.6 %. Some of the measured data values from C-Series FFF beam are compared with Truebeam representative data. 6MV-FFF beam parameter values like dmax, OP factors, beam symmetry and flatness and additional parameters for C-Series and Truebeam liancs will be presented and compared in graphical form and tabular data form if selected. Conclusion: The 6MV flattening filter (FF) beam data from C-Series & Truebeam and 6MV-FFF beam data from Truebeam has already presented. This particular analysis to compare 6MV-FFF beam from C-Series and Truebeam provides opportunity to better elaborate FFF mode on novel machines. It was found that C-Series and Truebeam 6MV-FFF dosimetric and beam data was quite similar.« less

Independent Monte-Carlo dose calculation for MLC based CyberKnife radiotherapy

NASA Astrophysics Data System (ADS)

Mackeprang, P.-H.; Vuong, D.; Volken, W.; Henzen, D.; Schmidhalter, D.; Malthaner, M.; Mueller, S.; Frei, D.; Stampanoni, M. F. M.; Dal Pra, A.; Aebersold, D. M.; Fix, M. K.; Manser, P.

2018-01-01

This work aims to develop, implement and validate a Monte Carlo (MC)-based independent dose calculation (IDC) framework to perform patient-specific quality assurance (QA) for multi-leaf collimator (MLC)-based CyberKnife® (Accuray Inc., Sunnyvale, CA) treatment plans. The IDC framework uses an XML-format treatment plan as exported from the treatment planning system (TPS) and DICOM format patient CT data, an MC beam model using phase spaces, CyberKnife MLC beam modifier transport using the EGS++ class library, a beam sampling and coordinate transformation engine and dose scoring using DOSXYZnrc. The framework is validated against dose profiles and depth dose curves of single beams with varying field sizes in a water tank in units of cGy/Monitor Unit and against a 2D dose distribution of a full prostate treatment plan measured with Gafchromic EBT3 (Ashland Advanced Materials, Bridgewater, NJ) film in a homogeneous water-equivalent slab phantom. The film measurement is compared to IDC results by gamma analysis using 2% (global)/2 mm criteria. Further, the dose distribution of the clinical treatment plan in the patient CT is compared to TPS calculation by gamma analysis using the same criteria. Dose profiles from IDC calculation in a homogeneous water phantom agree within 2.3% of the global max dose or 1 mm distance to agreement to measurements for all except the smallest field size. Comparing the film measurement to calculated dose, 99.9% of all voxels pass gamma analysis, comparing dose calculated by the IDC framework to TPS calculated dose for the clinical prostate plan shows 99.0% passing rate. IDC calculated dose is found to be up to 5.6% lower than dose calculated by the TPS in this case near metal fiducial markers. An MC-based modular IDC framework was successfully developed, implemented and validated against measurements and is now available to perform patient-specific QA by IDC.

SU-F-T-402: The Effect of Extremely Narrow MLC Leaf Width On the Plan Quality of VMAT for Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, J; Park, S; Kim, J

2016-06-15

Purpose: To investigate the effect of multi-leaf collimators (MLCs) with leaf width of 1.25 mm on the plan quality of volumetric modulated arc therapy (VMAT) for prostate cancer. Methods: A total of 20 patients with prostate cancer were retrospectively selected. Using a high definition MLC (HD MLC), primary and boost VMAT plans with two full arcs were generated for each patient (original plan). After that, by shifting patient CT images by 1.25 mm in the cranio-caudal direction between the 1st and the 2nd arc, we simulated fluences made with MLCs with leaf width of 1.25 mm. After shifting, primary andmore » boost plans were generated for each patient (shifted plan). A sum plan was generated by summation of the primary and boost plan for each patient. Dose-volumetric parameters were calculated and compared. Results: Both homogeneity index (HI) and conformity index (CI) of the shifted plans were better than those of the original plans in primary plans (HI = 0.044 vs. 0.040 with p < 0.001 and CI = 1.056 vs. 1.044 with p = 0.006). Similarly, the shifted plans for boost target volume showed better homogeneity and conformity than did the original plans (HI = 0.042 vs. 0.037 with p = 0.006 and CI = 1.015 vs. 1.009 with p < 0.001). The total body volumes of the original plans irradiated by the prescription dose were larger than those of the shifted plans in sum plans (60.9 cc vs. 49.0 cc with p = 0.007). Conclusion: Use of extremely narrow MLCs could increase dose homogeneity and conformity of the target volume for prostate VMAT. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (No. 2015R1C1A1A02036331).« less

Improvement of VMAT plan quality for head and neck cancer with high resolution fluences generated by couch shift between arcs.

PubMed

Park, Jong Min; Park, So-Yeon; Wu, Hong-Gyun; Kim, Jung-In

2018-02-01

To investigate the changes in quality of the volumetric modulated arc therapy (VMAT) plans with couch-shift between arcs by half of a multi-leaf collimator (MLC) leaf width. A total of 22 patients with head-and-neck cancer were retrospectively selected. Since the smallest MLC leaf width was 5 mm in this study, the couch was shifted by 2.5 mm in the longitudinal-direction between arcs to increase the resolution of fluence map. A total of three types of VMAT plans were generated for each patient; the three types of plans were a two-full-arc plan without couch-shift (NS plan), a two-half-arc-pair plan with couch-shift (HAS plan), and a two-full-arc pair plan with couch-shift (FAS plan). Changes in the dose-volumetric parameters were investigated. The FAS plan showed the best plan quality for the target volumes and organs at risk compared to the NS and HAS plans. However, the magnitudes of differences among the three types of plans were minimal, and every plan was clinically acceptable. The average integral doses of the NS, HAS, and FAS plans were 160,549 ± 37,600 Gy-cc, 147,828 ± 33,343 Gy-cc, and 156,030 ± 36,263 Gy-cc, respectively. The average monitor unit of the NS, HAS, and FAS plans were 717 ± 120 MU, 648 ± 100 MU, and 763 ± 158 MU, respectively. The HAS plan was better than the others in terms of normal tissue sparing and plan efficiency. By shifting the couch by half of the MLC leaf width in the longitudinal direction between arcs, the VMAT plan quality could be improved. Copyright © 2018 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Magnolol inhibits migration of vascular smooth muscle cells via cytoskeletal remodeling pathway to attenuate neointima formation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Karki, Rajendra; Department of Oriental Medicine Resources, Mokpo National University; Kim, Seong-Bin

Background: Increased proliferation and migration of vascular smooth muscle cells (VSMCs) contribute importantly to the formation of both atherosclerotic and restenotic lesions. The objective of this study was to investigate the effect of magnolol on VSMC migration. Methods: The proteolytic activity of matrix metalloproteinases (MMPs) in tumor necrosis factor alpha (TNF-α) stimulated VSMCs was performed by gelatin zymography. VSMC migration was assessed by wound healing and Boyden chamber methods. Collagen induced VSMC adhesion was determined by spectrofluorimeter and stress fibers formation was evaluated by fluorescence microscope. The expression of signaling molecules involved in stress fibers formation was determined by westernmore » blot. The phosphorylation of myosin light chain (MLC20) was determined by urea-glycerol polyacrylamide gel electrophoresis. Immunohistochemistry was performed to determine the expression of β1-integrin and collagen type I in the injured carotid arteries of rats on day 35 after vascular injury. Results: VSMC migration was strongly inhibited by magnolol without affecting MMPs expression. Also, magnolol inhibited β1-integrin expression, FAK phosphorylation and RhoA and Cdc42 activation to inhibit the collagen induced stress fibers formation. Moreover, magnolol inhibited the phosphorylation of MLC20. Our in vivo results showed that magnolol inhibited β1-integrin expression, collagen type I deposition and FAK phosphorylation in injured carotid arteries without affecting MMP-2 activity. Conclusions: Magnolol inhibited VSMC migration via inhibition of cytoskeletal remodeling pathway to attenuate neointima formation. General significance: This study provides a rationale for further evaluation of magnolol for the management of atherosclerosis and restenosis. - Highlights: • Magnolol strongly inhibited migration of VSMCs. • Magnolol inhibited stress fibers formation. • MLC20 phosphorylation was also inhibited by magnolol. • Anti-migratory effect of magnolol was cytoskeletal dependent. • Magnolol inhibited β1-integrin and collagen expression in vivo.« less

Dosimetric effect of Elekta Beam Modulator micromultileaf in three-dimensional conformal radiotherapy and intensity-modulated radiotherapy for prostate cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Carosi, Alessandra, E-mail: alessandra.carosi@katamail.com; Ingrosso, Gianluca; Ponti, Elisabetta

2014-07-01

The purpose of this study is to analyze the dosimetric effect of Elekta Beam Modulator in 3-dimensional conformal radiation therapy (3DCRT) and in intensity-modulated radiation therapy (IMRT) for localized prostate cancer. We compared treatment plans developed with 2 different Elekta multileaf collimators (MLC): Beam Modulator micro-MLC (mMLC) (4-mm leaf width at the isocenter) and standard MLC (10-mm leaf width at the isocenter). The comparison was performed for 15 patients with localized prostate cancer in 3DCRT and IMRT delivery; a total of 60 treatment plans were processed. The dose-volume histograms were used to provide the quantitative comparison between plans. In particular,more » we analyzed differences between rectum and bladder sparing in terms of a set of appropriate Vx (percentage of organ at risk [OAR] volume receiving the x dose) and differences between target conformity and coverage in terms of coverage factor and conformation number. Our analysis demonstrates that in 3DCRT there is an advantage in the use of Elekta Beam Modulator mMLC in terms of organ sparing; in particular, a significant decrease in rectal V{sub 60} and V{sub 50} (p = 0.001) and in bladder V{sub 70} and V{sub 65} (p = 0.007 and 0.002, respectively) was found. Moreover, a better target dose conformity was obtained (p = 0.002). IMRT plans comparison demonstrated no significant differences between the use of the 4 or 10-mm MLCs. Our analysis shows that in 3DCRT the use of the Elekta Beam Modulator mMLC gives a gain in target conformity and in OARs dose sparing whereas in IMRT plans there is no advantage.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thiyagarajan, Rajesh; Karrthick, KP; Kataria, Tejinder

Purpose: Performing DQA for Bilateral (B-L) breast tomotherapy is a challenging task due to the limitation of any commercially available detector array or film. Aim of this study is to perform DQA for B-L breast tomotherapy plan using MLC fluence sinogram. Methods: Treatment plan was generated on Tomotherapy system for B-L breast tumour. B-L breast targets were given 50.4 Gy prescribed over 28 fractions. Plan is generated with 6 MV photon beam & pitch was set to 0.3. As the width of the total target is 39 cm (left & right) length is 20 cm. DQA plan delivered without anymore » phantom on the mega voltage computed tomography (MCVT) detector system. The pulses recorded by MVCT system were exported to the delivery analysis software (Tomotherapy Inc.) for reconstruction. The detector signals are reconstructed to a sonogram and converted to MLC fluence sonogram. The MLC fluence sinogram compared with the planned fluence sinogram. Also point dose measured with cheese phantom and ionization chamber to verify the absolute dose component Results: Planned fluence sinogram and reconstructed MLC fluence sinogram were compared using Gamma metric. MLC positional difference and intensity of the beamlet were used as parameters to evaluate gamma. 3 mm positional difference and 3% beamlet intensity difference were used set for gamma calculation. A total of 26784 non-zero beamlets were included in the analysis out of which 161 beamlets had gamma more than 1. The gamma passing rate found to be 99.4%. Point dose measurements were within 1.3% of the calculated dose. Conclusion: MLC fluence sinogram based delivery quality assurance performed for bilateral breast irradiation. This would be a suitable alternate for large volume targets like bilateral breast, Total body irradiation etc. However conventional method of DQA should be used to validate this method periodically.« less

Testing the Role of Meander Cutoff in Promoting Gene Flow across a Riverine Barrier in Ground Skinks (Scincella lateralis)

PubMed Central

Jackson, Nathan D.; Austin, Christopher C.

2013-01-01

Despite considerable attention, the long-term impact of rivers on species diversification remains uncertain. Meander loop cutoff (MLC) is one river phenomenon that may compromise a river’s diversifying effects by passively transferring organisms from one side of the river to the other. However, the ability of MLC to promote gene flow across rivers has not been demonstrated empirically. Here, we test several predictions of MLC-mediated gene flow in populations of North American ground skinks (Scincella lateralis) separated by a well-established riverine barrier, the Mississippi River: 1) individuals collected from within meander cutoffs should be more closely related to individuals across the river than on the same side, 2) individuals within meander cutoffs should contain more immigrants than individuals away from meander cutoffs, 3) immigration rates estimated across the river should be highest in the direction of the cutoff event, and 4) the distribution of alleles native to one side of the river should be better predicted by the historical rather than current path of the river. To test these predictions we sampled 13 microsatellite loci and mitochondrial DNA from ground skinks collected near three ancient meander loops. These predictions were generally supported by genetic data, although support was stronger for mtDNA than for microsatellite data. Partial support for genetic divergence of samples within ancient meander loops also provides evidence for the MLC hypothesis. Although a role for MLC-mediated gene flow was supported here for ground skinks, the transient nature of river channels and morphologies may limit the long-term importance of MLC in stemming population divergence across major rivers. PMID:23658778

Multi-floor cascading ferroelectric nanostructures: multiple data writing-based multi-level non-volatile memory devices.

PubMed

Hyun, Seung; Kwon, Owoong; Lee, Bom-Yi; Seol, Daehee; Park, Beomjin; Lee, Jae Yong; Lee, Ju Hyun; Kim, Yunseok; Kim, Jin Kon

2016-01-21

Multiple data writing-based multi-level non-volatile memory has gained strong attention for next-generation memory devices to quickly accommodate an extremely large number of data bits because it is capable of storing multiple data bits in a single memory cell at once. However, all previously reported devices have failed to store a large number of data bits due to the macroscale cell size and have not allowed fast access to the stored data due to slow single data writing. Here, we introduce a novel three-dimensional multi-floor cascading polymeric ferroelectric nanostructure, successfully operating as an individual cell. In one cell, each floor has its own piezoresponse and the piezoresponse of one floor can be modulated by the bias voltage applied to the other floor, which means simultaneously written data bits in both floors can be identified. This could achieve multi-level memory through a multiple data writing process.

Feasibility of using Geant4 Monte Carlo simulation for IMRT dose calculations for the Novalis Tx with a HD-120 multi-leaf collimator

NASA Astrophysics Data System (ADS)

Jung, Hyunuk; Shin, Jungsuk; Chung, Kwangzoo; Han, Youngyih; Kim, Jinsung; Choi, Doo Ho

2015-05-01

The aim of this study was to develop an independent dose verification system by using a Monte Carlo (MC) calculation method for intensity modulated radiation therapy (IMRT) conducted by using a Varian Novalis Tx (Varian Medical Systems, Palo Alto, CA, USA) equipped with a highdefinition multi-leaf collimator (HD-120 MLC). The Geant4 framework was used to implement a dose calculation system that accurately predicted the delivered dose. For this purpose, the Novalis Tx Linac head was modeled according to the specifications acquired from the manufacturer. Subsequently, MC simulations were performed by varying the mean energy, energy spread, and electron spot radius to determine optimum values of irradiation with 6-MV X-ray beams by using the Novalis Tx system. Computed percentage depth dose curves (PDDs) and lateral profiles were compared to the measurements obtained by using an ionization chamber (CC13). To validate the IMRT simulation by using the MC model we developed, we calculated a simple IMRT field and compared the result with the EBT3 film measurements in a water-equivalent solid phantom. Clinical cases, such as prostate cancer treatment plans, were then selected, and MC simulations were performed. The accuracy of the simulation was assessed against the EBT3 film measurements by using a gamma-index criterion. The optimal MC model parameters to specify the beam characteristics were a 6.8-MeV mean energy, a 0.5-MeV energy spread, and a 3-mm electron radius. The accuracy of these parameters was determined by comparison of MC simulations with measurements. The PDDs and the lateral profiles of the MC simulation deviated from the measurements by 1% and 2%, respectively, on average. The computed simple MLC fields agreed with the EBT3 measurements with a 95% passing rate with 3%/3-mm gamma-index criterion. Additionally, in applying our model to clinical IMRT plans, we found that the MC calculations and the EBT3 measurements agreed well with a passing rate of greater than 95% on average with a 3%/3-mm gamma-index criterion. In summary, the Novalis Tx Linac head equipped with a HD-120 MLC was successfully modeled by using a Geant4 platform, and the accuracy of the Geant4 platform was successfully validated by comparisons with measurements. The MC model we have developed can be a useful tool for pretreatment quality assurance of IMRT plans and for commissioning of radiotherapy treatment planning.

Multi-floor cascading ferroelectric nanostructures: multiple data writing-based multi-level non-volatile memory devices

NASA Astrophysics Data System (ADS)

Hyun, Seung; Kwon, Owoong; Lee, Bom-Yi; Seol, Daehee; Park, Beomjin; Lee, Jae Yong; Lee, Ju Hyun; Kim, Yunseok; Kim, Jin Kon

2016-01-01

Multiple data writing-based multi-level non-volatile memory has gained strong attention for next-generation memory devices to quickly accommodate an extremely large number of data bits because it is capable of storing multiple data bits in a single memory cell at once. However, all previously reported devices have failed to store a large number of data bits due to the macroscale cell size and have not allowed fast access to the stored data due to slow single data writing. Here, we introduce a novel three-dimensional multi-floor cascading polymeric ferroelectric nanostructure, successfully operating as an individual cell. In one cell, each floor has its own piezoresponse and the piezoresponse of one floor can be modulated by the bias voltage applied to the other floor, which means simultaneously written data bits in both floors can be identified. This could achieve multi-level memory through a multiple data writing process.Multiple data writing-based multi-level non-volatile memory has gained strong attention for next-generation memory devices to quickly accommodate an extremely large number of data bits because it is capable of storing multiple data bits in a single memory cell at once. However, all previously reported devices have failed to store a large number of data bits due to the macroscale cell size and have not allowed fast access to the stored data due to slow single data writing. Here, we introduce a novel three-dimensional multi-floor cascading polymeric ferroelectric nanostructure, successfully operating as an individual cell. In one cell, each floor has its own piezoresponse and the piezoresponse of one floor can be modulated by the bias voltage applied to the other floor, which means simultaneously written data bits in both floors can be identified. This could achieve multi-level memory through a multiple data writing process. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr07377d

NOTE: Reducing the number of segments in unidirectional MLC segmentations

NASA Astrophysics Data System (ADS)

Mellado, X.; Cruz, S.; Artacho, J. M.; Canellas, M.

2010-02-01

In intensity-modulated radiation therapy (IMRT), fluence matrices obtained from a treatment planning system are usually delivered by a linear accelerator equipped with a multileaf collimator (MLC). A segmentation method is needed for decomposing these fluence matrices into segments suitable for the MLC, and the number of segments used is an important factor for treatment time. In this work, an algorithm for reduction of the number of segments (NS) is presented for unidirectional segmentations, where there is no backtracking of the MLC leaves. It uses a geometrical representation of the segmentation output for searching the key values in a fluence matrix that complicate its decomposition. The NS reduction is achieved by performing minor modifications in these values, under the conditions of avoiding substantial modifications of the dose-volume histogram, and does not increase in average the total number of monitor units delivered. The proposed method was tested using two clinical cases planned with the PCRT 3D® treatment planning system.

SU-E-T-01: 2-D Characterization of DLG Among All MLC Leaf Pairs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kumaraswamy, L; Xu, Z; Podgorsak, M

Purpose: The aim of this study is to evaluate the variation of dosimetric leaf-gap (DLG) along the travel path of each MLC leaf pair. This study evaluates whether the spatial variations in DLG could cause dose differences between TPS-calculated and measured dose. Methods: The 6MV DLG values were measured for all leaf pairs in the direction of leaf motion using a 2-D diode array and 0.6cc ion chamber. These measurements were performed on two Varian Linacs, employing the Millennium 120-leaf MLC and a 2-D-DLG variation map was created via in-house software. Several test plans were created with sweeping MLC fieldsmore » using constant gaps from 2mm to 10mm and corrected for 2-D variation utilizing in-house software. Measurements were performed utilizing the MapCHECK at 5.0cm depth for plans with and without the 2-D DLG correction and compared to the TPS calculated dose via gamma analysis (3%/3mm). Results: The measured DLGs for the middle 40 MLC leaf pairs (0.5cm width) were very similar along the central superior-inferior axis, with maximum variation of 0.2mm. The outer 20 MLC leaf pairs (1.0cm width) have DLG values from 0.32mm (mean) to 0.65mm (maximum) lower than the central leaf-pair, depending on off-axis distance. Gamma pass rates for the 2mm, 4mm, and 6mm sweep plans increased by 23.2%, 28.7%, and 26.0% respectively using the 2-D-DLG correction. The most improved dose points occur in areas modulated by the 1.0cm leaf-pairs. The gamma pass rate for the 10mm sweep plan increased by only 7.7%, indicating that the 2D variation becomes less significant for dynamic plans with larger MLC gaps. Conclusion: Fluences residing significantly off-axis with narrow sweeping gaps may exhibit significant variations from planned dose due to large differences between the true DLG exhibited by the 1.0cm leaf-pairs versus the constant DLG value utilized by the TPS for dose calculation.« less

Identification of T. gondii Myosin Light Chain-1 as a Direct Target of TachypleginA-2, a Small-Molecule Inhibitor of Parasite Motility and Invasion

PubMed Central

Leung, Jacqueline M.; Tran, Fanny; Pathak, Ravindra B.; Poupart, Séverine; Heaslip, Aoife T.; Ballif, Bryan A.; Westwood, Nicholas J.; Ward, Gary E.

2014-01-01

Motility of the protozoan parasite Toxoplasma gondii plays an important role in the parasite’s life cycle and virulence within animal and human hosts. Motility is driven by a myosin motor complex that is highly conserved across the Phylum Apicomplexa. Two key components of this complex are the class XIV unconventional myosin, TgMyoA, and its associated light chain, TgMLC1. We previously showed that treatment of parasites with a small-molecule inhibitor of T. gondii invasion and motility, tachypleginA, induces an electrophoretic mobility shift of TgMLC1 that is associated with decreased myosin motor activity. However, the direct target(s) of tachypleginA and the molecular basis of the compound-induced TgMLC1 modification were unknown. We show here by “click” chemistry labelling that TgMLC1 is a direct and covalent target of an alkyne-derivatized analogue of tachypleginA. We also show that this analogue can covalently bind to model thiol substrates. The electrophoretic mobility shift induced by another structural analogue, tachypleginA-2, was associated with the formation of a 225.118 Da adduct on S57 and/or C58, and treatment with deuterated tachypleginA-2 confirmed that the adduct was derived from the compound itself. Recombinant TgMLC1 containing a C58S mutation (but not S57A) was refractory to click labelling and no longer exhibited a mobility shift in response to compound treatment, identifying C58 as the site of compound binding on TgMLC1. Finally, a knock-in parasite line expressing the C58S mutation showed decreased sensitivity to compound treatment in a quantitative 3D motility assay. These data strongly support a model in which tachypleginA and its analogues inhibit the motility of T. gondii by binding directly and covalently to C58 of TgMLC1, thereby causing a decrease in the activity of the parasite’s myosin motor. PMID:24892871

SU-G-BRB-03: Assessing the Sensitivity and False Positive Rate of the Integrated Quality Monitor (IQM) Large Area Ion Chamber to MLC Positioning Errors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boehnke, E McKenzie; DeMarco, J; Steers, J

2016-06-15

Purpose: To examine both the IQM’s sensitivity and false positive rate to varying MLC errors. By balancing these two characteristics, an optimal tolerance value can be derived. Methods: An un-modified SBRT Liver IMRT plan containing 7 fields was randomly selected as a representative clinical case. The active MLC positions for all fields were perturbed randomly from a square distribution of varying width (±1mm to ±5mm). These unmodified and modified plans were measured multiple times each by the IQM (a large area ion chamber mounted to a TrueBeam linac head). Measurements were analyzed relative to the initial, unmodified measurement. IQM readingsmore » are analyzed as a function of control points. In order to examine sensitivity to errors along a field’s delivery, each measured field was divided into 5 groups of control points, and the maximum error in each group was recorded. Since the plans have known errors, we compared how well the IQM is able to differentiate between unmodified and error plans. ROC curves and logistic regression were used to analyze this, independent of thresholds. Results: A likelihood-ratio Chi-square test showed that the IQM could significantly predict whether a plan had MLC errors, with the exception of the beginning and ending control points. Upon further examination, we determined there was ramp-up occurring at the beginning of delivery. Once the linac AFC was tuned, the subsequent measurements (relative to a new baseline) showed significant (p <0.005) abilities to predict MLC errors. Using the area under the curve, we show the IQM’s ability to detect errors increases with increasing MLC error (Spearman’s Rho=0.8056, p<0.0001). The optimal IQM count thresholds from the ROC curves are ±3%, ±2%, and ±7% for the beginning, middle 3, and end segments, respectively. Conclusion: The IQM has proven to be able to detect not only MLC errors, but also differences in beam tuning (ramp-up). Partially supported by the Susan Scott Foundation.« less

TU-AB-BRC-04: Commissioning of a New MLC Model for the GEPTS Monte Carlo System: A Model Based On the Leaf and Interleaf Effective Density

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chibani, O; Tahanout, F; Ma, C

2016-06-15

Purpose: To commission a new MLC model for the GEPTS Monte Carlo system. The model is based on the concept of leaves and interleaves effective densities Methods: GEPTS is a Monte Carlo system to be used for external beam planning verification. GEPTS incorporates detailed photon and electron transport algorithms (Med.Phys. 29, 2002, 835). A new GEPTS model for the Varian Millennium MLC is presented. The model accounts for: 1) thick (1 cm) and thin (0.5 cm) leaves, 2) tongue-and-groove design, 3) High-Transmission (HT) and Low-Transmission (LT) interleaves, and 4) rounded leaf end. Leaf (and interleaf) height is set equal tomore » 6 cm. Instead of modeling air gaps, screw holes, and complex leaf heads, “effective densities” are assigned to: 1) thin leaves, 2) thick leaves, 3) HT-, and 4) LT-interleaves. Results: The new MLC model is used to calculate dose profiles for Closed-MLC and Tongue-and-Groove fields at 5 cm depth for 6, 10 and 15 MV Varian beams. Calculations are compared with 1) Pin-point ionization chamber transmission ratios and 2) EBT3 Radiochromic films. Pinpoint readings were acquired beneath thick and thin leaves, and HT and LT interleaves. The best fit of measured dose profiles was obtained for the following parameters: Thick-leaf density = 16.1 g/cc, Thin-leaf density = 17.2 g/cc; HT Interleaf density = 12.4 g/cc, LT Interleaf density = 14.3 g/cc; Interleaf thickness = 1.1 mm. Attached figures show comparison of calculated and measured transmission ratios for the 3 energies. Note this is the only study where transmission profiles are compared with measurements for 3 different energies. Conclusion: The new MLC model reproduces transmission measurements within 0.1%. The next step is to implement the MLC model for real plans and quantify the improvement in dose calculation accuracy gained using this model for IMRT plans with high modulation factors.« less

SU-G-TeP4-03: A Multileaf Collimator Calibration and Quality Assurance Technique Using An Electronic Portal Imaging Device

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lebron, S; Yan, G; Li, J

2016-06-15

Purpose: To develop an accurate and quick multileaf collimator (MLC) calibration and quality assurance technique using an electronic portal imaging device (EPID) Methods: The MLC models used include the MLCi and Agility (Elekta Ltd). This technique consists of two 22(L)x10(W) cm{sup 2} fields with 0{sup 0} and 180{sup 0} collimator angles centered to an offset EPID. The MLC opening is estimated by calculating the profile at the image’s center in the image’s horizontal direction. Scans in the image’s vertical direction were calculated every 20 pixels in the inner 70% of estimated MLC opening. The profiles’ edges were fitted with linearmore » equations to determine the image’s rotation angle. Then, crossline profiles were scanned at the center of each leaf taking into account the leaf’s width at isocenter and the rotation angle. The profiles’ edges determine the location of the leaves’ edges and these were subtracted from the reference leaf’s position in order to determine the relative leaf offsets. The edge location of all profiles was determined by using the parameterized gradient of the penumbra region. The technique was tested against an established diode array-based method, and for different MLC systems, patterns, gantry angles, days, energies, beam modalities and MLC openings. Results: The differences between the proposed and established methods were 0.26±0.19mm. The leaf offsets’ deviation was <0.3mm (5 months period). For pattern fields, the differences between predetermined and calculated offsets were 0.18±0.18mm. The leaf offset deviation of measurements with different energies and MLC openings were <0.1mm and <0.3mm, respectively. The differences between offsets of FF and FFF beams were 0.01±0.02mm (<0.07mm). The differences between the offsets at different gantry angles were 0.08±0.15mm. Conclusion: The proposed method proved to be accurate and efficient in calculating the relative leaf offsets. Parameterized field edge is essential to obtain accurate result by eliminating the noise from EPID.« less

Tolerability to prolonged lifting tasks. A validation of the recommended limits.

PubMed

Capodaglio, P; Bazzini, G

1997-01-01

Prolonged physical exertion is subjectively regulated by the perception of effort. This preliminary study was conducted to validate the use of subjective perceptions of effort in assessing objectively tolerable workloads for prolonged lifting tasks. Ten healthy male subjects tested their maximal lifting capacity (MLC) on a lift dynamometer (LidoLift, Loredan Biomed., West Sacramento, CA) and underwent incremental and 30-minute endurance lifting tests. Cardiorespiratory parameters were monitored with an oxygen uptake analyzer, mechanical parameters were calculated using a computerized dynamometer. Ratings of perceived exertion were given on Borg's 10-point scale. Physiological responses to repetitive lifting were matched with subjective perceptions. A single-variable statistical regression for power functions was performed to obtain the individual "iso-perception" curves as functions of the mechanical work exerted. We found that the "iso-perception" curve corresponding to a "moderate" perception of effort may represent the individual "tolerance threshold" for prolonged lifting tasks, since physiological responses at this level of intensity did not change significantly and the respiratory exchange ratio was less than one. The individually tolerable weight for lifting tasks lasting 30 min has been expressed as a percentage of the isoinertial MLC value and compared with the currently recommended limits for prolonged lifting tasks (Italian legislation D.L. 626/94). On the basis of our preliminary results a "tolerance threshold" of 20% MLC has been proposed for prolonged lifting tasks.

High Throughput Sequencing Identifies Misregulated Genes in the Drosophila Polypyrimidine Tract-Binding Protein (hephaestus) Mutant Defective in Spermatogenesis.

PubMed

Sridharan, Vinod; Heimiller, Joseph; Robida, Mark D; Singh, Ravinder

2016-01-01

The Drosophila polypyrimidine tract-binding protein (dmPTB or hephaestus) plays an important role during spermatogenesis. The heph2 mutation in this gene results in a specific defect in spermatogenesis, causing aberrant spermatid individualization and male sterility. However, the array of molecular defects in the mutant remains uncharacterized. Using an unbiased high throughput sequencing approach, we have identified transcripts that are misregulated in this mutant. Aberrant transcripts show altered expression levels, exon skipping, and alternative 5' ends. We independently verified these findings by reverse-transcription and polymerase chain reaction (RT-PCR) analysis. Our analysis shows misregulation of transcripts that have been connected to spermatogenesis, including components of the actomyosin cytoskeletal apparatus. We show, for example, that the Myosin light chain 1 (Mlc1) transcript is aberrantly spliced. Furthermore, bioinformatics analysis reveals that Mlc1 contains a high affinity binding site(s) for dmPTB and that the site is conserved in many Drosophila species. We discuss that Mlc1 and other components of the actomyosin cytoskeletal apparatus offer important molecular links between the loss of dmPTB function and the observed developmental defect in spermatogenesis. This study provides the first comprehensive list of genes misregulated in vivo in the heph2 mutant in Drosophila and offers insight into the role of dmPTB during spermatogenesis.

Potential of discrete Gaussian edge feathering method for improving abutment dosimetry in eMLC-delivered segmented-field electron conformal therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eley, John G.; Hogstrom, Kenneth R.; Matthews, Kenneth L.

2011-12-15

Purpose: The purpose of this work was to investigate the potential of discrete Gaussian edge feathering of the higher energy electron fields for improving abutment dosimetry in the planning volume when using an electron multileaf collimator (eMLC) to deliver segmented-field electron conformal therapy (ECT). Methods: A discrete (five-step) Gaussian edge spread function was used to match dose penumbras of differing beam energies (6-20 MeV) at a specified depth in a water phantom. Software was developed to define the leaf eMLC positions of an eMLC that most closely fit each electron field shape. The effect of 1D edge feathering of themore » higher energy field on dose homogeneity was computed and measured for segmented-field ECT treatment plans for three 2D PTVs in a water phantom, i.e., depth from the water surface to the distal PTV surface varied as a function of the x-axis (parallel to leaf motion) and remained constant along the y-axis (perpendicular to leaf motion). Additionally, the effect of 2D edge feathering was computed and measured for one radially symmetric, 3D PTV in a water phantom, i.e., depth from the water surface to the distal PTV surface varied as a function of both axes. For the 3D PTV, the feathering scheme was evaluated for 0.1-1.0-cm leaf widths. Dose calculations were performed using the pencil beam dose algorithm in the Pinnacle{sup 3} treatment planning system. Dose verification measurements were made using a prototype eMLC (1-cm leaf width). Results: 1D discrete Gaussian edge feathering reduced the standard deviation of dose in the 2D PTVs by 34, 34, and 39%. In the 3D PTV, the broad leaf width (1 cm) of the eMLC hindered the 2D application of the feathering solution to the 3D PTV, and the standard deviation of dose increased by 10%. However, 2D discrete Gaussian edge feathering with simulated eMLC leaf widths of 0.1-0.5 cm reduced the standard deviation of dose in the 3D PTV by 33-28%, respectively. Conclusions: A five-step discrete Gaussian edge spread function applied in 2D improves the abutment dosimetry but requires an eMLC leaf resolution better than 1 cm.« less

Matching extended-SSD electron beams to multileaf collimated photon beams in the treatment of head and neck cancer.

PubMed

Steel, Jared; Stewart, Allan; Satory, Philip

2009-09-01

Matching the penumbra of a 6 MeV electron beam to the penumbra of a 6 MV photon beam is a dose optimization challenge, especially when the electron beam is applied from an extended source-to-surface distance (SSD), as in the case of some head and neck treatments. Traditionally low melting point alloy blocks have been used to define the photon beam shielding over the spinal cord region. However, these are inherently time consuming to construct and employ in the clinical situation. Multileaf collimators (MLCs) provide a fast and reproducible shielding option but generate geometrically nonconformal approximations to the desired beam edge definition. The effects of substituting Cerrobend for the MLC shielding mode in the context of beam matching with extended-SSD electron beams are the subject of this investigation. Relative dose beam data from a Varian EX 2100 linear accelerator were acquired in a water tank under the 6 MeV electron beam at both standard and extended-SSD and under the 6 MV photon beam defined by Cerrobend and a number of MLC stepping regimes. The effect of increasing the electron beam SSD on the beam penumbra was assessed. MLC stepping was also assessed in terms of the effects on both the mean photon beam penumbra and the intraleaf dose-profile nonuniformity relative to the MLC midleaf. Computational techniques were used to combine the beam data so as to simulate composite relative dosimetry in the water tank, allowing fine control of beam abutment gap variation. Idealized volumetric dosimetry was generated based on the percentage depth-dose data for the beam modes and the abutment geometries involved. Comparison was made between each composite dosimetry dataset and the relevant ideal dosimetry dataset by way of subtraction. Weighted dose-difference volume histograms (DDVHs) were produced, and these, in turn, summed to provide an overall dosimetry score for each abutment and shielding type/angle combination. Increasing the electron beam SSD increased the penumbra width (defined as the lateral distance of the 80% and 20% isodose contours) by 8-10 mm at the depths of 10-20 mm. Mean photon beam penumbra width increased with increased MLC stepping, and the mean MLC penumbra was approximately 1.5 times greater than that across the corresponding Cerrobend shielding. Intraleaf dose discrepancy in the direction orthogonal to the beam edge also increased with MLC stepping. The weighted DDVH comparison techniques allowed the composite dosimetry resulting from the interplay of the abovementioned variables to be ranked. The MLC dosimetry ranked as good or better than that resulting from beam matching with Cerrobend for all except large field overlaps (-2.5 mm gap). The results for the linear-weighted DDVH comparison suggest that optimal MLC abutment dosimetry results from an optical surface gap of around 1 +/- 0.5 mm. Furthermore, this appears reasonably lenient to abutment gap variation, such as that arising from uncertainty in beam markup or other setup errors.

Immortalization of cat iris sphincter smooth muscle cells by SV40 virus: growth, morphological, biochemical and pharmacological characteristics.

PubMed

Ocklind, A; Yousufzai, S Y; Ghosh, S; Coca-Prados, M; St Jernschantz, J; Abdel-Latif, A A

1995-11-01

The purpose of this study was to establish immortalized cell cultures of cat iris sphincter smooth muscle cells for a model investigating ocular receptors and their signal transduction pathways. Cultured cat iris sphincter muscle cells were immortalized by viral transformation with SV40 virus and the morphological and immunocytochemical properties of the normal and immortalized cells were investigated. The transformed cell clone, SV-CISM-2, was further characterized biochemically and pharmacologically. The normal muscle cells showed characteristics of smooth muscle cells, as judged by their growth and the presence of smooth muscle alpha-actin and desmin. After seven passages the normal cells ceased to proliferate. In contrast, the immortalized cells retained their proliferative ability for more than 220 population doublings over 55 passages. The transformation phenotype in these cells was confirmed by their expression of the large T-antigen, the incorporation of viral DNA into cellular DNA, growth in agarose and in low-serum medium, and complete loss of contact inhibition. The immortalized cells expressed smooth muscle alpha-actin, desmin and MLC protein. Biochemical and pharmacological studies on the SV-CISM cells revealed the presence of several functional receptors including muscarinic cholinergic, beta-adrenergic, peptidergic (substance P and endothelin). Platelet-activating factor, and prostaglandin (PG). Muscarinic stimulation of these cells resulted in: (a) a dose-dependent increase in the release of arachidonic acid (AA) and (PGs) and enhancement in the production of inositol trisphosphate (IP3); and (b) a substantial increase in MLC phosphorylation (118%), an indicator of smooth muscle contractility. The stimulatory effects of carbachol on these responses were completely blocked by atropine, a muscarinic receptor antagonist. This study constitutes the first successful immortalization of iris sphincter smooth muscle cells. The SV-CISM-2 cells can serve as an important model system for investigations on the biochemical and pharmacological properties of receptors and their signal transduction pathways in smooth muscle. The advantage of these cells over normal iris sphincter cells is that they can be propagated over many generations without alterations in their morphological, biochemical and physiological characteristics.

Inhibition of Cardiomyocytes Differentiation of Mouse Embryonic Stem Cells by CD38/cADPR/Ca2+ Signaling Pathway*

PubMed Central

Wei, Wen-Jie; Sun, Hai-Ying; Ting, Kai Yiu; Zhang, Li-He; Lee, Hon-Cheung; Li, Gui-Rong; Yue, Jianbo

2012-01-01

Cyclic adenosine diphosphoribose (cADPR) is an endogenous Ca2+ mobilizing messenger that is formed by ADP-ribosyl cyclases from nicotinamide adenine dinucleotide (NAD). The main ADP-ribosyl cyclase in mammals is CD38, a multi-functional enzyme and a type II membrane protein. Here we explored the role of CD38-cADPR-Ca2+ in the cardiomyogenesis of mouse embryonic stem (ES) cells. We found that the mouse ES cells are responsive to cADPR and possess the key components of the cADPR signaling pathway. In vitro cardiomyocyte (CM) differentiation of mouse ES cells was initiated by embryoid body (EB) formation. Interestingly, beating cells appeared earlier and were more abundant in CD38 knockdown EBs than in control EBs. Real-time RT-PCR and Western blot analyses further showed that the expression of several cardiac markers, including GATA4, MEF2C, NKX2.5, and α-MLC, were increased markedly in CD38 knockdown EBs than those in control EBs. Similarly, FACS analysis showed that more cardiac Troponin T-positive CMs existed in CD38 knockdown or 8-Br-cADPR, a cADPR antagonist, treated EBs compared with that in control EBs. On the other hand, overexpression of CD38 in mouse ES cells significantly inhibited CM differentiation. Moreover, CD38 knockdown ES cell-derived CMs possess the functional properties characteristic of normal ES cell-derived CMs. Last, we showed that the CD38-cADPR pathway negatively modulated the FGF4-Erks1/2 cascade during CM differentiation of ES cells, and transiently inhibition of Erk1/2 blocked the enhanced effects of CD38 knockdown on the differentiation of CM from ES cells. Taken together, our data indicate that the CD38-cADPR-Ca2+ signaling pathway antagonizes the CM differentiation of mouse ES cells. PMID:22908234

Methods for quantitative measurement of tooth wear using the area and volume of virtual model cusps

PubMed Central

2018-01-01

Purpose Clinicians must examine tooth wear to make a proper diagnosis. However, qualitative methods of measuring tooth wear have many disadvantages. Therefore, this study aimed to develop and evaluate quantitative parameters using the cusp area and volume of virtual dental models. Methods The subjects of this study were the same virtual models that were used in our former study. The same age group classification and new tooth wear index (NTWI) scoring system were also reused. A virtual occlusal plane was generated with the highest cusp points and lowered vertically from 0.2 to 0.8 mm to create offset planes. The area and volume of each cusp was then measured and added together. In addition to the former analysis, the differential features of each cusp were analyzed. Results The scores of the new parameters differentiated the age and NTWI groups better than those analyzed in the former study. The Spearman ρ coefficients between the total area and the area of each cusp also showed higher scores at the levels of 0.6 mm (0.6A) and 0.8A. The mesiolingual cusp (MLC) showed a statistically significant difference (P<0.01) from the other cusps in the paired t-test. Additionally, the MLC exhibited the highest percentage of change at 0.6A in some age and NTWI groups. Regarding the age groups, the MLC showed the highest score in groups 1 and 2. For the NTWI groups, the MLC was not significantly different in groups 3 and 4. These results support the proposal that the lingual cusp exhibits rapid wear because it serves as a functional cusp. Conclusions Although this study has limitations due to its cross-sectional nature, it suggests better quantitative parameters and analytical tools for the characteristics of cusp wear. PMID:29770241

MO-H-19A-02: Investigation of Modulated Electron Arc (MeArc) Therapy for the Treatment of Scalp Tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eldib, A; Al-Azhar University, Cairo; Jin, L

2014-06-15

Purpose: Electron arc therapy has long been proposed as the most suitable technique for the treatment of superficial tumors that follow circularly curved surfaces. However it was challenged by unsuitability of the conventional applicators and the lack of adequate 3-D dose calculation tools for arc electron beams in the treatment planning systems (TPS). Now with the availability of an electron specific multi-leaf collimator (eMLC) and an in-house Monte Carlo (MC) based TPS, we were motivated to investigate more advanced modulated electron arc (MeARC) therapy and its beneficial outcome. Methods: We initiated the study by a film measurement conducted in amore » head and neck phantom, where we delivered electron arcs in a step and shoot manner using the light field as a guide to avoid fields abutments. This step was done to insure enough clearance for the arcs with eMLC. MCBEAM and MCPLAN MC codes were used for the treatment head simulation and phantom dose calculation, respectively. Treatment plans were generated for targets drawn in real patient CTs and head and neck phantom. We utilized beams eye view available from a commercial planning system to create beamlets having same isocenter and adjoined at the scalp surface. Then dose-deposition coefficients from those beamlets were calculated for all electron energies using MCPLAN. An in-house optimization code was then used to find the optimum weights needed from individual beamlets. Results: MeARC showed a nicely tailored dose distribution around the circular curved target on the scalp. Some hot spots were noticed and could be attributed to fields abutment problem owing to the bulging nature of electron profiles. Brain dose was shown to be at lower levels compared to photon treatment. Conclusion: MeARC was shown to be a promising modality for treating scalp cases and could be beneficial to all superficial tumors with a circular curvature.« less

Involvement of Rictor/mTORC2 in cardiomyocyte differentiation of mouse embryonic stem cells in vitro

PubMed Central

Zheng, Bei; Wang, Jiadan; Tang, Leilei; Tan, Chao; Zhao, Zhe; Xiao, Yi; Ge, Renshan; Zhu, Danyan

2017-01-01

Rictor is a key regulatory/structural subunit of the mammalian target of rapamycin complex 2 (mTORC2) and is required for phosphorylation of Akt at serine 473. It plays an important role in cell survival, actin cytoskeleton organization and other processes in embryogenesis. However, the role of Rictor/mTORC2 in the embryonic cardiac differentiation has been uncovered. In the present study, we examined a possible link between Rictor expression and cardiomyocyte differentiation of the mouse embryonic stem (mES) cells. Knockdown of Rictor by shRNA significantly reduced the phosphorylation of Akt at serine 473 followed by a decrease in cardiomyocyte differentiation detected by beating embryoid bodies. The protein levels of brachyury (mesoderm protein), Nkx2.5 (cardiac progenitor cell protein) and α-Actinin (cardiomyocyte biomarker) decreased in Rictor knockdown group during cardiogenesis. Furthermore, knockdown of Rictor specifically inhibited the ventricular-like cells differentiation of mES cells with reduced level of ventricular-specific protein, MLC-2v. Meanwhile, patch-clamp analysis revealed that shRNA-Rictor significantly increased the number of cardiomyocytes with abnormal electrophysiology. In addition, the expressions and distribution patterns of cell-cell junction proteins (Cx43/Desmoplakin/N-cadherin) were also affected in shRNA-Rictor cardiomyocytes. Taken together, the results demonstrated that Rictor/mTORC2 might play an important role in the cardiomyocyte differentiation of mES cells. Knockdown of Rictor resulted in inhibiting ventricular-like myocytes differentiation and induced arrhythmias symptom, which was accompanied by interfering the expression and distribution patterns of cell-cell junction proteins. Rictor/mTORC2 might become a new target for regulating cardiomyocyte differentiation and a useful reference for application of the induced pluripotent stem cells. PMID:28123351

Assessment of Classification Accuracies of SENTINEL-2 and LANDSAT-8 Data for Land Cover / Use Mapping

NASA Astrophysics Data System (ADS)

Hale Topaloğlu, Raziye; Sertel, Elif; Musaoğlu, Nebiye

2016-06-01

This study aims to compare classification accuracies of land cover/use maps created from Sentinel-2 and Landsat-8 data. Istanbul metropolitan city of Turkey, with a population of around 14 million, having different landscape characteristics was selected as study area. Water, forest, agricultural areas, grasslands, transport network, urban, airport- industrial units and barren land- mine land cover/use classes adapted from CORINE nomenclature were used as main land cover/use classes to identify. To fulfil the aims of this research, recently acquired dated 08/02/2016 Sentinel-2 and dated 22/02/2016 Landsat-8 images of Istanbul were obtained and image pre-processing steps like atmospheric and geometric correction were employed. Both Sentinel-2 and Landsat-8 images were resampled to 30m pixel size after geometric correction and similar spectral bands for both satellites were selected to create a similar base for these multi-sensor data. Maximum Likelihood (MLC) and Support Vector Machine (SVM) supervised classification methods were applied to both data sets to accurately identify eight different land cover/ use classes. Error matrix was created using same reference points for Sentinel-2 and Landsat-8 classifications. After the classification accuracy, results were compared to find out the best approach to create current land cover/use map of the region. The results of MLC and SVM classification methods were compared for both images.

Towards real-time VMAT verification using a prototype, high-speed CMOS active pixel sensor.

PubMed

Zin, Hafiz M; Harris, Emma J; Osmond, John P F; Allinson, Nigel M; Evans, Philip M

2013-05-21

This work investigates the feasibility of using a prototype complementary metal oxide semiconductor active pixel sensor (CMOS APS) for real-time verification of volumetric modulated arc therapy (VMAT) treatment. The prototype CMOS APS used region of interest read out on the chip to allow fast imaging of up to 403.6 frames per second (f/s). The sensor was made larger (5.4 cm × 5.4 cm) using recent advances in photolithographic technique but retains fast imaging speed with the sensor's regional read out. There is a paradigm shift in radiotherapy treatment verification with the advent of advanced treatment techniques such as VMAT. This work has demonstrated that the APS can track multi leaf collimator (MLC) leaves moving at 18 mm s(-1) with an automatic edge tracking algorithm at accuracy better than 1.0 mm even at the fastest imaging speed. Evaluation of the measured fluence distribution for an example VMAT delivery sampled at 50.4 f/s was shown to agree well with the planned fluence distribution, with an average gamma pass rate of 96% at 3%/3 mm. The MLC leaves motion and linac pulse rate variation delivered throughout the VMAT treatment can also be measured. The results demonstrate the potential of CMOS APS technology as a real-time radiotherapy dosimeter for delivery of complex treatments such as VMAT.

Modulation indices for volumetric modulated arc therapy.

PubMed

Park, Jong Min; Park, So-Yeon; Kim, Hyoungnyoun; Kim, Jin Ho; Carlson, Joel; Ye, Sung-Joon

2014-12-07

The aim of this study is to present a modulation index (MI) for volumetric modulated arc therapy (VMAT) based on the speed and acceleration analysis of modulating-parameters such as multi-leaf collimator (MLC) movements, gantry rotation and dose-rate, comprehensively. The performance of the presented MI (MIt) was evaluated with correlation analyses to the pre-treatment quality assurance (QA) results, differences in modulating-parameters between VMAT plans versus dynamic log files, and differences in dose-volumetric parameters between VMAT plans versus reconstructed plans using dynamic log files. For comparison, the same correlation analyses were performed for the previously suggested modulation complexity score (MCS(v)), leaf travel modulation complexity score (LTMCS) and MI by Li and Xing (MI Li&Xing). In the two-tailed unpaired parameter condition, p values were acquired. The Spearman's rho (r(s)) values of MIt, MCSv, LTMCS and MI Li&Xing to the local gamma passing rate with 2%/2 mm criterion were -0.658 (p < 0.001), 0.186 (p = 0.251), 0.312 (p = 0.05) and -0.455 (p = 0.003), respectively. The values of rs to the modulating-parameter (MLC positions) differences were 0.917, -0.635, -0.857 and 0.795, respectively (p < 0.001). For dose-volumetric parameters, MIt showed higher statistically significant correlations than the conventional MIs. The MIt showed good performance for the evaluation of the modulation-degree of VMAT plans.

A real-time dynamic-MLC control algorithm for delivering IMRT to targets undergoing 2D rigid motion in the beam's eye view.

PubMed

McMahon, Ryan; Berbeco, Ross; Nishioka, Seiko; Ishikawa, Masayori; Papiez, Lech

2008-09-01

An MLC control algorithm for delivering intensity modulated radiation therapy (IMRT) to targets that are undergoing two-dimensional (2D) rigid motion in the beam's eye view (BEV) is presented. The goal of this method is to deliver 3D-derived fluence maps over a moving patient anatomy. Target motion measured prior to delivery is first used to design a set of planned dynamic-MLC (DMLC) sliding-window leaf trajectories. During actual delivery, the algorithm relies on real-time feedback to compensate for target motion that does not agree with the motion measured during planning. The methodology is based on an existing one-dimensional (ID) algorithm that uses on-the-fly intensity calculations to appropriately adjust the DMLC leaf trajectories in real-time during exposure delivery [McMahon et al., Med. Phys. 34, 3211-3223 (2007)]. To extend the 1D algorithm's application to 2D target motion, a real-time leaf-pair shifting mechanism has been developed. Target motion that is orthogonal to leaf travel is tracked by appropriately shifting the positions of all MLC leaves. The performance of the tracking algorithm was tested for a single beam of a fractionated IMRT treatment, using a clinically derived intensity profile and a 2D target trajectory based on measured patient data. Comparisons were made between 2D tracking, 1D tracking, and no tracking. The impact of the tracking lag time and the frequency of real-time imaging were investigated. A study of the dependence of the algorithm's performance on the level of agreement between the motion measured during planning and delivery was also included. Results demonstrated that tracking both components of the 2D motion (i.e., parallel and orthogonal to leaf travel) results in delivered fluence profiles that are superior to those that track the component of motion that is parallel to leaf travel alone. Tracking lag time effects may lead to relatively large intensity delivery errors compared to the other sources of error investigated. However, the algorithm presented is robust in the sense that it does not rely on a high level of agreement between the target motion measured during treatment planning and delivery.

Gα12 facilitates shortening in human airway smooth muscle by modulating phosphoinositide 3-kinase-mediated activation in a RhoA-dependent manner.

PubMed

Yoo, Edwin J; Cao, Gaoyuan; Koziol-White, Cynthia J; Ojiaku, Christie A; Sunder, Krishna; Jude, Joseph A; Michael, James V; Lam, Hong; Pushkarsky, Ivan; Damoiseaux, Robert; Di Carlo, Dino; Ahn, Kwangmi; An, Steven S; Penn, Raymond B; Panettieri, Reynold A

2017-12-01

PI3K-dependent activation of Rho kinase (ROCK) is necessary for agonist-induced human airway smooth muscle cell (HASMC) contraction, and inhibition of PI3K promotes bronchodilation of human small airways. The mechanisms driving agonist-mediated PI3K/ROCK axis activation, however, remain unclear. Given that G 12 family proteins activate ROCK pathways in other cell types, their role in M 3 muscarinic acetylcholine receptor-stimulated PI3K/ROCK activation and contraction was examined. Gα 12 coupling was evaluated using co-immunoprecipitation and serum response element (SRE)-luciferase reporter assays. siRNA and pharmacological approaches, as well as overexpression of a regulator of G-protein signaling (RGS) proteins were applied in HASMCs. Phosphorylation levels of Akt, myosin phosphatase targeting subunit-1 (MYPT1), and myosin light chain-20 (MLC) were measured. Contraction and shortening were evaluated using magnetic twisting cytometry (MTC) and micro-pattern deformation, respectively. Human precision-cut lung slices (hPCLS) were utilized to evaluate bronchoconstriction. Knockdown of M 3 receptors or Gα 12 attenuated activation of Akt, MYPT1, and MLC phosphorylation. Gα 12 coimmunoprecipitated with M 3 receptors, and p115RhoGEF-RGS overexpression inhibited carbachol-mediated induction of SRE-luciferase reporter. p115RhoGEF-RGS overexpression inhibited carbachol-induced activation of Akt, HASMC contraction, and shortening. Moreover, inhibition of RhoA blunted activation of PI3K. Lastly, RhoA inhibitors induced dilation of hPCLS. Gα 12 plays a crucial role in HASMC contraction via RhoA-dependent activation of the PI3K/ROCK axis. Inhibition of RhoA activation induces bronchodilation in hPCLS, and targeting Gα 12 signaling may elucidate novel therapeutic targets in asthma. These findings provide alternative approaches to the clinical management of airway obstruction in asthma. © 2017 The British Pharmacological Society.

Dosimetric evaluation of the clinical implementation of the first commercial IMRT Monte Carlo treatment planning system at 6 MV

DOE Office of Scientific and Technical Information (OSTI.GOV)

Heath, Emily; Seuntjens, Jan; Sheikh-Bagheri, Daryoush

2004-10-01

In this work we dosimetrically evaluated the clinical implementation of a commercial Monte Carlo treatment planning software (PEREGRINE, North American Scientific, Cranberry Township, PA) intended for quality assurance (QA) of intensity modulated radiation therapy treatment plans. Dose profiles calculated in homogeneous and heterogeneous phantoms using this system were compared to both measurements and simulations using the EGSnrc Monte Carlo code for the 6 MV beam of a Varian CL21EX linear accelerator. For simple jaw-defined fields, calculations agree within 2% of the dose at d{sub max} with measurements in homogeneous phantoms with the exception of the buildup region where the calculationsmore » overestimate the dose by up to 8%. In heterogeneous lung and bone phantoms the agreement is within 3%, on average, up to 5% for a 1x1 cm{sup 2} field. We tested two consecutive implementations of the MLC model. After matching the calculated and measured MLC leakage, simulations of static and dynamic MLC-defined fields using the most recent MLC model agreed to within 2% with measurements.« less

Experimental verification of a Monte Carlo-based MLC simulation model for IMRT dose calculations in heterogeneous media

NASA Astrophysics Data System (ADS)

Tyagi, N.; Curran, B. H.; Roberson, P. L.; Moran, J. M.; Acosta, E.; Fraass, B. A.

2008-02-01

IMRT often requires delivering small fields which may suffer from electronic disequilibrium effects. The presence of heterogeneities, particularly low-density tissues in patients, complicates such situations. In this study, we report on verification of the DPM MC code for IMRT treatment planning in heterogeneous media, using a previously developed model of the Varian 120-leaf MLC. The purpose of this study is twofold: (a) design a comprehensive list of experiments in heterogeneous media for verification of any dose calculation algorithm and (b) verify our MLC model in these heterogeneous type geometries that mimic an actual patient geometry for IMRT treatment. The measurements have been done using an IMRT head and neck phantom (CIRS phantom) and slab phantom geometries. Verification of the MLC model has been carried out using point doses measured with an A14 slim line (SL) ion chamber inside a tissue-equivalent and a bone-equivalent material using the CIRS phantom. Planar doses using lung and bone equivalent slabs have been measured and compared using EDR films (Kodak, Rochester, NY).

Reduction of oxidative stress in liver cancer patients by oral green tea polyphenol tablets during hepatic arterial infusion chemotherapy

PubMed Central

BABA, YASUTAKA; SONODA, JUN-ICHIRO; HAYASHI, SADAO; TOSUJI, NANAKO; SONODA, SHUNRO; MAKISUMI, KANRO; NAKAJO, MASAYUKI

2012-01-01

Hepatic arterial infusion chemotherapy (HAI) using an implanted port system is the standard regimen for primary and metastatic liver cancers (MLCs). However, there have been few studies concerning HAI-induced oxidative stress and damage to the liver or other organs. The aim of the present study was to investigate the ability of green tea polyphenols (GTPs) to reduce the oxidative stress or increase the biological antioxidative potential in HAI-treated patients. A total of 19 patients with inoperable hepatocellular carcinoma (HCC) or MLC from colorectal malignancy were eligible for HAI with cisplatin (CDDP) and 5-fluorouracil (5FU). The study subjects were randomly assigned to either a 3 or a 6 oral GTP tablets per day group. Each tablet had a GTP content equivalent to 79 mg of epigallocatechin-3-gallate. The oxidative stress was assessed by measuring the levels of derivatives of reactive oxygen metabolites (d-ROMs) and the biological antioxidative potential (BAP) values in patient plasma using the Free Radical Analytical System 4 (FRAS4), and correlating the results with clinical laboratory data for the patients. The levels of d-ROMs were significantly reduced by the oral intake of 6 GTP tablets for 6–9 months (P=0.0463) but were not significantly reduced by the oral intake of 3 GTP tablets daily. BAP values remained constant in the 3 and 6 tablet groups for 6–9 months during the follow-up study. The total serum bilirubin (T-bil) levels increased significantly at 3 (P=0.028) and 9 (P=0.0151) months and the red blood cell (RBC) count decreased at 6 months (P=0.0458) after intake for the 6 GTP tablet group. Alkaline phosphatase (ALP) levels increased significantly at 9 months (P=0.0298). Cholinesterase (ChE) decreased significantly at 9 (P= 0.0127) and 12 (P= 0.0207) months after intake for the 3 GTP tablet group. The results indicate that the daily intake of 6 GTP tablets containing 474 mg polyphenols significantly reduces HAI-induced oxidative stress in HCC or MLC patients while the antioxidative potentials of the patients remain constant. PMID:23181117

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tien, C; Brewer, M; Studenski, M

Purpose: Dynamic-jaw tracking maximizes the area blocked by both jaw and MLC in RapidArc. We developed a method to quantify jaw tracking. Methods: An Eclipse Scripting API (ESAPI) was used to export beam parameters for each arc’s control points. The specific beam parameters extracted were: gantry angle, control point number, meterset, x-jaw positions, y-jaw positions, MLC bank-number, MLC leaf-number, and MLC leaf-position. Each arc contained 178 control points with 120 MLC positions. MATLAB routines were written to process these parameters in order to calculate both the beam aperture (unblocked) size for each control point. An average aperture size was weightedmore » by meterset. Jaw factor was defined as the ratio between dynamic-jaw to static-jaw aperture size. Jaw factor was determined for forty retrospectively replanned patients treated with static-jaw delivery sites including lung, brain, prostate, H&N, rectum, and bladder. Results: Most patients had multiple arcs and reduced-field boosts, resulting in 151 fields. Of these, the lowest (0.4722) and highest (0.9622) jaw factor was observed in prostate and rectal cases, respectively. The median jaw factor was 0.7917 meaning there is the potential unincreased blocking by 20%. Clinically, the dynamic-jaw tracking represents an area surrounding the target which would receive MLC-only leakage transmission of 1.68% versus 0.1% with jaws. Jaw-tracking was more pronounced at areas farther from the target. In prostate patients, the rectum and bladder had 5.5% and 6.3% lower mean dose, respectively; the structures closer to the prostate such as the rectum and bladder both had 1.4% lower mean dose. Conclusion: A custom ESAPI script was coupled with a MATLAB routine in order to extract beam parameters from static-jaw plans and their replanned dynamic-jaw deliveries. The effects were quantified using jaw factor which is the ratio between the meterset weighted aperture size for dynamic-jaw fields versus static-jaw fields.« less

SU-E-T-392: Evaluation of Ion Chamber/film and Log File Based QA to Detect Delivery Errors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nelson, C; Mason, B; Kirsner, S

2015-06-15

Purpose: Ion chamber and film (ICAF) is a method used to verify patient dose prior to treatment. More recently, log file based QA has been shown as an alternative for measurement based QA. In this study, we delivered VMAT plans with and without errors to determine if ICAF and/or log file based QA was able to detect the errors. Methods: Using two VMAT patients, the original treatment plan plus 7 additional plans with delivery errors introduced were generated and delivered. The erroneous plans had gantry, collimator, MLC, gantry and collimator, collimator and MLC, MLC and gantry, and gantry, collimator, andmore » MLC errors. The gantry and collimator errors were off by 4{sup 0} for one of the two arcs. The MLC error introduced was one in which the opening aperture didn’t move throughout the delivery of the field. For each delivery, an ICAF measurement was made as well as a dose comparison based upon log files. Passing criteria to evaluate the plans were ion chamber less and 5% and film 90% of pixels pass the 3mm/3% gamma analysis(GA). For log file analysis 90% of voxels pass the 3mm/3% 3D GA and beam parameters match what was in the plan. Results: Two original plans were delivered and passed both ICAF and log file base QA. Both ICAF and log file QA met the dosimetry criteria on 4 of the 12 erroneous cases analyzed (2 cases were not analyzed). For the log file analysis, all 12 erroneous plans alerted a mismatch in delivery versus what was planned. The 8 plans that didn’t meet criteria all had MLC errors. Conclusion: Our study demonstrates that log file based pre-treatment QA was able to detect small errors that may not be detected using an ICAF and both methods of were able to detect larger delivery errors.« less

SU-E-T-467: Implementation of Monte Carlo Dose Calculation for a Multileaf Collimator Equipped Robotic Radiotherapy System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, JS; Fan, J; Ma, C-M

Purpose: To improve the treatment efficiency and capabilities for full-body treatment, a robotic radiosurgery system has equipped with a multileaf collimator (MLC) to extend its accuracy and precision to radiation therapy. To model the MLC and include it in the Monte Carlo patient dose calculation is the goal of this work. Methods: The radiation source and the MLC were carefully modeled to consider the effects of the source size, collimator scattering, leaf transmission and leaf end shape. A source model was built based on the output factors, percentage depth dose curves and lateral dose profiles measured in a water phantom.more » MLC leaf shape, leaf end design and leaf tilt for minimizing the interleaf leakage and their effects on beam fluence and energy spectrum were all considered in the calculation. Transmission/leakage was added to the fluence based on the transmission factors of the leaf and the leaf end. The transmitted photon energy was tuned to consider the beam hardening effects. The calculated results with the Monte Carlo implementation was compared with measurements in homogeneous water phantom and inhomogeneous phantoms with slab lung or bone material for 4 square fields and 9 irregularly shaped fields. Results: The calculated output factors are compared with the measured ones and the difference is within 1% for different field sizes. The calculated dose distributions in the phantoms show good agreement with measurements using diode detector and films. The dose difference is within 2% inside the field and the distance to agreement is within 2mm in the penumbra region. The gamma passing rate is more than 95% with 2%/2mm criteria for all the test cases. Conclusion: Implementation of Monte Carlo dose calculation for a MLC equipped robotic radiosurgery system is completed successfully. The accuracy of Monte Carlo dose calculation with MLC is clinically acceptable. This work was supported by Accuray Inc.« less

SU-E-T-312: Dosimetric Consideration for the Agility MLC When Planning Rotational SRT/SBRT Treatments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kong, X; Harris, J; Spitznagel, D

2015-06-15

Purpose: To analyze the radiation transmission of the Agility MLC and make recommendation based on the MLC dosimetric characteristics for SRT, SBRT and VMAT planning Method and Materials: Agility MLC is the newest model from Elekta and has no back up diaphragm behind leaves for this generation. Leaves are single focused with rounded end; composed of leafs each 0.5cm wide, 9cm thick, constructed from tungsten alloy and provide low transmission <0.5%. Total radiation transmission from leaves and diaphragm is <0.13%. A 360degree arc was generated using iCom tools; leaves were programmed closed while keeping the diaphragm fully open to maximizemore » the MLC transmission effect. Gafchromic EBT films were sandwiched between 4cm of solid water and situated at midplane to take dose measurement. 5000MU was delivered using 6MV VersaHD, various collimator angles, and a 5cm central axis offset was tested also. Films were scanned with Epson 10000XL scanner and analyzed using DoseLab Pro. Results: Due to the rounded leaf end and nature of rotation therapy, dose accumulation through the leaf gap is significant. By offsetting the leaf gap from central axis, this accumulation can be greatly reduced. There are dark bands showing accumulation of interleaf transmission which is improved by increasing collimator angle from 0 to 45dgree. However for 45 degree, in most cases, there are larger volumes sweeping under MLC alone, which needs considered planning. Conclusions: While inter-leaf leakage is minimized by using collimator angles greater than 0 degrees, the location of the leaf gap must also be managed. The leaf gap position becomes critically important when the treatment area is off axis such is the case when more than one PTV is being treated. With VMAT for SRT, SBRT becoming a more popular planning technique, special attention needs to be paid when initially setting up the field geometry.« less

SU-E-T-610: Comparison of Treatment Times Between the MLCi and Agility Multileaf Collimators

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ramsey, C; Bowling, J

2014-06-01

Purpose: The Agility is a new 160-leaf MLC developed by Elekta for use in their Infinity and Versa HD linacs. As compared to the MLCi, the Agility increased the maximum leaf speed from 2 cm/s to 3.5 cm/s, and the maximum primary collimator speed from 1.5 cm/s to 9.0 cm/s. The purpose of this study was to determine if the Agility MLC resulted in improved plan quality and/or shorter treatment times. Methods: An Elekta Infinity that was originally equipped with a 80 leaf MLCi was upgraded to an 160 leaf Agility. Treatment plan quality was evaluated using the Pinnacle planningmore » system with SmartArc. Optimization was performed once for the MLCi and once for the Agility beam models using the same optimization parameters and the same number of iterations. Patient treatment times were measured for all IMRT, VMAT, and SBRT patients treated on the Infinity with the MLCi and Agility MLCs. Treatment times were extracted from the EMR and measured from when the patient first walked into the treatment room until exiting the treatment room. Results: 11,380 delivery times were measured for patients treated with the MLCi, and 1,827 measurements have been made for the Agility MLC. The average treatment times were 19.1 minutes for the MLCi and 20.8 minutes for the Agility. Using a t-test analysis, there was no difference between the two groups (t = 0.22). The dose differences between patients planned with the MLCi and the Agility MLC were minimal. For example, the dose difference for the PTV, GTV, and cord for a head and neck patient planned using Pinnacle were effectively equivalent. However, the dose to the parotid glands was slightly worse with the Agility MLC. Conclusion: There was no statistical difference in treatment time, or any significant dosimetric difference between the Agility MLC and the MLCi.« less

The effect of MLC speed and acceleration on the plan delivery accuracy of VMAT

PubMed Central

Park, J M; Wu, H-G; Kim, J H; Carlson, J N K

2015-01-01

Objective: To determine a new metric utilizing multileaf collimator (MLC) speeds and accelerations to predict plan delivery accuracy of volumetric modulated arc therapy (VMAT). Methods: To verify VMAT delivery accuracy, gamma evaluations, analysis of mechanical parameter difference between plans and log files, and analysis of changes in dose–volumetric parameters between plans and plans reconstructed with log files were performed with 40 VMAT plans. The average proportion of leaf speeds ranging from l to h cm s−1 (Sl–h and l–h = 0–0.4, 0.4–0.8, 0.8–1.2, 1.2–1.6 and 1.6–2.0), mean and standard deviation of MLC speeds were calculated for each VMAT plan. The same was carried out for accelerations in centimetre per second squared (Al–h and l–h = 0–4, 4–8, 8–12, 12–16 and 16–20). The correlations of those indicators to plan delivery accuracy were analysed with Spearman's correlation coefficient (rs). Results: The S1.2–1.6 and mean acceleration of MLCs showed generally higher correlations to plan delivery accuracy than did others. The highest rs values were observed between S1.2–1.6 and global 1%/2 mm (rs = −0.698 with p < 0.001) as well as mean acceleration and global 1%/2 mm (rs = −0.650 with p < 0.001). As the proportion of MLC speeds and accelerations >0.4 and 4 cm s−2 increased, the plan delivery accuracy of VMAT decreased. Conclusion: The variations in MLC speeds and accelerations showed considerable correlations to VMAT delivery accuracy. Advances in knowledge: As the MLC speeds and accelerations increased, VMAT delivery accuracy reduced. PMID:25734490

Verification of dosimetric accuracy on the TrueBeam STx: rounded leaf effect of the high definition MLC.

PubMed

Kielar, Kayla N; Mok, Ed; Hsu, Annie; Wang, Lei; Luxton, Gary

2012-10-01

The dosimetric leaf gap (DLG) in the Varian Eclipse treatment planning system is determined during commissioning and is used to model the effect of the rounded leaf-end of the multileaf collimator (MLC). This parameter attempts to model the physical difference between the radiation and light field and account for inherent leakage between leaf tips. With the increased use of single fraction high dose treatments requiring larger monitor units comes an enhanced concern in the accuracy of leakage calculations, as it accounts for much of the patient dose. This study serves to verify the dosimetric accuracy of the algorithm used to model the rounded leaf effect for the TrueBeam STx, and describes a methodology for determining best-practice parameter values, given the novel capabilities of the linear accelerator such as flattening filter free (FFF) treatments and a high definition MLC (HDMLC). During commissioning, the nominal MLC position was verified and the DLG parameter was determined using MLC-defined field sizes and moving gap tests, as is common in clinical testing. Treatment plans were created, and the DLG was optimized to achieve less than 1% difference between measured and calculated dose. The DLG value found was tested on treatment plans for all energies (6 MV, 10 MV, 15 MV, 6 MV FFF, 10 MV FFF) and modalities (3D conventional, IMRT, conformal arc, VMAT) available on the TrueBeam STx. The DLG parameter found during the initial MLC testing did not match the leaf gap modeling parameter that provided the most accurate dose delivery in clinical treatment plans. Using the physical leaf gap size as the DLG for the HDMLC can lead to 5% differences in measured and calculated doses. Separate optimization of the DLG parameter using end-to-end tests must be performed to ensure dosimetric accuracy in the modeling of the rounded leaf ends for the Eclipse treatment planning system. The difference in leaf gap modeling versus physical leaf gap dimensions is more pronounced in the more recent versions of Eclipse for both the HDMLC and the Millennium MLC. Once properly commissioned and tested using a methodology based on treatment plan verification, Eclipse is able to accurately model radiation dose delivered for SBRT treatments using the TrueBeam STx.

Empirical determination of collimator scatter data for use in Radcalc commercial monitor unit calculation software: Implication for prostate volumetric modulated-arc therapy calculations.

PubMed

Richmond, Neil; Tulip, Rachael; Walker, Chris

2016-01-01

The aim of this work was to determine, by measurement and independent monitor unit (MU) check, the optimum method for determining collimator scatter for an Elekta Synergy linac with an Agility multileaf collimator (MLC) within Radcalc, a commercial MU calculation software package. The collimator scatter factors were measured for 13 field shapes defined by an Elekta Agility MLC on a Synergy linac with 6MV photons. The value of the collimator scatter associated with each field was also calculated according to the equation Sc=Sc(mlc)+Sc(corr)(Sc(open)-Sc(mlc)) with Sc(corr) varied between 0 and 1, where Sc(open) is the value of collimator scatter calculated from the rectangular collimator-defined field and Sc(mlc) the value using only the MLC-defined field shape by applying sector integration. From this the optimum value of the correction was determined as that which gives the minimum difference between measured and calculated Sc. Single (simple fluence modulation) and dual-arc (complex fluence modulation) treatment plans were generated on the Monaco system for prostate volumetric modulated-arc therapy (VMAT) delivery. The planned MUs were verified by absolute dose measurement in phantom and by an independent MU calculation. The MU calculations were repeated with values of Sc(corr) between 0 and 1. The values of the correction yielding the minimum MU difference between treatment planning system (TPS) and check MU were established. The empirically derived value of Sc(corr) giving the best fit to the measured collimator scatter factors was 0.49. This figure however was not found to be optimal for either the single- or dual-arc prostate VMAT plans, which required 0.80 and 0.34, respectively, to minimize the differences between the TPS and independent-check MU. Point dose measurement of the VMAT plans demonstrated that the TPS MUs were appropriate for the delivered dose. Although the value of Sc(corr) may be obtained by direct comparison of calculation with measurement, the efficacy of the value determined for VMAT-MU calculations are very much dependent on the complexity of the MLC delivery. Copyright © 2016 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

TH-AB-202-05: BEST IN PHYSICS (JOINT IMAGING-THERAPY): First Online Ultrasound-Guided MLC Tracking for Real-Time Motion Compensation in Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ipsen, S; Bruder, R; Schweikard, A

Purpose: While MLC tracking has been successfully used for motion compensation of moving targets, current real-time target localization methods rely on correlation models with x-ray imaging or implanted electromagnetic transponders rather than direct target visualization. In contrast, ultrasound imaging yields volumetric data in real-time (4D) without ionizing radiation. We report the first results of online 4D ultrasound-guided MLC tracking in a phantom. Methods: A real-time tracking framework was installed on a 4D ultrasound station (Vivid7 dimension, GE) and used to detect a 2mm spherical lead marker inside a water tank. The volumetric frame rate was 21.3Hz (47ms). The marker wasmore » rigidly attached to a motion stage programmed to reproduce nine tumor trajectories (five prostate, four lung). The 3D marker position from ultrasound was used for real-time MLC aperture adaption. The tracking system latency was measured and compensated by prediction for lung trajectories. To measure geometric accuracy, anterior and lateral conformal fields with 10cm circular aperture were delivered for each trajectory. The tracking error was measured as the difference between marker position and MLC aperture in continuous portal imaging. For dosimetric evaluation, 358° VMAT fields were delivered to a biplanar diode array dosimeter using the same trajectories. Dose measurements with and without MLC tracking were compared to a static reference dose using a 3%/3 mm γ-test. Results: The tracking system latency was 170ms. The mean root-mean-square tracking error was 1.01mm (0.75mm prostate, 1.33mm lung). Tracking reduced the mean γ-failure rate from 13.9% to 4.6% for prostate and from 21.8% to 0.6% for lung with high-modulation VMAT plans and from 5% (prostate) and 18% (lung) to 0% with low modulation. Conclusion: Real-time ultrasound tracking was successfully integrated with MLC tracking for the first time and showed similar accuracy and latency as other methods while holding the potential to measure target motion non-invasively. SI was supported by the Graduate School for Computing in Medicine and Life Science, German Excellence Initiative [grant DFG GSC 235/1].« less

Analysis of a four lamp flash system for calibrating multi-junction solar cells under concentrated light

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schachtner, Michael, E-mail: michael.schachtner@ise.fraunhofer.de; Prado, Marcelo Loyo; Reichmuth, S. Kasimir

2015-09-28

It has been known for a long time that the precise characterization of multi-junction solar cells demands spectrally tunable solar simulators. The calibration of innovative multi-junction solar cells for CPV applications now requires tunable solar simulators which provide high irradiation levels. This paper describes the commissioning and calibration of a flash-based four-lamp simulator to be used for the measurement of multi-junction solar cells with up to four subcells under concentrated light.

Distributed Multi-Cell Resource Allocation with Price Based ICI Coordination in Downlink OFDMA Networks

NASA Astrophysics Data System (ADS)

Lv, Gangming; Zhu, Shihua; Hui, Hui

Multi-cell resource allocation under minimum rate request for each user in OFDMA networks is addressed in this paper. Based on Lagrange dual decomposition theory, the joint multi-cell resource allocation problem is decomposed and modeled as a limited-cooperative game, and a distributed multi-cell resource allocation algorithm is thus proposed. Analysis and simulation results show that, compared with non-cooperative iterative water-filling algorithm, the proposed algorithm can remarkably reduce the ICI level and improve overall system performances.

SU-E-T-478: Sliding Window Multi-Criteria IMRT Optimization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Craft, D; Papp, D; Unkelbach, J

2014-06-01

Purpose: To demonstrate a method for what-you-see-is-what-you-get multi-criteria Pareto surface navigation for step and shoot IMRT treatment planning. Methods: We show mathematically how multiple sliding window treatment plans can be averaged to yield a single plan whose dose distribution is the dosimetric average of the averaged plans. This is incorporated into the Pareto surface navigation based approach to treatment planning in such a way that as the user navigates the surface, the plans he/she is viewing are ready to be delivered (i.e. there is no extra ‘segment the plans’ step that often leads to unacceptable plan degradation in step andmore » shoot Pareto surface navigation). We also describe how the technique can be applied to VMAT. Briefly, sliding window VMAT plans are created such that MLC leaves paint out fluence maps every 15 degrees or so. These fluence map leaf trajectories are averaged in the same way the static beam IMRT ones are. Results: We show mathematically that fluence maps are exactly averaged using our leaf sweep averaging algorithm. Leaf transmission and output factor corrections effects, which are ignored in this work, can lead to small errors in terms of the dose distributions not being exactly averaged even though the fluence maps are. However, our demonstrations show that the dose distributions are almost exactly averaged as well. We demonstrate the technique both for IMRT and VMAT. Conclusions: By turning to sliding window delivery, we show that the problem of losing plan fidelity during the conversion of an idealized fluence map plan into a deliverable plan is remedied. This will allow for multicriteria optimization that avoids the pitfall that the planning has to be redone after the conversion into MLC segments due to plan quality decline. David Craft partially funded by RaySearch Laboratories.« less

Multi-scale modelling of the dynamics of cell colonies: insights into cell-adhesion forces and cancer invasion from in silico simulations.

PubMed

Schlüter, Daniela K; Ramis-Conde, Ignacio; Chaplain, Mark A J

2015-02-06

Studying the biophysical interactions between cells is crucial to understanding how normal tissue develops, how it is structured and also when malfunctions occur. Traditional experiments try to infer events at the tissue level after observing the behaviour of and interactions between individual cells. This approach assumes that cells behave in the same biophysical manner in isolated experiments as they do within colonies and tissues. In this paper, we develop a multi-scale multi-compartment mathematical model that accounts for the principal biophysical interactions and adhesion pathways not only at a cell-cell level but also at the level of cell colonies (in contrast to the traditional approach). Our results suggest that adhesion/separation forces between cells may be lower in cell colonies than traditional isolated single-cell experiments infer. As a consequence, isolated single-cell experiments may be insufficient to deduce important biological processes such as single-cell invasion after detachment from a solid tumour. The simulations further show that kinetic rates and cell biophysical characteristics such as pressure-related cell-cycle arrest have a major influence on cell colony patterns and can allow for the development of protrusive cellular structures as seen in invasive cancer cell lines independent of expression levels of pro-invasion molecules.

Characteristics of multilevel storage and switching dynamics in resistive switching cell of Al2O3/HfO2/Al2O3 sandwich structure

NASA Astrophysics Data System (ADS)

Liu, Jian; Yang, Huafeng; Ma, Zhongyuan; Chen, Kunji; Zhang, Xinxin; Huang, Xinfan; Oda, Shunri

2018-01-01

We reported an Al2O3/HfO2/Al2O3 sandwich structure resistive switching device with significant improvement of multilevel cell (MLC) operation capability, which exhibited that four stable and distinct resistance states (one low resistance state and three high resistance states) can be achieved by controlling the Reset stop voltages (V Reset-stop) during the Reset operation. The improved MLC operation capability can be attributed to the R HRS/R LRS ratio enhancement resulting from increasing of the series resistance and decreasing of leakage current by inserting two Al2O3 layers. For the high-speed switching applications, we studied the initial switching dynamics by using the measurements of the pulse width and amplitude dependence of Set and Reset switching characteristics. The results showed that under the same pulse amplitude conditions, the initial Set progress is faster than the initial Reset progress, which can be explained by thermal-assisted electric field induced rupture model in the oxygen vacancies conductive filament. Thus, proper combination of varying pulse amplitude and width can help us to optimize the device operation parameters. Moreover, the device demonstrated ultrafast program/erase speed (10 ns) and good pulse switching endurance (105 cycles) characteristics, which are suitable for high-density and fast-speed nonvolatile memory applications.

Dynamic simulation of motion effects in IMAT lung SBRT.

PubMed

Zou, Wei; Yin, Lingshu; Shen, Jiajian; Corradetti, Michael N; Kirk, Maura; Munbodh, Reshma; Fang, Penny; Jabbour, Salma K; Simone, Charles B; Yue, Ning J; Rengan, Ramesh; Teo, Boon-Keng Kevin

2014-11-01

Intensity modulated arc therapy (IMAT) has been widely adopted for Stereotactic Body Radiotherapy (SBRT) for lung cancer. While treatment dose is optimized and calculated on a static Computed Tomography (CT) image, the effect of the interplay between the target and linac multi-leaf collimator (MLC) motion is not well described and may result in deviations between delivered and planned dose. In this study, we investigated the dosimetric consequences of the inter-play effect on target and organs at risk (OAR) by simulating dynamic dose delivery using dynamic CT datasets. Fifteen stage I non-small cell lung cancer (NSCLC) patients with greater than 10 mm tumor motion treated with SBRT in 4 fractions to a dose of 50 Gy were retrospectively analyzed for this study. Each IMAT plan was initially optimized using two arcs. Simulated dynamic delivery was performed by associating the MLC leaf position, gantry angle and delivered beam monitor units (MUs) for each control point with different respiratory phases of the 4D-CT using machine delivery log files containing time stamps of the control points. Dose maps associated with each phase of the 4D-CT dose were calculated in the treatment planning system and accumulated using deformable image registration onto the exhale phase of the 4D-CT. The original IMAT plans were recalculated on the exhale phase of the CT for comparison with the dynamic simulation. The dose coverage of the PTV showed negligible variation between the static and dynamic simulation. There was less than 1.5% difference in PTV V95% and V90%. The average inter-fraction and cumulative dosimetric effects among all the patients were less than 0.5% for PTV V95% and V90% coverage and 0.8 Gy for the OARs. However, in patients where target is close to the organs, large variations were observed on great vessels and bronchus for as much as 4.9 Gy and 7.8 Gy. Limited variation in target dose coverage and OAR constraints were seen for each SBRT fraction as well as over all four fractions. Large dose variations were observed on critical organs in patients where these organs were closer to the target.

Multi-scale modelling of the dynamics of cell colonies: insights into cell-adhesion forces and cancer invasion from in silico simulations

PubMed Central

Schlüter, Daniela K.; Ramis-Conde, Ignacio; Chaplain, Mark A. J.

2015-01-01

Studying the biophysical interactions between cells is crucial to understanding how normal tissue develops, how it is structured and also when malfunctions occur. Traditional experiments try to infer events at the tissue level after observing the behaviour of and interactions between individual cells. This approach assumes that cells behave in the same biophysical manner in isolated experiments as they do within colonies and tissues. In this paper, we develop a multi-scale multi-compartment mathematical model that accounts for the principal biophysical interactions and adhesion pathways not only at a cell–cell level but also at the level of cell colonies (in contrast to the traditional approach). Our results suggest that adhesion/separation forces between cells may be lower in cell colonies than traditional isolated single-cell experiments infer. As a consequence, isolated single-cell experiments may be insufficient to deduce important biological processes such as single-cell invasion after detachment from a solid tumour. The simulations further show that kinetic rates and cell biophysical characteristics such as pressure-related cell-cycle arrest have a major influence on cell colony patterns and can allow for the development of protrusive cellular structures as seen in invasive cancer cell lines independent of expression levels of pro-invasion molecules. PMID:25519994

Space exploration by dendritic cells requires maintenance of myosin II activity by IP3 receptor 1

PubMed Central

Solanes, Paola; Heuzé, Mélina L; Maurin, Mathieu; Bretou, Marine; Lautenschlaeger, Franziska; Maiuri, Paolo; Terriac, Emmanuel; Thoulouze, Maria-Isabel; Launay, Pierre; Piel, Matthieu; Vargas, Pablo; Lennon-Duménil, Ana-Maria

2015-01-01

Dendritic cells (DCs) patrol the interstitial space of peripheral tissues. The mechanisms that regulate their migration in such constrained environment remain unknown. We here investigated the role of calcium in immature DCs migrating in confinement. We found that they displayed calcium oscillations that were independent of extracellular calcium and more frequently observed in DCs undergoing strong speed fluctuations. In these cells, calcium spikes were associated with fast motility phases. IP3 receptors (IP3Rs) channels, which allow calcium release from the endoplasmic reticulum, were identified as required for immature DCs to migrate at fast speed. The IP3R1 isoform was further shown to specifically regulate the locomotion persistence of immature DCs, that is, their capacity to maintain directional migration. This function of IP3R1 results from its ability to control the phosphorylation levels of myosin II regulatory light chain (MLC) and the back/front polarization of the motor protein. We propose that by upholding myosin II activity, constitutive calcium release from the ER through IP3R1 maintains DC polarity during migration in confinement, facilitating the exploration of their environment. PMID:25637353

Space exploration by dendritic cells requires maintenance of myosin II activity by IP3 receptor 1.

PubMed

Solanes, Paola; Heuzé, Mélina L; Maurin, Mathieu; Bretou, Marine; Lautenschlaeger, Franziska; Maiuri, Paolo; Terriac, Emmanuel; Thoulouze, Maria-Isabel; Launay, Pierre; Piel, Matthieu; Vargas, Pablo; Lennon-Duménil, Ana-Maria

2015-03-12

Dendritic cells (DCs) patrol the interstitial space of peripheral tissues. The mechanisms that regulate their migration in such constrained environment remain unknown. We here investigated the role of calcium in immature DCs migrating in confinement. We found that they displayed calcium oscillations that were independent of extracellular calcium and more frequently observed in DCs undergoing strong speed fluctuations. In these cells, calcium spikes were associated with fast motility phases. IP₃ receptors (IP₃Rs) channels, which allow calcium release from the endoplasmic reticulum, were identified as required for immature DCs to migrate at fast speed. The IP₃R1 isoform was further shown to specifically regulate the locomotion persistence of immature DCs, that is, their capacity to maintain directional migration. This function of IP₃R1 results from its ability to control the phosphorylation levels of myosin II regulatory light chain (MLC) and the back/front polarization of the motor protein. We propose that by upholding myosin II activity, constitutive calcium release from the ER through IP₃R1 maintains DC polarity during migration in confinement, facilitating the exploration of their environment. © 2015 Institut Curie/Inserm. Published under the terms of the CC BY NC ND 4.0 license.

SU-F-P-36: Automation of Linear Accelerator Star Shot Measurement with Advanced XML Scripting and Electronic Portal Imaging Device

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nguyen, N; Knutson, N; Schmidt, M

Purpose: To verify a method used to automatically acquire jaw, MLC, collimator and couch star shots for a Varian TrueBeam linear accelerator utilizing Developer Mode and an Electronic Portal Imaging Device (EPID). Methods: An XML script was written to automate motion of the jaws, MLC, collimator and couch in TrueBeam Developer Mode (TBDM) to acquire star shot measurements. The XML script also dictates MV imaging parameters to facilitate automatic acquisition and recording of integrated EPID images. Since couch star shot measurements cannot be acquired using a combination of EPID and jaw/MLC collimation alone due to a fixed imager geometry, amore » method utilizing a 5mm wide steel ruler placed on the table and centered within a 15×15cm2 open field to produce a surrogate of the narrow field aperture was investigated. Four individual star shot measurements (X jaw, Y jaw, MLC and couch) were obtained using our proposed as well as traditional film-based method. Integrated EPID images and scanned measurement films were analyzed and compared. Results: Star shot (X jaw, Y jaw, MLC and couch) measurements were obtained in a single 5 minute delivery using the TBDM XML script method compared to 60 minutes for equivalent traditional film measurements. Analysis of the images and films demonstrated comparable isocentricity results, agreeing within 0.3mm of each other. Conclusion: The presented automatic approach of acquiring star shot measurements using TBDM and EPID has proven to be more efficient than the traditional film approach with equivalent results.« less

Real-time auto-adaptive margin generation for MLC-tracked radiotherapy

NASA Astrophysics Data System (ADS)

Glitzner, M.; Fast, M. F.; de Senneville, B. Denis; Nill, S.; Oelfke, U.; Lagendijk, J. J. W.; Raaymakers, B. W.; Crijns, S. P. M.

2017-01-01

In radiotherapy, abdominal and thoracic sites are candidates for performing motion tracking. With real-time control it is possible to adjust the multileaf collimator (MLC) position to the target position. However, positions are not perfectly matched and position errors arise from system delays and complicated response of the electromechanic MLC system. Although, it is possible to compensate parts of these errors by using predictors, residual errors remain and need to be compensated to retain target coverage. This work presents a method to statistically describe tracking errors and to automatically derive a patient-specific, per-segment margin to compensate the arising underdosage on-line, i.e. during plan delivery. The statistics of the geometric error between intended and actual machine position are derived using kernel density estimators. Subsequently a margin is calculated on-line according to a selected coverage parameter, which determines the amount of accepted underdosage. The margin is then applied onto the actual segment to accommodate the positioning errors in the enlarged segment. The proof-of-concept was tested in an on-line tracking experiment and showed the ability to recover underdosages for two test cases, increasing {{V}90 %} in the underdosed area about 47 % and 41 % , respectively. The used dose model was able to predict the loss of dose due to tracking errors and could be used to infer the necessary margins. The implementation had a running time of 23 ms which is compatible with real-time requirements of MLC tracking systems. The auto-adaptivity to machine and patient characteristics makes the technique a generic yet intuitive candidate to avoid underdosages due to MLC tracking errors.

A role for long chain myosin light chain kinase (MLCK-210) in microvascular hyperpermeability during severe burns.

PubMed

Reynoso, Rashell; Perrin, Rachel M; Breslin, Jerome W; Daines, Dayle A; Watson, Katherine D; Watterson, D Martin; Wu, Mack H; Yuan, Sarah

2007-11-01

Microvascular leakage has been implicated in the pathogenesis of multiple organ dysfunction during trauma. Previous studies suggest the involvement of myosin light chain (MLC) phosphorylation-triggered endothelial contraction in the development of microvascular hyperpermeability. Myosin light chain kinase (MLCK) plays a key role in the control of MLC-phosphorylation status; thus, it is thought to modulate barrier function through its regulation of intracellular contractile machinery. The aim of this study was to further investigate the endothelial mechanism of MLC-dependent barrier injury in burns, focusing on the long isoform of MLCK (MLCK-210) that has recently been identified as the predominant isoform expressed in vascular endothelial cells. An MLCK-210 knockout mouse model was subjected to third-degree scald burn covering 25% total body surface area. The mesenteric microcirculation was observed using intravital microscopy, and the microvascular permeability was assessed by measuring the transvenular flux of fluorescein isothiocyanate-albumin. In a separate experiment, in vivo mesenteric hydraulic conductivity (Lp) was measured using the modified Landis technique. The injury caused a profound microvascular leakage, as indicated by a 2-fold increase in albumin flux and 4-fold increase in Lp at the early stages, which was associated with a high mortality within the 24-h period. Compared with wild-type control, the MLCK-210-deficient mice displayed a significantly improved survival with a greatly attenuated microvascular hyperpermeability response to albumin and fluid. These results provide direct evidence for a role of MLCK-210 in mediating burn-induced microvascular barrier injury and validate MLCK-210 as a potential therapeutic target in the treatment of burn edema.

Protein Kinase C as Regulator of Vascular Smooth Muscle Function and Potential Target in Vascular Disorders.

PubMed

Ringvold, H C; Khalil, R A

2017-01-01

Vascular smooth muscle (VSM) plays an important role in maintaining vascular tone. In addition to Ca 2+ -dependent myosin light chain (MLC) phosphorylation, protein kinase C (PKC) is a major regulator of VSM function. PKC is a family of conventional Ca 2+ -dependent α, β, and γ, novel Ca 2+ -independent δ, ɛ, θ, and η, and atypical ξ, and ι/λ isoforms. Inactive PKC is mainly cytosolic, and upon activation it undergoes phosphorylation, maturation, and translocation to the surface membrane, the nucleus, endoplasmic reticulum, and other cell organelles; a process facilitated by scaffold proteins such as RACKs. Activated PKC phosphorylates different substrates including ion channels, pumps, and nuclear proteins. PKC also phosphorylates CPI-17 leading to inhibition of MLC phosphatase, increased MLC phosphorylation, and enhanced VSM contraction. PKC could also initiate a cascade of protein kinases leading to phosphorylation of the actin-binding proteins calponin and caldesmon, increased actin-myosin interaction, and VSM contraction. Increased PKC activity has been associated with vascular disorders including ischemia-reperfusion injury, coronary artery disease, hypertension, and diabetic vasculopathy. PKC inhibitors could test the role of PKC in different systems and could reduce PKC hyperactivity in vascular disorders. First-generation PKC inhibitors such as staurosporine and chelerythrine are not very specific. Isoform-specific PKC inhibitors such as ruboxistaurin have been tested in clinical trials. Target delivery of PKC pseudosubstrate inhibitory peptides and PKC siRNA may be useful in localized vascular disease. Further studies of PKC and its role in VSM should help design isoform-specific PKC modulators that are experimentally potent and clinically safe to target PKC in vascular disease. © 2017 Elsevier Inc. All rights reserved.

HRR Upgrade to mass loss calorimeter and modified Schlyter test for FR Wood

Treesearch

Mark A. Dietenberger; Charles R. Boardman

2013-01-01

Enhanced Heat Release Rate (HRR) methodology has been extended to the Mass Loss Calorimeter (MLC) and the Modified Schlyter flame spread test to evaluate fire retardant effectiveness used on wood based materials. Modifications to MLC include installation of thermopile on the chimney walls to correct systematic errors to the sensible HRR calculations to account for...

Dose calculation of dynamic trajectory radiotherapy using Monte Carlo.

PubMed

Manser, P; Frauchiger, D; Frei, D; Volken, W; Terribilini, D; Fix, M K

2018-04-06

Using volumetric modulated arc therapy (VMAT) delivery technique gantry position, multi-leaf collimator (MLC) as well as dose rate change dynamically during the application. However, additional components can be dynamically altered throughout the dose delivery such as the collimator or the couch. Thus, the degrees of freedom increase allowing almost arbitrary dynamic trajectories for the beam. While the dose delivery of such dynamic trajectories for linear accelerators is technically possible, there is currently no dose calculation and validation tool available. Thus, the aim of this work is to develop a dose calculation and verification tool for dynamic trajectories using Monte Carlo (MC) methods. The dose calculation for dynamic trajectories is implemented in the previously developed Swiss Monte Carlo Plan (SMCP). SMCP interfaces the treatment planning system Eclipse with a MC dose calculation algorithm and is already able to handle dynamic MLC and gantry rotations. Hence, the additional dynamic components, namely the collimator and the couch, are described similarly to the dynamic MLC by defining data pairs of positions of the dynamic component and the corresponding MU-fractions. For validation purposes, measurements are performed with the Delta4 phantom and film measurements using the developer mode on a TrueBeam linear accelerator. These measured dose distributions are then compared with the corresponding calculations using SMCP. First, simple academic cases applying one-dimensional movements are investigated and second, more complex dynamic trajectories with several simultaneously moving components are compared considering academic cases as well as a clinically motivated prostate case. The dose calculation for dynamic trajectories is successfully implemented into SMCP. The comparisons between the measured and calculated dose distributions for the simple as well as for the more complex situations show an agreement which is generally within 3% of the maximum dose or 3mm. The required computation time for the dose calculation remains the same when the additional dynamic moving components are included. The results obtained for the dose comparisons for simple and complex situations suggest that the extended SMCP is an accurate dose calculation and efficient verification tool for dynamic trajectory radiotherapy. This work was supported by Varian Medical Systems. Copyright © 2018. Published by Elsevier GmbH.

SU-F-T-364: Monte Carlo-Dose Verification of Volumetric Modulated Arc Therapy Plans Using AAPM TG-119 Test Patterns

DOE Office of Scientific and Technical Information (OSTI.GOV)

Onizuka, R; Araki, F; Ohno, T

2016-06-15

Purpose: To investigate the Monte Carlo (MC)-based dose verification for VMAT plans by a treatment planning system (TPS). Methods: The AAPM TG-119 test structure set was used for VMAT plans by the Pinnacle3 (convolution/superposition), using a Synergy radiation head of a 6 MV beam with the Agility MLC. The Synergy was simulated with the EGSnrc/BEAMnrc code, and VMAT dose distributions were calculated with the EGSnrc/DOSXYZnrc code by the same irradiation conditions as TPS. VMAT dose distributions of TPS and MC were compared with those of EBT3 film, by 2-D gamma analysis of ±3%/3 mm criteria with a threshold of 30%more » of prescribed doses. VMAT dose distributions between TPS and MC were also compared by DVHs and 3-D gamma analysis of ±3%/3 mm criteria with a threshold of 10%, and 3-D passing rates for PTVs and OARs were analyzed. Results: TPS dose distributions differed from those of film, especially for Head & neck. The dose difference between TPS and film results from calculation accuracy for complex motion of MLCs like tongue and groove effect. In contrast, MC dose distributions were in good agreement with those of film. This is because MC can model fully the MLC configuration and accurately reproduce the MLC motion between control points in VMAT plans. D95 of PTV for Prostate, Head & neck, C-shaped, and Multi Target was 97.2%, 98.1%, 101.6%, and 99.7% for TPS and 95.7%, 96.0%, 100.6%, and 99.1% for MC, respectively. Similarly, 3-D gamma passing rates of each PTV for TPS vs. MC were 100%, 89.5%, 99.7%, and 100%, respectively. 3-D passing rates of TPS reduced for complex VMAT fields like Head & neck because MLCs are not modeled completely for TPS. Conclusion: MC-calculated VMAT dose distributions is useful for the 3-D dose verification of VMAT plans by TPS.« less

p21-Activated kinase (Pak) regulates airway smooth muscle contraction by regulating paxillin complexes that mediate actin polymerization.

PubMed

Zhang, Wenwu; Huang, Youliang; Gunst, Susan J

2016-09-01

In airway smooth muscle, tension development caused by a contractile stimulus requires phosphorylation of the 20 kDa myosin light chain (MLC), which activates crossbridge cycling and the polymerization of a pool of submembraneous actin. The p21-activated kinases (Paks) can regulate the contractility of smooth muscle and non-muscle cells, and there is evidence that this occurs through the regulation of MLC phosphorylation. We show that Pak has no effect on MLC phosphorylation during the contraction of airway smooth muscle, and that it regulates contraction by mediating actin polymerization. We find that Pak phosphorylates the adhesion junction protein, paxillin, on Ser273, which promotes the formation of a signalling complex that activates the small GTPase, cdc42, and the actin polymerization catalyst, neuronal Wiskott-Aldrich syndrome protein (N-WASP). These studies demonstrate a novel role for Pak in regulating the contractility of smooth muscle by regulating actin polymerization. The p21-activated kinases (Pak) can regulate contractility in smooth muscle and other cell and tissue types, but the mechanisms by which Paks regulate cell contractility are unclear. In airway smooth muscle, stimulus-induced contraction requires phosphorylation of the 20 kDa light chain of myosin, which activates crossbridge cycling, as well as the polymerization of a small pool of actin. The role of Pak in airway smooth muscle contraction was evaluated by inhibiting acetylcholine (ACh)-induced Pak activation through the expression of a kinase inactive mutant, Pak1 K299R, or by treating tissues with the Pak inhibitor, IPA3. Pak inhibition suppressed actin polymerization and contraction in response to ACh, but it did not affect myosin light chain phosphorylation. Pak activation induced paxillin phosphorylation on Ser273; the paxillin mutant, paxillin S273A, inhibited paxillin Ser273 phosphorylation and inhibited actin polymerization and contraction. Immunoprecipitation analysis of tissue extracts and proximity ligation assays in dissociated cells showed that Pak activation and paxillin Ser273 phosphorylation triggered the formation of an adhesion junction signalling complex with paxillin that included G-protein-coupled receptor kinase-interacting protein (GIT1) and the cdc42 guanine exchange factor, βPIX (Pak interactive exchange factor). Assembly of the Pak-GIT1-βPIX-paxillin complex was necessary for cdc42 and neuronal Wiskott-Aldrich syndrome protein (N-WASP) activation, actin polymerization and contraction in response to ACh. RhoA activation was also required for the recruitment of Pak to adhesion junctions, Pak activation, paxillin Ser273 phosphorylation and paxillin complex assembly. These studies demonstrate a novel role for Pak in the regulation of N-WASP activation, actin dynamics and cell contractility. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

p21‐Activated kinase (Pak) regulates airway smooth muscle contraction by regulating paxillin complexes that mediate actin polymerization

PubMed Central

Zhang, Wenwu; Huang, Youliang

2016-01-01

Key points In airway smooth muscle, tension development caused by a contractile stimulus requires phosphorylation of the 20 kDa myosin light chain (MLC), which activates crossbridge cycling and the polymerization of a pool of submembraneous actin.The p21‐activated kinases (Paks) can regulate the contractility of smooth muscle and non‐muscle cells, and there is evidence that this occurs through the regulation of MLC phosphorylation.We show that Pak has no effect on MLC phosphorylation during the contraction of airway smooth muscle, and that it regulates contraction by mediating actin polymerization.We find that Pak phosphorylates the adhesion junction protein, paxillin, on Ser273, which promotes the formation of a signalling complex that activates the small GTPase, cdc42, and the actin polymerization catalyst, neuronal Wiskott–Aldrich syndrome protein (N‐WASP).These studies demonstrate a novel role for Pak in regulating the contractility of smooth muscle by regulating actin polymerization. Abstract The p21‐activated kinases (Pak) can regulate contractility in smooth muscle and other cell and tissue types, but the mechanisms by which Paks regulate cell contractility are unclear. In airway smooth muscle, stimulus‐induced contraction requires phosphorylation of the 20 kDa light chain of myosin, which activates crossbridge cycling, as well as the polymerization of a small pool of actin. The role of Pak in airway smooth muscle contraction was evaluated by inhibiting acetylcholine (ACh)‐induced Pak activation through the expression of a kinase inactive mutant, Pak1 K299R, or by treating tissues with the Pak inhibitor, IPA3. Pak inhibition suppressed actin polymerization and contraction in response to ACh, but it did not affect myosin light chain phosphorylation. Pak activation induced paxillin phosphorylation on Ser273; the paxillin mutant, paxillin S273A, inhibited paxillin Ser273 phosphorylation and inhibited actin polymerization and contraction. Immunoprecipitation analysis of tissue extracts and proximity ligation assays in dissociated cells showed that Pak activation and paxillin Ser273 phosphorylation triggered the formation of an adhesion junction signalling complex with paxillin that included G‐protein‐coupled receptor kinase‐interacting protein (GIT1) and the cdc42 guanine exchange factor, βPIX (Pak interactive exchange factor). Assembly of the Pak–GIT1–βPIX–paxillin complex was necessary for cdc42 and neuronal Wiskott–Aldrich syndrome protein (N‐WASP) activation, actin polymerization and contraction in response to ACh. RhoA activation was also required for the recruitment of Pak to adhesion junctions, Pak activation, paxillin Ser273 phosphorylation and paxillin complex assembly. These studies demonstrate a novel role for Pak in the regulation of N‐WASP activation, actin dynamics and cell contractility. PMID:27038336

Assessment of human MAPCs for stem cell transplantation and cardiac regeneration after myocardial infarction in SCID mice.

PubMed

Dimomeletis, Ilias; Deindl, Elisabeth; Zaruba, Marc; Groebner, Michael; Zahler, Stefan; Laslo, Saskia M; David, Robert; Kostin, Sawa; Deutsch, Markus A; Assmann, Gerd; Mueller-Hoecker, Josef; Feuring-Buske, Michaela; Franz, Wolfgang M

2010-11-01

Clinical studies suggest that transplantation of total bone marrow (BM) after myocardial infarction (MI) is feasible and potentially effective. However, focusing on a defined BM-derived stem cell type may enable a more specific and optimized treatment. Multilineage differentiation potential makes BM-derived multipotent adult progenitor cells (MAPCs) a promising stem cell pool for regenerative purposes. We analyzed the cardioregenerative potential of human MAPCs in a murine model of myocardial infarction. Human MAPCs were selected by negative depletion of CD45(+)/glycophorin(+) BM cells and plated on fibronectin-coated dishes. In vitro, stem cells were analyzed by reverse transcription polymerase chain reaction. In vivo, we transplanted human MAPCs (5 × 10(5)) by intramyocardial injection after MI in severe combined immunodeficient (SCID) beige mice. Six and 30 days after the surgical procedure, pressure-volume relationships were investigated in vivo. Heart tissues were analyzed immunohistochemically. Reverse transcription polymerase chain reaction experiments on early human MAPC passages evidenced an expression of Oct-4, a stem cell marker indicating pluripotency. In later passages, cardiac markers (Nkx2.5, GATA4, MLC-2v, MLC-2a, ANP, cTnT, cTnI,) and smooth muscle cell markers (SMA, SM22α) were expressed. Transplantation of human MAPCs into the ischemic border zone after MI resulted in an improved cardiac function at day 6 (ejection fraction, 26% vs 20%) and day 30 (ejection fraction, 30% vs 23%). Confirmation of human MAPC marker vimentin in immunohistochemistry demonstrated that human MAPC integrated in the peri-infarct region. The proliferation marker Ki67 was absent in immunohistochemistry and teratoma formation was not found, indicating no tumorous potential of transplanted human MAPCs in the tumor-sensitive SCID model. Transplantation of human MAPCs after MI ameliorates myocardial function, which may be explained by trophic effects of human MAPCs. Lack of evidence of tumorous potential in the tumor-sensitive SCID model indicates that human MAPCs may deliver an effective and safe stem cell pool for potential treatment of ischemic heart disease. Copyright © 2010 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.

Identifying EGFR-Expressed Cells and Detecting EGFR Multi-Mutations at Single-Cell Level by Microfluidic Chip

NASA Astrophysics Data System (ADS)

Li, Ren; Zhou, Mingxing; Li, Jine; Wang, Zihua; Zhang, Weikai; Yue, Chunyan; Ma, Yan; Peng, Hailin; Wei, Zewen; Hu, Zhiyuan

2018-03-01

EGFR mutations companion diagnostics have been proved to be crucial for the efficacy of tyrosine kinase inhibitor targeted cancer therapies. To uncover multiple mutations occurred in minority of EGFR-mutated cells, which may be covered by the noises from majority of un-mutated cells, is currently becoming an urgent clinical requirement. Here we present the validation of a microfluidic-chip-based method for detecting EGFR multi-mutations at single-cell level. By trapping and immunofluorescently imaging single cells in specifically designed silicon microwells, the EGFR-expressed cells were easily identified. By in situ lysing single cells, the cell lysates of EGFR-expressed cells were retrieved without cross-contamination. Benefited from excluding the noise from cells without EGFR expression, the simple and cost-effective Sanger's sequencing, but not the expensive deep sequencing of the whole cell population, was used to discover multi-mutations. We verified the new method with precisely discovering three most important EGFR drug-related mutations from a sample in which EGFR-mutated cells only account for a small percentage of whole cell population. The microfluidic chip is capable of discovering not only the existence of specific EGFR multi-mutations, but also other valuable single-cell-level information: on which specific cells the mutations occurred, or whether different mutations coexist on the same cells. This microfluidic chip constitutes a promising method to promote simple and cost-effective Sanger's sequencing to be a routine test before performing targeted cancer therapy.[Figure not available: see fulltext.

Blebbistatin, a myosin II inhibitor, suppresses Ca(2+)-induced and "sensitized"-contraction of skinned tracheal muscles from guinea pig.

PubMed

Yumoto, Masatoshi; Watanabe, Masaru

2013-01-01

Blebbistatin, a potent inhibitor of myosin II, has inhibiting effects on Ca(2+)-induced contraction and contractile filament organization without affecting the Ca(2+)-sensitivity to the force and phosphorylation level of myosin regulatory light chain (MLC20) in skinned (cell membrane permeabilized) taenia cecum from the guinea pig (Watanabe et al., Am J Physiol Cell Physiol. 2010; 298: C1118-26). In the present study, we investigated blebbistatin effects on the contractile force of skinned tracheal muscle, in which myosin filaments organization is more labile than that in the taenia cecum. Blebbistatin at 10 μM or higher suppressed Ca(2+)-induced tension development at any given Ca(2+) concentration, but had little effects on the Ca(2+)- induced myosin light chain phosphorylation. Also blebbistatin at 10 μM and higher significantly suppressed GTP-γS-induced "sensitized" force development. Since the force inhibiting effects of blebbistatin on the skinned trachea were much stronger than those in skinned taenia cecum, blebbistatin might directly affect myosin filaments organization.

Error Characterization and Mitigation for 16Nm MLC NAND Flash Memory Under Total Ionizing Dose Effect

NASA Technical Reports Server (NTRS)

Li, Yue (Inventor); Bruck, Jehoshua (Inventor)

2018-01-01

A data device includes a memory having a plurality of memory cells configured to store data values in accordance with a predetermined rank modulation scheme that is optional and a memory controller that receives a current error count from an error decoder of the data device for one or more data operations of the flash memory device and selects an operating mode for data scrubbing in accordance with the received error count and a program cycles count.

Molecular prenatal diagnosis of megalencephalic leukoencephalopathy with subcortical cysts in a child from southwest of Iran.

PubMed

Shariati, Gholamreza; Hamid, Mohammad; Saberi, Alihossein; Andashti, Behnaz; Galehdari, Hamid

2015-02-01

Megalencephalic leukoencephalopathy (MLC) is a rare neurological disorder with an autosomal recessive pattern. Clinical diagnosis was based on macrocephaly, recurrent seizure, and magnetic resonance imaging (MRI). Here we report first finding of a novel homozygous single base deletion in the MLC1 gene in an affected Iranian child causing a premature stop codon (p.L150fs.160X).

Development of a Multileaf Collimator for Proton Radiotherapy

DTIC Science & Technology

2007-06-01

for proton radiotherapy, and the first year of the project to develop image guided treatment protocols for proton therapy . This research...multileaf collimator (MLC) for proton therapy and investigates the issues that must be resolved to use an MLC in proton therapy . The second technology...the contract included three development agreements directly related to the work supported by this grant to develop technology for proton therapy .

MLC Libraries--A School Library's Journey with Students, Staff and Web 2.0 Technologies: Blogs, Wikis and E-Books--Where Are We Going Next?

ERIC Educational Resources Information Center

Viner, Jane; Lucas, Amanda; Ricchini, Tracey; Ri, Regina

2010-01-01

This workshop paper explores the Web 2.0 journey of the MLC Libraries' teacher-librarians, librarian, library and audio visual technicians. Our journey was initially inspired by Will Richardson and supported by the School Library Association of Victoria (SLAV) Web 2.0 professional development program. The 12 week technological skills program…

Linking log files with dosimetric accuracy--A multi-institutional study on quality assurance of volumetric modulated arc therapy.

PubMed

Pasler, Marlies; Kaas, Jochem; Perik, Thijs; Geuze, Job; Dreindl, Ralf; Künzler, Thomas; Wittkamper, Frits; Georg, Dietmar

2015-12-01

To systematically evaluate machine specific quality assurance (QA) for volumetric modulated arc therapy (VMAT) based on log files by applying a dynamic benchmark plan. A VMAT benchmark plan was created and tested on 18 Elekta linacs (13 MLCi or MLCi2, 5 Agility) at 4 different institutions. Linac log files were analyzed and a delivery robustness index was introduced. For dosimetric measurements an ionization chamber array was used. Relative dose deviations were assessed by mean gamma for each control point and compared to the log file evaluation. Fourteen linacs delivered the VMAT benchmark plan, while 4 linacs failed by consistently terminating the delivery. The mean leaf error (±1SD) was 0.3±0.2 mm for all linacs. Large MLC maximum errors up to 6.5 mm were observed at reversal positions. Delivery robustness index accounting for MLC position correction (0.8-1.0) correlated with delivery time (80-128 s) and depended on dose rate performance. Dosimetric evaluation indicated in general accurate plan reproducibility with γ(mean)(±1 SD)=0.4±0.2 for 1 mm/1%. However single control point analysis revealed larger deviations and attributed well to log file analysis. The designed benchmark plan helped identify linac related malfunctions in dynamic mode for VMAT. Log files serve as an important additional QA measure to understand and visualize dynamic linac parameters. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

SU-F-T-384: Step and Shoot IMRT, VMAT and Autoplan VMAT Nasopharnyx Plan Robustness to Linear Accelerator Delivery Errors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pogson, EM; Liverpool and Macarthur Cancer Therapy Centres, Liverpool, NSW; Ingham Institute for Applied Medical Research, Sydney, NSW

Purpose: To identify the robustness of different treatment techniques in respect to simulated linac errors on the dose distribution to the target volume and organs at risk for step and shoot IMRT (ssIMRT), VMAT and Autoplan generated VMAT nasopharynx plans. Methods: A nasopharynx patient dataset was retrospectively replanned with three different techniques: 7 beam ssIMRT, one arc manual generated VMAT and one arc automatically generated VMAT. Treatment simulated uncertainties: gantry, collimator, MLC field size and MLC shifts, were introduced into these plans at increments of 5,2,1,−1,−2 and −5 (degrees or mm) and recalculated in Pinnacle. The mean and maximum dosesmore » were calculated for the high dose PTV, parotids, brainstem, and spinal cord and then compared to the original baseline plan. Results: Simulated gantry angle errors have <1% effect on the PTV, ssIMRT is most sensitive. The small collimator errors (±1 and ±2 degrees) impacted the mean PTV dose by <2% for all techniques, however for the ±5 degree errors mean target varied by up to 7% for the Autoplan VMAT and 10% for the max dose to the spinal cord and brain stem, seen in all techniques. The simulated MLC shifts introduced the largest errors for the Autoplan VMAT, with the larger MLC modulation presumably being the cause. The most critical error observed, was the MLC field size error, where even small errors of 1 mm, caused significant changes to both the PTV and the OAR. The ssIMRT is the least sensitive and the Autoplan the most sensitive, with target errors of up to 20% over and under dosages observed. Conclusion: For a nasopharynx patient the plan robustness observed is highest for the ssIMRT plan and lowest for the Autoplan generated VMAT plan. This could be caused by the more complex MLC modulation seen for the VMAT plans. This project is supported by a grant from NSW Cancer Council.« less

Long-term outcomes after hepatic resection combined with radiofrequency ablation for initially unresectable multiple and bilobar liver malignancies.

PubMed

Qiu, Jianguo; Chen, Shuting; Wu, Hong

2014-05-01

Hepatic resection (HRE) combined with radiofrequency ablation (RFA) offers a surgical option to a group of patients with multiple and bilobar liver malignancies who are traditionally unresectable for inadequate functional hepatic reserve. The aims of the present study were to assess the perioperative outcomes, recurrence, and long-term survival rates for patients treated with HRE plus RFA in the management of primary hepatocellular carcinoma (HCC) and metastatic liver cancer (MLC). Data from all consecutive patients with primary and secondary hepatic malignancies who were treated with HRE combined with RFA between 2007 and 2013 were prospectively collected and retrospectively reviewed. A total of 112 patients, with 368 hepatic tumors underwent HRE combined with ultrasound-guided RFA, were included in the present study. There were 40 cases of HCC with 117 tumors and 72 cases of MLC with 251 metastases. Most cases of liver metastases originated from the gastrointestinal tract (44, 61.1%). Other uncommon lesions included breast cancer (5, 6.9%), pancreatic cancer (3, 4.2%), lung cancer (4, 5.6%), cholangiocarcinoma (4, 5.6%), and so on. The ablation success rates were 93.3% for HCC and 96.7% for MLC. The 1-, 2-, 3-, 4-, and 5-y overall recurrence rates were 52.5%, 59.5%, 72.3%, 75%, and 80% for the HCC group and 44.4%, 52.7%, 56.1%, 69.4%, and 77.8% for the MLC group, respectively. The 1-, 2-, 3-, 4-, and 5-y overall survival rates for the HCC patients were 67.5%, 50%, 32.5%, 22.5%, and 12.5% and for the MLC patients were 66.5%, 55.5%, 50%, 30.5%, and 19.4%, respectively. The corresponding recurrence-free survival rates for the HCC patients were 52.5%, 35%, 22.5%, 15%, and 10% and for the MLC patients were 58.3%, 41.6%, 23.6%, 16.9%, and 12.5%, respectively. HRE combined with RFA provides an effective treatment approach for patients with primary and secondary liver malignancies who are initially unsuitable for radical resection, with high local tumor control rates and promising survival data. Copyright © 2014 Elsevier Inc. All rights reserved.

TomoTherapy MLC verification using exit detector data

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen Quan; Westerly, David; Fang Zhenyu

2012-01-15

Purpose: Treatment delivery verification (DV) is important in the field of intensity modulated radiation therapy (IMRT). While IMRT and image guided radiation therapy (IGRT), allow us to create more conformal plans and enables the use of tighter margins, an erroneously executed plan can have detrimental effects on the treatment outcome. The purpose of this study is to develop a DV technique to verify TomoTherapy's multileaf collimator (MLC) using the onboard mega-voltage CT detectors. Methods: The proposed DV method uses temporal changes in the MVCT detector signal to predict actual leaf open times delivered on the treatment machine. Penumbra and scatteredmore » radiation effects may produce confounding results when determining leaf open times from the raw detector data. To reduce the impact of the effects, an iterative, Richardson-Lucy (R-L) deconvolution algorithm is applied. Optical sensors installed on each MLC leaf are used to verify the accuracy of the DV technique. The robustness of the DV technique is examined by introducing different attenuation materials in the beam. Additionally, the DV technique has been used to investigate several clinical plans which failed to pass delivery quality assurance (DQA) and was successful in identifying MLC timing discrepancies as the root cause. Results: The leaf open time extracted from the exit detector showed good agreement with the optical sensors under a variety of conditions. Detector-measured leaf open times agreed with optical sensor data to within 0.2 ms, and 99% of the results agreed within 8.5 ms. These results changed little when attenuation was added in the beam. For the clinical plans failing DQA, the dose calculated from reconstructed leaf open times played an instrumental role in discovering the root-cause of the problem. Throughout the retrospective study, it is found that the reconstructed dose always agrees with measured doses to within 1%. Conclusions: The exit detectors in the TomoTherapy treatment systems can provide valuable information about MLC behavior during delivery. A technique to estimate the TomoTherapy binary MLC leaf open time from exit detector signals is described. This technique is shown to be both robust and accurate for delivery verification.« less

An MLC-based linac QA procedure for the characterization of radiation isocenter and room lasers' position.

PubMed

Rosca, Florin; Lorenz, Friedlieb; Hacker, Fred L; Chin, Lee M; Ramakrishna, Naren; Zygmanski, Piotr

2006-06-01

We have designed and implemented a new stereotactic linac QA test with stereotactic precision. The test is used to characterize gantry sag, couch wobble, cone placement, MLC offsets, and room lasers' positions relative to the radiation isocenter. Two MLC star patterns, a cone pattern, and the laser line patterns are recorded on the same imaging medium. Phosphor plates are used as imaging medium due to their sensitivity to red light. The red light of room lasers erases some of the irradiation information stored on the phosphor plates enabling accurate and direct measurements for the position of room lasers and radiation isocenter. Using film instead of the phosphor plate as imaging medium is possible, however, it is less practical. The QA method consists of irradiating four phosphor plates that record the gantry sag between the 0 degrees and 180 degrees gantry angles, the position and stability of couch rotational axis, the sag between the 90 degrees and 270 degrees gantry angles, the accuracy of cone placement on the collimator, the MLC offsets from the collimator rotational axis, and the position of laser lines relative to the radiation isocenter. The estimated accuracy of the method is +/- 0.2 mm. The observed reproducibility of the method is about +/- 0.1 mm. The total irradiation/ illumination time is about 10 min per image. Data analysis, including the phosphor plate scanning, takes less than 5 min for each image. The method characterizes the radiation isocenter geometry with the high accuracy required for the stereotactic radiosurgery. In this respect, it is similar to the standard ball test for stereotactic machines. However, due to the usage of the MLC instead of the cross-hair/ball, it does not depend on the cross-hair/ball placement errors with respect to the lasers and it provides more information on the mechanical integrity of the linac/couch/laser system. Alternatively, it can be used as a highly accurate QA procedure for the nonstereotactic machines. Noteworthy is its ability to characterize the MLC position accuracy, which is an important factor in IMRT delivery.

Monte Carlo modeling of HD120 multileaf collimator on Varian TrueBeam linear accelerator for verification of 6X and 6X FFF VMAT SABR treatment plans

PubMed Central

Gete, Ermias; Duzenli, Cheryl; Teke, Tony

2014-01-01

A Monte Carlo (MC) validation of the vendor‐supplied Varian TrueBeam 6 MV flattened (6X) phase‐space file and the first implementation of the Siebers‐Keall MC MLC model as applied to the HD120 MLC (for 6X flat and 6X flattening filterfree (6X FFF) beams) are described. The MC model is validated in the context of VMAT patient‐specific quality assurance. The Monte Carlo commissioning process involves: 1) validating the calculated open‐field percentage depth doses (PDDs), profiles, and output factors (OF), 2) adapting the Siebers‐Keall MLC model to match the new HD120‐MLC geometry and material composition, 3) determining the absolute dose conversion factor for the MC calculation, and 4) validating this entire linac/MLC in the context of dose calculation verification for clinical VMAT plans. MC PDDs for the 6X beams agree with the measured data to within 2.0% for field sizes ranging from 2 × 2 to 40 × 40 cm2. Measured and MC profiles show agreement in the 50% field width and the 80%‐20% penumbra region to within 1.3 mm for all square field sizes. MC OFs for the 2 to 40 cm2 square fields agree with measurement to within 1.6%. Verification of VMAT SABR lung, liver, and vertebra plans demonstrate that measured and MC ion chamber doses agree within 0.6% for the 6X beam and within 2.0% for the 6X FFF beam. A 3D gamma factor analysis demonstrates that for the 6X beam, > 99% of voxels meet the pass criteria (3%/3 mm). For the 6X FFF beam, > 94% of voxels meet this criteria. The TrueBeam accelerator delivering 6X and 6X FFF beams with the HD120 MLC can be modeled in Monte Carlo to provide an independent 3D dose calculation for clinical VMAT plans. This quality assurance tool has been used clinically to verify over 140 6X and 16 6X FFF TrueBeam treatment plans. PACS number: 87.55.K‐ PMID:24892341

Dynamic tumor tracking using the Elekta Agility MLC

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fast, Martin F., E-mail: martin.fast@icr.ac.uk; Nill, Simeon, E-mail: simeon.nill@icr.ac.uk; Bedford, James L.

2014-11-01

Purpose: To evaluate the performance of the Elekta Agility multileaf collimator (MLC) for dynamic real-time tumor tracking. Methods: The authors have developed a new control software which interfaces to the Agility MLC to dynamically program the movement of individual leaves, the dynamic leaf guides (DLGs), and the Y collimators (“jaws”) based on the actual target trajectory. A motion platform was used to perform dynamic tracking experiments with sinusoidal trajectories. The actual target positions reported by the motion platform at 20, 30, or 40 Hz were used as shift vectors for the MLC in beams-eye-view. The system latency of the MLCmore » (i.e., the average latency comprising target device reporting latencies and MLC adjustment latency) and the geometric tracking accuracy were extracted from a sequence of MV portal images acquired during irradiation for the following treatment scenarios: leaf-only motion, jaw + leaf motion, and DLG + leaf motion. Results: The portal imager measurements indicated a clear dependence of the system latency on the target position reporting frequency. Deducting the effect of the target frequency, the leaf adjustment latency was measured to be 38 ± 3 ms for a maximum target speed v of 13 mm/s. The jaw + leaf adjustment latency was 53 ± 3 at a similar speed. The system latency at a target position frequency of 30 Hz was in the range of 56–61 ms for the leaves (v ≤ 31 mm/s), 71–78 ms for the jaw + leaf motion (v ≤ 25 mm/s), and 58–72 ms for the DLG + leaf motion (v ≤ 59 mm/s). The tracking accuracy showed a similar dependency on the target position frequency and the maximum target speed. For the leaves, the root-mean-squared error (RMSE) was between 0.6–1.5 mm depending on the maximum target speed. For the jaw + leaf (DLG + leaf) motion, the RMSE was between 0.7–1.5 mm (1.9–3.4 mm). Conclusions: The authors have measured the latency and geometric accuracy of the Agility MLC, facilitating its future use for clinical tracking applications.« less

Catabolic regulation analysis of Escherichia coli and its crp, mlc, mgsA, pgi and ptsG mutants

PubMed Central

2011-01-01

Background Most bacteria can use various compounds as carbon sources. These carbon sources can be either co-metabolized or sequentially metabolized, where the latter phenomenon typically occurs as catabolite repression. From the practical application point of view of utilizing lignocellulose for the production of biofuels etc., it is strongly desirable to ferment all sugars obtained by hydrolysis from lignocellulosic materials, where simultaneous consumption of sugars would benefit the formation of bioproducts. However, most organisms consume glucose prior to consumption of other carbon sources, and exhibit diauxic growth. It has been shown by fermentation experiments that simultaneous consumption of sugars can be attained by ptsG, mgsA mutants etc., but its mechanism has not been well understood. It is strongly desirable to understand the mechanism of metabolic regulation for catabolite regulation to improve the performance of fermentation. Results In order to make clear the catabolic regulation mechanism, several continuous cultures were conducted at different dilution rates of 0.2, 0.4, 0.6 and 0.7 h-1 using wild type Escherichia coli. The result indicates that the transcript levels of global regulators such as crp, cra, mlc and rpoS decreased, while those of fadR, iclR, soxR/S increased as the dilution rate increased. These affected the metabolic pathway genes, which in turn affected fermentation result where the specific glucose uptake rate, the specific acetate formation rate, and the specific CO2 evolution rate (CER) were increased as the dilution rate was increased. This was confirmed by the 13C-flux analysis. In order to make clear the catabolite regulation, the effect of crp gene knockout (Δcrp) and crp enhancement (crp+) as well as mlc, mgsA, pgi and ptsG gene knockout on the metabolism was then investigated by the continuous culture at the dilution rate of 0.2 h-1 and by some batch cultures. In the case of Δcrp (and also Δmlc) mutant, TCA cycle and glyoxylate were repressed, which caused acetate accumulation. In the case of crp+ mutant, glycolysis, TCA cycle, and gluconeogenesis were activated, and simultaneous consumption of multiple carbon sources can be attained, but the glucose consumption rate became less due to repression of ptsG and ptsH by the activation of Mlc. Simultaneous consumption of multiple carbon sources could be attained by mgsA, pgi, and ptsG mutants due to increase in crp as well as cyaA, while glucose consumption rate became lower. Conclusions The transcriptional catabolite regulation mechanism was made clear for the wild type E. coli, and its crp, mlc, ptsG, pgi, and mgsA gene knockout mutants. The results indicate that catabolite repression can be relaxed and crp as well as cyaA can be increased by crp+, mgsA, pgi, and ptsG mutants, and thus simultaneous consumption of multiple carbon sources including glucose can be made, whereas the glucose uptake rate became lower as compared to wild type due to inactivation of ptsG in all the mutants considered. PMID:21831320

Raf-1 levels determine the migration rate of primary endometrial stromal cells of patients with endometriosis

PubMed Central

Yotova, Iveta; Quan, Ping; Gaba, Aulona; Leditznig, Nadja; Pateisky, Petra; Kurz, Christine; Tschugguel, Walter

2012-01-01

Endometriosis is a disease characterized by the localization of endometrial tissue outside the uterine cavity. The differences observed in migration of human endometrial stromal cells (hESC) obtained from patients with endometriosis versus healthy controls were proposed to correlate with the abnormal activation of Raf-1/ROCKII signalling pathway. To evaluate the mechanism by which Raf-1 regulates cytoskeleton reorganization and motility, we used primary eutopic (Eu-, n = 16) and ectopic (Ec-, n = 8; isolated from ovarian cysts) hESC of patients with endometriosis and endometriosis-free controls (Co-hESC, n = 14). Raf-1 siRNA knockdown in Co- and Eu-hESC resulted in contraction and decreased migration versus siRNA controls. This phenotype was reversed following the re-expression of Raf-1 in these cells. Lowest Raf-1 levels in Ec-hESC were associated with hyperactivated ROCKII and ezrin/radixin/moesin (E/R/M), impaired migration and a contracted phenotype similar to Raf-1 knockdown in Co- and Eu-hESC. We further show that the mechanism by which Raf-1 mediates migration in hESC includes direct myosin light chain phosphatase (MYPT1) phosphorylation and regulation of the levels of E/R/M, paxillin, MYPT1 and myosin light chain (MLC) phosphorylation indirectly via the hyperactivation of ROCKII kinase. Furthermore, we suggest that in contrast to Co-and Eu-hESC, where the cellular Raf-1 levels regulate the rate of migration, the low cellular Raf-1 content in Ec-hESC, might ensure their restricted migration by preserving the contracted cellular phenotype. In conclusion, our findings suggest that cellular levels of Raf-1 adjust the threshold of hESC migration in endometriosis. PMID:22225925

Homogeneous-oxide stack in IGZO thin-film transistors for multi-level-cell NAND memory application

NASA Astrophysics Data System (ADS)

Ji, Hao; Wei, Yehui; Zhang, Xinlei; Jiang, Ran

2017-11-01

A nonvolatile charge-trap-flash memory that is based on amorphous indium-gallium-zinc-oxide thin film transistors was fabricated with a homogeneous-oxide structure for a multi-level-cell application. All oxide layers, i.e., tunneling layer, charge trapping layer, and blocking layer, were fabricated with Al2O3 films. The fabrication condition (including temperature and deposition method) of the charge trapping layer was different from those of the other oxide layers. This device demonstrated a considerable large memory window of 4 V between the states fully erased and programmed with the operation voltage less than 14 V. This kind of device shows a good prospect for multi-level-cell memory applications.

A new application of micellar liquid chromatography in the determination of free ampicillin concentration in the drug-human serum albumin standard solution in comparison with the adsorption method.

PubMed

Stępnik, Katarzyna E; Malinowska, Irena; Maciejewska, Małgorzata

2016-06-01

The determination of free drug concentration is a very important issue in the field of pharmacology because only the unbound drug fraction can achieve a pharmacological effect. Due to the ability to solubilize many different compounds in micellar aggregates, micellar liquid chromatography (MLC) can be used for direct determination of free drug concentration. Proteins are not retained on the stationary phase probably due to the formation of protein - surfactant complexes which are excluded from the pores of stationary phase. The micellar method is simple and fast. It does not require any pre-preparation of the tested samples for analysis. The main aim of this paper is to demonstrate a completely new applicability of the analytical use of MLC concerning the determination of free drug concentration in the standard solution of human serum albumin. The well-known adsorption method using RP-HPLC and the spectrophotometric technique was applied as the reference method. The results show that the free drug concentration value obtained in the MLC system (based on the RP-8 stationary phase and CTAB) is similar to that obtained by the adsorption method: both RP-HPLC (95.83μgmL(-1), 79.86% of free form) and spectrophotometry (95.71μgmL(-1), 79.76%). In the MLC the free drug concentration was 93.98μgmL(-1) (78.3%). This indicates that the obtained results are within the analytical range of % of free ampicillin fraction and the MLC with direct sample injection can be treated like a promising method for the determination of free drug concentration. Copyright © 2016 Elsevier B.V. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, X; Yang, F

Purpose: Knowing MLC leaf positioning error over the course of treatment would be valuable for treatment planning, QA design, and patient safety. The objective of the current study was to quantify the MLC positioning accuracy for VMAT delivery of head and neck treatment plans. Methods: A total of 837 MLC log files were collected from 14 head and neck cancer patients undergoing full arc VMAT treatment on one Varian Trilogy machine. The actual and planned leaf gaps were extracted from the retrieved MLC log files. For a given patient, the leaf gap error percentage (LGEP), defined as the ratio ofmore » the actual leaf gap over the planned, was evaluated for each leaf pair at all the gantry angles recorded over the course of the treatment. Statistics describing the distribution of the largest LGEP (LLGEP) of the 60 leaf pairs including the maximum, minimum, mean, Kurtosis, and skewness were evaluated. Results: For the 14 studied patients, their PTV located at tonsil, base of tongue, larynx, supraglottis, nasal cavity, and thyroid gland with volume ranging from 72.0 cm{sup 3} to 602.0 cm{sup 3}. The identified LLGEP differed between patients. It ranged from 183.9% to 457.7% with a mean of 368.6%. For the majority of the patients, the LLGEP distributions peaked at non-zero positions and showed no obvious dependence on gantry rotations. Kurtosis and skewness, with minimum/maximum of 66.6/217.9 and 6.5/12.6, respectively, suggested relatively more peaked while right-skewed leaf error distribution pattern. Conclusion: The results indicate pattern of MLC leaf gap error differs between patients of lesion located at similar anatomic site. Understanding the systemic mechanisms underlying these observed error patterns necessitates examining more patient-specific plan parameters in a large patient cohort setting.« less

A dosimetric evaluation of the Eclipse AAA algorithm and Millennium 120 MLC for cranial intensity-modulated radiosurgery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Calvo Ortega, Juan Francisco, E-mail: jfcdrr@yahoo.es; Moragues, Sandra; Pozo, Miquel

2014-07-01

The aim of this study is to assess the accuracy of a convolution-based algorithm (anisotropic analytical algorithm [AAA]) implemented in the Eclipse planning system for intensity-modulated radiosurgery (IMRS) planning of small cranial targets by using a 5-mm leaf-width multileaf collimator (MLC). Overall, 24 patient-based IMRS plans for cranial lesions of variable size (0.3 to 15.1 cc) were planned (Eclipse, AAA, version 10.0.28) using fixed field-based IMRS produced by a Varian linear accelerator equipped with a 120 MLC (5-mm width on central leaves). Plan accuracy was evaluated according to phantom-based measurements performed with radiochromic film (EBT2, ISP, Wayne, NJ). Film 2Dmore » dose distributions were performed with the FilmQA Pro software (version 2011, Ashland, OH) by using the triple-channel dosimetry method. Comparison between computed and measured 2D dose distributions was performed using the gamma method (3%/1 mm). Performance of the MLC was checked by inspection of the DynaLog files created by the linear accelerator during the delivery of each dynamic field. The absolute difference between the calculated and measured isocenter doses for all the IMRS plans was 2.5% ± 2.1%. The gamma evaluation method resulted in high average passing rates of 98.9% ± 1.4% (red channel) and 98.9% ± 1.5% (blue and green channels). DynaLog file analysis revealed a maximum root mean square error of 0.46 mm. According to our results, we conclude that the Eclipse/AAA algorithm provides accurate cranial IMRS dose distributions that may be accurately delivered by a Varian linac equipped with a Millennium 120 MLC.« less

Poster — Thur Eve — 19: Performance assessment of a 160-leaf beam collimation system

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ali, E. S. M.; La Russa, D. J.; Vandervoort, E.

2014-08-15

In this study, the performance of the new beam collimation system with 160 leaves, each with a 5 mm leaf width projected at isocenter, is evaluated in terms of positional accuracy and plan/delivery quality. Positional accuracy was evaluated using a set of static and dynamic MLC/jaw delivery patterns at different gantry angles, dose rates, and MLC/jaw speeds. The impact on IMRT plan quality was assessed by comparing against a previous generation collimation system using the same optimization parameters, while delivery quality was quantified using a combination of patient-specific QA measurements with ion chambers, film, and a bi-planar diode array. Positionalmore » accuracy for four separate units was comparable. The field size accuracy, junction width, and total displacement over 16 cm leaf travel are 0.3 ± 0.2 mm, 0.4 ± 0.3 mm, and 0.5 ± 0.2 mm, respectively. The typical leaf minor offset is 0.05 ± 0.04 mm, and MLC hysteresis effects are 0.2 ± 0.1 mm over 16 cm travel. The dynamic output is linear with MU and MLC/jaw speed, and is within 0.7 ± 0.3 % of the planning system value. Plan quality is significantly improved both in terms of target coverage and OAR sparing due, in part, to the larger allowable MLC and jaw speeds. γ-index pass rates for the patient-specific QA measurements exceeded 97% using criteria of 2%/2 mm. In conclusion, the performance of the Agility system is consistent among four separate installations, and is superior to its previous generations of collimation systems.« less

Greater epitope recognition of shrimp allergens by children than by adults suggests that shrimp sensitization decreases with age.

PubMed

Ayuso, Rosalía; Sánchez-Garcia, Silvia; Lin, Jing; Fu, Zhiyan; Ibáñez, María Dolores; Carrillo, Teresa; Blanco, Carlos; Goldis, Marina; Bardina, Ludmila; Sastre, Joaquín; Sampson, Hugh A

2010-06-01

Shellfish allergy is a long-lasting disorder typically affecting adults. Despite its high prevalence, there is limited information about allergenic shrimp proteins and the epitopes implicated in such allergic reactions. We sought to identify the IgE-binding epitopes of the 4 shrimp allergens and to characterize epitope recognition profiles of children and adults with shrimp allergy. Fifty-three subjects, 34 children and 19 adults, were selected with immediate allergic reactions to shrimp, increased shrimp-specific serum IgE levels, and positive immunoblot binding to shrimp. Study subjects and 7 nonatopic control subjects were tested by means of peptide microarray for IgE binding with synthetic overlapping peptides spanning the sequences of Litopenaeus vannamei shrimp tropomyosin, arginine kinase (AK), myosin light chain (MLC), and sarcoplasmic calcium-binding protein (SCP). The Wilcoxon test was used to determine significant differences in z scores between patients and control subjects. The median shrimp IgE level was 4-fold higher in children than in adults (47 vs 12.5 kU(A)/L). The frequency of allergen recognition was higher in children (tropomyosin, 81% [94% for children and 61% for adults]; MLC, 57% [70% for children and 31% for adults]; AK, 51% [67% for children and 21% for adults]; and SCP, 45% [59% for children and 21% for adults]), whereas control subjects showed negligible binding. Seven IgE-binding regions were identified in tropomyosin by means of peptide microarray, confirming previously identified shrimp epitopes. In addition, 3 new epitopes were identified in tropomyosin (epitopes 1, 3, and 5b-c), 5 epitopes were identified in MLC, 3 epitopes were identified in SCP, and 7 epitopes were identified in AK. Interestingly, frequency of individual epitope recognition, as well as intensity of IgE binding, was significantly greater in children than in adults for all 4 proteins. Children with shrimp allergy have greater shrimp-specific IgE antibody levels and show more intense binding to shrimp peptides and greater epitope diversity than adults. Copyright (c) 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Actin-myosin-based contraction is responsible for apoptotic nuclear disintegration.

PubMed

Croft, Daniel R; Coleman, Mathew L; Li, Shuixing; Robertson, David; Sullivan, Teresa; Stewart, Colin L; Olson, Michael F

2005-01-17

Membrane blebbing during the apoptotic execution phase results from caspase-mediated cleavage and activation of ROCK I. Here, we show that ROCK activity, myosin light chain (MLC) phosphorylation, MLC ATPase activity, and an intact actin cytoskeleton, but not microtubular cytoskeleton, are required for disruption of nuclear integrity during apoptosis. Inhibition of ROCK or MLC ATPase activity, which protect apoptotic nuclear integrity, does not affect caspase-mediated degradation of nuclear proteins such as lamins A, B1, or C. The conditional activation of ROCK I was sufficient to tear apart nuclei in lamin A/C null fibroblasts, but not in wild-type fibroblasts. Thus, apoptotic nuclear disintegration requires actin-myosin contractile force and lamin proteolysis, making apoptosis analogous to, but distinct from, mitosis where nuclear disintegration results from microtubule-based forces and from lamin phosphorylation and depolymerization.

Actin-myosin–based contraction is responsible for apoptotic nuclear disintegration

PubMed Central

Croft, Daniel R.; Coleman, Mathew L.; Li, Shuixing; Robertson, David; Sullivan, Teresa; Stewart, Colin L.; Olson, Michael F.

2005-01-01

Membrane blebbing during the apoptotic execution phase results from caspase-mediated cleavage and activation of ROCK I. Here, we show that ROCK activity, myosin light chain (MLC) phosphorylation, MLC ATPase activity, and an intact actin cytoskeleton, but not microtubular cytoskeleton, are required for disruption of nuclear integrity during apoptosis. Inhibition of ROCK or MLC ATPase activity, which protect apoptotic nuclear integrity, does not affect caspase-mediated degradation of nuclear proteins such as lamins A, B1, or C. The conditional activation of ROCK I was sufficient to tear apart nuclei in lamin A/C null fibroblasts, but not in wild-type fibroblasts. Thus, apoptotic nuclear disintegration requires actin-myosin contractile force and lamin proteolysis, making apoptosis analogous to, but distinct from, mitosis where nuclear disintegration results from microtubule-based forces and from lamin phosphorylation and depolymerization. PMID:15657395

Interface Message Processors for the ARPA Computer Network

DTIC Science & Technology

1975-04-01

Pluribus IMP construction and checkout; sizeable changes to the i*4P message-processing algorithms: and Satellite IMP issues. The IMP message...extremely low cost modification design. We have begun to consider changes to the MLC design which would enable the MLC to suppress continuous breaks...existing authentication mechanisms need not make these changes . 2.7 Other Topics During the first quarter BBN constructed an environmental test chamber

Development and validation of a BEAMnrc component module for a miniature multileaf collimator.

PubMed

Doerner, E; Hartmann, G H

2012-05-21

A new component module (CM) named mini multileaf collimator (mMLC) was developed for the Monte Carlo code BEAMnrc. It models the geometry of the add-on miniature multileaf collimator ModuLeaf (MRC Systems GmbH, Heidelberg, Germany, now part of Siemens, Erlangen, Germany). The new CM is partly based on the existing CM called DYNVMLC. The development was performed using a modified EGSnrc platform which enables us to work in the Microsoft Visual Studio environment. In order to validate the new CM, the PRIMUS linac with 6 MV x-rays (Siemens OCS, Concord, CA, USA) equipped with the ModuLeaf mMLC was modelled. Validation was performed by two methods: (a) a ray-tracing method to check the correct geometry of the multileaf collimator (MLC) and (b) a comparison of calculated and measured results of the following dosimetrical parameters: output factors, dose profiles, field edge position penumbra, MLC interleaf leakage and transmission values. Excellent agreement was found for all parameters. It was, in particular, found that the relationship between leaf position and field edge depending on the shape of the leaf ends can be investigated with a higher accuracy by this new CM than by measurements demonstrating the usefulness of the new CM.

Development and validation of a BEAMnrc component module for a miniature multileaf collimator

NASA Astrophysics Data System (ADS)

Doerner, E.; Hartmann, G. H.

2012-05-01

A new component module (CM) named mini multileaf collimator (mMLC) was developed for the Monte Carlo code BEAMnrc. It models the geometry of the add-on miniature multileaf collimator ModuLeaf (MRC Systems GmbH, Heidelberg, Germany, now part of Siemens, Erlangen, Germany). The new CM is partly based on the existing CM called DYNVMLC. The development was performed using a modified EGSnrc platform which enables us to work in the Microsoft Visual Studio environment. In order to validate the new CM, the PRIMUS linac with 6 MV x-rays (Siemens OCS, Concord, CA, USA) equipped with the ModuLeaf mMLC was modelled. Validation was performed by two methods: (a) a ray-tracing method to check the correct geometry of the multileaf collimator (MLC) and (b) a comparison of calculated and measured results of the following dosimetrical parameters: output factors, dose profiles, field edge position penumbra, MLC interleaf leakage and transmission values. Excellent agreement was found for all parameters. It was, in particular, found that the relationship between leaf position and field edge depending on the shape of the leaf ends can be investigated with a higher accuracy by this new CM than by measurements demonstrating the usefulness of the new CM.

A Liver-centric Multiscale Modeling Framework for Xenobiotics ...

EPA Pesticide Factsheets

We describe a multi-scale framework for modeling acetaminophen-induced liver toxicity. Acetaminophen is a widely used analgesic. Overdose of acetaminophen can result in liver injury via its biotransformation into toxic product, which further induce massive necrosis. Our study focuses on developing a multi-scale computational model to characterize both phase I and phase II metabolism of acetaminophen, by bridging Physiologically Based Pharmacokinetic (PBPK) modeling at the whole body level, cell movement and blood flow at the tissue level and cell signaling and drug metabolism at the sub-cellular level. To validate the model, we estimated our model parameters by fi?tting serum concentrations of acetaminophen and its glucuronide and sulfate metabolites to experiments, and carried out sensitivity analysis on 35 parameters selected from three modules. Our study focuses on developing a multi-scale computational model to characterize both phase I and phase II metabolism of acetaminophen, by bridging Physiologically Based Pharmacokinetic (PBPK) modeling at the whole body level, cell movement and blood flow at the tissue level and cell signaling and drug metabolism at the sub-cellular level. This multiscale model bridges the CompuCell3D tool used by the Virtual Tissue project with the httk tool developed by the Rapid Exposure and Dosimetry project.

Antifungal activity of phenolic-rich Lavandula multifida L. essential oil.

PubMed

Zuzarte, M; Vale-Silva, L; Gonçalves, M J; Cavaleiro, C; Vaz, S; Canhoto, J; Pinto, E; Salgueiro, L

2012-07-01

This study evaluates the antifungal activity and mechanism of action of a new chemotype of Lavandula multifida from Portugal. The essential oil was analyzed by gas chromatography (GC) and gas chromatography/mass spectrometry (GC/MS), and the minimal inhibitory concentration (MIC) and minimal lethal concentration (MLC) of the oil and its major compounds were determined against several pathogenic fungi responsible for candidosis, meningitis, dermatophytosis, and aspergillosis. The influence of the oil on the dimorphic transition in Candida albicans was also studied, as well as propidium iodide (PI) and FUN-1 staining of C. albicans cells by flow cytometry. The essential oil was characterized by high contents of monoterpenes, with carvacrol and cis-β-ocimene being the main constituents. The oil was more effective against dermatophytes and Cryptococcus neoformans, with MIC and MLC values of 0.16 μL/mL and 0.32 μL/mL, respectively. The oil was further shown to completely inhibit filamentation in C. albicans at concentrations below the respective MIC (0.08 μL/mL), with cis-β-ocimene being the main compound responsible for this inhibition (0.02 μL/mL). The flow cytometry results suggest a mechanism of action ultimately leading to cytoplasmic membrane disruption and cell death. L. multifida essential oil may be useful in complementary therapy to treat disseminated candidosis, since the inhibition of filamentation alone appears to be sufficient to treat this type of infection.

Solar power generation system for reducing leakage current

NASA Astrophysics Data System (ADS)

Wu, Jinn-Chang; Jou, Hurng-Liahng; Hung, Chih-Yi

2018-04-01

This paper proposes a transformer-less multi-level solar power generation system. This solar power generation system is composed of a solar cell array, a boost power converter, an isolation switch set and a full-bridge inverter. A unipolar pulse-width modulation (PWM) strategy is used in the full-bridge inverter to attenuate the output ripple current. Circuit isolation is accomplished by integrating the isolation switch set between the solar cell array and the utility, to suppress the leakage current. The isolation switch set also determines the DC bus voltage for the full-bridge inverter connecting to the solar cell array or the output of the boost power converter. Accordingly, the proposed transformer-less multi-level solar power generation system generates a five-level voltage, and the partial power of the solar cell array is also converted to AC power using only the full-bridge inverter, so the power efficiency is increased. A prototype is developed to validate the performance of the proposed transformer-less multi-level solar power generation system.

Multi-cellular natural killer (NK) cell clusters enhance NK cell activation through localizing IL-2 within the cluster

NASA Astrophysics Data System (ADS)

Kim, Miju; Kim, Tae-Jin; Kim, Hye Mi; Doh, Junsang; Lee, Kyung-Mi

2017-01-01

Multi-cellular cluster formation of natural killer (NK) cells occurs during in vivo priming and potentiates their activation to IL-2. However, the precise mechanism underlying this synergy within NK cell clusters remains unclear. We employed lymphocyte-laden microwell technologies to modulate contact-mediated multi-cellular interactions among activating NK cells and to quantitatively assess the molecular events occurring in multi-cellular clusters of NK cells. NK cells in social microwells, which allow cell-to-cell contact, exhibited significantly higher levels of IL-2 receptor (IL-2R) signaling compared with those in lonesome microwells, which prevent intercellular contact. Further, CD25, an IL-2R α chain, and lytic granules of NK cells in social microwells were polarized toward MTOC. Live cell imaging of lytic granules revealed their dynamic and prolonged polarization toward neighboring NK cells without degranulation. These results suggest that IL-2 bound on CD25 of one NK cells triggered IL-2 signaling of neighboring NK cells. These results were further corroborated by findings that CD25-KO NK cells exhibited lower proliferation than WT NK cells, and when mixed with WT NK cells, underwent significantly higher level of proliferation. These data highlights the existence of IL-2 trans-presentation between NK cells in the local microenvironment where the availability of IL-2 is limited.

Myosin IIA-related Actomyosin Contractility Mediates Oxidative Stress-induced Neuronal Apoptosis

PubMed Central

Wang, Yan; Xu, Yingqiong; Liu, Qian; Zhang, Yuanyuan; Gao, Zhen; Yin, Mingzhu; Jiang, Nan; Cao, Guosheng; Yu, Boyang; Cao, Zhengyu; Kou, Junping

2017-01-01

Oxidative stress-induced neuronal apoptosis plays an important role in the progression of central nervous system (CNS) diseases. In our study, when neuronal cells were exposed to hydrogen peroxide (H2O2), an exogenous oxidant, cell apoptosis was observed with typical morphological changes including membrane blebbing, neurite retraction and cell contraction. The actomyosin system is considered to be responsible for the morphological changes, but how exactly it regulates oxidative stress-induced neuronal apoptosis and the distinctive functions of different myosin II isoforms remain unclear. We demonstrate that myosin IIA was required for neuronal contraction, while myosin IIB was required for neuronal outgrowth in normal conditions. During H2O2-induced neuronal apoptosis, myosin IIA, rather than IIB, interacted with actin filaments to generate contractile forces that lead to morphological changes. Moreover, myosin IIA knockout using clustered regularly interspaced short palindromic repeats/CRISPR-associated protein-9 nuclease (CRISPR/Cas9) reduced H2O2-induced neuronal apoptosis and the associated morphological changes. We further demonstrate that caspase-3/Rho-associated kinase 1 (ROCK1) dependent phosphorylation of myosin light chain (MLC) was required for the formation of the myosin IIA-actin complex. Meanwhile, either inhibition of myosin II ATPase with blebbistatin or knockdown of myosin IIA with siRNA reversely attenuated caspase-3 activation, suggesting a positive feedback loop during oxidative stress-induced apoptosis. Based on our observation, myosin IIA-actin complex contributes to actomyosin contractility and is associated with the positive feedback loop of caspase-3/ROCK1/MLC pathway. This study unravels the biochemical and mechanistic mechanisms during oxidative stress-induced neuronal apoptosis and may be applicable for the development of therapies for CNS diseases. PMID:28352215

Dynamic temperature response of electrocaloric multilayer capacitors

NASA Astrophysics Data System (ADS)

Kwon, Beomjin; Roh, Im-Jun; Baek, Seung-Hyub; Keun Kim, Seong; Kim, Jin-Sang; Kang, Chong-Yun

2014-05-01

We measure and model the dynamic temperature response of electrocaloric (EC) multilayer capacitors (MLCs) which have been recently highlighted as novel solid-state refrigerators. The MLC temperature responses depend on the operation voltage waveform, thus we consider three types of voltage waveforms, which include square, triangular, and trapezoidal. Further, to implement an effective refrigeration cycle, the waveform frequency and duty cycle should be carefully chosen. First, our model is fitted to the measurements to evaluate an effective EC power and thermal properties, and calculates an effective cooling power for an EC MLC. The prediction shows that for a MLC with a thermal relaxation time for cooling, trc, a square voltage waveform with a duty cycle of 0 < d ≤ 0.3 and a period of trc < P ≤ 1.4trc provides the maximum cooling power. This work will help to improve the implementing methods for EC refrigeration cycles.

Rho kinase regulates the survival and transformation of cells bearing oncogenic forms of KIT, FLT3 and BCR-ABL

PubMed Central

Mali, Raghuveer Singh; Ramdas, Baskar; Ma, Peilin; Shi, Jianjian; Munugalavadla, Veerendra; Sims, Emily; Wei, Lei; Vemula, Sasidhar; Nabinger, Sarah C.; Goodwin, Charles B.; Chan, Rebecca J.; Traina, Fabiola; Visconte, Valeria; Tiu, Ramon V.; Lewis, Timothy A.; Stern, Andrew M.; Wen, Qiang; Crispino, John D.; Boswell, H. Scott; Kapur, Reuben

2011-01-01

Summary We show constitutive activation of Rho kinase (ROCK) in cells bearing oncogenic forms of KIT, FLT3 and BCR-ABL, which is dependent on PI3K and Rho GTPase. Genetic or pharmacologic inhibition of ROCK in oncogene bearing cells impaired their growth as well as the growth of acute myeloid leukemia patient derived blasts and prolonged the life span of mice bearing myeloproliferative disease. Downstream from ROCK, rapid dephosphorylation or loss of expression of myosin light chain resulted in enhanced apoptosis, reduced growth and loss of actin polymerization in oncogene bearing cells leading to significantly prolonged life span of leukemic mice. In summary, we describe a pathway involving PI3K/Rho/ROCK/MLC which may contribute to myeloproliferative disease and/or acute myeloid leukemia in humans. PMID:21907926

Failure Modes in Capacitors When Tested Under a Time-Varying Stress

NASA Technical Reports Server (NTRS)

Liu, David (Donhang)

2011-01-01

Power-on failure has been the prevalent failure mechanism for solid tantalum capacitors in decoupling applications. A surge step stress test (SSST) has been previously applied to identify the critical stress level of a capacitor batch to give some predictability to the power-on failure mechanism [1]. But SSST can also be viewed as an electrically destructive test under a time-varying stress (voltage). It consists of rapidly charging the capacitor with incremental voltage increases, through a low resistance in series, until the capacitor under test is electrically shorted. When the reliability of capacitors is evaluated, a highly accelerated life test (HALT) is usually adopted since it is a time-efficient method of determining the failure mechanism; however, a destructive test under a time-varying stress such as SSST is even more time efficient. It usually takes days or weeks to complete a HALT test, but it only takes minutes for a time-varying stress test to produce failures. The advantage of incorporating a specific time-varying stress profile into a statistical model is significant in providing an alternative life test method for quickly revealing the failure mechanism in capacitors. In this paper, a time-varying stress that mimics a typical SSST has been incorporated into the Weibull model to characterize the failure mechanism in different types of capacitors. The SSST circuit and transient conditions for correctly surge testing capacitors are discussed. Finally, the SSST was applied for testing Ta capacitors, polymer aluminum capacitors (PA capacitors), and multi-layer ceramic (MLC) capacitors with both precious metal electrodes (PME) and base metal electrodes (BME). The test results are found to be directly associated with the dielectric layer breakdown in Ta and PA capacitors and are independent of the capacitor values, the way the capacitors were built, and the capacitors manufacturers. The test results also show that MLC capacitors exhibit surge breakdown voltages much higher than the rated voltage and that the breakdown field is inversely proportional to the dielectric layer thickness. The SSST data can also be used to comparatively evaluate the voltage robustness of capacitors for decoupling applications.

SU-F-T-604: Dosimetric Evaluation of Intracranial Stereotactic Radiotherapy Plans On a LINAC

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sheth, N; Tabibian, A; Rose, J

2016-06-15

Purpose: To evaluate the dosimetry of cranial stereotactic radiotherapy (SRT) plans of varying techniques on linac that meets appropriate TG-142 tolerances using 1 cm leaf width multileaf collimator (MLC). Methods: Seventeen spherical targets were generated in the center of a head phantom with diameters ranging 8 mm to 40 mm. SRT plans used 100° non-coplanar arcs and 5 couch angles with 35° spacing. The field size was target plus 1 mm margin. Four plans were created for each target: symmetrical jaws blocking for 5 arcs with 0° collimator (J1C), symmetrical jaws blocking with 5 clockwise arcs with 0° collimator andmore » 5 counter-clockwise arcs with 45° collimator (J2C), MLC blocking for 5 dynamic conformal arcs with 0° collimator (M1C), and MLC blocking for 5 clockwise dynamic conformal arcs with 0° collimators and 5 counter-clockwise dynamic conformal arcs with 45° collimator (M2C).Conformity was evaluated using a ratio of Rx to target volume (PITV). Heterogeneity was determined using a ratio of maximum dose to Rx dose. Falloff was scored using CGIg: difference of effective radii of spheres equal to half and full Rx volumes. Results: All plans met RTOG SRS criteria for conformity and heterogeneity. The mean PITV was 1.52±0.07, 1.49±0.08, 1.39±0.05, and 1.37±0.04 for J1C, J2C, M1C, and M2C plans respectively. The mean CGIg was 75.35±15.79, 74.19±16.66, 77.14±15.12, and 76.28±15.78 for J1C, J2C, M1C, and M2C plans respectively. The mean MDPD was 1.25±0.00 for all techniques. Conclusion: Clinically acceptable SRT plans for spherical targets were created on a linac with 1 cm MLC. Adding two collimator angles and MLC to arcs each improved conformity. The MLC improved the dose falloff while two collimator angles degraded it. This technique can expand the availability of SRT to patients especially to those who cannot travel to a facility with a dedicated stereotactic radiosurgery machine.« less

Magnetic decoupling of the linac in a low field biplanar linac-MR system.

PubMed

St Aubin, J; Steciw, S; Fallone, B G

2010-09-01

The integration of a low field biplanar magnetic resonance (MR) imager and linear accelerator (linac) causes magnetic interference at the linac due to the MR fringe fields. In order to eliminate this interference, passive and active magnetic shielding designs are investigated. The optimized design of passive magnetic shielding was performed using the finite element method. The design was required to achieve no greater than a 20% electron beam loss within the linac waveguide and electron gun, no greater than 0.06 T at the multileaf collimator (MLC) motors, and generate a distortion of the main MR imaging volume of no greater than 300 ppm. Through the superposition of the analytical solution for a single current carrying wire loop, active shielding designs in the form of three and four sets of coil pairs surrounding the linac waveguide and electron gun were also investigated. The optimized current and coil center locations that yielded the best cancellation of the MR fringe fields at the linac were determined using sequential quadratic programming. Optimized passive shielding in the form of two steel cylinders was designed to meet the required constraints. When shielding the MLC motors along with the waveguide and electron gun, the thickness of the cylinders was less than 1 mm. If magnetically insensitive MLC motors are used, no MLC shielding would be required and the waveguide shield (shielding the waveguide and electron gun) became 1.58 mm thick. In addition, the optimized current and coil spacing for active shielding was determined for both three and four coil pair configurations. The results of the active shielding optimization produced no beam loss within the waveguide and electron gun and a maximum MR field distortion of 91 ppm over a 30 cm diameter spherical volume. Very simple passive and active shielding designs have been shown to magnetically decouple the linac from the MR imager in a low field biplanar linac-MR system. The MLC passive shielding produced the largest distortion of the MR field over the imaging volume. With the use of magnetically insensitive motors, the MR field distortion drops substantially since no MLC shield is required. The active shielding designs yielded no electron beam loss within the linac.

Do technological advances in linear accelerators improve dosimetric outcomes in stereotaxy? A head-on comparison of seven linear accelerators using volumetric modulated arc therapy-based stereotactic planning.

PubMed

Sarkar, B; Pradhan, A; Munshi, A

2016-01-01

Linear accelerator (Linac) based stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT) using volumetric modulated arc therapy (VMAT) has been used for treating small intracranial lesions. Recent development in the Linacs such as inbuilt micro multileaf collimator (MLC) and flattening filter free (FFF) beam are intended to provide a better dose conformity and faster delivery when using VMAT technique. This study was aimed to compare the dosimetric outcomes and monitor units (MUs) of the stereotactic treatment plans for different commercially available MLC models and beam profiles. Ten patients having 12 planning target volume (PTV)/gross target volume's (GTVs) who received the SRS/SRT treatment in our clinic using Axesse Linac (considered reference arm gold standard) were considered for this study. The test arms comprised of plans using Elekta Agility with FFF, Elekta Agility with the plane beam, Elekta APEX, Varian Millennium 120, Varian Millennium 120HD, and Elekta Synergy in Monaco treatment planning system. Planning constraints and calculation grid spacing were not altered in the test plans. To objectively evaluate the efficacy of MLC-beam model, the resultant dosimetric outcomes were subtracted from the reference arm parameters. V95%, V100%, V105%, D1%, maximum dose, and mean dose of PTV/GTV showed a maximum inter MLC - beam model variation of 1.5% and 2% for PTV and GTV, respectively. Average PTV conformity index and heterogeneity index shows a variation in the range 0.56-0.63 and 1.08-1.11, respectively. Mean dose difference (excluding Axesse) for all organs varied between 1.1 cGy and 74.8 cGy (mean dose = 6.1 cGy standard deviation [SD] = 26.9 cGy) and 1.7 cGy-194.5 cGy (mean dose 16.1 cGy SD = 57.2 cGy) for single and multiple fraction, respectively. The dosimetry of VMAT-based SRS/SRT treatment plan had minimal dependence on MLC and beam model variations. All tested MLC and beam model could fulfil the desired PTV coverage and organs at risk dose constraints. The only notable difference was the halving of the MU for FFF beam as compared to the plane beam. This has the potential to reduce the total patient on couch time by 15% (approximately 2 min).

Effect of tertiary multileaf collimator (MLC) on foetal dose during three-dimensional conformal radiation therapy (3DCRT) of a brain tumour during pregnancy.

PubMed

Sharma, Dayananda S; Jalali, Rakesh; Tambe, Chandrashekhar M; Animesh; Deshpande, Deepak D

2004-01-01

The aim of this work was to measure the dose to foetus both in vivo and in vitro during three-dimensional conformal radiation therapy (3DCRT) in a pregnant patient with a pituitary adenoma. The study was then extended to assess the components contributing to the foetal dose such as collimator scatter, internal scatter, head leakage, wedge scatter and multileaf collimator (MLC) effect. A 30-year-old pregnant woman with a non-functioning pituitary macroadenoma was planned for 3DCRT with 6MV X-ray using four equally weighted MLC-shaped non-coplanar wedged portals. In vivo dosimetry was carried out using thermoluminescent (TL) phosphor powder, which was placed at different positions on the patient, corresponding to different locations in the uterus and also at external os. In vitro measurements were also performed on a simulated phantom using the same set-up parameters and beam arrangement to verify the in vivo measured dose. Experiments were carried out to measure the respective contributions of different components towards peripheral dose. In vitro measured dose to foetus was found to be slightly more than that of in vivo measurement with a maximum of 0.044% of the prescribed dose of 45Gy, which corresponded to 0.0199+/-0.0008Gy. Thermoluminescence dosimeter (TLD) kept at the external os of the patient showed a dose of 0.031% of the prescribed dose. Among the various components of the peripheral dose (foetal dose) measured, head leakage was found to be the leading cause contributing 52%, followed by wedge scatter (31%), collimator scatter (14%) and internal scatter (13%). The use of MLC reduced not only the volume of normal brain irradiation as compared to open fields but also the peripheral dose by 10%. Radiotherapy of brain tumours during pregnancy poses a unique clinical situation and decisions to deliver radiotherapy should be taken after detailed in vitro and in vivo dosimetric measurements. Our findings suggest that the beam arrangement using 3-4-fields generally used for 3DCRT of brain tumour with MLC for optimal coverage can be employed for pregnant patients even in early trimester. A possible increase in foetal dose from wedges to a large extent can be compensated with the use of MLC.

Experimental investigation of a moving averaging algorithm for motion perpendicular to the leaf travel direction in dynamic MLC target tracking.

PubMed

Yoon, Jai-Woong; Sawant, Amit; Suh, Yelin; Cho, Byung-Chul; Suh, Tae-Suk; Keall, Paul

2011-07-01

In dynamic multileaf collimator (MLC) motion tracking with complex intensity-modulated radiation therapy (IMRT) fields, target motion perpendicular to the MLC leaf travel direction can cause beam holds, which increase beam delivery time by up to a factor of 4. As a means to balance delivery efficiency and accuracy, a moving average algorithm was incorporated into a dynamic MLC motion tracking system (i.e., moving average tracking) to account for target motion perpendicular to the MLC leaf travel direction. The experimental investigation of the moving average algorithm compared with real-time tracking and no compensation beam delivery is described. The properties of the moving average algorithm were measured and compared with those of real-time tracking (dynamic MLC motion tracking accounting for both target motion parallel and perpendicular to the leaf travel direction) and no compensation beam delivery. The algorithm was investigated using a synthetic motion trace with a baseline drift and four patient-measured 3D tumor motion traces representing regular and irregular motions with varying baseline drifts. Each motion trace was reproduced by a moving platform. The delivery efficiency, geometric accuracy, and dosimetric accuracy were evaluated for conformal, step-and-shoot IMRT, and dynamic sliding window IMRT treatment plans using the synthetic and patient motion traces. The dosimetric accuracy was quantified via a tgamma-test with a 3%/3 mm criterion. The delivery efficiency ranged from 89 to 100% for moving average tracking, 26%-100% for real-time tracking, and 100% (by definition) for no compensation. The root-mean-square geometric error ranged from 3.2 to 4.0 mm for moving average tracking, 0.7-1.1 mm for real-time tracking, and 3.7-7.2 mm for no compensation. The percentage of dosimetric points failing the gamma-test ranged from 4 to 30% for moving average tracking, 0%-23% for real-time tracking, and 10%-47% for no compensation. The delivery efficiency of moving average tracking was up to four times higher than that of real-time tracking and approached the efficiency of no compensation for all cases. The geometric accuracy and dosimetric accuracy of the moving average algorithm was between real-time tracking and no compensation, approximately half the percentage of dosimetric points failing the gamma-test compared with no compensation.

Prognostic Factors and Pattern of Long-Term Recovery with MLC601 (NeuroAiD™) in the Chinese Medicine NeuroAiD Efficacy on Stroke Recovery - Extension Study.

PubMed

Venketasubramanian, Narayanaswamy; Lee, Chun Fan; Young, Sherry H; Tay, San San; Umapathi, Thirugnanam; Lao, Annabelle Y; Gan, Herminigildo H; Baroque Ii, Alejandro C; Navarro, Jose C; Chang, Hui Meng; Advincula, Joel M; Muengtaweepongsa, Sombat; Chan, Bernard P L; Chua, Carlos L; Wijekoon, Nirmala; de Silva, H Asita; Hiyadan, John Harold B; Suwanwela, Nijasri C; Wong, K S Lawrence; Poungvarin, Niphon; Eow, Gaik Bee; Chen, Christopher L H

2017-01-01

The Chinese Medicine NeuroAiD Efficacy on Stroke recovery - Extension (CHIMES-E) study is among the few acute stroke trials with long-term outcome data. We aimed to evaluate the recovery pattern and the influence of prognostic factors on treatment effect of MLC601 over 2 years. The CHIMES-E study evaluated the 2 years outcome of subjects aged ≥18 years with acute ischemic stroke, National Institutes of Health Stroke Scale (NIHSS) score 6-14, pre-stroke modified Rankin Scale (mRS) score ≤1 included in a multicenter, randomized, double-blind, placebo-controlled trial of MLC601 for 3 months. Standard stroke care and rehabilitation were allowed during follow-up with mRS score being assessed in-person at month (M) 3 and by telephone at M1, M6, M12, M18 and M24. Data from 880 subjects were analyzed. There was no difference in baseline characteristics between treatment groups. The proportion of subjects with mRS score 0-1 increased over time in favor of MLC601 most notably from M3 to M6, thereafter remaining stable up to M24, while the proportion deteriorating to mRS score ≥2 remained low at all time points. Older age (p < 0.01), female sex (p = 0.06), higher baseline NIHSS score (p < 0.01) and longer onset to treatment time (OTT; p < 0.01) were found to be predictors of poorer outcome at M3. Greater treatment effect, with more subjects improving on MLC601 than placebo, was seen among subjects with 2 or more prognostic factors (OR 1.65 at M3, 1.78 at M6, 1.90 at M12, 1.65 at M18, 1.39 at M24), especially in subjects with more severe stroke or longer OTT. The sustained benefits of MLC601 over 2 years were due to more subjects improving to functional independence at M6 and beyond compared to placebo. Selection of subjects with poorer prognosis, particularly those with more severe NIHSS score and longer OTT delay, as well as a long follow-up period, may improve the power of future trials investigating the treatment effect of neuroprotective or neurorestorative therapies. © 2016 The Author(s) Published by S. Karger AG, Basel.

Fast leaf-fitting with generalized underdose/overdose constraints for real-time MLC tracking

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moore, Douglas, E-mail: douglas.moore@utsouthwestern.edu; Sawant, Amit; Ruan, Dan

2016-01-15

Purpose: Real-time multileaf collimator (MLC) tracking is a promising approach to the management of intrafractional tumor motion during thoracic and abdominal radiotherapy. MLC tracking is typically performed in two steps: transforming a planned MLC aperture in response to patient motion and refitting the leaves to the newly generated aperture. One of the challenges of this approach is the inability to faithfully reproduce the desired motion-adapted aperture. This work presents an optimization-based framework with which to solve this leaf-fitting problem in real-time. Methods: This optimization framework is designed to facilitate the determination of leaf positions in real-time while accounting for themore » trade-off between coverage of the PTV and avoidance of organs at risk (OARs). Derived within this framework, an algorithm is presented that can account for general linear transformations of the planned MLC aperture, particularly 3D translations and in-plane rotations. This algorithm, together with algorithms presented in Sawant et al. [“Management of three-dimensional intrafraction motion through real-time DMLC tracking,” Med. Phys. 35, 2050–2061 (2008)] and Ruan and Keall [Presented at the 2011 IEEE Power Engineering and Automation Conference (PEAM) (2011) (unpublished)], was applied to apertures derived from eight lung intensity modulated radiotherapy plans subjected to six-degree-of-freedom motion traces acquired from lung cancer patients using the kilovoltage intrafraction monitoring system developed at the University of Sydney. A quality-of-fit metric was defined, and each algorithm was evaluated in terms of quality-of-fit and computation time. Results: This algorithm is shown to perform leaf-fittings of apertures, each with 80 leaf pairs, in 0.226 ms on average as compared to 0.082 and 64.2 ms for the algorithms of Sawant et al., Ruan, and Keall, respectively. The algorithm shows approximately 12% improvement in quality-of-fit over the Sawant et al. approach, while performing comparably to Ruan and Keall. Conclusions: This work improves upon the quality of the Sawant et al. approach, but does so without sacrificing run-time performance. In addition, using this framework allows for complex leaf-fitting strategies that can be used to account for PTV/OAR trade-off during real-time MLC tracking.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chengqiang, L; Yin, Y; Chen, L

Purpose: To investigate the impact of MLC position errors on simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) for patients with nasopharyngeal carcinoma. Methods: To compare the dosimetric differences between the simulated plans and the clinical plans, ten patients with locally advanced NPC treated with SIB-IMRT were enrolled in this study. All plans were calculated with an inverse planning system (Pinnacle3, Philips Medical System{sub )}. Random errors −2mm to 2mm{sub )},shift errors{sub (} 2mm,1mm and 0.5mm) and systematic extension/ contraction errors (±2mm, ±1mm and ±0.5mm) of the MLC leaf position were introduced respectively into the original plans to create the simulated plans.more » Dosimetry factors were compared between the original and the simulated plans. Results: The dosimetric impact of the random and system shift errors of MLC position was insignificant within 2mm, the maximum changes in D95% of PGTV,PTV1,PTV2 were-0.92±0.51%,1.00±0.24% and 0.62±0.17%, the maximum changes in the D0.1cc of spinal cord and brainstem were 1.90±2.80% and −1.78±1.42%, the maximum changes in the Dmean of parotids were1.36±1.23% and −2.25±2.04%.However,the impact of MLC extension or contraction errors was found significant. For 2mm leaf extension errors, the average changes in D95% of PGTV,PTV1,PTV2 were 4.31±0.67%,4.29±0.65% and 4.79±0.82%, the averaged value of the D0.1cc to spinal cord and brainstem were increased by 7.39±5.25% and 6.32±2.28%,the averaged value of the mean dose to left and right parotid were increased by 12.75±2.02%,13.39±2.17% respectively. Conclusion: The dosimetric effect was insignificant for random MLC leaf position errors up to 2mm. There was a high sensitivity to dose distribution for MLC extension or contraction errors.We should pay attention to the anatomic changes in target organs and anatomical structures during the course,individual radiotherapy was recommended to ensure adaptive doses.« less

Species differences in the effects of prostanoids on MAP kinase phosphorylation, myosin light chain phosphorylation and contraction in bovine and cat iris sphincter smooth muscle.

PubMed

Kaddour-Djebbar, I; Ansari, H R; Akhtar, R A; Abdel-Latif, A A

2005-01-01

There is evidence from our own laboratory and that of others that EP-receptor ligands are strong contractile agonists in bovine iris sphincter and that FP-receptor agonists are strong contractile agonists in cat iris sphincter. Here, we have investigated the effects of prostaglandin (PG) receptor agonists of the FP-, EP-, TP- and DP-class on myosin light chain (MLC) phosphorylation, p42/p44 MAP kinase phosphorylation and contraction in the iris sphincter of bovine and cat. Using three signal transduction mechanism assays, namely MLC phosphorylation, MAP kinase phosphorylation and contraction, we demonstrated that in bovine iris sphincter the rank order of potency of the PG agonists in the contractile and MLC phosphorylation assays is as follows: E2>U46619>F2alpha>D2, and in cat F2alpha>D2>E2>U46619. In the MAP kinase assay, in bovine iris sphincter the rank order of potency is E2>F2alpha and in cat F2alpha>E2. These conclusions are supported by the following findings: (1) In the contractile assay, in the bovine sphincter the EC50s for PGF2alpha, PGE2, U46619 and PGD2 were found to be 1.4x10(-7), 5.0x10(-9), 9.0x10(-9) and 1.3x10(-6)M, respectively, and the corresponding values in the cat were 1.9x10(-8), 2.3x10(-7), 1.5x10(-6) and 6.9x10(-8)M, respectively. (2) In the MLC phophorylation assay, in the bovine sphincter PGF2alpha, PGE2, U46619 and PGD2 increased MLC phophorylation by 118%, 165%, 153% and 72%, respectively, and the corresponding values in cat were 175%, 99%, 90% and 95%, respectively. (3) In the MAP kinase assay, in the bovine iris sphincter PGF2alpha and PGE2, increased MAP kinase phosphorylation by 276% and 328%, respectively, and the corresponding values in cat were 308% and 245%, respectively. The data presented demonstrate pronounced species differences in the effects of the prostanoids on the MLC kinase signaling pathway in bovine and cat irides and furthermore confirm the existence of FP-receptors in that of the bovine.

Positive Selection of γδ CTL by TL Antigen Expressed in the Thymus

PubMed Central

Tsujimura, Kunio; Takahashi, Toshitada; Morita, Akimichi; Hasegawa-Nishiwaki, Hitomi; Iwase, Shigeru; Obata, Yuichi

1996-01-01

To elucidate the function of the mouse TL antigen in the thymus, we have derived two TL transgenic mouse strains by introducing Tla a -3 of A strain origin with its own promoter onto a C3H background with no expression of TL in the thymus. These transgenic mouse strains, both of which express high levels of Tlaa-3-TL antigen in their thymus, were analyzed for their T cell function with emphasis on cytotoxic T lymphocyte (CTL) generation. A T cell response against TL was induced in Tg.Tlaa-3-1, Tg.Tlaa-3-2, and control C3H mice by skin grafts from H-2K b/T3 b transgenic mice, Tg.Con.3-1, expressing T3b-TL ubiquitously. Spleen cells from mice that had rejected the T3b-TL positive skin grafts were restimulated in vitro with Tg.Con.3-1 irradiated spleen cells. In mixed lymphocyte cultures (MLC), approximately 20% and 15% of Thy-1+ T cells derived from Tg.Tlaa-3-1 and Tg.Tlaa-3-2, respectively, expressed TCRγδ, whereas almost all those from C3H expressed TCRαβ. The MLC from Tg.Tlaa-3-2 and C3H demonstrated high CTL activity against TL, while those from Tg.Tlaa-3-1 had little or none. The generation of γδ CTL recognizing TL in Tg.Tlaa-3-2, but not C3H mice, was confirmed by the establishment of CTL clones. A total of 14 γδ CTL clones were established from Tg.Tlaa-3-2, whereas none were obtained from C3H. Of the 14 γδ CTL clones, 8 were CD8+ and 6 were CD4−CD8− double negative. The CTL activity of all these clones was TL specific and inhibited by anti-TL, but not by anti-H-2 antibodies, demonstrating that they recognize TL directly without antigen presentation by H-2. The CTL activity was blocked by antibodies to TCRγδ and CD3, and also by antibodies to CD8α and CD8β in CD8+ clones, showing that the activity was mediated by TCRγδ and coreceptors. The thymic origin of these γδ CTL clones was indicated by the expression of Thy-1 and Ly-1 (CD5), and also CD8αβ heterodimers in CD8+ clones on their surfaces and by the usage of TCR Vγ4 chains in 12 of the 14 clones. Taken together, these results suggest that Tlaa-3-TL antigen expressed in the thymus engages in positive selection of a sizable population of γδ T cells. PMID:8976173

Using narrow beam profiles to quantify focal spot size, for accurate Monte Carlo simulations of SRS/SRT systems

NASA Astrophysics Data System (ADS)

Kairn, T.; Crowe, S. B.; Charles, P. H.; Trapp, J. V.

2014-03-01

This study investigates the variation of photon field penumbra shape with initial electron beam diameter, for very narrow beams. A Varian Millenium MLC (Varian Medical Systems, Palo Alto, USA) and a Brainlab m3 microMLC (Brainlab AB. Feldkirchen, Germany) were used, with one Varian iX linear accelerator, to produce fields that were (nominally) 0.20 cm across. Dose profiles for these fields were measured using radiochromic film and compared with the results of simulations completed using BEAMnrc and DOSXYZnrc, where the initial electron beam was set to FWHM = 0.02, 0.10, 0.12, 0.15, 0.20 and 0.50 cm. Increasing the electron-beam FWHM produced increasing occlusion of the photon source by the closely spaced collimator leaves and resulted in blurring of the simulated profile widths from 0.24 to 0.58 cm, for the MLC, from 0.11 to 0.40 cm, for the microMLC. Comparison with measurement data suggested that the electron spot size in the clinical linear accelerator was between FWHM = 0.10 and 0.15 cm, encompassing the result of our previous output-factor based work, which identified a FWHM of 0.12 cm. Investigation of narrow-beam penumbra variation has been found to be a useful procedure, with results varying noticeably with linear accelerator spot size and allowing FWHM estimates obtained using other methods to be verified.

Quality assurance of dynamic parameters in volumetric modulated arc therapy.

PubMed

Manikandan, A; Sarkar, B; Holla, R; Vivek, T R; Sujatha, N

2012-07-01

The purpose of this study was to demonstrate quality assurance checks for accuracy of gantry speed and position, dose rate and multileaf collimator (MLC) speed and position for a volumetric modulated arc treatment (VMAT) modality (Synergy S; Elekta, Stockholm, Sweden), and to check that all the necessary variables and parameters were synchronous. Three tests (for gantry position-dose delivery synchronisation, gantry speed-dose delivery synchronisation and MLC leaf speed and positions) were performed. The average error in gantry position was 0.5° and the average difference was 3 MU for a linear and a parabolic relationship between gantry position and delivered dose. In the third part of this test (sawtooth variation), the maximum difference was 9.3 MU, with a gantry position difference of 1.2°. In the sweeping field method test, a linear relationship was observed between recorded doses and distance from the central axis, as expected. In the open field method, errors were encountered at the beginning and at the end of the delivery arc, termed the "beginning" and "end" errors. For MLC position verification, the maximum error was -2.46 mm and the mean error was 0.0153 ±0.4668 mm, and 3.4% of leaves analysed showed errors of >±1 mm. This experiment demonstrates that the variables and parameters of the Synergy S are synchronous and that the system is suitable for delivering VMAT using a dynamic MLC.

Skeletal Muscle-specific G Protein-coupled Receptor Kinase 2 Ablation Alters Isolated Skeletal Muscle Mechanics and Enhances Clenbuterol-stimulated Hypertrophy*

PubMed Central

Woodall, Benjamin P.; Woodall, Meryl C.; Luongo, Timothy S.; Grisanti, Laurel A.; Tilley, Douglas G.; Elrod, John W.; Koch, Walter J.

2016-01-01

GRK2, a G protein-coupled receptor kinase, plays a critical role in cardiac physiology. Adrenergic receptors are the primary target for GRK2 activity in the heart; phosphorylation by GRK2 leads to desensitization of these receptors. As such, levels of GRK2 activity in the heart directly correlate with cardiac contractile function. Furthermore, increased expression of GRK2 after cardiac insult exacerbates injury and speeds progression to heart failure. Despite the importance of this kinase in both the physiology and pathophysiology of the heart, relatively little is known about the role of GRK2 in skeletal muscle function and disease. In this study we generated a novel skeletal muscle-specific GRK2 knock-out (KO) mouse (MLC-Cre:GRK2fl/fl) to gain a better understanding of the role of GRK2 in skeletal muscle physiology. In isolated muscle mechanics testing, GRK2 ablation caused a significant decrease in the specific force of contraction of the fast-twitch extensor digitorum longus muscle yet had no effect on the slow-twitch soleus muscle. Despite these effects in isolated muscle, exercise capacity was not altered in MLC-Cre:GRK2fl/fl mice compared with wild-type controls. Skeletal muscle hypertrophy stimulated by clenbuterol, a β2-adrenergic receptor (β2AR) agonist, was significantly enhanced in MLC-Cre:GRK2fl/fl mice; mechanistically, this seems to be due to increased clenbuterol-stimulated pro-hypertrophic Akt signaling in the GRK2 KO skeletal muscle. In summary, our study provides the first insights into the role of GRK2 in skeletal muscle physiology and points to a role for GRK2 as a modulator of contractile properties in skeletal muscle as well as β2AR-induced hypertrophy. PMID:27566547

Brazilin isolated from the heartwood of Caesalpinia sappan L induces endothelium-dependent and -independent relaxation of rat aortic rings

PubMed Central

Yan, Yu; Chen, Yu-cai; Lin, Yi-huang; Guo, Jing; Niu, Zi-ran; Li, Li; Wang, Shou-bao; Fang, Lian-hua; Du, Guan-hua

2015-01-01

Aim: Brazilin is one of the major constituents of Caesalpinia sappan L with various biological activities. This study sought to investigate the vasorelaxant effect of brazilin on isolated rat thoracic aorta and explore the underlying mechanisms. Methods: Endothelium-intact and -denuded aortic rings were prepared from rats. The tension of the preparations was recorded isometrically with a force displacement transducer connected to a polygraph. The phosphorylation levels of ERK1/2 and myosin light chain (MLC) were analyzed using Western blotting assay. Results: Application of brazilin (10–100 μmol/L) dose-dependently relaxed the NE- or high K+-induced sustained contraction of endothelium-intact aortic rings (the EC50 was 83.51±5.6 and 79.79±4.57 μmol/L, respectively). The vasorelaxant effect of brazilin was significantly attenuated by endothelium removal or by pre-incubation with L-NAME, methylene blue or indomethacin. In addition, pre-incubation with brazilin dose-dependently attenuated the vasoconstriction induced by KCl, NE or Ang II. Pre-incubation with brazilin also markedly suppressed the high K+-induced extracellular Ca2+ influx and NE-induced intracellular Ca2+ release in endothelium-denuded aortic rings. Pre-incubation with brazilin dose-dependently inhibited the NE-stimulated phosphorylation of ERK1/2 and MLC in both endothelium-intact and -denuded aortic rings. Conclusion: Brazilin induces relaxation in rat aortic rings via both endothelium-dependent and -independent ways as well as inhibiting NE-stimulated phosphorylation of ERK1/2 and MLC. Brazilin also attenuates vasoconstriction via blocking voltage- and receptor-operated Ca2+ channels. PMID:26564314

Comparison of the helical tomotherapy against the multileaf collimator-based intensity-modulated radiotherapy and 3D conformal radiation modalities in lung cancer radiotherapy

PubMed Central

Mavroidis, P; Shi, C; Plataniotis, G A; Delichas, M G; Costa Ferreira, B; Rodriguez, S; Lind, B K; Papanikolaou, N

2011-01-01

Objectives The aim of this study was to compare three-dimensional (3D) conformal radiotherapy and the two different forms of IMRT in lung cancer radiotherapy. Methods Cases of four lung cancer patients were investigated by developing a 3D conformal treatment plan, a linac MLC-based step-and-shoot IMRT plan and an HT plan for each case. With the use of the complication-free tumour control probability (P+) index and the uniform dose concept as the common prescription point of the plans, the different treatment plans were compared based on radiobiological measures. Results The applied plan evaluation method shows the MLC-based IMRT and the HT treatment plans are almost equivalent over the clinically useful dose prescription range; however, the 3D conformal plan inferior. At the optimal dose levels, the 3D conformal treatment plans give an average P+ of 48.1% for a effective uniform dose to the internal target volume (ITV) of 62.4 Gy, whereas the corresponding MLC-based IMRT treatment plans are more effective by an average ΔP+ of 27.0% for a Δ effective uniform dose of 16.3 Gy. Similarly, the HT treatment plans are more effective than the 3D-conformal plans by an average ΔP+ of 23.8% for a Δ effective uniform dose of 11.6 Gy. Conclusion A radiobiological treatment plan evaluation can provide a closer association of the delivered treatment with the clinical outcome by taking into account the dose–response relations of the irradiated tumours and normal tissues. The use of P – effective uniform dose diagrams can complement the traditional tools of evaluation to compare and effectively evaluate different treatment plans. PMID:20858664

Increasing O-GlcNAcylation level on organ culture of soleus modulates the calcium activation parameters of muscle fibers.

PubMed

Cieniewski-Bernard, Caroline; Montel, Valerie; Berthoin, Serge; Bastide, Bruno

2012-01-01

O-N-acetylglucosaminylation is a reversible post-translational modification which presents a dynamic and highly regulated interplay with phosphorylation. New insights suggest that O-GlcNAcylation might be involved in striated muscle physiology, in particular in contractile properties such as the calcium activation parameters. By the inhibition of O-GlcNAcase, we investigated the effect of the increase of soleus O-GlcNAcylation level on the contractile properties by establishing T/pCa relationships. We increased the O-GlcNAcylation level on soleus biopsies performing an organ culture of soleus treated or not with PUGNAc or Thiamet-G, two O-GlcNAcase inhibitors. The enhancement of O-GlcNAcylation pattern was associated with an increase of calcium affinity on slow soleus skinned fibers. Analysis of the glycoproteins pattern showed that this effect is solely due to O-GlcNAcylation of proteins extracted from skinned biopsies. We also characterized the O-GlcNAcylated contractile proteins using a proteomic approach, and identified among others troponin T and I as being O-GlcNAc modified. We quantified the variation of O-GlcNAc level on all these identified proteins, and showed that several regulatory contractile proteins, predominantly fast isoforms, presented a drastic increase in their O-GlcNAc level. Since the only slow isoform of contractile protein presenting an increase of O-GlcNAc level was MLC2, the effect of enhanced O-GlcNAcylation pattern on calcium activation parameters could involve the O-GlcNAcylation of sMLC2, without excluding that an unidentified O-GlcNAc proteins, such as TnC, could be potentially involved in this mechanism. All these data strongly linked O-GlcNAcylation to the modulation of contractile activity of skeletal muscle.

SU-G-TeP4-07: Automatic EPID-Based 2D Measurement of MLC Leaf Offset as a Quality Control Tool

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ritter, T; Moran, J; Schultz, B

Purpose: The MLC dosimetric leaf gap (DLG) and transmission are measured parameters which impact the dosimetric accuracy of IMRT and VMAT plans. This investigation aims to develop an efficient and accurate routine constancy check of the physical DLG in two dimensions. Methods: The manufacturer’s recommended DLG measurement method was modified by using 5 fields instead of 11 and by utilizing the Electronic Portal Imaging Device (EPID). Validations were accomplished using an ion chamber (IC) in solid water and a 2D IC array. EPID data was collected for 6 months on multiple TrueBeam linacs using both Millennium and HD MLCs atmore » 5 different clinics in an international consortium. Matlab code was written to automatically analyze the images and calculate the 2D results. Sensitivity was investigated by introducing deliberate leaf position errors. MLC calibration and initialization history was recorded to allow quantification of their impact. Results were analyzed using statistical process control (SPC). Results: The EPID method took approximately 5 minutes. Due to detector response, the EPID measured DLG and transmission differed from the IC values but were reproducible and consistent with changes measured using the ICs. For the Millennium MLC, the EPID measured DLG and transmission were both consistently lower than IC results. The EPID method was implemented as leaf offset and transmission constancy tests (LOC and TC). Based on 6 months of measurements, the initial leaf-specific action thresholds for changes from baseline were set to 0.1 mm. Upper and lower control limits for variation were developed for each machine. Conclusion: Leaf offset and transmission constancy tests were implemented on Varian HD and Millennium MLCs using an EPID and found to be efficient and accurate. The test is effective for monitoring MLC performance using dynamic delivery and performing process control on the DLG in 2D, thus enhancing dosimetric accuracy. This work was supported by a grant from Varian Medical Systems.« less

Role of Telokin in Regulating Murine Gastric Fundus Smooth Muscle Tension

PubMed Central

An, Changlong; Bhetwal, Bhupal P.; Sanders, Kenton M.; Somlyo, Avril V.; Perrino, Brian A.

2015-01-01

Telokin phosphorylation by cyclic GMP-dependent protein kinase facilitates smooth muscle relaxation. In this study we examined the relaxation of gastric fundus smooth muscles from basal tone, or pre-contracted with KCl or carbachol (CCh), and the phosphorylation of telokin S13, myosin light chain (MLC) S19, MYPT1 T853, T696, and CPI-17 T38 in response to 8-Bromo-cGMP, the NO donor sodium nitroprusside (SNP), or nitrergic neurotransmission. We compared MLC phosphorylation and the contraction and relaxation responses of gastric fundus smooth muscles from telokin-/- mice and their wild-type littermates to KCl or CCh, and 8-Bromo-cGMP, SNP, or nitrergic neurotransmission, respectively. We compared the relaxation responses and telokin phosphorylation of gastric fundus smooth muscles from wild-type mice and W/W V mice which lack ICC-IM, to 8-Bromo-cGMP, SNP, or nitrergic neurotransmission. We found that telokin S13 is basally phosphorylated and that 8-Bromo-cGMP and SNP increased basal telokin phosphorylation. In muscles pre-contracted with KCl or CCh, 8-Bromo-cGMP and SNP had no effect on CPI-17 or MYPT1 phosphorylation, but increased telokin phosphorylation and reduced MLC phosphorylation. In telokin-/- gastric fundus smooth muscles, basal tone and constitutive MLC S19 phosphorylation were increased. Pre-contracted telokin-/- gastric fundus smooth muscles have increased contractile responses to KCl, CCh, or cholinergic neurotransmission and reduced relaxation to 8-Bromo-cGMP, SNP, and nitrergic neurotransmission. However, basal telokin phosphorylation was not increased when muscles were stimulated with lower concentrations of SNP or when the muscles were stimulated by nitrergic neurotransmission. SNP, but not nitrergic neurotransmission, increased telokin Ser13 phosphorylation in both wild-type and W/W V gastric fundus smooth muscles. Our findings indicate that telokin may play a role in attenuating constitutive MLC phosphorylation and provide an additional mechanism to augment gastric fundus mechanical responses to inhibitory neurotransmission. PMID:26258553

SU-E-I-49: The Evaluation of Usability of Multileaf Collimator for Diagnostic Radiation in Cephalometric Exposure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Han, S; Kim, K; Jung, H

Purpose: This study evaluated usability of Multileaf collimator (MLC) for diagnostic radiation in cephalometric exposure using optical stimulated luminance dosimeters (OSLDs) Methods: The MLC material was made alloy tool steel (SKD-11) and the density of it is 7.89g/m3 that is similar to it of steel (Fe, 7.85 g/m3) and the MLC was attached to general radiography unit (Rex-650R, Listem Inc, Korea) for cephalometric exposure. The OSLDs that used were nanoDotTM Dosimeter (Landauer Inc, Glenwood, USA) and we read out OSLDs with micro star system (Landauer Inc, Glenwood, USA). The Optical annealing system contained fluorescent lamps (Osram lumilux, 24 W, 280more » ∼780 nm). To measure absorbed dose using OSLDs, was carried out dosimetric characteristics of OSLDs. Based on these, we evaluated dose reduction of critical organ (Eyes, Thyroids) with MLC in cephalometric exposure Results: The dosimetric characteristics were following that batch homogeneity was 1.21% and reproducibility was 0.96% of the coefficient of variation The linearity was that the correlation of between dose and count was fitted by linear function (dose,mGy = 0.00029 × Count, R2 =0.997). The range of angular dependence was from −3.6% to 3.7% variation when each degree was normalized by zero degree. The organ dose of Rt. eye, Lt eye, thyroids were 77.8 μGy, 337.0 μGy, 323.1μGy, respectively in open field and the dose reduction of organ dose was 10.6%(8.3μGy), 12.4 %(42 μGy), 87.1%(281.4μGy) with MLC Conclusion: We certified dose reduction of organ dose in cephalometric exposure. The dose reduction of Eye was 11% because of reduction of field size and it of thyroids was 87% by primary beam shielding.« less

SU-E-T-774: Use of a Scintillator-Mirror-Camera System for the Measurement of MLC Leakage Radiation with the CyberKnife M6 System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Goggin, L; Kilby, W; Noll, M

2015-06-15

Purpose: A technique using a scintillator-mirror-camera system to measure MLC leakage was developed to provide an efficient alternative to film dosimetry while maintaining high spatial resolution. This work describes the technique together with measurement uncertainties. Methods: Leakage measurements were made for the InCise™ MLC using the Logos XRV-2020A device. For each measurement approximately 170 leakage and background images were acquired using optimized camera settings. Average background was subtracted from each leakage frame before filtering the integrated leakage image to replace anomalous pixels. Pixel value to dose conversion was performed using a calibration image. Mean leakage was calculated within an ROImore » corresponding to the primary beam, and maximum leakage was determined by binning the image into overlapping 1mm x 1mm ROIs. 48 measurements were performed using 3 cameras and multiple MLC-linac combinations in varying beam orientations, with each compared to film dosimetry. Optical and environmental influences were also investigated. Results: Measurement time with the XRV-2020A was 8 minutes vs. 50 minutes using radiochromic film, and results were available immediately. Camera radiation exposure degraded measurement accuracy. With a relatively undamaged camera, mean leakage agreed with film measurement to ≤0.02% in 92% cases, ≤0.03% in 100% (for maximum leakage the values were 88% and 96%) relative to reference open field dose. The estimated camera lifetime over which this agreement is maintained is at least 150 measurements, and can be monitored using reference field exposures. A dependency on camera temperature was identified and a reduction in sensitivity with distance from image center due to optical distortion was characterized. Conclusion: With periodic monitoring of the degree of camera radiation damage, the XRV-2020A system can be used to measure MLC leakage. This represents a significant time saving when compared to the traditional film-based approach without any substantial reduction in accuracy.« less

MO-FG-202-04: Gantry-Resolved Linac QA for VMAT: A Comprehensive and Efficient System Using An Electronic Portal Imaging Device

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zwan, B J; University of Newcastle, Newcastle, NSW; Barnes, M

2016-06-15

Purpose: To automate gantry-resolved linear accelerator (linac) quality assurance (QA) for volumetric modulated arc therapy (VMAT) using an electronic portal imaging device (EPID). Methods: A QA system for VMAT was developed that uses an EPID, frame-grabber assembly and in-house developed image processing software. The system relies solely on the analysis of EPID image frames acquired without the presence of a phantom. Images were acquired at 8.41 frames per second using a frame grabber and ancillary acquisition computer. Each image frame was tagged with a gantry angle from the linac’s on-board gantry angle encoder. Arc-dynamic QA plans were designed to assessmore » the performance of each individual linac component during VMAT. By analysing each image frame acquired during the QA deliveries the following eight machine performance characteristics were measured as a function of gantry angle: MLC positional accuracy, MLC speed constancy, MLC acceleration constancy, MLC-gantry synchronisation, beam profile constancy, dose rate constancy, gantry speed constancy, dose-gantry angle synchronisation and mechanical sag. All tests were performed on a Varian iX linear accelerator equipped with a 120 leaf Millennium MLC and an aS1000 EPID (Varian Medical Systems, Palo Alto, CA, USA). Results: Machine performance parameters were measured as a function of gantry angle using EPID imaging and compared to machine log files and the treatment plan. Data acquisition is currently underway at 3 centres, incorporating 7 treatment units, at 2 weekly measurement intervals. Conclusion: The proposed system can be applied for streamlined linac QA and commissioning for VMAT. The set of test plans developed can be used to assess the performance of each individual components of the treatment machine during VMAT deliveries as a function of gantry angle. The methodology does not require the setup of any additional phantom or measurement equipment and the analysis is fully automated to allow for regular routine testing.« less

SU-E-T-418: Explore the Sensitive of the Planar Quality Assurance to the MLC Error with Different Beam Complexity in Intensity-Modulate Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, J; Peng, J; Xie, J

2015-06-15

Purpose: The purpose of this study is to investigate the sensitivity of the planar quality assurance to MLC errors with different beam complexities in intensity-modulate radiation therapy. Methods: sixteen patients’ planar quality assurance (QA) plans in our institution were enrolled in this study, including 10 dynamic MLC (DMLC) IMRT plans measured by Portal Dosimetry and 6 static MLC (SMLC) IMRT plans measured by Mapcheck. The gamma pass rate was calculated using vender’s software. The field numbers were 74 and 40 for DMLC and SMLC, respectively. A random error was generated and introduced to these fields. The modified gamma pass ratemore » was calculated by comparing the original measured fluence and modified fields’ fluence. A decreasing gamma pass rate was acquired using the original gamma pass rate minus the modified gamma pass rate. Eight complexity scores were calculated in MATLAB based on the fluence and MLC sequence of these fields. The complexity scores include fractal dimension, monitor unit of field, modulation index, fluence map complexity, weighted average of field area, weighted average of field perimeter, and small aperture ratio ( <5cm{sup 2} and <50cm{sup 2}). The Spearman’s rank correlation coefficient was implemented to analyze the correlation between these scores and decreasing gamma rate. Results: The relation between the decreasing gamma pass rate and field complexity was insignificant for most complexity scores. The most significant complexity score was fluence map complexity for SMLC, which have ρ =0.4274 (p-value=0.0063). For DMLC, the most significant complex score was fractal dimension, which have ρ=−0.3068 (p-value=0.0081). Conclusions: According to the primarily Result of this study, the sensitivity gamma pass rate was not strongly relate to the field complexity.« less

Role of guanine nucleotide-binding proteins--ras-family or trimeric proteins or both--in Ca2+ sensitization of smooth muscle.

PubMed Central

Gong, M C; Iizuka, K; Nixon, G; Browne, J P; Hall, A; Eccleston, J F; Sugai, M; Kobayashi, S; Somlyo, A V; Somlyo, A P

1996-01-01

The purpose of this study was to identify guanine nucleotide-binding proteins (G proteins) involved in the agonist- and guanosine 5'-[gamma-thio]triphosphate (GTP[gamma-S])-induced increase in the Ca2+ sensitivity of 20-kDa myosin light chain (MLC20) phosphorylation and contraction in smooth muscle. A constitutively active, recombinant val14p21rhoA.GTP expressed in the baculovirus/Sf9 system, but not the protein expressed without posttranslational modification in Escherichia coli, induced at constant Ca2+ (pCa 6.4) a slow contraction associated with increased MLC20 phosphorylation from 19.8% to 29.5% (P < 0.05) in smooth muscle permeabilized with beta-esein. The effect of val14p21rhoA.GTP was inhibited by ADP-ribosylation of the protein and was absent in smooth muscle extensively permeabilized with Triton X-100. ADP-ribosylation of endogenous p21rho with epidermal cell differentiation inhibitor (EDIN) inhibited Ca2+ sensitization induced by GTP [in rabbit mesenteric artery (RMA) and rabbit ileum smooth muscles], by carbachol (in rabbit ileum), and by endothelin (in RMA), but not by phenylephrine (in RMA), and only slowed the rate without reducing the amplitude of contractions induced in RMA by 1 microM GTP[gamma-S] at constant Ca2+ concentrations. AlF(4-)-induced Ca2+ sensitization was inhibited by both guanosine 5'-[beta-thio]diphosphate (GDP[beta-S]) and by EDIN. EDIN also inhibited, to a lesser extent, contractions induced by Ca2+ alone (pCa 6.4) in both RMA and rabbit ileum. ADP-ribosylation of trimeric G proteins with pertussis toxin did not inhibit Ca2+ sensitization. We conclude that p21rho may play a role in physiological Ca2+ sensitization as a cofactor with other messengers, rather than as a sole direct inhibitor of smooth muscle MLC20 phosphatase. Images Fig. 3 Fig. 4 PMID:8577766

Multi-scale lung modeling.

PubMed

Tawhai, Merryn H; Bates, Jason H T

2011-05-01

Multi-scale modeling of biological systems has recently become fashionable due to the growing power of digital computers as well as to the growing realization that integrative systems behavior is as important to life as is the genome. While it is true that the behavior of a living organism must ultimately be traceable to all its components and their myriad interactions, attempting to codify this in its entirety in a model misses the insights gained from understanding how collections of system components at one level of scale conspire to produce qualitatively different behavior at higher levels. The essence of multi-scale modeling thus lies not in the inclusion of every conceivable biological detail, but rather in the judicious selection of emergent phenomena appropriate to the level of scale being modeled. These principles are exemplified in recent computational models of the lung. Airways responsiveness, for example, is an organ-level manifestation of events that begin at the molecular level within airway smooth muscle cells, yet it is not necessary to invoke all these molecular events to accurately describe the contraction dynamics of a cell, nor is it necessary to invoke all phenomena observable at the level of the cell to account for the changes in overall lung function that occur following methacholine challenge. Similarly, the regulation of pulmonary vascular tone has complex origins within the individual smooth muscle cells that line the blood vessels but, again, many of the fine details of cell behavior average out at the level of the organ to produce an effect on pulmonary vascular pressure that can be described in much simpler terms. The art of multi-scale lung modeling thus reduces not to being limitlessly inclusive, but rather to knowing what biological details to leave out.

A multi-level model accounting for the effects of JAK2-STAT5 signal modulation in erythropoiesis.

PubMed

Lai, Xin; Nikolov, Svetoslav; Wolkenhauer, Olaf; Vera, Julio

2009-08-01

We develop a multi-level model, using ordinary differential equations, based on quantitative experimental data, accounting for murine erythropoiesis. At the sub-cellular level, the model includes a description of the regulation of red blood cell differentiation through Epo-stimulated JAK2-STAT5 signalling activation, while at the cell population level the model describes the dynamics of (STAT5-mediated) red blood cell differentiation from their progenitors. Furthermore, the model includes equations depicting the hypoxia-mediated regulation of hormone erythropoietin blood levels. Take all together, the model constitutes a multi-level, feedback loop-regulated biological system, involving processes in different organs and at different organisational levels. We use our model to investigate the effect of deregulation in the proteins involved in the JAK2-STAT5 signalling pathway in red blood cells. Our analysis results suggest that down-regulation in any of the three signalling system components affects the hematocrit level in an individual considerably. In addition, our analysis predicts that exogenous Epo injection (an already existing treatment for several blood diseases) may compensate the effects of single down-regulation of Epo hormone level, STAT5 or EpoR/JAK2 expression level, and that it may be insufficient to counterpart a combined down-regulation of all the elements in the JAK2-STAT5 signalling cascade.

Evaluation of the dose calculation accuracy for small fields defined by jaw or MLC for AAA and Acuros XB algorithms.

PubMed

Fogliata, Antonella; Lobefalo, Francesca; Reggiori, Giacomo; Stravato, Antonella; Tomatis, Stefano; Scorsetti, Marta; Cozzi, Luca

2016-10-01

Small field measurements are challenging, due to the physical characteristics coming from the lack of charged particle equilibrium, the partial occlusion of the finite radiation source, and to the detector response. These characteristics can be modeled in the dose calculations in the treatment planning systems. Aim of the present work is to evaluate the MU calculation accuracy for small fields, defined by jaw or MLC, for anisotropic analytical algorithm (AAA) and Acuros XB algorithms, relative to output measurements on the beam central axis. Single point output factor measurement was acquired with a PTW microDiamond detector for 6 MV, 6 and 10 MV unflattened beams generated by a Varian TrueBeam STx equipped with high definition-MLC. Fields defined by jaw or MLC apertures were set; jaw-defined: 0.6 × 0.6, 0.8 × 0.8, 1 × 1, 2 × 2, 3 × 3, 4 × 4, 5 × 5, and 10 × 10 cm 2 ; MLC-defined: 0.5 × 0.5 cm 2 to the maximum field defined by the jaw, with 0.5 cm stepping, and jaws set to: 2 × 2, 3 × 3, 4 × 4, 5 × 5, and 10 × 10 cm 2 . MU calculation was obtained with 1 mm grid in a virtual water phantom for the same fields, for AAA and Acuros algorithms implemented in the Varian eclipse treatment planning system (version 13.6). Configuration parameters as the effective spot size (ESS) and the dosimetric leaf gap (DLG) were varied to find the best parameter setting. Differences between calculated and measured doses were analyzed. Agreement better than 0.5% was found for field sizes equal to or larger than 2 × 2 cm 2 for both algorithms. A dose overestimation was present for smaller jaw-defined fields, with the best agreement, averaged over all the energies, of 1.6% and 4.6% for a 1 × 1 cm 2 field calculated by AAA and Acuros, respectively, for a configuration with ESS = 1 mm for both X and Y directions for AAA, and ESS = 1.5 and 0 mm for X and Y directions for Acuros. Conversely, a calculated dose underestimation was found for small MLC-defined fields, with the best agreement averaged over all the energies, of -3.9% and 0.2% for a 1 × 1 cm 2 field calculated by AAA and Acuros, respectively, for a configuration with ESS = 0 mm for both directions and both algorithms. For optimal setting applied in the algorithm configuration phase, the agreement of Acuros calculations with measurements could achieve the 3% for MLC-defined fields as small as 0.5 × 0.5 cm 2 . Similar agreement was found for AAA for fields as small as 1 × 1 cm 2 .

A novel method for routine quality assurance of volumetric-modulated arc therapy.

PubMed

Wang, Qingxin; Dai, Jianrong; Zhang, Ke

2013-10-01

Volumetric-modulated arc therapy (VMAT) is delivered through synchronized variation of gantry angle, dose rate, and multileaf collimator (MLC) leaf positions. The delivery dynamic nature challenges the parameter setting accuracy of linac control system. The purpose of this study was to develop a novel method for routine quality assurance (QA) of VMAT linacs. ArcCheck is a detector array with diodes distributing in spiral pattern on cylindrical surface. Utilizing its features, a QA plan was designed to strictly test all varying parameters during VMAT delivery on an Elekta Synergy linac. In this plan, there are 24 control points. The gantry rotates clockwise from 181° to 179°. The dose rate, gantry speed, and MLC positions cover their ranges commonly used in clinic. The two borders of MLC-shaped field seat over two columns of diodes of ArcCheck when the gantry rotates to the angle specified by each control point. The ratio of dose rate between each of these diodes and the diode closest to the field center is a certain value and sensitive to the MLC positioning error of the leaf crossing the diode. Consequently, the positioning error can be determined by the ratio with the help of a relationship curve. The time when the gantry reaches the angle specified by each control point can be acquired from the virtual inclinometer that is a feature of ArcCheck. The gantry speed between two consecutive control points is then calculated. The aforementioned dose rate is calculated from an acm file that is generated during ArcCheck measurements. This file stores the data measured by each detector in 50 ms updates with each update in a separate row. A computer program was written in MATLAB language to process the data. The program output included MLC positioning errors and the dose rate at each control point as well as the gantry speed between control points. To evaluate this method, this plan was delivered for four consecutive weeks. The actual dose rate and gantry speed were compared with the QA plan specified. Additionally, leaf positioning errors were intentionally introduced to investigate the sensitivity of this method. The relationship curves were established for detecting MLC positioning errors during VMAT delivery. For four consecutive weeks measured, 98.4%, 94.9%, 89.2%, and 91.0% of the leaf positioning errors were within ± 0.5 mm, respectively. For the intentionally introduced leaf positioning systematic errors of -0.5 and +1 mm, the detected leaf positioning errors of 20 Y1 leaf were -0.48 ± 0.14 and 1.02 ± 0.26 mm, respectively. The actual gantry speed and dose rate closely followed the values specified in the VMAT QA plan. This method can assess the accuracy of MLC positions and the dose rate at each control point as well as the gantry speed between control points at the same time. It is efficient and suitable for routine quality assurance of VMAT.

Magnolol inhibits migration of vascular smooth muscle cells via cytoskeletal remodeling pathway to attenuate neointima formation.

PubMed

Karki, Rajendra; Kim, Seong-Bin; Kim, Dong-Wook

2013-12-10

Increased proliferation and migration of vascular smooth muscle cells (VSMCs) contribute importantly to the formation of both atherosclerotic and restenotic lesions. The objective of this study was to investigate the effect of magnolol on VSMC migration. The proteolytic activity of matrix metalloproteinases (MMPs) in tumor necrosis factor alpha (TNF-α) stimulated VSMCs was performed by gelatin zymography. VSMC migration was assessed by wound healing and Boyden chamber methods. Collagen induced VSMC adhesion was determined by spectrofluorimeter and stress fibers formation was evaluated by fluorescence microscope. The expression of signaling molecules involved in stress fibers formation was determined by western blot. The phosphorylation of myosin light chain (MLC20) was determined by urea-glycerol polyacrylamide gel electrophoresis. Immunohistochemistry was performed to determine the expression of β1-integrin and collagen type I in the injured carotid arteries of rats on day 35 after vascular injury. VSMC migration was strongly inhibited by magnolol without affecting MMPs expression. Also, magnolol inhibited β1-integrin expression, FAK phosphorylation and RhoA and Cdc42 activation to inhibit the collagen induced stress fibers formation. Moreover, magnolol inhibited the phosphorylation of MLC20. Our in vivo results showed that magnolol inhibited β1-integrin expression, collagen type I deposition and FAK phosphorylation in injured carotid arteries without affecting MMP-2 activity. Magnolol inhibited VSMC migration via inhibition of cytoskeletal remodeling pathway to attenuate neointima formation. This study provides a rationale for further evaluation of magnolol for the management of atherosclerosis and restenosis. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

Distinct Temporal-Spatial Roles for Rho Kinase and Myosin Light Chain Kinase in Epithelial Purse-String Wound Closure

PubMed Central

RUSSO, JOHN M.; FLORIAN, PETER; SHEN, LE; GRAHAM, W. VALLEN; TRETIAKOVA, MARIA S.; GITTER, ALFRED H.; MRSNY, RANDALL J.; TURNER, JERROLD R.

2005-01-01

Background & Aims Small epithelial wounds heal by purse-string contraction of an actomyosin ring that is regulated by myosin light chain (MLC) kinase (MLCK) and rho kinase (ROCK). These studies aimed to define the roles of these kinases in purse-string wound closure. Methods Oligocellular and single-cell wounds were created in intestinal epithelial monolayers. Fluorescence imaging and electrophysiologic data were collected during wound closure. Human biopsies were studied immunohistochemically. Results Live-cell imaging of enhanced green fluorescent protein-β-actin defined rapid actin ring assembly within 2 minutes after wounding. This progressed to a circumferential ring within 8 minutes that subsequently contracted and closed the wound. We therefore divided this process into 2 phases: ring assembly and wound contraction. Activated rho and ROCK localized to the wound edge during ring assembly. Consistent with a primary role in the assembly phase, ROCK inhibition prevented actin ring assembly and wound closure. ROCK inhibition after ring assembly was complete had no effect. Recruitment and activation of MLCK occurred after ring assembly was complete and coincided with ring contraction. MLCK inhibition slowed and then stopped contraction but did not prevent ring assembly. MLCK inhibition also delayed barrier function recovery. Studies of human colonic biopsy specimens suggest that purse-string wound closure also occurs in vivo, because MLC phosphorylation was enhanced surrounding oligocellular wounds. Conclusions These results suggest complementary roles for these kinases in purse-string closure of experimental and in vivo oligocellular epithelial wounds; rho and ROCK are critical for actin ring assembly, while the activity of MLCK drives contraction. PMID:15825080

Quantification of interplay and gradient effects for lung stereotactic ablative radiotherapy (SABR) treatments.

PubMed

Tyler, Madelaine K

2016-01-08

This study quantified the interplay and gradient effects on GTV dose coverage for 3D CRT, dMLC IMRT, and VMAT SABR treatments for target amplitudes of 5-30 mm using 3DVH v3.1 software incorporating 4D Respiratory MotionSim (4D RMS) module. For clinically relevant motion periods (5 s), the interplay effect was small, with deviations in the minimum dose covering the target volume (D99%) of less than ± 2.5% for target amplitudes up to 30 mm. Increasing the period to 60 s resulted in interplay effects of up to ± 15.0% on target D99% dose coverage. The gradient effect introduced by target motion resulted in deviations of up to ± 3.5% in D99% target dose coverage. VMAT treatments showed the largest deviation in dose metrics, which was attributed to the long delivery times in comparison to dMLC IMRT. Retrospective patient analysis indicated minimal interplay and gradient effects for patients treated with dMLC IMRT at the NCCI.

[Ambulatory laparoscopic cholecystectomy by minilaparoscopy versus traditional multiport ambulatory laparoscopic cholecystectomy. Prospective randomized trial].

PubMed

Planells Roig, Manuel; Arnal Bertomeu, Consuelo; Garcia Espinosa, Rafael; Cervera Delgado, Maria; Carrau Giner, Miguel

2016-02-01

Difference analysis of ambulatorization rate, pain, analgesic requirements and daily activities recovery in patients undergoing laparoscopic cholecystectomy with standard multiport access (CLMP) versus a minilaparoscopic, 3mm size, technique. Prospective randomized trial of 40 consecutive patients undergoing laparoscopic cholecystectomy. Comparison criteria included predictive ultrasound factors of difficult cholecystectomy, previous history of complicated biliary disease and demographics. Results are analyzed in terms of ambulatorization rate, pain, analgesic requirements, postoperative recovery, technical difficulty, hemorrhage intensity, overnight stay, readmission rate and total or partial conversion. Both procedures were similar in surgery time, technical score and hemorrhage score. MLC was associated with similar ambulatorization rate, 85%, and over-night stay 15%, with only 15% partial conversion rate. MLC showed less postoperative pain (P=.026), less analgesic consumption (P=.006) and similar DAR (P=.879). MLC is similar to CLMP in terms of ambulatorization with less postoperative pain and analgesic requirements without differences in postoperative recovery. Copyright © 2014 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

Rate adaptive multilevel coded modulation with high coding gain in intensity modulation direct detection optical communication

NASA Astrophysics Data System (ADS)

Xiao, Fei; Liu, Bo; Zhang, Lijia; Xin, Xiangjun; Zhang, Qi; Tian, Qinghua; Tian, Feng; Wang, Yongjun; Rao, Lan; Ullah, Rahat; Zhao, Feng; Li, Deng'ao

2018-02-01

A rate-adaptive multilevel coded modulation (RA-MLC) scheme based on fixed code length and a corresponding decoding scheme is proposed. RA-MLC scheme combines the multilevel coded and modulation technology with the binary linear block code at the transmitter. Bits division, coding, optional interleaving, and modulation are carried out by the preset rule, then transmitted through standard single mode fiber span equal to 100 km. The receiver improves the accuracy of decoding by means of soft information passing through different layers, which enhances the performance. Simulations are carried out in an intensity modulation-direct detection optical communication system using MATLAB®. Results show that the RA-MLC scheme can achieve bit error rate of 1E-5 when optical signal-to-noise ratio is 20.7 dB. It also reduced the number of decoders by 72% and realized 22 rate adaptation without significantly increasing the computing time. The coding gain is increased by 7.3 dB at BER=1E-3.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Duan, J

Purpose: The aim of this work is to study the dosimetric impact of leaf interdigitation in prostate cancer dynamic IMRT treatment planning. Methods: Fifteen previously treated prostate cancer patients were replanned for dynamic IMRT (dMLC) with and without leaf interdigitation using Monaco 3.3 TPS on the Elekta Synergy linear accelerator. The prescription dose of PTV was 70Gy/35 fractions. Various dosimetric variables, such as PTV coverage, OAR sparing, delivery efficiency and optimization time, were evaluated for each plan. Results: Interdigitation did not improve the coverage, HI and CI for PTV. Regarding OARs, sparing was equivalent with and without interdigitation. Interdigitation shownmore » an increase in MUs and segments. It was worth noting that leaf interdigitation saved the optimization time. Conclusion: This study shows that leaf interdigitation does not improve plan quality when performing dMLC treatment plan for prostate cancer. However, it influences delivery efficiency and optimization time. Interdigitation may gain efficiency for dosimetrist when designing the prostate cancer dMLC plans.« less

Comparison of two Classification methods (MLC and SVM) to extract land use and land cover in Johor Malaysia

NASA Astrophysics Data System (ADS)

Rokni Deilmai, B.; Ahmad, B. Bin; Zabihi, H.

2014-06-01

Mapping is essential for the analysis of the land use and land cover, which influence many environmental processes and properties. For the purpose of the creation of land cover maps, it is important to minimize error. These errors will propagate into later analyses based on these land cover maps. The reliability of land cover maps derived from remotely sensed data depends on an accurate classification. In this study, we have analyzed multispectral data using two different classifiers including Maximum Likelihood Classifier (MLC) and Support Vector Machine (SVM). To pursue this aim, Landsat Thematic Mapper data and identical field-based training sample datasets in Johor Malaysia used for each classification method, which results indicate in five land cover classes forest, oil palm, urban area, water, rubber. Classification results indicate that SVM was more accurate than MLC. With demonstrated capability to produce reliable cover results, the SVM methods should be especially useful for land cover classification.

Rho/ROCK pathway is essential to the expansion, differentiation, and morphological rearrangements of human neural stem/progenitor cells induced by lysophosphatidic acid.

PubMed

Frisca, Frisca; Crombie, Duncan E; Dottori, Mirella; Goldshmit, Yona; Pébay, Alice

2013-05-01

We previously reported that lysophosphatidic acid (LPA) inhibits the neuronal differentiation of human embryonic stem cells (hESC). We extended these studies by analyzing LPA's effects on the expansion of neural stem/progenitor cells (NS/PC) derived from hESCs and human induced pluripotent stem cells (iPSC), and we assessed whether data obtained on the neural differentiation of hESCs were relevant to iPSCs. We showed that hESCs and iPSCs exhibited comparable mRNA expression profiles of LPA receptors and producing enzymes upon neural differentiation. We demonstrated that LPA inhibited the expansion of NS/PCs of both origins, mainly by increased apoptosis in a Rho/Rho-associated kinase (ROCK)-dependent mechanism. Furthermore, LPA inhibited the neuronal differentiation of iPSCs. Lastly, LPA induced neurite retraction of NS/PC-derived early neurons through Rho/ROCK, which was accompanied by myosin light chain (MLC) phosphorylation. Our data demonstrate the consistency of LPA effects across various sources of human NS/PCs, rendering hESCs and iPSCs valuable models for studying lysophospholipid signaling in human neural cells. Our data also highlight the importance of the Rho/ROCK pathway in human NS/PCs. As LPA levels are increased in the central nervous system (CNS) following injury, LPA-mediated effects on NS/PCs and early neurons could contribute to the poor neurogenesis observed in the CNS following injury.

Multi-Node Thermal System Model for Lithium-Ion Battery Packs: Preprint

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shi, Ying; Smith, Kandler; Wood, Eric

Temperature is one of the main factors that controls the degradation in lithium ion batteries. Accurate knowledge and control of cell temperatures in a pack helps the battery management system (BMS) to maximize cell utilization and ensure pack safety and service life. In a pack with arrays of cells, a cells temperature is not only affected by its own thermal characteristics but also by its neighbors, the cooling system and pack configuration, which increase the noise level and the complexity of cell temperatures prediction. This work proposes to model lithium ion packs thermal behavior using a multi-node thermal network model,more » which predicts the cell temperatures by zones. The model was parametrized and validated using commercial lithium-ion battery packs. neighbors, the cooling system and pack configuration, which increase the noise level and the complexity of cell temperatures prediction. This work proposes to model lithium ion packs thermal behavior using a multi-node thermal network model, which predicts the cell temperatures by zones. The model was parametrized and validated using commercial lithium-ion battery packs.« less

The influence of plan modulation on the interplay effect in VMAT liver SBRT treatments.

PubMed

Hubley, Emily; Pierce, Greg

2017-08-01

Volumetric modulated arc therapy (VMAT) uses multileaf collimator (MLC) leaves, gantry speed, and dose rate to modulate beam fluence, producing the highly conformal doses required for liver radiotherapy. When targets that move with respiration are treated with a dynamic fluence, there exists the possibility for interplay between the target and leaf motions. This study employs a novel motion simulation technique to determine if VMAT liver SBRT plans with an increase in MLC leaf modulation are more susceptible to dosimetric differences in the GTV due to interplay effects. For ten liver SBRT patients, two VMAT plans with different amounts of MLC leaf modulation were created. Motion was simulated using a random starting point in the respiratory cycle for each fraction. To isolate the interplay effect, motion was also simulated using four specific starting points in the respiratory cycle. The dosimetric differences caused by different starting points were examined by subtracting resultant dose distributions from each other. When motion was simulated using random starting points for each fraction, or with specific starting points, there were significantly more dose differences in the GTV (maximum 100cGy) for more highly modulated plans, but the overall plan quality was not adversely affected. Plans with more MLC leaf modulation are more susceptible to interplay effects, but dose differences in the GTV are clinically negligible in magnitude. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Quality assurance of dynamic parameters in volumetric modulated arc therapy

PubMed Central

Manikandan, A; Sarkar, B; Holla, R; Vivek, T R; Sujatha, N

2012-01-01

Objectives The purpose of this study was to demonstrate quality assurance checks for accuracy of gantry speed and position, dose rate and multileaf collimator (MLC) speed and position for a volumetric modulated arc treatment (VMAT) modality (Synergy® S; Elekta, Stockholm, Sweden), and to check that all the necessary variables and parameters were synchronous. Methods Three tests (for gantry position–dose delivery synchronisation, gantry speed–dose delivery synchronisation and MLC leaf speed and positions) were performed. Results The average error in gantry position was 0.5° and the average difference was 3 MU for a linear and a parabolic relationship between gantry position and delivered dose. In the third part of this test (sawtooth variation), the maximum difference was 9.3 MU, with a gantry position difference of 1.2°. In the sweeping field method test, a linear relationship was observed between recorded doses and distance from the central axis, as expected. In the open field method, errors were encountered at the beginning and at the end of the delivery arc, termed the “beginning” and “end” errors. For MLC position verification, the maximum error was −2.46 mm and the mean error was 0.0153 ±0.4668 mm, and 3.4% of leaves analysed showed errors of >±1 mm. Conclusion This experiment demonstrates that the variables and parameters of the Synergy® S are synchronous and that the system is suitable for delivering VMAT using a dynamic MLC. PMID:22745206

Fabrication of a multi-layer three-dimensional scaffold with controlled porous micro-architecture for application in small intestine tissue engineering.

PubMed

Knight, Toyin; Basu, Joydeep; Rivera, Elias A; Spencer, Thomas; Jain, Deepak; Payne, Richard

2013-01-01

Various methods can be employed to fabricate scaffolds with characteristics that promote cell-to-material interaction. This report examines the use of a novel technique combining compression molding with particulate leaching to create a unique multi-layered scaffold with differential porosities and pore sizes that provides a high level of control to influence cell behavior. These cell behavioral responses were primarily characterized by bridging and penetration of two cell types (epithelial and smooth muscle cells) on the scaffold in vitro. Larger pore sizes corresponded to an increase in pore penetration, and a decrease in pore bridging. In addition, smaller cells (epithelial) penetrated further into the scaffold than larger cells (smooth muscle cells). In vivo evaluation of a multi-layered scaffold was well tolerated for 75 d in a rodent model. This data shows the ability of the components of multi-layered scaffolds to influence cell behavior, and demonstrates the potential for these scaffolds to promote desired tissue outcomes in vivo.

Influence of Projected Changes in North American Snow Cover Extent on Mid-Latitude Cyclone Progression

NASA Astrophysics Data System (ADS)

Clare, R. M.; Desai, A. R.; Martin, J. E.; Notaro, M.; Vavrus, S. J.

2017-12-01

It has long been hypothesized that snow cover and snow extent have an influence on the development or steering of synoptic mid-latitude cyclones (MLCs). Rydzik and Desai (2014) showed a robust statistical relationship among snow cover extent, generation of low-level baroclinicity, and MLC tracks. Though snow cover extent is highly variable year to year, the changing global climate is expected to continue an already observed pattern of poleward retreat of mean snow cover in North America, particularly in late winter and spring. For this experiment, large ensemble simulations with the Weather Research and Forecasting model (WRF) were forced with output from the Community Earth System Model (CESM) to test the effect contributed solely by snow cover and the projected effects of a changing climate. Our experiment induces an adjustment to the extent of snow cover in North America according to CESM RCP 8.5 projections for each decade from 2020 to 2100 before and during several cases of MLCs moving east across the Great Plains near the snow line. To evaluate mechanisms of pre-existing and current snow influence on MLCs, model cases are started with snow line adjustment occurring from three days prior up to the storm's arrival over the Great Plains. We demonstrate that snow cover changes do alter MLC intensity and path via modification of low-level potential vorticity.

SU-G-BRA-16: Target Dose Comparison for Dynamic MLC Tracking and Mid- Ventilation Planning in Lung Radiotherapy Subject to Intrafractional Baseline Drifts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Menten, MJ; Fast, MF; Nill, S

Purpose: Lung tumor motion during radiotherapy can be accounted for by expanded treatment margins, for example using a mid-ventilation planning approach, or by localizing the tumor in real-time and adapting the treatment beam with multileaf collimator (MLC) tracking. This study evaluates the effect of intrafractional changes in the average tumor position (baseline drifts) on these two treatment techniques. Methods: Lung stereotactic treatment plans (9-beam IMRT, 54Gy/3 fractions, mean treatment time: 9.63min) were generated for three patients: either for delivery with MLC tracking (isotropic GTV-to-PTV margin: 2.6mm) or planned with a mid-ventilation approach and delivered without online motion compensation (GTV-to-PTV margin:more » 4.4-6.3mm). Delivery to a breathing patient was simulated using DynaTrack, our in-house tracking and delivery software. Baseline drifts in cranial and posterior direction were simulated at a rate of 0.5, 1.0 or 1.5mm/min. For dose reconstruction, the corresponding 4DCT phase was selected for each time point of the delivery. Baseline drifts were accounted for by rigidly shifting the CT to ensure correct relative beam-to-target positioning. Afterwards, the doses delivered to each 4DCT phase were accumulated deformably on the mid-ventilation phase using research RayStation v4.6 and dose coverage of the GTV was evaluated. Results: When using the mid-ventilation planning approach, dose coverage of the tumor deteriorated substantially in the presence of baseline drifts. The reduction in D98% coverage of the GTV in a single fraction ranged from 0.4-1.2, 0.6-3.3 and 4.5-6.2Gy, respectively, for the different drift rates. With MLC tracking the GTV D98% coverage remained unchanged (+/− 0.1Gy) regardless of drift. Conclusion: Intrafractional baseline drifts reduce the tumor dose in treatments based on mid-ventilation planning. In rare, large target baseline drifts tumor dose coverage may drop below the prescription, potentially affecting clinical outcome in hypofractionated treatment protocols. Dynamic MLC tracking preserves tumor dose coverage even in the presence of extreme baseline drifts. We acknowledge financial and technical support of the MLC tracking research from Elekta AB. Research at ICR is supported by CRUK under Programme C33589/A19727 and NHS funding to the NIHR Biomedical Research Centre at RMH and ICR. MFF is supported by CRUK under Programme C33589/A19908.« less

Cost Trade Between Multi-Junction, Gallium Arsenide, and Silicon Solar Cells

NASA Technical Reports Server (NTRS)

Gaddy, Edward M.

1995-01-01

Multi-junction (MJ), gallium arsenide (GaAs), and silicon (Si) solar cells have respective test efficiencies of approximately 24%, 18.5% and 14.8%. Multi-junction and gallium arsenide solar cells weigh more than silicon solar 2 cells and cost approximately five times as much per unit power at the cell level. A trade is performed for the TRMM spacecraft to determine which of these cell types would have offered an overall performance and price advantage to the spacecraft. A trade is also performed for the multi-junction cells under the assumption that they will cost over ten times that of silicon cells at the cell level. The trade shows that the TRMM project, less the cost of the instrument, ground systems and mission operations, would spend approximately $552,000 dollars per kilogram to launch and suppon3science in the case of the spacecraft equipped with silicon solar cells. If these cells are changed out for gallium arsenide solar cells, an additional 31 kilograms of science can be launched and serviced at a price of approximately $90 thousand per kilogram. The weight reduction is shown to derive from the smaller area of the array and hence reductions in the weight of the array substrate and supporting structure. ff the silicon solar cells are changed out for multi-junction solar cells, an additional 45 kilograms of science above the silicon base line can be launched and supported at a price of approximately $58,000 per kilogram. The trade shows that even if the multi-junction cells are priced over ten times that of silicon cells, a price that is much higher than projected, that the additional 45 kilograms of science are launched and serviced at $180,000 per kilogram. This is still much less than the original $552,000 per kilogram to launch and service the science. Data and qualitative factors are presented to show that these figures are subject to a great deal of uncertainty. Nonetheless, the benefit of the higher efficiency solar cells for TRMM is far greater than the uncertainties in the analysis.

Identifying tropical dry forests extent and succession via the use of machine learning techniques

NASA Astrophysics Data System (ADS)

Li, Wei; Cao, Sen; Campos-Vargas, Carlos; Sanchez-Azofeifa, Arturo

2017-12-01

Information on ecosystem services as a function of the successional stage for secondary tropical dry forests (TDFs) is scarce and limited. Secondary TDFs succession is defined as regrowth following a complete forest clearance for cattle growth or agriculture activities. In the context of large conservation initiatives, the identification of the extent, structure and composition of secondary TDFs can serve as key elements to estimate the effectiveness of such activities. As such, in this study we evaluate the use of a Hyperspectral MAPper (HyMap) dataset and a waveform LIDAR dataset for characterization of different levels of intra-secondary forests stages at the Santa Rosa National Park (SRNP) Environmental Monitoring Super Site located in Costa Rica. Specifically, a multi-task learning based machine learning classifier (MLC-MTL) is employed on the first shortwave infrared (SWIR1) of HyMap in order to identify the variability of aboveground biomass of secondary TDFs along a successional gradient. Our paper recognizes that the process of ecological succession is not deterministic but a combination of transitional forests types along a stochastic path that depends on ecological, edaphic, land use, and micro-meteorological conditions, and our results provide a new way to obtain the spatial distribution of three main types of TDFs successional stages.

A Rapidly Deployable Bridge System

DTIC Science & Technology

2013-01-15

17 - 4PH SS H1150 Hinge Pins 30x106 psi (2) 143 ksi (4) 157 ksi (4) - 104.7 ksi SS T316 Cables 30x106 psi - 116 ksi - 77.3 ksi The stress...CLASSIFICATION OF: 17 . LIMITATION OF ABSTRACT Public Release 18. NUMBER OF PAGES 12 19a. NAME OF RESPONSIBLE PERSON a. REPORT unclassified b...an MLC30/12m configuration. The MLC50/20m system uses 17 modules in a 9/8 configuration. The connection of the modules to each other is by means of

Straw man trade between multi-junction, gallium arsenide, and silicon solar cells

NASA Technical Reports Server (NTRS)

Gaddy, Edward M.

1995-01-01

Multi-junction (MJ), gallium arsenide (GaAs), and silicon (Si) solar cells have respective test efficiencies of approximately 24%, 18.5% and 14.8%. Multi-junction and gallium arsenide solar cells weigh more than silicon solar cells and cost approximately five times as much per unit power at the cell level. A straw man trade is performed for the TRMM spacecraft to determine which of these cell types would have offered an overall performance and price advantage to the spacecraft. A straw man trade is also performed for the multi-junction cells under the assumption that they will cost over ten times that of silicon cells at the cell level. The trade shows that the TRMM project, less the cost of the instrument, ground systems and mission operations, would spend approximately $552 thousand dollars per kilogram to launch and service science in the case of the spacecraft equipped with silicon solar cells. If these cells are changed out for gallium arsenide solar cells, an additional 31 kilograms of science can be launched and serviced at a price of approximately $90 thousand per kilogram. The weight reduction is shown to derive from the smaller area of the array and hence reductions in the weight of the array substrate and supporting structure. If the silicon solar cells are changed out for multi-junction solar cells, an additional 45 kilograms of science above the silicon base line can be launched and serviced at a price of approximately $58 thousand per kilogram. The trade shows that even if the multi-junction arrays are priced over ten times that of silicon cells, a price that is much higher than projected, that the additional 45 kilograms of science are launched and serviced at $182 thousand per kilogram. This is still much less than original $552 thousand per kilogram to launch and service the science. Data and qualitative factors are presented to show that these figures are subject to a great deal of uncertainty. Nonetheless, the benefit of the higher efficiency solar cells for TRMM is far greater than the uncertainties in the analysis.

Simultaneous inhibition of multiple oncogenic miRNAs by a multi-potent microRNA sponge.

PubMed

Jung, Jaeyun; Yeom, Chanjoo; Choi, Yeon-Sook; Kim, Sinae; Lee, EunJi; Park, Min Ji; Kang, Sang Wook; Kim, Sung Bae; Chang, Suhwan

2015-08-21

The roles of oncogenic miRNAs are widely recognized in many cancers. Inhibition of single miRNA using antagomiR can efficiently knock-down a specific miRNA. However, the effect is transient and often results in subtle phenotype, as there are other miRNAs contribute to tumorigenesis. Here we report a multi-potent miRNA sponge inhibiting multiple miRNAs simultaneously. As a model system, we targeted miR-21, miR-155 and miR-221/222, known as oncogenic miRNAs in multiple tumors including breast and pancreatic cancers. To achieve efficient knockdown, we generated perfect and bulged-matched miRNA binding sites (MBS) and introduced multiple copies of MBS, ranging from one to five, in the multi-potent miRNA sponge. Luciferase reporter assay showed the multi-potent miRNA sponge efficiently inhibited 4 miRNAs in breast and pancreatic cancer cells. Furthermore, a stable and inducible version of the multi-potent miRNA sponge cell line showed the miRNA sponge efficiently reduces the level of 4 target miRNAs and increase target protein level of these oncogenic miRNAs. Finally, we showed the miRNA sponge sensitize cells to cancer drug and attenuate cell migratory activity. Altogether, our study demonstrates the multi-potent miRNA sponge is a useful tool to examine the functional impact of simultaneous inhibition of multiple miRNAs and proposes a therapeutic potential.

SU-F-T-295: MLCs Performance and Patient-Specific IMRT QA Using Log File Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Osman, A; American University of Biuret Medical Center, Biuret; Maalej, N

2016-06-15

Purpose: To analyze the performance of the multi-leaf collimators (MLCs) from the log files recorded during the intensity modulated radiotherapy (IMRT) treatment and to construct the relative fluence maps and do the gamma analysis to compare the planned and executed MLCs movement. Methods: We developed a program to extract and analyze the data from dynamic log files (dynalog files) generated from sliding window IMRT delivery treatments. The program extracts the planned and executed (actual or delivered) MLCs movement, calculates and compares the relative planned and executed fluences. The fluence maps were used to perform the gamma analysis (with 3% dosemore » difference and 3 mm distance to agreement) for 3 IMR patients. We compared our gamma analysis results with those obtained from portal dose image prediction (PDIP) algorithm performed using the EPID. Results: For 3 different IMRT patient treatments, the maximum difference between the planned and the executed MCLs positions was 1.2 mm. The gamma analysis results of the planned and delivered fluences were in good agreement with the gamma analysis from portal dosimetry. The maximum difference for number of pixels passing the gamma criteria (3%/3mm) was 0.19% with respect to portal dosimetry results. Conclusion: MLC log files can be used to verify the performance of the MLCs. Patientspecific IMRT QA based on MLC movement log files gives similar results to EPID dosimetry results. This promising method for patient-specific IMRT QA is fast, does not require dose measurements in a phantom, can be done before the treatment and for every fraction, and significantly reduces the IMRT workload. The author would like to thank King Fahd University of petroleum and Minerals for the support.« less

Quantitative evaluation of patient-specific quality assurance using online dosimetry system

NASA Astrophysics Data System (ADS)

Jung, Jae-Yong; Shin, Young-Ju; Sohn, Seung-Chang; Min, Jung-Whan; Kim, Yon-Lae; Kim, Dong-Su; Choe, Bo-Young; Suh, Tae-Suk

2018-01-01

In this study, we investigated the clinical performance of an online dosimetry system (Mobius FX system, MFX) by 1) dosimetric plan verification using gamma passing rates and dose volume metrics and 2) error-detection capability evaluation by deliberately introduced machine error. Eighteen volumetric modulated arc therapy (VMAT) plans were studied. To evaluate the clinical performance of the MFX, we used gamma analysis and dose volume histogram (DVH) analysis. In addition, to evaluate the error-detection capability, we used gamma analysis and DVH analysis utilizing three types of deliberately introduced errors (Type 1: gantry angle-independent multi-leaf collimator (MLC) error, Type 2: gantry angle-dependent MLC error, and Type 3: gantry angle error). A dosimetric verification comparison of physical dosimetry system (Delt4PT) and online dosimetry system (MFX), gamma passing rates of the two dosimetry systems showed very good agreement with treatment planning system (TPS) calculation. For the average dose difference between the TPS calculation and the MFX measurement, most of the dose metrics showed good agreement within a tolerance of 3%. For the error-detection comparison of Delta4PT and MFX, the gamma passing rates of the two dosimetry systems did not meet the 90% acceptance criterion with the magnitude of error exceeding 2 mm and 1.5 ◦, respectively, for error plans of Types 1, 2, and 3. For delivery with all error types, the average dose difference of PTV due to error magnitude showed good agreement between calculated TPS and measured MFX within 1%. Overall, the results of the online dosimetry system showed very good agreement with those of the physical dosimetry system. Our results suggest that a log file-based online dosimetry system is a very suitable verification tool for accurate and efficient clinical routines for patient-specific quality assurance (QA).

Incorrect dosimetric leaf separation in IMRT and VMAT treatment planning: Clinical impact and correlation with pretreatment quality assurance.

PubMed

Sjölin, Maria; Edmund, Jens Morgenthaler

2016-07-01

Dynamic treatment planning algorithms use a dosimetric leaf separation (DLS) parameter to model the multi-leaf collimator (MLC) characteristics. Here, we quantify the dosimetric impact of an incorrect DLS parameter and investigate whether common pretreatment quality assurance (QA) methods can detect this effect. 16 treatment plans with intensity modulated radiation therapy (IMRT) or volumetric modulated arc therapy (VMAT) technique for multiple treatment sites were calculated with a correct and incorrect setting of the DLS, corresponding to a MLC gap difference of 0.5mm. Pretreatment verification QA was performed with a bi-planar diode array phantom and the electronic portal imaging device (EPID). Measurements were compared to the correct and incorrect planned doses using gamma evaluation with both global (G) and local (L) normalization. Correlation, specificity and sensitivity between the dose volume histogram (DVH) points for the planning target volume (PTV) and the gamma passing rates were calculated. The change in PTV and organs at risk DVH parameters were 0.4-4.1%. Good correlation (>0.83) between the PTVmean dose deviation and measured gamma passing rates was observed. Optimal gamma settings with 3%L/3mm (per beam and composite plan) and 3%G/2mm (composite plan) for the diode array phantom and 2%G/2mm (composite plan) for the EPID system were found. Global normalization and per beam ROC analysis of the diode array phantom showed an area under the curve <0.6. A DLS error can worsen pretreatment QA using gamma analysis with reasonable credibility for the composite plan. A low detectability was demonstrated for a 3%G/3mm per beam gamma setting. Copyright © 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Acute toxicity of two lampricides, 3-trifluoromethyl-4-nitrophenol (TFM) and a TFM: 1% niclosamide mixture, to sea lamprey, three species of unionids, haliplid water beetles, and American eel

USGS Publications Warehouse

Boogaard, Michael A.; Rivera, Jane E.

2011-01-01

We conducted a series of toxicological treatments with 3-trifluoromethyl-4-nitrophenol (TFM) and a TFM:1% 2′,5-dichloro-4′-nitrosalicylanilide (niclosamide) mixture, two compounds used to control larval sea lamprey (Petromyzon marinus) in Great Lakes tributaries, to evaluate the acute toxicity of the lampricides to a number of nontarget species of concern. Treatments were conducted with yellow stage American eel (Anguilla rostrata), adult and larval haliplid water beetles (Haliplus spp.), a surrogate for the endangered Hungerford’s crawling water beetle (Brychius hungerfordi), and adults of three unionid species—giant floater (Pyganadon grandis), fragile papershell (Leptodea fragilis), and pink heelsplitter (Potamilus alatus). Treatments were conducted using a serial dilution system consisting of nine test concentrations and an untreated control with 20% dilution between concentrations. Narcosis was evident among giant floaters exposed to the TFM and the TFM:1% niclosamide mixture and among pink heelsplitters exposed to the TFM:1% niclosamide mixture only but mostly at concentrations greater than 2-fold that required to kill 100% of larval sea lamprey (minimum lethal concentration (MLC)). Tests with the haliplid beetle suggest the risks to the Hungerford’s crawling water beetle associated with TFM applications are minimal. Concentrations over 2-fold the sea lamprey MLC did not kill adult or larval water beetles. Preliminary behavioral observations suggest water beetles may avoid treatment by crawling out of the water. Adult water beetles exposed to TFM at 3-fold the sea lamprey MLC were observed above the water line more often than controls. The lampricide TFM was not acutely toxic to American eel. Mortalities were rare among American eel exposed to TFM concentrations up to 7-fold the observed sea lamprey MLC. Similarly, for the TFM:1% niclosamide mixture, mortalities were rare among American eel exposed to nearly 5-fold the observed sea lamprey MLC. Overall, acute TFM toxicity was not evident among any of the species examined in this study at concentrations targeted to control larval sea lamprey. Results for the adult unionids should be viewed with caution due to the lack of replication in the treatments.

SU-E-T-195: Commissioning the Neutron Production of a Varian TrueBeam Linac

DOE Office of Scientific and Technical Information (OSTI.GOV)

Irazola, L; Brualla, L; Rosello, J

2015-06-15

Purpose: The purpose of this work is the characterization of a new Varian TrueBeam™ facility in terms of neutron production, in order to estimate neutron equivalent dose in organs during radiotherapy treatments. Methods: The existing methodology [1] was used with the reference SRAMnd detector, calibrated in terms of thermal neutron fluence at the reference field operated by PTB (Physikalisch-Technische-Bundesanstalt) at the GeNF (Geesthacht-Neutron-Facility) with the GKSS reactor FRG-1 [2]. Thermal neutron fluence for the 5 available possibilities was evaluated: 15 MV and 10&6 MV with and without Flattening Filter (FF and FFF, respectively). Irradiation conditions are as described in [3].more » In addition, three different collimator-MLC configurations were studied for 15 MV: (a) collimator of 10×10 cm{sup 2} and MLC fully retracted (reference), (b) field sizes of 20×20 cm{sup 2} and 10×10 cm{sup 2} for collimator and MLC respectively, and (c) collimator and MLC aperture of 10×10 cm{sup 2}. Results: Thermal fluence rate at the “reference point” [3], as a consequence of the neutron production, obtained for (a) conformation in 15 MV is (1.45±0.11) x10{sup 4} n•cm{sup 2}/MU. Configurations (b) and (c) gave fluences of 96.6% and 97.8% of the reference (a). Neutron production decreases up to 8.6% and 5.7% for the 10 MV FF and FFF beams, respectively. Finally, it decreases up to 2.8% and 0.1% for the 6 MV FF and FFF modes, respectively. Conclusion: This work evaluates thermal neutron production of Varian TrueBeam™ system for organ equivalent dose estimation. The small difference in collimator-MLC configuration shows the universality of the methodology [3]. A decrease in this production is shown when decreasing energy from 15 to 10 MV and an almost negligible production was found for 6 MV. Moreover, a lower neutron contribution is observed for the FFF modes.[1]Phys Med Biol,2012;57:6167–6191.[2]Radiat Meas,2010;45:1513–1517.[3]Med Phys,2015;42:276–281.« less

SU-E-T-598: Clinical Experience of Configuration, Commission and Implementation for SmartArc with MOSAIQ R&V System.

PubMed

Kong, X; Clausen, C; Wang, S

2012-06-01

Clinical experience for configuration, commission and implementation of SmartArc with MOSAIQ R&V system. SmartArc is Pinnacle's solution for VMAT. On July 2011 we updated to Pinnacle 9.0 and purchased SmartArc. A standalone Eclipse workstation has been used 3 years for VMAT planning. Our clinical setting: Mosaiq 2.2; Varian Trilogy driven by 4DiTC and Varian 21ex driven by sequencer. Some key physics parameters have been studied: machine dose rate; MLC leaf speed; Leaf motion per gantry rotation. Tabletop was created by user to improve the dose accuracy for planning. In-house sandwich phantom was used with MapCheck for planner dose verification. A PTW 0.6cc ion chamber was included for absolute dose comparison. A copy of current machine data with default highest dose rate is recommended. It is due to after 10th iteration of optimization, the default dose rate will kick in. 2.5cm/s is the constraint for Varian Millennium 120 MLC; a buffer zone of 10% is suggested to reduce the MLC error on treatment. 2.25cm/s is used in our configuration. This results in MLC interlock if not configured correct. Maximum leaf motion per gantry rotation of 0.46cm/degree has to be checked for planning with Mosaiq R&V. Otherwise, undeliverable plan will show up sometimes on 4DiTC.Tabletop was exported as a DICOM structure from Eclipse to Pinnacle; we created a ROI template based on the matched tabletop.QA using in-house phantom for different sites were tested. Results for both planner dose and absolute chamber measurement are satisfactory. Special attentions need to be paid for dose rate, MLC leaf speed, leaf motion per gantry rotation when configuring SmartArc. Varian 21ex is supported but is slow for clinical delivery. Users need to create your own tabletop to improve planning accuracy. Conventional commission procedures for RapidArc also apply for SmartArc. © 2012 American Association of Physicists in Medicine.

SU-F-T-371: Development of a Linac Monte Carlo Model to Calculate Surface Dose

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prajapati, S; Yan, Y; Gifford, K

2016-06-15

Purpose: To generate and validate a linac Monte Carlo (MC) model for surface dose prediction. Methods: BEAMnrc V4-2.4.0 was used to model 6 and 18 MV photon beams for a commercially available linac. DOSXYZnrc V4-2.4.0 calculated 3D dose distributions in water. Percent depth dose (PDD) and beam profiles were extracted for comparison to measured data. Surface dose and at depths in the buildup region was measured with radiochromic film at 100 cm SSD for 4 × 4 cm{sup 2} and 10 × 10 cm{sup 2} collimator settings for open and MLC collimated fields. For the 6 MV beam, films weremore » placed at depths ranging from 0.015 cm to 2 cm and for 18 MV, 0.015 cm to 3.5 cm in Solid Water™. Films were calibrated for both photon energies at their respective dmax. PDDs and profiles were extracted from the film and compared to the MC data. The MC model was adjusted to match measured PDD and profiles. Results: For the 6 MV beam, the mean error(ME) in PDD between film and MC for open fields was 1.9%, whereas it was 2.4% for MLC. For the 18 MV beam, the ME in PDD for open fields was 2% and was 3.5% for MLC. For the 6 MV beam, the average root mean square(RMS) deviation for the central 80% of the beam profile for open fields was 1.5%, whereas it was 1.6% for MLC. For the 18 MV beam, the maximum RMS for open fields was 3%, and was 3.1% for MLC. Conclusion: The MC model of a linac agreed to within 4% of film measurements for depths ranging from the surface to dmax. Therefore, the MC linac model can predict surface dose for clinical applications. Future work will focus on adjusting the linac MC model to reduce RMS error and improve accuracy.« less

MO-FG-BRA-06: Electromagnetic Beacon Insertion in Lung Cancer Patients and Resultant Surrogacy Errors for Dynamic MLC Tumour Tracking

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hardcastle, N; Booth, J; Caillet, V

Purpose: To assess endo-bronchial electromagnetic beacon insertion and to quantify the geometric accuracy of using beacons as a surrogate for tumour motion in real-time multileaf collimator (MLC) tracking of lung tumours. Methods: The LIGHT SABR trial is a world-first clinical trial in which the MLC leaves move with lung tumours in real time on a standard linear accelerator. Tracking is performed based on implanted electromagnetic beacons (CalypsoTM, Varian Medical Systems, USA) as a surrogate for tumour motion. Five patients have been treated and have each had three beacons implanted endo-bronchially under fluoroscopic guidance. The centre of mass (C.O.M) has beenmore » used to adapt the MLC in real-time. The geometric error in using the beacon C.O.M as a surrogate for tumour motion was measured by measuring the tumour and beacon C.O.M in all phases of the respiratory cycle of a 4DCT. The surrogacy error was defined as the difference in beacon and tumour C.O.M relative to the reference phase (maximum exhale). Results: All five patients have had three beacons successfully implanted with no migration between simulation and end of treatment. Beacon placement relative to tumour C.O.M varied from 14 to 74 mm and in one patient spanned two lobes. Surrogacy error was measured in each patient on the simulation 4DCT and ranged from 0 to 3 mm. Surrogacy error as measured on 4DCT was subject to artefacts in mid-ventilation phases. Surrogacy error was a function of breathing phase and was typically larger at maximum inhale. Conclusion: Beacon placement and thus surrogacy error is a major component of geometric uncertainty in MLC tracking of lung tumours. Surrogacy error must be measured on each patient and incorporated into margin calculation. Reduction of surrogacy error is limited by airway anatomy, however should be taken into consideration when performing beacon insertion and planning. This research is funded by Varian Medical Systems via a collaborative research agreement.« less

Durability of the beneficial effect of MLC601 (NeuroAiD™) on functional recovery among stroke patients from the Philippines in the CHIMES and CHIMES-E studies.

PubMed

Navarro, Jose C; Chen, Christopher Lh; Lee, Chun F; Gan, Herminigildo H; Lao, Annabelle Y; Baroque, Alejandro C; Hiyadan, John Harold B; Chua, Carlos L; San Jose, Ma Cristina; Advincula, Joel M; Venketasubramanian, Narayanaswamy

2017-04-01

Background and Aim A pre-specified country analysis of subjects from the Philippines in the CHInese Medicine NeuroAiD Efficacy on Stroke recovery (CHIMES) Study showed significantly improved functional and neurological outcomes on MLC601 at month (M) 3. We aimed to assess these effects on long-term functional recovery in the Filipino cohort. Methods The CHIMES-E (extension) Study evaluated subjects who completed three months of randomized placebo-controlled treatment in CHIMES up to two years. Blinding of treatment allocation was maintained and all subjects received standard stroke care and rehabilitation. Modified Rankin Score (mRS) and Barthel Index (BI) were assessed in-person at M3 and by telephone at M6, M12, M18, M24. Odds ratios (OR) with corresponding 95% confidence intervals (CI) for functional recovery using ordinal analysis of mRS and for achieving functional independence (mRS 0-1 or BI ≥ 95) at each time point were calculated, adjusting for age, sex, baseline National Institute of Health Stroke Scale (NIHSS), onset-to-treatment time (OTT) and pre-stroke mRS. Results The 378 subjects (MLC601 192, placebo 186) included in CHIMES-E from the Philippines (mean age 60.2 ± 11.1) had more women ( p < 0.001), worse baseline NIHSS ( p < 0.001) and longer onset to treatment time ( p = 0.002) compared to other countries. Baseline characteristics were similar between treatment groups. The treatment effect of MLC601 seen at M3 peaked at M6 with OR for mRS shift of 1.53 (95% CI 1.05-2.22), mRS dichotomy 0-1 of 1.77 (95% CI 1.10-2.83), and BI ≥ 95 of 1.87 (95% CI 1.16-3.02). The beneficial effect persisted up to M24. Conclusion The beneficial effect of MLC601 seen at M3 in the Filipino cohort is durable up to two years after stroke.

Rounded leaf end modeling in Pinnacle VMAT treatment planning for fixed jaw linacs

PubMed Central

Yang, Fei; Cao, Ning; Meyer, Juergen

2016-01-01

During volume‐modulated arc therapies (VMAT), dosimetric errors are introduced by multiple open dynamic leaf gaps that are present in fixed diaphragm linear accelerators. The purpose of this work was to develop a methodology for adjusting the rounded leaf end modeling parameters to improve out‐of‐field dose agreement in SmartArc VMAT treatment plans delivered by fixed jaw linacs where leaf gap dose is not negligible. Leaf gap doses were measured for an Elekta beam modulator linac with 0.4 cm micro‐multileaf collimators (MLC) using an A16 micro‐ionization chamber, a MatriXX ion chamber detector array, and Kodak EDR2 film dosimetry in a solid water phantom. The MLC offset and rounded end tip radius were adjusted in the Pinnacle treatment planning system (TPS) to iteratively arrive at the optimal configuration for 6 MV and 10 MV photon energies. Improvements in gamma index with a 3%/3 mm acceptance criteria and an inclusion threshold of 5% of maximum dose were measured, analyzed, and validated using an ArcCHECK diode detector array for field sizes ranging from 1.6 to 14 cm square field arcs and Task Group (TG) 119 VMAT test cases. The best results were achieved for a rounded leaf tip radius of 13 cm with a 0.1 cm MLC offset. With the optimized MLC model, measured gamma indices ranged between 99.9% and 91.7% for square field arcs with sizes between 3.6 cm and 1.6 cm, with a maximum improvement of 42.7% for the 1.6 cm square field size. Gamma indices improved up to 2.8% in TG‐119 VMAT treatment plans. Imaging and Radiation Oncology Core (IROC) credentialing of a VMAT plan with the head and neck phantom passed with a gamma index of 100%. Fine‐tune adjustments to MLC rounded leaf ends may improve patient‐specific QA pass rates and provide more accurate predictions of dose deposition to avoidance structures. PACS number(s): 87.55.D‐, 87.55.kd, 87.55.kh PMID:27929490

Planning and delivery of four-dimensional radiation therapy with multileaf collimators

NASA Astrophysics Data System (ADS)

McMahon, Ryan L.

This study is an investigation of the application of multileaf collimators (MLCs) to the treatment of moving anatomy with external beam radiation therapy. First, a method for delivering intensity modulated radiation therapy (IMRT) to moving tumors is presented. This method uses an MLC control algorithm that calculates appropriate MLC leaf speeds in response to feedback from real-time imaging. The algorithm does not require a priori knowledge of a tumor's motion, and is based on the concept of self-correcting DMLC leaf trajectories . This gives the algorithm the distinct advantage of allowing for correction of DMLC delivery errors without interrupting delivery. The algorithm is first tested for the case of one-dimensional (1D) rigid tumor motion in the beam's eye view (BEV). For this type of motion, it is shown that the real-time tracking algorithm results in more accurate deliveries, with respect to delivered intensity, than those which ignore motion altogether. This is followed by an appropriate extension of the algorithm to two-dimensional (2D) rigid motion in the BEV. For this type of motion, it is shown that the 2D real-time tracking algorithm results in improved accuracy (in the delivered intensity) in comparison to deliveries which ignore tumor motion or only account for tumor motion which is aligned with MLC leaf travel. Finally, a method is presented for designing DMLC leaf trajectories which deliver a specified intensity over a moving tumor without overexposing critical structures which exhibit motion patterns that differ from that of the tumor. In addition to avoiding overexposure of critical organs, the method can, in the case shown, produce deliveries that are superior to anything achievable using stationary anatomy. In this regard, the method represents a systematic way to include anatomical motion as a degree of freedom in the optimization of IMRT while producing treatment plans that are deliverable with currently available technology. These results, combined with those related to the real-time MLC tracking algorithm, show that an MLC is a promising tool to investigate for the delivery of four-dimensional radiation therapy.

Multileaf collimator tracking integrated with a novel x-ray imaging system and external surrogate monitoring

NASA Astrophysics Data System (ADS)

Krauss, Andreas; Fast, Martin F.; Nill, Simeon; Oelfke, Uwe

2012-04-01

We have previously developed a tumour tracking system, which adapts the aperture of a Siemens 160 MLC to electromagnetically monitored target motion. In this study, we exploit the use of a novel linac-mounted kilovoltage x-ray imaging system for MLC tracking. The unique in-line geometry of the imaging system allows the detection of target motion perpendicular to the treatment beam (i.e. the directions usually featuring steep dose gradients). We utilized the imaging system either alone or in combination with an external surrogate monitoring system. We equipped a Siemens ARTISTE linac with two flat panel detectors, one directly underneath the linac head for motion monitoring and the other underneath the patient couch for geometric tracking accuracy assessments. A programmable phantom with an embedded metal marker reproduced three patient breathing traces. For MLC tracking based on x-ray imaging alone, marker position was detected at a frame rate of 7.1 Hz. For the combined external and internal motion monitoring system, a total of only 85 x-ray images were acquired prior to or in between the delivery of ten segments of an IMRT beam. External motion was monitored with a potentiometer. A correlation model between external and internal motion was established. The real-time component of the MLC tracking procedure then relied solely on the correlation model estimations of internal motion based on the external signal. Geometric tracking accuracies were 0.6 mm (1.1 mm) and 1.8 mm (1.6 mm) in directions perpendicular and parallel to the leaf travel direction for the x-ray-only (the combined external and internal) motion monitoring system in spite of a total system latency of ˜0.62 s (˜0.51 s). Dosimetric accuracy for a highly modulated IMRT beam-assessed through radiographic film dosimetry-improved substantially when tracking was applied, but depended strongly on the respective geometric tracking accuracy. In conclusion, we have for the first time integrated MLC tracking with x-ray imaging in the in-line geometry and demonstrated highly accurate respiratory motion tracking.

Remotely Piloted Vehicle (RPV) Two versus Three Level Maintenance Support Concept Study.

DTIC Science & Technology

1988-01-15

Abri:.ms ML-C, Technic:al Arid lysi!;&2jp7 f D~onnie Joyce Al ler Ad:va-.ncecd Sys.tems Coric epts oft ic.e, -,Je etaty Robo r t Bac-et RPV Pti...en ter, Al TN Conccept,-* & [h ct norii ’’ t Fort Lee, VA 2D501 ,c ient f ii: Advisor , ATIN: ATCI. SP(A, At my C eq 1 t mPFr [ pp Ft VA :27: C.1. Do

Fabrication of multi-well chips for spheroid cultures and implantable constructs through rapid prototyping techniques.

PubMed

Lopa, Silvia; Piraino, Francesco; Kemp, Raymond J; Di Caro, Clelia; Lovati, Arianna B; Di Giancamillo, Alessia; Moroni, Lorenzo; Peretti, Giuseppe M; Rasponi, Marco; Moretti, Matteo

2015-07-01

Three-dimensional (3D) culture models are widely used in basic and translational research. In this study, to generate and culture multiple 3D cell spheroids, we exploited laser ablation and replica molding for the fabrication of polydimethylsiloxane (PDMS) multi-well chips, which were validated using articular chondrocytes (ACs). Multi-well ACs spheroids were comparable or superior to standard spheroids, as revealed by glycosaminoglycan and type-II collagen deposition. Moreover, the use of our multi-well chips significantly reduced the operation time for cell seeding and medium refresh. Exploiting a similar approach, we used clinical-grade fibrin to generate implantable multi-well constructs allowing for the precise distribution of multiple cell types. Multi-well fibrin constructs were seeded with ACs generating high cell density regions, as shown by histology and cell fluorescent staining. Multi-well constructs were compared to standard constructs with homogeneously distributed ACs. After 7 days in vitro, expression of SOX9, ACAN, COL2A1, and COMP was increased in both constructs, with multi-well constructs expressing significantly higher levels of chondrogenic genes than standard constructs. After 5 weeks in vivo, we found that despite a dramatic size reduction, the cell distribution pattern was maintained and glycosaminoglycan content per wet weight was significantly increased respect to pre-implantation samples. In conclusion, multi-well chips for the generation and culture of multiple cell spheroids can be fabricated by low-cost rapid prototyping techniques. Furthermore, these techniques can be used to generate implantable constructs with defined architecture and controlled cell distribution, allowing for in vitro and in vivo investigation of cell interactions in a 3D environment. © 2015 Wiley Periodicals, Inc.

Comparison between micellar liquid chromatography and capillary zone electrophoresis for the determination of hydrophobic basic drugs in pharmaceutical preparations.

PubMed

Torres-Cartas, S; Martín-Biosca, Y; Sagrado, S; Villanueva-Camañas, R M; Medina-Hernández, M J

2007-01-01

The determination of highly hydrophobic basic compounds by means of conventional reversed-phase liquid chromatographic methods has several drawbacks. Owing to the characteristics of micellar liquid chromatography (MLC) and capillary electrophoresis (CE), these techniques could be advantageous alternatives to reversed-phase chromatographic methods for the determination of these kinds of compounds. The objective of this study was to develop and compare MLC and CE methods for the determination of antipsychotic basic drugs (amitryptiline, haloperidol, perphenazine and thioridazine) in pharmaceutical preparations. The chromatographic determination of the analytes was performed on a Kromasil C(18) analytical column; the mobile phase was 0.04 m cetyltrimethylammonium bromide (CTAB), at pH 3, containing 5% 1-butanol, at a flow rate of 1 mL/min. The CE separation was performed in a fused-silica capillary with a 50 mm tris-(hydroxymethyl)-aminomethane buffer, pH 7, at an applied voltage of 20 kV, using barbital as internal stardard. The proposed methods are suitable for a reliable quantitation of these compounds in the commercial tablets and drops in terms of accuracy and precision and require a very simple pre-treatment of the samples. By comparing the performance characteristics and experimental details of the MLC and CE methods we conclude that CE seems to be slightly better than MLC in the determination of highly hydrophobic compounds in pharmaceuticals in terms of resolution and economy, taking into account that the limits of detection are not a handicap in pharmaceutical samples. Copyright 2006 John Wiley & Sons, Ltd.

On the use of biomathematical models in patient-specific IMRT dose QA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhen Heming; Nelms, Benjamin E.; Tome, Wolfgang A.

2013-07-15

Purpose: To investigate the use of biomathematical models such as tumor control probability (TCP) and normal tissue complication probability (NTCP) as new quality assurance (QA) metrics.Methods: Five different types of error (MLC transmission, MLC penumbra, MLC tongue and groove, machine output, and MLC position) were intentionally induced to 40 clinical intensity modulated radiation therapy (IMRT) patient plans (20 H and N cases and 20 prostate cases) to simulate both treatment planning system errors and machine delivery errors in the IMRT QA process. The changes in TCP and NTCP for eight different anatomic structures (H and N: CTV, GTV, both parotids,more » spinal cord, larynx; prostate: CTV, rectal wall) were calculated as the new QA metrics to quantify the clinical impact on patients. The correlation between the change in TCP/NTCP and the change in selected DVH values was also evaluated. The relation between TCP/NTCP change and the characteristics of the TCP/NTCP curves is discussed.Results:{Delta}TCP and {Delta}NTCP were summarized for each type of induced error and each structure. The changes/degradations in TCP and NTCP caused by the errors vary widely depending on dose patterns unique to each plan, and are good indicators of each plan's 'robustness' to that type of error.Conclusions: In this in silico QA study the authors have demonstrated the possibility of using biomathematical models not only as patient-specific QA metrics but also as objective indicators that quantify, pretreatment, a plan's robustness with respect to possible error types.« less

Gluten-induced symptoms in diarrhea-predominant irritable bowel syndrome are associated with increased myosin light chain kinase activity and claudin-15 expression

PubMed Central

Wu, Richard Licheng; Vazquez-Roque, Maria; Carlson, Paula; Burton, Duane; Grover, Madhusudan; Camilleri, Michael; Turner, Jerrold R.

2016-01-01

The mechanisms underlying diarrhea-predominant irritable bowel syndrome (IBS-D) are poorly understood, but increased intestinal permeability is thought to contribute to symptoms. A recent clinical trial of gluten-free diet (GFD) demonstrated symptomatic improvement, relative to gluten-containing diet (GCD), that was associated with reduced intestinal permeability in non-celiac disease IBS-D patients. The aim of this study was to characterize intestinal epithelial tight junction composition in IBS-D before and after dietary gluten challenge. Biopsies from 27 IBS-D patients (13 GFD; 14 GCD) were examined by H&E staining and semi-quantitative immunohistochemistry for phosphorylated myosin II regulatory light chain (MLC), MLC kinase, claudin-2, claudin-8, and claudin-15. Diet-induced changes were assessed and correlated with urinary mannitol excretion (after oral administration). In the small intestine, epithelial MLC phosphorylation was increased or decreased by GCD or GFD, respectively, and this correlated with increased intestinal permeability (P < 0.03). Colonocyte expression of the paracellular Na+ channel claudin-15 was also markedly augmented following GCD challenge (P < 0.05). Conversely, colonic claudin-2 expression correlated with reduced intestinal permeability (P < 0.03). Claudin-8 expression was not affected by dietary challenge. These data show that alterations in MLC phosphorylation and claudin-15 and claudin-2 expression are associated with gluten-induced symptomatology and intestinal permeability changes in IBS-D. The results provide new insight into IBS-D mechanisms and can explain permeability responses to gluten challenge in these patients. PMID:27869798

Quantification of interplay and gradient effects for lung stereotactic ablative radiotherapy (SABR) treatments

PubMed Central

2016-01-01

This study quantified the interplay and gradient effects on GTV dose coverage for 3D CRT, dMLC IMRT, and VMAT SABR treatments for target amplitudes of 5–30 mm using 3DVH v3.1 software incorporating 4D Respiratory MotionSim (4D RMS) module. For clinically relevant motion periods (5 s), the interplay effect was small, with deviations in the minimum dose covering the target volume (D99%) of less than ±2.5% for target amplitudes up to 30 mm. Increasing the period to 60 s resulted in interplay effects of up to ±15.0% on target D99% dose coverage. The gradient effect introduced by target motion resulted in deviations of up to ±3.5% in D99% target dose coverage. VMAT treatments showed the largest deviation in dose metrics, which was attributed to the long delivery times in comparison to dMLC IMRT. Retrospective patient analysis indicated minimal interplay and gradient effects for patients treated with dMLC IMRT at the NCCI. PACS numbers: 87.55.km, 87.56.Fc PMID:26894347

Comparative analysis of cardiomyocyte differentiation from human embryonic stem cells under 3-D and 2-D culture conditions.

PubMed

Pal, Rajarshi; Mamidi, Murali Krishna; Das, Anjan Kumar; Bhonde, Ramesh

2013-02-01

Post-myocardial infarction cardiomyocytes are the most important target cell types for cardiac repair. Many of the applications envisaged for human embryonic stem cells (hESC)-derived cardiomyocytes demand that the differentiation procedure be robust, cost effective and high yielding. Various lines of evidence including our earlier study suggest that hESCs have distinct preferences to become heart cells. However, a direct comparison between different protocols has not yet been reported to date. Here, we performed a logical and systematic comparison of cardiomyocytes obtained from hESCs via embryoid bodies (EBs) in suspension versus adherent static cultures of feeder-free hES colonies representing three-dimensional (3-D) and two-dimensional (2-D) culture systems, respectively. An in-depth characterization of the beating cells revealed appropriate cardiac marker expression both at gene and protein levels. Despite using similar media, 3-D and 2-D cultures showed significant variation in growth and ability to form beating areas. While the expression of pre-cardiac mesoderm markers like GATA-4, HAND1, Myf5, Msx1, and BMP-IIR remained unaltered; levels of functional heart-specific markers such as MLC-2A/2V, cTnT, ANP, Phospholamban, α-MHC and KV4.3 were substantially up-regulated in 3-D compared to 2-D cultures. Concurrently we observed a sharp decline in the expression of ESC, ectoderm and endoderm markers including Oct-4, Sox-2, NFH, Sox-1, Sox-17 and AFP. Further immunocytochemistry and flow cytometry demonstrated a higher percentage of cells positive for Brachyury, desmin and cardiac troponin in 3-D cultures. Our results underscore the higher efficiency of cardiomyocytes derived via 3-D cultures. This finding enriches our basic understanding of the differentiation pattern in hESC-derived cardiomyocytes. Copyright © 2012 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Strange non-chaotic attractors in a state controlled-cellular neural network-based quasiperiodically forced MLC circuit

NASA Astrophysics Data System (ADS)

Ezhilarasu, P. Megavarna; Inbavalli, M.; Murali, K.; Thamilmaran, K.

2018-07-01

In this paper, we report the dynamical transitions to strange non-chaotic attractors in a quasiperiodically forced state controlled-cellular neural network (SC-CNN)-based MLC circuit via two different mechanisms, namely the Heagy-Hammel route and the gradual fractalisation route. These transitions were observed through numerical simulations and hardware experiments and confirmed using statistical tools, such as maximal Lyapunov exponent spectrum and its variance and singular continuous spectral analysis. We find that there is a remarkable agreement of the results from both numerical simulations as well as from hardware experiments.

Design of neural networks for classification of remotely sensed imagery

NASA Technical Reports Server (NTRS)

Chettri, Samir R.; Cromp, Robert F.; Birmingham, Mark

1992-01-01

Classification accuracies of a backpropagation neural network are discussed and compared with a maximum likelihood classifier (MLC) with multivariate normal class models. We have found that, because of its nonparametric nature, the neural network outperforms the MLC in this area. In addition, we discuss techniques for constructing optimal neural nets on parallel hardware like the MasPar MP-1 currently at GSFC. Other important discussions are centered around training and classification times of the two methods, and sensitivity to the training data. Finally, we discuss future work in the area of classification and neural nets.

[Investigation of Elekta linac characteristics for VMAT].

PubMed

Luo, Guangwen; Zhang, Kunyi

2012-01-01

The aim of this study is to investigate the characteristics of Elekta delivery system for volumetric modulated arc therapy (VMAT). Five VMAT plans were delivered in service mode and dose rates, and speed of gantry and MLC leaves were analyzed by log files. Results showed that dose rates varied between 6 dose rates. Gantry and MLC leaf speed dynamically varied during delivery. The technique of VMAT requires linac to dynamically control more parameters, and these key dynamic variables during VMAT delivery can be checked by log files. Quality assurance procedure should be carried out for VMAT related parameter.

SU-E-T-88: Comprehensive Automated Daily QA for Hypo- Fractionated Treatments

DOE Office of Scientific and Technical Information (OSTI.GOV)

McGuinness, C; Morin, O

2014-06-01

Purpose: The trend towards more SBRT treatments with fewer high dose fractions places increased importance on daily QA. Patient plan specific QA with 3%/3mm gamma analysis and daily output constancy checks may not be enough to guarantee the level of accuracy required for SBRT treatments. But increasing the already extensive amount of QA procedures that are required is a daunting proposition. We performed a feasibility study for more comprehensive automated daily QA that could improve the diagnostic capabilities of QA without increasing workload. Methods: We performed the study on a Siemens Artiste linear accelerator using the integrated flat panel EPID.more » We included square fields, a picket fence, overlap and representative IMRT fields to measure output, flatness, symmetry, beam center, and percent difference from the standard. We also imposed a set of machine errors: MLC leaf position, machine output, and beam steering to compare with the standard. Results: Daily output was consistent within +/− 1%. Change in steering current by 1.4% and 2.4% resulted in a 3.2% and 6.3% change in flatness. 1 and 2mm MLC leaf offset errors were visibly obvious in difference plots, but passed a 3%/3mm gamma analysis. A simple test of transmission in a picket fence can catch a leaf offset error of a single leaf by 1mm. The entire morning QA sequence is performed in less than 30 minutes and images are automatically analyzed. Conclusion: Automated QA procedures could be used to provide more comprehensive information about the machine with less time and human involvement. We have also shown that other simple tests are better able to catch MLC leaf position errors than a 3%/3mm gamma analysis commonly used for IMRT and modulated arc treatments. Finally, this information could be used to watch trends of the machine and predict problems before they lead to costly machine downtime.« less

Skeletal Muscle-specific G Protein-coupled Receptor Kinase 2 Ablation Alters Isolated Skeletal Muscle Mechanics and Enhances Clenbuterol-stimulated Hypertrophy.

PubMed

Woodall, Benjamin P; Woodall, Meryl C; Luongo, Timothy S; Grisanti, Laurel A; Tilley, Douglas G; Elrod, John W; Koch, Walter J

2016-10-14

GRK2, a G protein-coupled receptor kinase, plays a critical role in cardiac physiology. Adrenergic receptors are the primary target for GRK2 activity in the heart; phosphorylation by GRK2 leads to desensitization of these receptors. As such, levels of GRK2 activity in the heart directly correlate with cardiac contractile function. Furthermore, increased expression of GRK2 after cardiac insult exacerbates injury and speeds progression to heart failure. Despite the importance of this kinase in both the physiology and pathophysiology of the heart, relatively little is known about the role of GRK2 in skeletal muscle function and disease. In this study we generated a novel skeletal muscle-specific GRK2 knock-out (KO) mouse (MLC-Cre:GRK2 fl/fl ) to gain a better understanding of the role of GRK2 in skeletal muscle physiology. In isolated muscle mechanics testing, GRK2 ablation caused a significant decrease in the specific force of contraction of the fast-twitch extensor digitorum longus muscle yet had no effect on the slow-twitch soleus muscle. Despite these effects in isolated muscle, exercise capacity was not altered in MLC-Cre:GRK2 fl/fl mice compared with wild-type controls. Skeletal muscle hypertrophy stimulated by clenbuterol, a β 2 -adrenergic receptor (β 2 AR) agonist, was significantly enhanced in MLC-Cre:GRK2 fl/fl mice; mechanistically, this seems to be due to increased clenbuterol-stimulated pro-hypertrophic Akt signaling in the GRK2 KO skeletal muscle. In summary, our study provides the first insights into the role of GRK2 in skeletal muscle physiology and points to a role for GRK2 as a modulator of contractile properties in skeletal muscle as well as β 2 AR-induced hypertrophy. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Estimating the uncertainty of calculated out-of-field organ dose from a commercial treatment planning system.

PubMed

Wang, Lilie; Ding, George X

2018-06-12

Therapeutic radiation to cancer patients is accompanied by unintended radiation to organs outside the treatment field. It is known that the model-based dose algorithm has limitation in calculating the out-of-field doses. This study evaluated the out-of-field dose calculated by the Varian Eclipse treatment planning system (v.11 with AAA algorithm) in realistic treatment plans with the goal of estimating the uncertainties of calculated organ doses. Photon beam phase-space files for TrueBeam linear accelerator were provided by Varian. These were used as incident sources in EGSnrc Monte Carlo simulations of radiation transport through the downstream jaws and MLC. Dynamic movements of the MLC leaves were fully modeled based on treatment plans using IMRT or VMAT techniques. The Monte Carlo calculated out-of-field doses were then compared with those calculated by Eclipse. The dose comparisons were performed for different beam energies and treatment sites, including head-and-neck, lung, and pelvis. For 6 MV (FF/FFF), 10 MV (FF/FFF), and 15 MV (FF) beams, Eclipse underestimated out-of-field local doses by 30%-50% compared with Monte Carlo calculations when the local dose was <1% of prescribed dose. The accuracy of out-of-field dose calculations using Eclipse is improved when collimator jaws were set at the smallest possible aperture for MLC openings. The Eclipse system consistently underestimates out-of-field dose by a factor of 2 for all beam energies studied at the local dose level of less than 1% of prescribed dose. These findings are useful in providing information on the uncertainties of out-of-field organ doses calculated by Eclipse treatment planning system. © 2018 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

Multi-level characterization of balanced inhibitory-excitatory cortical neuron network derived from human pluripotent stem cells.

PubMed

Nadadhur, Aishwarya G; Emperador Melero, Javier; Meijer, Marieke; Schut, Desiree; Jacobs, Gerbren; Li, Ka Wan; Hjorth, J J Johannes; Meredith, Rhiannon M; Toonen, Ruud F; Van Kesteren, Ronald E; Smit, August B; Verhage, Matthijs; Heine, Vivi M

2017-01-01

Generation of neuronal cultures from induced pluripotent stem cells (hiPSCs) serve the studies of human brain disorders. However we lack neuronal networks with balanced excitatory-inhibitory activities, which are suitable for single cell analysis. We generated low-density networks of hPSC-derived GABAergic and glutamatergic cortical neurons. We used two different co-culture models with astrocytes. We show that these cultures have balanced excitatory-inhibitory synaptic identities using confocal microscopy, electrophysiological recordings, calcium imaging and mRNA analysis. These simple and robust protocols offer the opportunity for single-cell to multi-level analysis of patient hiPSC-derived cortical excitatory-inhibitory networks; thereby creating advanced tools to study disease mechanisms underlying neurodevelopmental disorders.

Rapid construction of mechanically- confined multi- cellular structures using dendrimeric intercellular linker.

PubMed

Mo, Xuejun; Li, Qiushi; Yi Lui, Lena Wai; Zheng, Baixue; Kang, Chiang Huen; Nugraha, Bramasta; Yue, Zhilian; Jia, Rui Rui; Fu, Hong Xia; Choudhury, Deepak; Arooz, Talha; Yan, Jie; Lim, Chwee Teck; Shen, Shali; Hong Tan, Choon; Yu, Hanry

2010-10-01

Tissue constructs that mimic the in vivo cell-cell and cell-matrix interactions are especially useful for applications involving the cell- dense and matrix- poor internal organs. Rapid and precise arrangement of cells into functional tissue constructs remains a challenge in tissue engineering. We demonstrate rapid assembly of C3A cells into multi- cell structures using a dendrimeric intercellular linker. The linker is composed of oleyl- polyethylene glycol (PEG) derivatives conjugated to a 16 arms- polypropylenimine hexadecaamine (DAB) dendrimer. The positively charged multivalent dendrimer concentrates the linker onto the negatively charged cell surface to facilitate efficient insertion of the hydrophobic oleyl groups into the cellular membrane. Bringing linker- treated cells into close proximity to each other via mechanical means such as centrifugation and micromanipulation enables their rapid assembly into multi- cellular structures within minutes. The cells exhibit high levels of viability, proliferation, three- dimensional (3D) cell morphology and other functions in the constructs. We constructed defined multi- cellular structures such as rings, sheets or branching rods that can serve as potential tissue building blocks to be further assembled into complex 3D tissue constructs for biomedical applications. 2010 Elsevier Ltd. All rights reserved.

Human Embryonic Stem Cell-Derived Cardiomyocytes Self-Arrange with Areas of Different Subtypes During Differentiation.

PubMed

Vestergaard, Maj Linea; Grubb, Søren; Koefoed, Karen; Anderson-Jenkins, Zoe; Grunnet-Lauridsen, Kristina; Calloe, Kirstine; Clausen, Christian; Christensen, Søren Tvorup; Møllgård, Kjeld; Andersen, Claus Yding

2017-11-01

The derivation of functional cardiomyocytes (CMs) from human embryonic stem cells (hESCs) represents a unique way of studying human cardiogenesis, including the development of CM subtypes. In this study, we investigated the development and organization of hESC-derived cardiomyocytes (hESC-CMs) and examined how the expression levels of CM subtypes correspond to human in vivo cardiogenesis. Beating clusters were used to determine cardiac differentiation, which was evaluated by the expression of cardiac genes GATA4 and TNNT2 and subcellular localization of GATA4 and NKX2.5. Sharp electrode recordings to determine action potentials (APs) further revealed spatial organization of intracluster CM subtypes (ie, complex clusters). Nodal-, atrial-, and ventricular-like AP morphologies were detected within distinct regions of complex clusters. The ability of different CM subtypes to self-organize was documented by immunohistochemical analyses and a differential spatial expression of β-III tubulin, myosin light chain 2v (MLC-2V), and α-smooth muscle actin (α-SMA). Furthermore, all hESC-CM subtypes formed expressed primary cilia, which are known to coordinate cellular signaling pathways during cardiomyogenesis and heart development. This study expands the foundation for studying regulatory pathways for spatial and temporal CM differentiation during human cardiogenesis.

Magnetic resonance imaging for precise radiotherapy of small laboratory animals.

PubMed

Frenzel, Thorsten; Kaul, Michael Gerhard; Ernst, Thomas Michael; Salamon, Johannes; Jäckel, Maria; Schumacher, Udo; Krüll, Andreas

2017-03-01

Radiotherapy of small laboratory animals (SLA) is often not as precisely applied as in humans. Here we describe the use of a dedicated SLA magnetic resonance imaging (MRI) scanner for precise tumor volumetry, radiotherapy treatment planning, and diagnostic imaging in order to make the experiments more accurate. Different human cancer cells were injected at the lower trunk of pfp/rag2 and SCID mice to allow for local tumor growth. Data from cross sectional MRI scans were transferred to a clinical treatment planning system (TPS) for humans. Manual palpation of the tumor size was compared with calculated tumor size of the TPS and with tumor weight at necropsy. As a feasibility study MRI based treatment plans were calculated for a clinical 6MV linear accelerator using a micro multileaf collimator (μMLC). In addition, diagnostic MRI scans were used to investigate animals which did clinical poorly during the study. MRI is superior in precise tumor volume definition whereas manual palpation underestimates their size. Cross sectional MRI allow for treatment planning so that conformal irradiation of mice with a clinical linear accelerator using a μMLC is in principle feasible. Several internal pathologies were detected during the experiment using the dedicated scanner. MRI is a key technology for precise radiotherapy of SLA. The scanning protocols provided are suited for tumor volumetry, treatment planning, and diagnostic imaging. Copyright © 2016. Published by Elsevier GmbH.

Interleukin-12 (IL-12)-driven alloimmune responses in vitro and in vivo: requirement for beta1 subunit of the IL-12 receptor.

PubMed

Piccotti, J R; Li, K; Chan, S Y; Eichwald, E J; Bishop, D K

1999-06-15

Interleukin-12 (IL-12) mediates its biologic activities via binding high-affinity receptors on T and natural killer cells. Although emphasis has been placed on the requirement for IL-12Rbeta2 in IL-12 bioactivity, the role of IL-12Rbeta1 is less well defined. The current study evaluated the effects of exogenous IL-12 on alloantigen-specific immune responses and determined the requirement for IL-12Rbeta1 in IL-12-mediated alloimmunity. The mouse heterotopic cardiac transplant model was employed to evaluate the effects of IL-12 on alloantigen-specific immune responses in vivo. In addition, IFN-gamma production in mixed lymphocyte cultures (MLC) supplemented with IL-12 was measured to assess the effects of IL-12 on Th1 function in vitro. Mice deficient in IL-12Rbeta1 (IL-12Rbeta1-/-) were used to determine the requirement for this receptor component in IL-12-driven alloimmune responses. Addition of IL-12 to MLC consisting of wild-type splenocytes enhanced alloantigen-specific proliferative responses and Th1 development. In contrast, IL-12 did not alter these in vitro immune parameters in IL-12Rbeta1-/- MLC. Treatment of wild-type cardiac allograft recipients with IL-12 resulted in high concentrations of serum interferon-gamma (IFN-gamma) and a 10-fold increase in IFN-gamma production by recipient splenocytes after restimulation in vitro. However, this fulminate Th1 response did not accelerate allograft rejection. Importantly, IL-12 had no effect on serum IFN-gamma or in vivo priming of Thl in IL-12Rbeta1-/- recipients. Finally, administration of IL-12 to WT allograft recipients resulted in a bimodal alloantibody response: antibody production was suppressed at high doses of IL-12, and enhanced at lower doses. IL-12 markedly enhances alloantigen-specific immune function; however, these exaggerated Th1-driven responses do not culminate in accelerated allograft rejection. Further, these data indicate that IL-12Rbeta1 is essential for the enhancement of both in vitro and in vivo alloimmune responses by exogenous IL-12.

Turning behaviors of T cells climbing up ramp-like structures are regulated by myosin light chain kinase activity and lamellipodia formation.

PubMed

Song, Kwang Hoon; Lee, Jaehyun; Jung, Hong-Ryul; Park, HyoungJun; Doh, Junsang

2017-09-14

T cells navigate diverse microenvironments to perform immune responses. Micro-scale topographical structures within the tissues, which may inherently exist in normal tissues or may be formed by inflammation or injury, can influence T cell migration, but how T cell migration is affected by such topographical structures have not been investigated. In this study, we fabricated ramp-like structures with a 5 μm height and various slopes, and observed T cells climbing up the ramp-like structures. T cells encountering the ramp-like structures exhibited MLC accumulation near head-tail junctions contacting the ramp-like structures, and made turns to the direction perpendicular to the ramp-like structures. Pharmacological study revealed that lamellipodia formation mediated by arp2/3 and contractility regulated by myosin light chain kinase (MLCK) were responsible for the intriguing turning behavior of T cells climbing the ramp-like structures. Arp2/3 or MLCK inhibition substantially reduced probability of T cells climbing sharp-edged ramp-like structures, indicating intriguing turning behavior of T cells mediated by lamellipodia formation and MLCK activity may be important for T cells to access inflamed or injured tissues with abrupt topographical changes.

Inflammation response at the transcriptional level of HepG2 cells induced by multi-walled carbon nanotubes

NASA Astrophysics Data System (ADS)

Piret, Jean-Pascal; Vankoningsloo, Sébastien; Noël, Florence; Mejia Mendoza, Jorge; Lucas, Stéphane; Saout, Christelle; Toussaint, Olivier

2011-07-01

Poor information are currently available about the biological effects of multi-walled carbon nanotubes (MWCNT) on the liver. In this study, we evaluated the effects of MWCNT at the transcriptional level on the classical in vitro model of HepG2 hepatocarcinoma cells. The expression levels of 96 transcript species implicated in the inflammatory and immune responses was studied after a 24h incubation of HepG2 cells in presence of raw MWCNT dispersed in water by stirring. Among the 46 transcript species detected, only a few transcripts including mRNA coding for interleukine-7, chemokines receptor of the C-C families CCR7, as well as Endothelin-1, were statistically more abundant after treatment with MWCNT. Altogether, these data indicate that MWCNT can only induce a weak inflammatory response in HepG2 cells.

EF-hand proteins and the regulation of actin-myosin interaction in the eutardigrade Hypsibius klebelsbergi (tardigrada).

PubMed

Prasath, Thiruketheeswaran; Greven, Hartmut; D'Haese, Jochen

2012-06-01

Many tardigrade species resist harsh environmental conditions by entering anhydrobiosis or cryobiosis. Desiccation as well as freeze resistance probably leads to changes of the ionic balance that includes the intracellular calcium concentration. In order to search for protein modifications affecting the calcium homoeostasis, we studied the regulatory system controlling actin-myosin interaction of the eutardigrade Hypsibius klebelsbergi and identified full-length cDNA clones for troponin C (TnC, 824 bp), calmodulin (CaM, 1,407 bp), essential myosin light chain (eMLC, 1,015 bp), and regulatory myosin light chain (rMLC, 984 bp) from a cDNA library. All four proteins belong to the EF-hand superfamily typified by a calcium coordinating helix-loop-helix motif. Further, we cloned and obtained recombinant TnC and both MLCs. CaM and TnC revealed four and two potential calcium-binding domains, respectively. Gel mobility shift assays demonstrated calcium-induced conformational transition of TnC. From both MLCs, only the rMLC showed one potential N-terminal EF-hand domain. Additionally, sequence properties suggest phosphorylation of this myosin light chain. Based on our results, we suggest a dual-regulated system at least in somatic muscles for tardigrades with a calcium-dependent tropomyosin-troponin complex bound to the actin filaments and a phosphorylation of the rMLC turning on and off both actin and myosin. Our results indicate no special modifications of the molecular structure and function of the EF-hand proteins in tardigrades. Phylogenetic trees of 131 TnCs, 96 rMLCs, and 62 eMLCs indicate affinities to Ecdysozoa, but also to some other taxa suggesting that our results reflect the complex evolution of these proteins rather than phylogenetic relationships. © 2012 WILEY PERIODICALS, INC.

Dissecting the molecular assembly of the Toxoplasma gondii MyoA motility complex.

PubMed

Powell, Cameron J; Jenkins, Meredith L; Parker, Michelle L; Ramaswamy, Raghavendran; Kelsen, Anne; Warshaw, David M; Ward, Gary E; Burke, John E; Boulanger, Martin J

2017-11-24

Apicomplexan parasites such as Toxoplasma gondii rely on a unique form of locomotion known as gliding motility. Generating the mechanical forces to support motility are divergent class XIV myosins (MyoA) coordinated by accessory proteins known as light chains. Although the importance of the MyoA-light chain complex is well-established, the detailed mechanisms governing its assembly and regulation are relatively unknown. To establish a molecular blueprint of this dynamic complex, we first mapped the adjacent binding sites of light chains MLC1 and ELC1 on the MyoA neck (residues 775-818) using a combination of hydrogen-deuterium exchange mass spectrometry and isothermal titration calorimetry. We then determined the 1.85 Å resolution crystal structure of MLC1 in complex with its cognate MyoA peptide. Structural analysis revealed a bilobed architecture with MLC1 clamping tightly around the helical MyoA peptide, consistent with the stable 10 nm K d measured by isothermal titration calorimetry. We next showed that coordination of calcium by an EF-hand in ELC1 and prebinding of MLC1 to the MyoA neck enhanced the affinity of ELC1 for the MyoA neck 7- and 8-fold, respectively. When combined, these factors enhanced ELC1 binding 49-fold (to a K d of 12 nm). Using the full-length MyoA motor (residues 1-831), we then showed that, in addition to coordinating the neck region, ELC1 appears to engage the MyoA converter subdomain, which couples the motor domain to the neck. These data support an assembly model where staged binding events cooperate to yield high-affinity complexes that are able to maximize force transduction. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Determination of the optimal tolerance for MLC positioning in sliding window and VMAT techniques

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hernandez, V., E-mail: vhernandezmasgrau@gmail.com; Abella, R.; Calvo, J. F.

2015-04-15

Purpose: Several authors have recommended a 2 mm tolerance for multileaf collimator (MLC) positioning in sliding window treatments. In volumetric modulated arc therapy (VMAT) treatments, however, the optimal tolerance for MLC positioning remains unknown. In this paper, the authors present the results of a multicenter study to determine the optimal tolerance for both techniques. Methods: The procedure used is based on dynalog file analysis. The study was carried out using seven Varian linear accelerators from five different centers. Dynalogs were collected from over 100 000 clinical treatments and in-house software was used to compute the number of tolerance faults as amore » function of the user-defined tolerance. Thus, the optimal value for this tolerance, defined as the lowest achievable value, was investigated. Results: Dynalog files accurately predict the number of tolerance faults as a function of the tolerance value, especially for low fault incidences. All MLCs behaved similarly and the Millennium120 and the HD120 models yielded comparable results. In sliding window techniques, the number of beams with an incidence of hold-offs >1% rapidly decreases for a tolerance of 1.5 mm. In VMAT techniques, the number of tolerance faults sharply drops for tolerances around 2 mm. For a tolerance of 2.5 mm, less than 0.1% of the VMAT arcs presented tolerance faults. Conclusions: Dynalog analysis provides a feasible method for investigating the optimal tolerance for MLC positioning in dynamic fields. In sliding window treatments, the tolerance of 2 mm was found to be adequate, although it can be reduced to 1.5 mm. In VMAT treatments, the typically used 5 mm tolerance is excessively high. Instead, a tolerance of 2.5 mm is recommended.« less

Electron intensity modulation for mixed-beam radiation therapy with an x-ray multi-leaf collimator

NASA Astrophysics Data System (ADS)

Weinberg, Rebecca

The current standard treatment for head and neck cancer at our institution uses intensity-modulated x-ray therapy (IMRT), which improves target coverage and sparing of critical structures by delivering complex fluence patterns from a variety of beam directions to conform dose distributions to the shape of the target volume. The standard treatment for breast patients is field-in-field forward-planned IMRT, with initial tangential fields and additional reduced-weight tangents with blocking to minimize hot spots. For these treatment sites, the addition of electrons has the potential of improving target coverage and sparing of critical structures due to rapid dose falloff with depth and reduced exit dose. In this work, the use of mixed-beam therapy (MBT), i.e., combined intensity-modulated electron and x-ray beams using the x-ray multi-leaf collimator (MLC), was explored. The hypothesis of this study was that addition of intensity-modulated electron beams to existing clinical IMRT plans would produce MBT plans that were superior to the original IMRT plans for at least 50% of selected head and neck and 50% of breast cases. Dose calculations for electron beams collimated by the MLC were performed with Monte Carlo methods. An automation system was created to facilitate communication between the dose calculation engine and the treatment planning system. Energy and intensity modulation of the electron beams was accomplished by dividing the electron beams into 2x2-cm2 beamlets, which were then beam-weight optimized along with intensity-modulated x-ray beams. Treatment plans were optimized to obtain equivalent target dose coverage, and then compared with the original treatment plans. MBT treatment plans were evaluated by participating physicians with respect to target coverage, normal structure dose, and overall plan quality in comparison with original clinical plans. The physician evaluations did not support the hypothesis for either site, with MBT selected as superior in 1 out of the 15 head and neck cases (p=1) and 6 out of 18 breast cases (p=0.95). While MBT was not shown to be superior to IMRT, reductions were observed in doses to critical structures distal to the target along the electron beam direction and to non-target tissues, at the expense of target coverage and dose homogeneity.

From single cells to tissue architecture-a bottom-up approach to modelling the spatio-temporal organisation of complex multi-cellular systems.

PubMed

Galle, J; Hoffmann, M; Aust, G

2009-01-01

Collective phenomena in multi-cellular assemblies can be approached on different levels of complexity. Here, we discuss a number of mathematical models which consider the dynamics of each individual cell, so-called agent-based or individual-based models (IBMs). As a special feature, these models allow to account for intracellular decision processes which are triggered by biomechanical cell-cell or cell-matrix interactions. We discuss their impact on the growth and homeostasis of multi-cellular systems as simulated by lattice-free models. Our results demonstrate that cell polarisation subsequent to cell-cell contact formation can be a source of stability in epithelial monolayers. Stroma contact-dependent regulation of tumour cell proliferation and migration is shown to result in invasion dynamics in accordance with the migrating cancer stem cell hypothesis. However, we demonstrate that different regulation mechanisms can equally well comply with present experimental results. Thus, we suggest a panel of experimental studies for the in-depth validation of the model assumptions.

A Multi-Modality CMOS Sensor Array for Cell-Based Assay and Drug Screening.

PubMed

Chi, Taiyun; Park, Jong Seok; Butts, Jessica C; Hookway, Tracy A; Su, Amy; Zhu, Chengjie; Styczynski, Mark P; McDevitt, Todd C; Wang, Hua

2015-12-01

In this paper, we present a fully integrated multi-modality CMOS cellular sensor array with four sensing modalities to characterize different cell physiological responses, including extracellular voltage recording, cellular impedance mapping, optical detection with shadow imaging and bioluminescence sensing, and thermal monitoring. The sensor array consists of nine parallel pixel groups and nine corresponding signal conditioning blocks. Each pixel group comprises one temperature sensor and 16 tri-modality sensor pixels, while each tri-modality sensor pixel can be independently configured for extracellular voltage recording, cellular impedance measurement (voltage excitation/current sensing), and optical detection. This sensor array supports multi-modality cellular sensing at the pixel level, which enables holistic cell characterization and joint-modality physiological monitoring on the same cellular sample with a pixel resolution of 80 μm × 100 μm. Comprehensive biological experiments with different living cell samples demonstrate the functionality and benefit of the proposed multi-modality sensing in cell-based assay and drug screening.

Toward a noncytotoxic glioblastoma therapy: blocking MCP-1 with the MTZ Regimen

PubMed Central

Salacz, Michael E; Kast, Richard E; Saki, Najmaldin; Brüning, Ansgar; Karpel-Massler, Georg; Halatsch, Marc-Eric

2016-01-01

To improve the prognosis of glioblastoma, we developed an adjuvant treatment directed to a neglected aspect of glioblastoma growth, the contribution of nonmalignant monocyte lineage cells (MLCs) (monocyte, macrophage, microglia, dendritic cells) that infiltrated a main tumor mass. These nonmalignant cells contribute to glioblastoma growth and tumor homeostasis. MLCs comprise of approximately 10%–30% of glioblastoma by volume. After integration into the tumor mass, these become polarized toward an M2 immunosuppressive, pro-angiogenic phenotype that promotes continued tumor growth. Glioblastoma cells initiate and promote this process by synthesizing 13 kDa MCP-1 that attracts circulating monocytes to the tumor. Infiltrating monocytes, after polarizing toward an M2 phenotype, synthesize more MCP-1, forming an amplification loop. Three noncytotoxic drugs, an antibiotic – minocycline, an antihypertensive drug – telmisartan, and a bisphosphonate – zoledronic acid, have ancillary attributes of MCP-1 synthesis inhibition and could be re-purposed, singly or in combination, to inhibit or reverse MLC-mediated immunosuppression, angiogenesis, and other growth-enhancing aspects. Minocycline, telmisartan, and zoledronic acid – the MTZ Regimen – have low-toxicity profiles and could be added to standard radiotherapy and temozolomide. Re-purposing older drugs has advantages of established safety and low drug cost. Four core observations support this approach: 1) malignant glioblastoma cells require a reciprocal trophic relationship with nonmalignant macrophages or microglia to thrive; 2) glioblastoma cells secrete MCP-1 to start the cycle, attracting MLCs, which subsequently also secrete MCP-1 perpetuating the recruitment cycle; 3) increasing cytokine levels in the tumor environment generate further immunosuppression and tumor growth; and 4) MTZ regimen may impede MCP-1-driven processes, thereby interfering with glioblastoma growth. PMID:27175087

RhoA/ROCK pathway is the major molecular determinant of basal tone in intact human internal anal sphincter.

PubMed

Rattan, Satish; Singh, Jagmohan

2012-04-01

The knowledge of molecular control mechanisms underlying the basal tone in the intact human internal anal sphincter (IAS) is critical for the pathophysiology and rational therapy for a number of debilitating rectoanal motility disorders. We determined the role of RhoA/ROCK and PKC pathways by comparing the effects of ROCK- and PKC-selective inhibitors Y 27632 and Gö 6850 (10(-8) to 10(-4) M), respectively, on the basal tone in the IAS vs. the rectal smooth muscle (RSM). Western blot studies were performed to determine the levels of RhoA/ROCK II, PKC-α, MYPT1, CPI-17, and MLC(20) in the unphosphorylated and phosphorylated forms, in the IAS vs. RSM. Confocal microscopic studies validated the membrane distribution of ROCK II. Finally, to confirm a direct relationship, we examined the enzymatic activities and changes in the basal IAS tone and p-MYPT1, p-CPI-17, and p-MLC(20), before and after Y 27632 and Gö 6850. Data show higher levels of RhoA/ROCK II and related downstream signal transduction proteins in the IAS vs. RSM. In addition, data show a significant correlation between the active RhoA/ROCK levels, ROCK enzymatic activity, downstream proteins, and basal IAS tone, before and after ROCK inhibitor. From these data we conclude 1) RhoA/ROCK and downstream signaling are constitutively active in the IAS, and this pathway (in contrast with PKC) is the critical determinant of the basal tone in intact human IAS; and 2) RhoA and ROCK are potential therapeutic targets for a number of rectoanal motility disorders for which currently there is no satisfactory treatment.

RhoA/ROCK pathway is the major molecular determinant of basal tone in intact human internal anal sphincter

PubMed Central

Singh, Jagmohan

2012-01-01

The knowledge of molecular control mechanisms underlying the basal tone in the intact human internal anal sphincter (IAS) is critical for the pathophysiology and rational therapy for a number of debilitating rectoanal motility disorders. We determined the role of RhoA/ROCK and PKC pathways by comparing the effects of ROCK- and PKC-selective inhibitors Y 27632 and Gö 6850 (10−8 to 10−4 M), respectively, on the basal tone in the IAS vs. the rectal smooth muscle (RSM). Western blot studies were performed to determine the levels of RhoA/ROCK II, PKC-α, MYPT1, CPI-17, and MLC20 in the unphosphorylated and phosphorylated forms, in the IAS vs. RSM. Confocal microscopic studies validated the membrane distribution of ROCK II. Finally, to confirm a direct relationship, we examined the enzymatic activities and changes in the basal IAS tone and p-MYPT1, p-CPI-17, and p-MLC20, before and after Y 27632 and Gö 6850. Data show higher levels of RhoA/ROCK II and related downstream signal transduction proteins in the IAS vs. RSM. In addition, data show a significant correlation between the active RhoA/ROCK levels, ROCK enzymatic activity, downstream proteins, and basal IAS tone, before and after ROCK inhibitor. From these data we conclude 1) RhoA/ROCK and downstream signaling are constitutively active in the IAS, and this pathway (in contrast with PKC) is the critical determinant of the basal tone in intact human IAS; and 2) RhoA and ROCK are potential therapeutic targets for a number of rectoanal motility disorders for which currently there is no satisfactory treatment. PMID:22241857

Comparative Analysis of Different Measurement Techniques for MLC Characterization: Preliminary Results

DOE Office of Scientific and Technical Information (OSTI.GOV)

Larraga-Gutierrez, J. M.; Ballesteros-Zebadua, P.; Garcia-Garduno, O. A.

2008-08-11

Radiation transmission, leakage and beam penumbra are essential dosimetric parameters related to the commissioning of a multileaf collimation system. This work shows a comparative analysis of commonly used film detectors: X-OMAT V2 and EDR2 radiographic films, and GafChromic EBT registered radiochromic film. The results show that X-OMAT over-estimates radiation leakage and 80-20% beam penumbra. However, according to the reference values reported by the manufacturer for these dosimetric parameters, all three films are adequate for MLC dosimetric characterization, but special care must be taken when X-OMAT V2 film is used due to its low energy photon dependence.

Synthesis of water-soluble curcumin derivatives and their inhibition on lysozyme amyloid fibrillation

NASA Astrophysics Data System (ADS)

Wang, Sujuan; Peng, Xixi; Cui, Liangliang; Li, Tongtong; Yu, Bei; Ma, Gang; Ba, Xinwu

2018-02-01

The potential application of curcumin was heavily limited in biomedicine because of its poor solubility in pure water. To circumvent the detracting feature, two novel water-soluble amino acid modified curcumin derivatives (MLC and DLC) have been synthesized through the condensation reaction between curcumin and Nα-Fmoc-Nε-Boc-L-lysine. Benefiting from the enhanced solubility of 3.32 × 10- 2 g/mL for MLC and 4.66 × 10- 2 g/mL for DLC, the inhibition effects of the as-prepared derivatives on the amyloid fibrillation of lysozyme (HEWL) were investigated detaily in water solution. The obtained results showed that the amyloid fibrillation of HEWL was inhibited to a great extent when the concentrations of MLC and DLC reach to 20.139 mM and 49.622 mM, respectively. The fluorescence quenching upon the addition of curcumin to HEWL provide a support for static and dynamic recombination quenching process. The binding driving force was assigned to classical hydrophobic interaction between curcumin derivatives and HEWL. In addition, UV-Vis absorption and circular dichroism (CD) spectra confirmed the change of the conformation of HEWL.

Beam focal spot position determination for an Elekta linac with the Agility® head; practical guide with a ready-to-go procedure.

PubMed

Chojnowski, Jacek M; Taylor, Lee M; Sykes, Jonathan R; Thwaites, David I

2018-05-14

A novel phantomless, EPID-based method of measuring the beam focal spot offset of a linear accelerator was proposed and validated for Varian machines. In this method, one set of jaws and the MLC were utilized to form a symmetric field and then a 180 o collimator rotation was utilized to determine the radiation isocenter defined by the jaws and the MLC, respectively. The difference between these two isocentres is directly correlated with the beam focal spot offset of the linear accelerator. In the current work, the method has been considered for Elekta linacs. An Elekta linac with the Agility ® head does not have two set of jaws, therefore, a modified method is presented making use of one set of diaphragms, the MLC and a full 360 o collimator rotation. The modified method has been tested on two Elekta Synergy ® linacs with Agility ® heads and independently validated. A practical guide with instructions and a MATLAB ® code is attached for easy implementation. © 2018 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

SU-E-T-804: Verification of the BJR-25 Method of KQ Determination for CyberKnife Absolute Dosimetry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gersh, J; Spectrum Medical Physics, LLC - Greenville, SC; Willett, B

2015-06-15

Purpose: Absolute calibration of the CyberKnife is performed using a 6cm-diameter cone defined at 80cm SAD. Since kQ is defined using PDD values determined using 10×10 cm fields at 100cm SSD, the PDD must be corrected in order to correctly apply the quality conversion factor. The accepted method is based on equivalent field-size conversions of PDD values using BJR25. Using the new InCise MLC system, the CK is capable of generating a rectangular field equivalent to 10×10 cm square field. In this study, a comparison is made between kQ values determined using the traditional BJR25 method and the MLC methodmore » introduced herein. Methods: First, kQ(BJR) is determined: a PDD is acquired using a 6cm circular field at 100cm SSD, its field size converted to an equivalent square, and PDD converted to a 10×10cm field using the appropriate BJR25 table. Maintaining a consistent setup, the collimator is changed, and the MLC method is used. Finally, kQ is determined using PDDs acquired with a 9.71×10.31cm at 100cm SSD. This field is produced by setting the field to a size of 7.77×8.25cm (since it is defined at 80cm SAD). An exact 10×10cm field since field size is relegated to increments of its leaf width (0.25cm). This comparison is made using an Exradin A1SL, IBA CC08, IBA CC13, and an Exradin A19. For each detector and collimator type, the beam injector was adjusted to give 5 different beam qualities; representing a range of clinical systems. Results: Averaging across all beam qualities, kQ(MLC) differed from kQ(BJR) by less than 0.15%. The difference between the values increased with detector volume. Conclusion: For CK users with standard cone collimators, the BJR25 method has been verified. For CK users the MLC system, a technique is described to determine kQ. Primary author is the President/Owner of Spectrum Medical Physics, LLC, a company which maintains contracts with Siemens Healthcare and Standard Imaging, Inc.« less

Incorporating geometric ray tracing to generate initial conditions for intensity modulated arc therapy optimization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Oliver, Mike; Gladwish, Adam; Craig, Jeff

2008-07-15

Purpose and background: Intensity modulated arc therapy (IMAT) is a rotational variant of Intensity modulated radiation therapy (IMRT) that is achieved by allowing the multileaf collimator (MLC) positions to vary as the gantry rotates around the patient. This work describes a method to generate an IMAT plan through the use of a fast ray tracing technique based on dosimetric and geometric information for setting initial MLC leaf positions prior to final IMAT optimization. Methods and materials: Three steps were used to generate an IMAT plan. The first step was to generate arcs based on anatomical contours. The second step wasmore » to generate ray importance factor (RIF) maps by ray tracing the dose distribution inside the planning target volume (PTV) to modify the MLC leaf positions of the anatomical arcs to reduce the maximum dose inside the PTV. The RIF maps were also segmented to create a new set of arcs to improve the dose to low dose voxels within the PTV. In the third step, the MLC leaf positions from all arcs were put through a leaf position optimization (LPO) algorithm and brought into a fast Monte Carlo dose calculation engine for a final dose calculation. The method was applied to two phantom cases, a clinical prostate case and the Radiological Physics Center (RPC)'s head and neck phantom. The authors assessed the plan improvements achieved by each step and compared plans with and without using RIF. They also compared the IMAT plan with an IMRT plan for the RPC phantom. Results: All plans that incorporated RIF and LPO had lower objective function values than those that incorporated LPO only. The objective function value was reduced by about 15% after the generation of RIF arcs and 52% after generation of RIF arcs and leaf position optimization. The IMAT plan for the RPC phantom had similar dose coverage for PTV1 and PTV2 (the same dose volume histogram curves), however, slightly lower dose to the normal tissues compared to a six-field IMRT plan. Conclusion: The use of a ray importance factor can generate initial IMAT arcs efficiently for further MLC leaf position optimization to obtain more favorable IMAT plan.« less

High-resolution field shaping utilizing a masked multileaf collimator.

PubMed

Williams, P C; Cooper, P

2000-08-01

Multileaf collimators (MLCs) have become an important tool in the modern radiotherapy department. However, the current limit of resolution (1 cm at isocentre) can be too coarse for acceptable shielding of all fields. A number of mini- and micro-MLCs have been developed, with thinner leaves to achieve approved resolution. Currently however, such devices are limited to modest field sizes and stereotactic applications. This paper proposes a new method of high-resolution beam collimation by use of a tertiary grid collimator situated below the conventional MLC. The width of each slit in the grid is a submultiple of the MLC width. A composite shaped field is thus built up from a series of subfields, with the main MLC defining the length of each strip within each subfield. Presented here are initial findings using a prototype device. The beam uniformity achievable with such a device was examined by measuring transmission profiles through the grid using a diode. Profiles thus measured were then copied and superposed to generate composite beams, from which the uniformity achievable could be assessed. With the average dose across the profile normalized to 100%, hot spots up to 5.0% and troughs of 3% were identified for a composite beam of 2 x 5.0 mm grids, as measured at Dmax for a 6 MV beam. For a beam composed from 4 x 2.5 mm grids, the maximum across the profile was 3.0% above the average, and the minimum 2.5% below. Actual composite profiles were also formed using the integrating properties of film, with the subfield indexing performed using an engineering positioning stage. The beam uniformity for these fields compared well with that achieved in theory using the diode measurements. Finally sine wave patterns were generated to demonstrate the potential improvements in field shaping and conformity using this device as opposed to the conventional MLC alone. The scalloping effect on the field edge commonly seen on MLC fields was appreciably reduced by use of 2 x 5.0 mm grids, and still further by the use of 4 x 2.5 mm grids, as would be expected. This was also achieved with a small or negligible broadening of the beam penumbra as measured at Dmax.

SU-F-T-506: Development and Commissioning of the Effective and Efficient Grid Therapy Using High Dose Rate Flattening Filter Free Beam and Multileaf Collimator

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, M; Wen, N; Beyer, C

Purpose: Treating bulky tumors with grid therapy (GT) has demonstrated high response rates. Long delivery time (∼15min), with consequent increased risk of intrafraction motion, is a major disadvantage of conventional MLC-based GT (MLC-GT). The goal of this study was to develop and commission a MLC-GT technique with similar dosimetric characteristics, but more efficient delivery. Methods: Grid plan was designed with 10X-FFF (2400MU/min) beam and MLC in a commercial treatment planning system (TPS). Grid size was 1cm by 1cm and grid-to-grid distance was 2cm. Field-in-field technique was used to flatten the dose profile at depth of 10cm. Prescription was 15Gy atmore » 1.5cm depth. Doses were verified at depths of 1.5cm, 5cm and 10cm. Point dose was measured with a plastic scintillator detector (PSD) while the planar dose was measured with calibrated Gafchromic EBT3 films in a 20cm think, 30cmx30cm solid water phantom. The measured doses were compared to the doses calculated in the treatment planning system. Percent depth dose (PDD) within the grid was also measured using EBT3 film. Five clinical cases were planned to compare beam-on time. Results: The valley-to-peak dose ratio at the 3 depths was approximately 10–15%, which is very similar to published result. The average point dose difference between the PSD measurements and TPS calculation is 2.1±0.6%. Film dosimetry revealed good agreement between the delivered and calculated dose. The average gamma passing rates at the 3 depths were 95% (3%, 1mm). The average percent difference between the measured PDD and calculated PDD was 2.1% within the depth of 20cm. The phantom plan delivery time was 3.6 min. Average beam-on time was reduced by 66.1±5.6% for the 5 clinical cases. Conclusion: An effective and efficient GT technique was developed and commissioned for the treatment of bulky tumors using FFF beam combined with MLC and automation. The Department of Radiation Oncology at Henry Ford Health System receives research support from Varian Medical Systems and Philips Health Care.« less

Emergent Stratification in Solid Tumors Selects for Reduced Cohesion of Tumor Cells: A Multi-Cell, Virtual-Tissue Model of Tumor Evolution Using CompuCell3D.

PubMed

Swat, Maciej H; Thomas, Gilberto L; Shirinifard, Abbas; Clendenon, Sherry G; Glazier, James A

2015-01-01

Tumor cells and structure both evolve due to heritable variation of cell behaviors and selection over periods of weeks to years (somatic evolution). Micro-environmental factors exert selection pressures on tumor-cell behaviors, which influence both the rate and direction of evolution of specific behaviors, especially the development of tumor-cell aggression and resistance to chemotherapies. In this paper, we present, step-by-step, the development of a multi-cell, virtual-tissue model of tumor somatic evolution, simulated using the open-source CompuCell3D modeling environment. Our model includes essential cell behaviors, microenvironmental components and their interactions. Our model provides a platform for exploring selection pressures leading to the evolution of tumor-cell aggression, showing that emergent stratification into regions with different cell survival rates drives the evolution of less cohesive cells with lower levels of cadherins and higher levels of integrins. Such reduced cohesivity is a key hallmark in the progression of many types of solid tumors.

Emergent Stratification in Solid Tumors Selects for Reduced Cohesion of Tumor Cells: A Multi-Cell, Virtual-Tissue Model of Tumor Evolution Using CompuCell3D

PubMed Central

Swat, Maciej H.; Thomas, Gilberto L.; Shirinifard, Abbas; Clendenon, Sherry G.; Glazier, James A.

2015-01-01

Tumor cells and structure both evolve due to heritable variation of cell behaviors and selection over periods of weeks to years (somatic evolution). Micro-environmental factors exert selection pressures on tumor-cell behaviors, which influence both the rate and direction of evolution of specific behaviors, especially the development of tumor-cell aggression and resistance to chemotherapies. In this paper, we present, step-by-step, the development of a multi-cell, virtual-tissue model of tumor somatic evolution, simulated using the open-source CompuCell3D modeling environment. Our model includes essential cell behaviors, microenvironmental components and their interactions. Our model provides a platform for exploring selection pressures leading to the evolution of tumor-cell aggression, showing that emergent stratification into regions with different cell survival rates drives the evolution of less cohesive cells with lower levels of cadherins and higher levels of integrins. Such reduced cohesivity is a key hallmark in the progression of many types of solid tumors. PMID:26083246

Propofol administration to the fetal-maternal unit reduces cardiac oxidative stress in preterm lambs subjected to prenatal asphyxia and cardiac arrest.

PubMed

Seehase, Matthias; Houthuizen, Patrick; Collins, Jennifer J P; Zimmermann, Luc J; Kramer, Boris W

2016-05-01

Little is known about the effects of propofol on oxidative stress and its effect on key structures of the contractile apparatus as the myosin light chain 2 (MLC2) and the p38MAPK survival pathway in the preterm heart. We hypothesized that propofol administration could attenuate the hypoxic myocardial injury after birth asphyxia. Pregnant ewes were randomized to receive either propofol or isoflurane anesthesia. A total of 44 late-preterm lambs were subjected to in utero umbilical cord occlusion (UCO), resulting in asphyxia and cardiac arrest, or sham treatment. After emergency cesarean delivery, each fetus was resuscitated, mechanically ventilated, and supported under anesthesia for 8 h using the same anesthetic as the one received by its mother. At 8 h after UCO, occurrence of reactive oxygen species and activation of inducible nitric oxide synthase in the heart were lower in association with propofol anesthesia than with isoflurane. This was accompanied by less degradation of MLC2 but higher p38MAPK level and in echocardiography with a trend toward a higher median left ventricular fractional shortening. The use of propofol resulted in less oxidative stress and was associated with less cytoskeletal damage of the contractile apparatus than the use of isoflurane anesthesia.

Myocardin-related transcription factors and SRF are required for cytoskeletal dynamics and experimental metastasis.

PubMed

Medjkane, Souhila; Perez-Sanchez, Cristina; Gaggioli, Cedric; Sahai, Erik; Treisman, Richard

2009-03-01

Rho GTPases control cytoskeletal dynamics through cytoplasmic effectors and regulate transcriptional activation through myocardin-related transcription factors (MRTFs), which are co-activators for serum response factor (SRF). We used RNA interference to investigate the contribution of the MRTF-SRF pathway to cytoskeletal dynamics in MDA-MB-231 breast carcinoma and B16F2 melanoma cells, in which basal MRTF-SRF activity is Rho-dependent. Depletion of MRTFs or SRF reduced cell adhesion, spreading, invasion and motility in culture, without affecting proliferation or inducing apoptosis. MRTF-depleted tumour cell xenografts showed reduced cell motility but proliferated normally. Tumour cells depleted of MRTF or SRF failed to colonize the lung from the bloodstream, being unable to persist after their arrival in the lung. Only a few genes show MRTF-dependent expression in both cell lines. Two of these, MYH9 (NMHCIIa) and MYL9 (MLC2), are also required for invasion and lung colonization. Conversely, expression of activated MAL/MRTF-A increases lung colonization by poorly metastatic B16F0 cells. Actin-based cell behaviour and experimental metastasis thus require Rho-dependent nuclear signalling through the MRTF-SRF network.

ROCK-1 mediates diabetes-induced retinal pigment epithelial and endothelial cell blebbing: Contribution to diabetic retinopathy.

PubMed

Rothschild, Pierre-Raphaël; Salah, Sawsen; Berdugo, Marianne; Gélizé, Emmanuelle; Delaunay, Kimberley; Naud, Marie-Christine; Klein, Christophe; Moulin, Alexandre; Savoldelli, Michèle; Bergin, Ciara; Jeanny, Jean-Claude; Jonet, Laurent; Arsenijevic, Yvan; Behar-Cohen, Francine; Crisanti, Patricia

2017-08-18

In diabetic retinopathy, the exact mechanisms leading to retinal capillary closure and to retinal barriers breakdown remain imperfectly understood. Rho-associated kinase (ROCK), an effector of the small GTPase Rho, involved in cytoskeleton dynamic regulation and cell polarity is activated by hyperglycemia. In one year-old Goto Kakizaki (GK) type 2 diabetic rats retina, ROCK-1 activation was assessed by its cellular distribution and by phosphorylation of its substrates, MYPT1 and MLC. In both GK rat and in human type 2 diabetic retinas, ROCK-1 is activated and associated with non-apoptotic membrane blebbing in retinal vessels and in retinal pigment epithelium (RPE) that respectively form the inner and the outer barriers. Activation of ROCK-1 induces focal vascular constrictions, endoluminal blebbing and subsequent retinal hypoxia. In RPE cells, actin cytoskeleton remodeling and membrane blebs in RPE cells contributes to outer barrier breakdown. Intraocular injection of fasudil, significantly reduces both retinal hypoxia and RPE barrier breakdown. Diabetes-induced cell blebbing may contribute to ischemic maculopathy and represent an intervention target.

Human development VIII: a theory of "deep" quantum chemistry and cell consciousness: quantum chemistry controls genes and biochemistry to give cells and higher organisms consciousness and complex behavior.

PubMed

Ventegodt, Søren; Hermansen, Tyge Dahl; Flensborg-Madsen, Trine; Nielsen, Maj Lyck; Merrick, Joav

2006-11-14

Deep quantum chemistry is a theory of deeply structured quantum fields carrying the biological information of the cell, making it able to remember, intend, represent the inner and outer world for comparison, understand what it "sees", and make choices on its structure, form, behavior and division. We suggest that deep quantum chemistry gives the cell consciousness and all the qualities and abilities related to consciousness. We use geometric symbolism, which is a pre-mathematical and philosophical approach to problems that cannot yet be handled mathematically. Using Occam's razor we have started with the simplest model that works; we presume this to be a many-dimensional, spiral fractal. We suggest that all the electrons of the large biological molecules' orbitals make one huge "cell-orbital", which is structured according to the spiral fractal nature of quantum fields. Consciousness of single cells, multi cellular structures as e.g. organs, multi-cellular organisms and multi-individual colonies (like ants) and human societies can thus be explained by deep quantum chemistry. When biochemical activity is strictly controlled by the quantum-mechanical super-orbital of the cell, this orbital can deliver energetic quanta as biological information, distributed through many fractal levels of the cell to guide form and behavior of an individual single or a multi-cellular organism. The top level of information is the consciousness of the cell or organism, which controls all the biochemical processes. By this speculative work inspired by Penrose and Hameroff we hope to inspire other researchers to formulate more strict and mathematically correct hypothesis on the complex and coherence nature of matter, life and consciousness.

Human Development VIII: A Theory of “Deep” Quantum Chemistry and Cell Consciousness: Quantum Chemistry Controls Genes and Biochemistry to Give Cells and Higher Organisms Consciousness and Complex Behavior

PubMed Central

Ventegodt, Søren; Hermansen, Tyge Dahl; Flensborg-Madsen, Trine; Nielsen, Maj Lyck; Merrick, Joav

2006-01-01

Deep quantum chemistry is a theory of deeply structured quantum fields carrying the biological information of the cell, making it able to remember, intend, represent the inner and outer world for comparison, understand what it “sees”, and make choices on its structure, form, behavior and division. We suggest that deep quantum chemistry gives the cell consciousness and all the qualities and abilities related to consciousness. We use geometric symbolism, which is a pre-mathematical and philosophical approach to problems that cannot yet be handled mathematically. Using Occams razor we have started with the simplest model that works; we presume this to be a many-dimensional, spiral fractal. We suggest that all the electrons of the large biological molecules orbitals make one huge “cell-orbital”, which is structured according to the spiral fractal nature of quantum fields. Consciousness of single cells, multi cellular structures as e.g. organs, multi-cellular organisms and multi-individual colonies (like ants) and human societies can thus be explained by deep quantum chemistry. When biochemical activity is strictly controlled by the quantum-mechanical super-orbital of the cell, this orbital can deliver energetic quanta as biological information, distributed through many fractal levels of the cell to guide form and behavior of an individual single or a multi-cellular organism. The top level of information is the consciousness of the cell or organism, which controls all the biochemical processes. By this speculative work inspired by Penrose and Hameroff we hope to inspire other researchers to formulate more strict and mathematically correct hypothesis on the complex and coherence nature of matter, life and consciousness. PMID:17115084

Development of an in vitro periodontal biofilm model for assessing antimicrobial and host modulatory effects of bioactive molecules.

PubMed

Millhouse, Emma; Jose, Anto; Sherry, Leighann; Lappin, David F; Patel, Nisha; Middleton, Andrew M; Pratten, Jonathan; Culshaw, Shauna; Ramage, Gordon

2014-06-28

Inflammation within the oral cavity occurs due to dysregulation between microbial biofilms and the host response. Understanding how different oral hygiene products influence inflammatory properties is important for the development of new products. Therefore, creation of a robust host-pathogen biofilm platform capable of evaluating novel oral healthcare compounds is an attractive option. We therefore devised a multi-species biofilm co-culture model to evaluate the naturally derived polyphenol resveratrol (RSV) and gold standard chlorhexidine (CHX) with respect to anti-biofilm and anti-inflammatory properties. An in vitro multi-species biofilm containing S. mitis, F. nucleatum, P. gingivalis and A. actinomycetemcomitans was created to represent a disease-associated biofilm and the oral epithelial cell in OKF6-TERT2. Cytotoxicity studies were performed using RSV and CHX. Multi-species biofilms were either treated with either molecule, or alternatively epithelial cells were treated with these prior to biofilm co-culture. Biofilm composition was evaluated and inflammatory responses quantified at a transcriptional and protein level. CHX was toxic to epithelial cells and multi-species biofilms at concentrations ranging from 0.01-0.2%. RSV did not effect multi-species biofilm composition, but was toxic to epithelial cells at concentrations greater than 0.01%. In co-culture, CHX-treated biofilms resulted in down regulation of the inflammatory chemokine IL-8 at both mRNA and protein level. RSV-treated epithelial cells in co-culture were down-regulated in the release of IL-8 protein, but not mRNA. CHX possesses potent bactericidal properties, which may impact downstream inflammatory mediators. RSV does not appear to have bactericidal properties against multi-species biofilms, however it did appear to supress epithelial cells from releasing inflammatory mediators. This study demonstrates the potential to understand the mechanisms by which different oral hygiene products may influence gingival inflammation, thereby validating the use of a biofilm co-culture model.

Multi-Leu PACE4 Inhibitor Retention within Cells Is PACE4 Dependent and a Prerequisite for Antiproliferative Activity

PubMed Central

Ly, Kévin; Levesque, Christine; Kwiatkowska, Anna; Ait-Mohand, Samia; Desjardins, Roxane; Guérin, Brigitte; Day, Robert

2015-01-01

The overexpression as well as the critical implication of the proprotein convertase PACE4 in prostate cancer progression has been previously reported and supported the development of peptide inhibitors. The multi-Leu peptide, a PACE4-specific inhibitor, was further generated and its capability to be uptaken by tumor xenograft was demonstrated with regard to its PACE4 expression status. To investigate whether the uptake of this inhibitor was directly dependent of PACE4 levels, uptake and efflux from cancer cells were evaluated and correlations were established with PACE4 contents on both wild type and PACE4-knockdown cell lines. PACE4-knockdown associated growth deficiencies were established on the knockdown HepG2, Huh7, and HT1080 cells as well as the antiproliferative effects of the multi-Leu peptide supporting the growth capabilities of PACE4 in cancer cells. PMID:26114115

Potential benefits of dosimetric VMAT tracking verified with 3D film measurements.

PubMed

Crijns, Wouter; Defraene, Gilles; Van Herck, Hans; Depuydt, Tom; Haustermans, Karin; Maes, Frederik; Van den Heuvel, Frank

2016-05-01

To evaluate three different plan adaptation strategies using 3D film-stack dose measurements of both focal boost and hypofractionated prostate VMAT treatments. The adaptation strategies (a couch shift, geometric tracking, and dosimetric tracking) were applied for three realistic intrafraction prostate motions. A focal boost (35 × 2.2 and 35 × 2.7 Gy) and a hypofractionated (5 × 7.25 Gy) prostate VMAT plan were created for a heterogeneous phantom that allows for internal prostate motion. For these plans geometric tracking and dosimetric tracking were evaluated by ionization chamber (IC) point dose measurements (zero-D) and measurements using a stack of EBT3 films (3D). The geometric tracking applied translations, rotations, and scaling of the MLC aperture in response to realistic prostate motions. The dosimetric tracking additionally corrected the monitor units to resolve variations due to difference in depth, tissue heterogeneity, and MLC-aperture. The tracking was based on the positions of four fiducial points only. The film measurements were compared to the gold standard (i.e., IC measurements) and the planned dose distribution. Additionally, the 3D measurements were converted to dose volume histograms, tumor control probability, and normal tissue complication probability parameters (DVH/TCP/NTCP) as a direct estimate of clinical relevance of the proposed tracking. Compared to the planned dose distribution, measurements without prostate motion and tracking showed already a reduced homogeneity of the dose distribution. Adding prostate motion further blurs the DVHs for all treatment approaches. The clinical practice (no tracking) delivered the dose distribution inside the PTV but off target (CTV), resulting in boost dose errors up to 10%. The geometric and dosimetric tracking corrected the dose distribution's position. Moreover, the dosimetric tracking could achieve the planned boost DVH, but not the DVH of the more homogeneously irradiated prostate. A drawback of both the geometric and dosimetric tracking was a reduced MLC blocking caused by the rotational component of the MLC aperture corrections. Because of the used CTV to PTV margins and the high doses in the considered fractionation schemes, the TCP differed less than 0.02 from the planned value for all targets and all correction methods. The rectal NTCP constraints, however, could not be realized using any of these methods. The geometric and dosimetric tracking use only a limited input, but they deposit the dose distribution with higher geometric accuracy than the clinical practice. The latter case has boost dose errors up to 10%. The increased accuracy has a modest impact [Δ(NT)CP < 0.02] because of the applied margins and the high dose levels used. To allow further margin reduction tracking methods are vital. The proposed methodology could further be improved by implementing a rotational correction using collimator rotations.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Crijns, Wouter, E-mail: wouter.crijns@uzleuven.be; Depuydt, Tom; Haustermans, Karin

Purpose: To evaluate three different plan adaptation strategies using 3D film-stack dose measurements of both focal boost and hypofractionated prostate VMAT treatments. The adaptation strategies (a couch shift, geometric tracking, and dosimetric tracking) were applied for three realistic intrafraction prostate motions. Methods: A focal boost (35 × 2.2 and 35 × 2.7 Gy) and a hypofractionated (5 × 7.25 Gy) prostate VMAT plan were created for a heterogeneous phantom that allows for internal prostate motion. For these plans geometric tracking and dosimetric tracking were evaluated by ionization chamber (IC) point dose measurements (zero-D) and measurements using a stack of EBT3more » films (3D). The geometric tracking applied translations, rotations, and scaling of the MLC aperture in response to realistic prostate motions. The dosimetric tracking additionally corrected the monitor units to resolve variations due to difference in depth, tissue heterogeneity, and MLC-aperture. The tracking was based on the positions of four fiducial points only. The film measurements were compared to the gold standard (i.e., IC measurements) and the planned dose distribution. Additionally, the 3D measurements were converted to dose volume histograms, tumor control probability, and normal tissue complication probability parameters (DVH/TCP/NTCP) as a direct estimate of clinical relevance of the proposed tracking. Results: Compared to the planned dose distribution, measurements without prostate motion and tracking showed already a reduced homogeneity of the dose distribution. Adding prostate motion further blurs the DVHs for all treatment approaches. The clinical practice (no tracking) delivered the dose distribution inside the PTV but off target (CTV), resulting in boost dose errors up to 10%. The geometric and dosimetric tracking corrected the dose distribution’s position. Moreover, the dosimetric tracking could achieve the planned boost DVH, but not the DVH of the more homogeneously irradiated prostate. A drawback of both the geometric and dosimetric tracking was a reduced MLC blocking caused by the rotational component of the MLC aperture corrections. Because of the used CTV to PTV margins and the high doses in the considered fractionation schemes, the TCP differed less than 0.02 from the planned value for all targets and all correction methods. The rectal NTCP constraints, however, could not be realized using any of these methods. Conclusions: The geometric and dosimetric tracking use only a limited input, but they deposit the dose distribution with higher geometric accuracy than the clinical practice. The latter case has boost dose errors up to 10%. The increased accuracy has a modest impact [Δ(NT)CP < 0.02] because of the applied margins and the high dose levels used. To allow further margin reduction tracking methods are vital. The proposed methodology could further be improved by implementing a rotational correction using collimator rotations.« less

Superoxide constricts rat pulmonary arteries via Rho-kinase-mediated Ca2+ sensitization

PubMed Central

Shaifta, Yasin; Connolly, Michelle; Drndarski, Svetlana; Noah, Anthony; Pourmahram, Ghazaleh E.; Becker, Silke; Aaronson, Philip I.; Ward, Jeremy P.T.

2018-01-01

Reactive oxygen species play a key role in vascular disease, pulmonary hypertension, and hypoxic pulmonary vasoconstriction. We investigated contractile responses, intracellular Ca2+ ([Ca2+]i), Rho-kinase translocation, and phosphorylation of the regulatory subunit of myosin phosphatase (MYPT-1) and of myosin light chain (MLC20) in response to LY83583, a generator of superoxide anion, in small intrapulmonary arteries (IPA) of rat. LY83583 caused concentration-dependent constrictions in IPA and greatly enhanced submaximal PGF2α-mediated preconstriction. In small femoral or mesenteric arteries of rat, LY83583 alone was without effect, but it relaxed a PGF2α-mediated preconstriction. Constrictions in IPA were inhibited by superoxide dismutase and tempol, but not catalase, and were endothelium and guanylate cyclase independent. Constrictions were also inhibited by the Rho-kinase inhibitor Y27632 and the Src-family kinase inhibitor SU6656. LY83583 did not raise [Ca2+]i, but caused a Y27632-sensitive constriction in α-toxin-permeabilized IPA. LY83583 triggered translocation of Rho-kinase from the nucleus to the cytosol in pulmonary artery smooth muscle cells and enhanced phosphorylation of MYPT-1 at Thr-855 and of MLC20 at Ser-19 in IPA. This enhancement was inhibited by superoxide dismutase and abolished by Y27632. Hydrogen peroxide did not activate Rho-kinase. We conclude that in rat small pulmonary artery, superoxide triggers Rho-kinase-mediated Ca2+ sensitization and vasoconstriction independent of hydrogen peroxide. PMID:19103285

Homozygous deletion in MYL9 expands the molecular basis of megacystis-microcolon-intestinal hypoperistalsis syndrome.

PubMed

Moreno, Carolina Araujo; Sobreira, Nara; Pugh, Elizabeth; Zhang, Peng; Steel, Gary; Torres, Fábio Rossi; Cavalcanti, Denise Pontes

2018-05-01

Megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) is a severe disease characterized by functional obstruction in the urinary and gastrointestinal tract. The molecular basis of this condition started to be defined recently, and the genes related to the syndrome (ACTG2-heterozygous variant in sporadic cases; and MYH11 (myosin heavy chain 11), LMOD1 (leiomodin 1) and MYLK (myosin light chain (MLC) kinase)-autosomal recessive inheritance), encode proteins involved in the smooth muscle contraction, supporting a myopathic basis for the disease. In the present article, we described a family with two affected siblings with MMIHS born to consanguineous parents and the molecular investigation performed to define the genetic etiology. Previous whole exome sequencing of the affected child and parents did not identify a candidate gene for the disease in this family, but now we present a reanalysis of the data that led to the identification of a homozygous deletion encompassing the last exon of MYL9 (myosin regulatory light chain 9) in the affected individual. MYL9 gene encodes a regulatory myosin MLC and the phosphorylation of this protein is a crucial step in the contraction process of smooth muscle cell. Despite the absence of human or animal phenotype related to MYL9, a cause-effect relationship between MYL9 and the MMIHS seems biologically plausible. The present study reveals a strong candidate gene for autosomal recessive forms of MMIHS, expanding the molecular basis of this disease and reinforces the myopathic basis of this condition.

Self-balanced modulation and magnetic rebalancing method for parallel multilevel inverters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Hui; Shi, Yanjun

A self-balanced modulation method and a closed-loop magnetic flux rebalancing control method for parallel multilevel inverters. The combination of the two methods provides for balancing of the magnetic flux of the inter-cell transformers (ICTs) of the parallel multilevel inverters without deteriorating the quality of the output voltage. In various embodiments a parallel multi-level inverter modulator is provide including a multi-channel comparator to generate a multiplexed digitized ideal waveform for a parallel multi-level inverter and a finite state machine (FSM) module coupled to the parallel multi-channel comparator, the FSM module to receive the multiplexed digitized ideal waveform and to generate amore » pulse width modulated gate-drive signal for each switching device of the parallel multi-level inverter. The system and method provides for optimization of the output voltage spectrum without influence the magnetic balancing.« less

Losartan counteracts the effects of cardiomyocyte swelling on glucose uptake and insulin receptor substrate-1 levels.

PubMed

Gerena, Yamil; Lozada, Janice Griselle; Collazo, Bryan Jael; Méndez-Álvarez, Jarold; Méndez-Estrada, Jennifer; De Mello, Walmor C

2017-10-01

A growing body of evidence demonstrates an association between Angiotensin II (Ang II) receptor blockers (ARBs) and enhanced glucose metabolism during ischemic heart disease. Despite these encouraging results, the mechanisms responsible for these effects during ischemia remain poorly understood. In this study we investigated the influence of losartan, an AT1 receptor blocker, and secreted Ang II (sAng II) on glucose uptake and insulin receptor substrate (IRS-1) levels during cardiomyocyte swelling. H9c2 cells were differentiated to cardiac muscle and the levels of myogenin, Myosin Light Chain (MLC), and membrane AT1 receptors were measured using flow cytometry. Intracellular Ang II (iAng II) was overexpressed in differentiated cardiomyocytes and swelling was induced after incubation with hypotonic solution for 40min. Glucose uptake and IRS-1 levels were monitored by flow cytometry using 2-NBDG fluorescent glucose (10μM) or an anti-IRS-1 monoclonal antibody in the presence or absence of losartan (10 -7 M). Secreted Angiotensin II was quantified from the medium using a specific Ang II-EIA kit. To evaluate the relationship between sAng II and losartan effects on glucose uptake, transfected cells were pretreated with the drug for 24h and then exposed to hypotonic solution in the presence or absence of the secreted peptide. The results indicate that: (1) swelling of transfected cardiomyocytes decreased glucose uptake and induced the secretion of Ang II to the extracellular medium; (2) losartan antagonized the effects of swelling on glucose uptake and IRS-1 levels in transfected cardiomyocytes; (3) the effects of losartan on glucose uptake were observed during swelling only in the presence of sAng II in the culture medium. Our study demonstrates that both losartan and sAng II have essential roles in glucose metabolism during cardiomyocyte swelling. Copyright © 2017 Elsevier Inc. All rights reserved.

Contractility of the cell rear drives invasion of breast tumor cells in 3D Matrigel

PubMed Central

Poincloux, Renaud; Collin, Olivier; Lizárraga, Floria; Romao, Maryse; Debray, Marcel; Piel, Matthieu; Chavrier, Philippe

2011-01-01

Cancer cells use different modes of migration, including integrin-dependent mesenchymal migration of elongated cells along elements of the 3D matrix as opposed to low-adhesion-, contraction-based amoeboid motility of rounded cells. We report that MDA-MB-231 human breast adenocarcinoma cells invade 3D Matrigel with a characteristic rounded morphology and with F-actin and myosin-IIa accumulating at the cell rear in a uropod-like structure. MDA-MB-231 cells display neither lamellipodia nor bleb extensions at the leading edge and do not require Arp2/3 complex activity for 3D invasion in Matrigel. Accumulation of phospho-MLC and blebbing activity were restricted to the uropod as reporters of actomyosin contractility, and velocimetric analysis of fluorescent beads embedded within the 3D matrix showed that pulling forces exerted to the matrix are restricted to the side and rear of cells. Inhibition of actomyosin contractility or β1 integrin function interferes with uropod formation, matrix deformation, and invasion through Matrigel. These findings support a model whereby actomyosin-based uropod contractility generates traction forces on the β1 integrin adhesion system to drive cell propulsion within the 3D matrix, with no contribution of lamellipodia extension or blebbing to movement. PMID:21245302

Multi-Cellular Logistics of Collective Cell Migration

PubMed Central

Yamao, Masataka; Naoki, Honda; Ishii, Shin

2011-01-01

During development, the formation of biological networks (such as organs and neuronal networks) is controlled by multicellular transportation phenomena based on cell migration. In multi-cellular systems, cellular locomotion is restricted by physical interactions with other cells in a crowded space, similar to passengers pushing others out of their way on a packed train. The motion of individual cells is intrinsically stochastic and may be viewed as a type of random walk. However, this walk takes place in a noisy environment because the cell interacts with its randomly moving neighbors. Despite this randomness and complexity, development is highly orchestrated and precisely regulated, following genetic (and even epigenetic) blueprints. Although individual cell migration has long been studied, the manner in which stochasticity affects multi-cellular transportation within the precisely controlled process of development remains largely unknown. To explore the general principles underlying multicellular migration, we focus on the migration of neural crest cells, which migrate collectively and form streams. We introduce a mechanical model of multi-cellular migration. Simulations based on the model show that the migration mode depends on the relative strengths of the noise from migratory and non-migratory cells. Strong noise from migratory cells and weak noise from surrounding cells causes “collective migration,” whereas strong noise from non-migratory cells causes “dispersive migration.” Moreover, our theoretical analyses reveal that migratory cells attract each other over long distances, even without direct mechanical contacts. This effective interaction depends on the stochasticity of the migratory and non-migratory cells. On the basis of these findings, we propose that stochastic behavior at the single-cell level works effectively and precisely to achieve collective migration in multi-cellular systems. PMID:22205934

The Partition of Multi-Resolution LOD Based on Qtm

NASA Astrophysics Data System (ADS)

Hou, M.-L.; Xing, H.-Q.; Zhao, X.-S.; Chen, J.

2011-08-01

The partition hierarch of Quaternary Triangular Mesh (QTM) determine the accuracy of spatial analysis and application based on QTM. In order to resolve the problem that the partition hierarch of QTM is limited by the level of the computer hardware, the new method that Multi- Resolution LOD (Level of Details) based on QTM will be discussed in this paper. This method can make the resolution of the cells varying with the viewpoint position by partitioning the cells of QTM, selecting the particular area according to the viewpoint; dealing with the cracks caused by different subdivisions, it satisfies the request of unlimited partition in part.

Variable cycle control model for intersection based on multi-source information

NASA Astrophysics Data System (ADS)

Sun, Zhi-Yuan; Li, Yue; Qu, Wen-Cong; Chen, Yan-Yan

2018-05-01

In order to improve the efficiency of traffic control system in the era of big data, a new variable cycle control model based on multi-source information is presented for intersection in this paper. Firstly, with consideration of multi-source information, a unified framework based on cyber-physical system is proposed. Secondly, taking into account the variable length of cell, hysteresis phenomenon of traffic flow and the characteristics of lane group, a Lane group-based Cell Transmission Model is established to describe the physical properties of traffic flow under different traffic signal control schemes. Thirdly, the variable cycle control problem is abstracted into a bi-level programming model. The upper level model is put forward for cycle length optimization considering traffic capacity and delay. The lower level model is a dynamic signal control decision model based on fairness analysis. Then, a Hybrid Intelligent Optimization Algorithm is raised to solve the proposed model. Finally, a case study shows the efficiency and applicability of the proposed model and algorithm.

Software tool for portal dosimetry research.

PubMed

Vial, P; Hunt, P; Greer, P B; Oliver, L; Baldock, C

2008-09-01

This paper describes a software tool developed for research into the use of an electronic portal imaging device (EPID) to verify dose for intensity modulated radiation therapy (IMRT) beams. A portal dose image prediction (PDIP) model that predicts the EPID response to IMRT beams has been implemented into a commercially available treatment planning system (TPS). The software tool described in this work was developed to modify the TPS PDIP model by incorporating correction factors into the predicted EPID image to account for the difference in EPID response to open beam radiation and multileaf collimator (MLC) transmitted radiation. The processes performed by the software tool include; i) read the MLC file and the PDIP from the TPS, ii) calculate the fraction of beam-on time that each point in the IMRT beam is shielded by MLC leaves, iii) interpolate correction factors from look-up tables, iv) create a corrected PDIP image from the product of the original PDIP and the correction factors and write the corrected image to file, v) display, analyse, and export various image datasets. The software tool was developed using the Microsoft Visual Studio.NET framework with the C# compiler. The operation of the software tool was validated. This software provided useful tools for EPID dosimetry research, and it is being utilised and further developed in ongoing EPID dosimetry and IMRT dosimetry projects.