The ICT monitoring system of the ASTRI SST-2M prototype proposed for the Cherenkov Telescope Array

NASA Astrophysics Data System (ADS)

Gianotti, F.; Bruno, P.; Tacchini, A.; Conforti, V.; Fioretti, V.; Tanci, C.; Grillo, A.; Leto, G.; Malaguti, G.; Trifoglio, M.

2016-08-01

In the framework of the international Cherenkov Telescope Array (CTA) observatory, the Italian National Institute for Astrophysics (INAF) has developed a dual mirror, small sized, telescope prototype (ASTRI SST-2M), installed in Italy at the INAF observing station located at Serra La Nave, Mt. Etna. The ASTRI SST-2M prototype is the basis of the ASTRI telescopes that will form the mini-array proposed to be installed at the CTA southern site during its preproduction phase. This contribution presents the solutions implemented to realize the monitoring system for the Information and Communication Technology (ICT) infrastructure of the ASTRI SST-2M prototype. The ASTRI ICT monitoring system has been implemented by integrating traditional tools used in computer centers, with specific custom tools which interface via Open Platform Communication Unified Architecture (OPC UA) to the Alma Common Software (ACS) that is used to operate the ASTRI SST-2M prototype. The traditional monitoring tools are based on Simple Network Management Protocol (SNMP) and commercial solutions and features embedded in the devices themselves. They generate alerts by email and SMS. The specific custom tools convert the SNMP protocol into the OPC UA protocol and implement an OPC UA server. The server interacts with an OPC UA client implemented in an ACS component that, through the ACS Notification Channel, sends monitor data and alerts to the central console of the ASTRI SST-2M prototype. The same approach has been proposed also for the monitoring of the CTA onsite ICT infrastructures.

Conditional Deletion of the L-Type Calcium Channel Cav1.2 in NG2-Positive Cells Impairs Remyelination in Mice.

PubMed

Santiago González, Diara A; Cheli, Veronica T; Zamora, Norma N; Lama, Tenzing N; Spreuer, Vilma; Murphy, Geoffrey G; Paez, Pablo M

2017-10-18

Exploring the molecular mechanisms that drive the maturation of oligodendrocyte progenitor cells (OPCs) during the remyelination process is essential to developing new therapeutic tools to intervene in demyelinating diseases such as multiple sclerosis. To determine whether L-type voltage-gated calcium channels (L-VGCCs) are required for OPC development during remyelination, we generated an inducible conditional knock-out mouse in which the L-VGCC isoform Cav1.2 was deleted in NG2-positive OPCs (Cav1.2 KO ). Using the cuprizone (CPZ) model of demyelination and mice of either sex, we establish that Cav1.2 deletion in OPCs leads to less efficient remyelination of the adult brain. Specifically, Cav1.2 KO OPCs mature slower and produce less myelin than control oligodendrocytes during the recovery period after CPZ intoxication. This reduced remyelination was accompanied by an important decline in the number of myelinating oligodendrocytes and in the rate of OPC proliferation. Furthermore, during the remyelination phase of the CPZ model, the corpus callosum of Cav1.2 KO animals presented a significant decrease in the percentage of myelinated axons and a substantial increase in the mean g-ratio of myelinated axons compared with controls. In addition, in a mouse line in which the Cav1.2 KO OPCs were identified by a Cre reporter, we establish that Cav1.2 KO OPCs display a reduced maturational rate through the entire remyelination process. These results suggest that Ca 2+ influx mediated by L-VGCCs in oligodendroglial cells is necessary for normal remyelination and is an essential Ca 2+ channel for OPC maturation during the remyelination of the adult brain. SIGNIFICANCE STATEMENT Ion channels implicated in oligodendrocyte differentiation and maturation may induce positive signals for myelin recovery. Voltage-gated Ca 2+ channels (VGCCs) are important for normal myelination by acting at several critical steps during oligodendrocyte progenitor cell (OPC) development. To determine whether voltage Ca 2+ entry is involved in oligodendrocyte differentiation and remyelination, we used a conditional knockout mouse for VGCCs in OPCs. Our results indicate that VGCCs can modulate oligodendrocyte maturation in the demyelinated brain and suggest that voltage-gated Ca 2+ influx in OPCs is critical for remyelination. These findings could lead to novel approaches for obtaining a better understanding of the factors that control OPC maturation in order to stimulate this pool of progenitors to replace myelin in demyelinating diseases. Copyright © 2017 the authors 0270-6474/17/3710038-14$15.00/0.

PARP activity and inhibition in fetal and adult oligodendrocyte precursor cells: Effect on cell survival and differentiation.

PubMed

Baldassarro, Vito A; Marchesini, Alessandra; Giardino, Luciana; Calzà, Laura

2017-07-01

Poly (ADP-ribose) polymerase (PARP) family members are ubiquitously expressed and play a key role in cellular processes, including DNA repair and cell death/survival balance. Accordingly, PARP inhibition is an emerging pharmacological strategy for cancer and neurodegenerative diseases. Consistent evidences support the critical involvement of PARP family members in cell differentiation and phenotype maturation. In this study we used an oligodendrocyte precursor cells (OPCs) enriched system derived from fetal and adult brain to investigate the role of PARP in OPCs proliferation, survival, and differentiation. The PARP inhibitors PJ34, TIQ-A and Olaparib were used as pharmacological tools. The main results of the study are: (i) PARP mRNA expression and PARP activity are much higher in fetal than in adult-derived OPCs; (ii) the culture treatment with PARP inhibitors is cytotoxic for OPCs derived from fetal, but not from adult, brain; (iii) PARP inhibition reduces cell number, according to the inhibitory potency of the compounds; (iv) PARP inhibition effect on fetal OPCs is a slow process; (v) PARP inhibition impairs OPCs maturation into myelinating OL in fetal, but not in adult cultures, according to the inhibitory potency of the compounds. These results have implications for PARP-inhibition therapies for diseases and lesions of the central nervous system, in particular for neonatal hypoxic/ischemic encephalopathy. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Optimizing Culture Medium Composition to Improve Oligodendrocyte Progenitor Cell Yields In Vitro from Subventricular Zone-Derived Neural Progenitor Cell Neurospheres

PubMed Central

Franco, Paula G.; Pasquini, Juana M.; Silvestroff, Lucas

2015-01-01

Neural Stem and Progenitor Cells (NSC/NPC) are gathering tangible recognition for their uses in cell therapy and cell replacement therapies for human disease, as well as a model system to continue research on overall neural developmental processes in vitro. The Subventricular Zone is one of the largest NSC/NPC niches in the developing mammalian Central Nervous System, and persists through to adulthood. Oligodendrocyte progenitor cell (OPC) enriched cultures are usefull tools for in vitro studies as well as for cell replacement therapies for treating demyelination diseases. We used Subventricular Zone-derived NSC/NPC primary cultures from newborn mice and compared the effects of different growth factor combinations on cell proliferation and OPC yield. The Platelet Derived Growth Factor-AA and BB homodimers had a positive and significant impact on OPC generation. Furthermore, heparin addition to the culture media contributed to further increase overall culture yields. The OPC generated by this protocol were able to mature into Myelin Basic Protein-expressing cells and to interact with neurons in an in vitro co-culture system. As a whole, we describe an optimized in vitro method for increasing OPC. PMID:25837625

Detecting measurement outliers: remeasure efficiently

NASA Astrophysics Data System (ADS)

Ullrich, Albrecht

2010-09-01

Shrinking structures, advanced optical proximity correction (OPC) and complex measurement strategies continually challenge critical dimension (CD) metrology tools and recipe creation processes. One important quality ensuring task is the control of measurement outlier behavior. Outliers could trigger false positive alarm for specification violations impacting cycle time or potentially yield. Constant high level of outliers not only deteriorates cycle time but also puts unnecessary stress on tool operators leading eventually to human errors. At tool level the sources of outliers are natural variations (e.g. beam current etc.), drifts, contrast conditions, focus determination or pattern recognition issues, etc. Some of these can result from suboptimal or even wrong recipe settings, like focus position or measurement box size. Such outliers, created by an automatic recipe creation process faced with more complicated structures, would manifest itself rather as systematic variation of measurements than the one caused by 'pure' tool variation. I analyzed several statistical methods to detect outliers. These range from classical outlier tests for extrema, robust metrics like interquartile range (IQR) to methods evaluating the distribution of different populations of measurement sites, like the Cochran test. The latter suits especially the detection of systematic effects. The next level of outlier detection entwines additional information about the mask and the manufacturing process with the measurement results. The methods were reviewed for measured variations assumed to be normally distributed with zero mean but also for the presence of a statistically significant spatial process signature. I arrive at the conclusion that intelligent outlier detection can influence the efficiency and cycle time of CD metrology greatly. In combination with process information like target, typical platform variation and signature, one can tailor the detection to the needs of the photomask at hand. By monitoring the outlier behavior carefully, weaknesses of the automatic recipe creation process can be spotted.

Model based high NA anamorphic EUV RET

NASA Astrophysics Data System (ADS)

Jiang, Fan; Wiaux, Vincent; Fenger, Germain; Clifford, Chris; Liubich, Vlad; Hendrickx, Eric

2018-03-01

With the announcement of the extension of the Extreme Ultraviolet (EUV) roadmap to a high NA lithography tool that utilizes anamorphic optics design, an investigation of design tradeoffs unique to the imaging of anamorphic lithography tool is shown. An anamorphic optical proximity correction (OPC) solution has been developed that models fully the EUV near field electromagnetic effects and the anamorphic imaging using the Domain Decomposition Method (DDM). Clips of imec representative for the N3 logic node were used to demonstrate the OPC solutions on critical layers that will benefit from the increased contrast at high NA using anamorphic imaging. However, unlike isomorphic case, from wafer perspective, OPC needs to treat x and y differently. In the paper, we show a design trade-off seen unique to Anamorphic EUV, namely that using a mask rule of 48nm (mask scale), approaching current state of the art, limitations are observed in the available correction that can be applied to the mask. The metal pattern has a pitch of 24nm and CD of 12nm. During OPC, the correction of the metal lines oriented vertically are being limited by the mask rule of 12nm 1X. The horizontally oriented lines do not suffer from this mask rule limitation as the correction is allowed to go to 6nm 1X. For this example, the masks rules will need to be more aggressive to allow complete correction, or design rules and wafer processes (wafer rotation) would need to be created that utilize the orientation that can image more aggressive features. When considering VIA or block level correction, aggressive polygon corner to corner designs can be handled with various solutions, including applying a 45 degree chop. Multiple solutions are discussed with the metrics of edge placement error (EPE) and Process Variation Bands (PVBands), together with all the mask constrains. Noted in anamorphic OPC, the 45 degree chop is maintained at the mask level to meet mask manufacturing constraints, but results in skewed angle edge in wafer level correction. In this paper, we used both contact (Via/block) patterns and metal patterns for OPC practice. By comparing the EPE of horizontal and vertical patterns with a fixed mask rule check (MRC), and the PVBand, we focus on the challenges and the solutions of OPC with anamorphic High-NA lens.

Proanthocyanidin trimer gallate modulates lipid deposition and fatty acid desaturation in Caenorhabditis elegans.

PubMed

Nie, Yu; Littleton, Brad; Kavanagh, Thomas; Abbate, Vincenzo; Bansal, Sukhvinder S; Richards, David; Hylands, Peter; Stürzenbaum, Stephen R

2017-11-01

The incidence of obesity is rising at an alarming rate. Despite its recognition as an urgent healthcare concern, obesity remains largely an unsolved medical problem. A comprehensive screen for functional dietary phytochemicals identified proanthocyanidins as putative targets to ameliorate obesity. A full-scale purification of oligomeric proanthocyanidins (OPCs) derived from grape seed extract yielded pure OPC dimer, trimer, tetramer, and their gallates (pOPCs). Forward chemical screening conducted in Caenorhabditis elegans suggested that pOPCs reduced the activity of lipase in vitro and triglyceride storage capacity in vivo Proanthocyanidin trimer gallate in particular modified lipid desaturation in C. elegans , revealed by hyperspectral coherent anti-Stokes Raman scattering microscopy. Exposure to trimer gallate resulted in the transcriptional down-regulation of nhr-49 (an ortholog of the human peroxisome proliferator-activated receptor-α), and a key regulator of fat metabolism, and 2 downstream genes: fat-5 and acs-2 A combination exposure of 2 or 3 pOPCs (dimer gallate, trimer and/or trimer gallate) suggested the absence of synergistic potential. By using the whole-organism C. elegans coupled with versatile biochemical, biophysical, and genetic tools, we provide an account of the composition and bioactivity of individual OPCs and more generally highlight the potential of traditional Chinese medicine-derived drug leads.-Nie, Y., Littleton, B., Kavanagh, T., Abbate, V., Bansal, S. S., Richards, D., Hylands, P., Sturzenbaum, S. R. Proanthocyanidin trimer gallate modulates lipid deposition and fatty acid desaturation in Caenorhabditis elegans . © FASEB.

Early stage hot spot analysis through standard cell base random pattern generation

NASA Astrophysics Data System (ADS)

Jeon, Joong-Won; Song, Jaewan; Kim, Jeong-Lim; Park, Seongyul; Yang, Seung-Hune; Lee, Sooryong; Kang, Hokyu; Madkour, Kareem; ElManhawy, Wael; Lee, SeungJo; Kwan, Joe

2017-04-01

Due to limited availability of DRC clean patterns during the process and RET recipe development, OPC recipes are not tested with high pattern coverage. Various kinds of pattern can help OPC engineer to detect sensitive patterns to lithographic effects. Random pattern generation is needed to secure robust OPC recipe. However, simple random patterns without considering real product layout style can't cover patterning hotspot in production levels. It is not effective to use them for OPC optimization thus it is important to generate random patterns similar to real product patterns. This paper presents a strategy for generating random patterns based on design architecture information and preventing hotspot in early process development stage through a tool called Layout Schema Generator (LSG). Using LSG, we generate standard cell based on random patterns reflecting real design cell structure - fin pitch, gate pitch and cell height. The output standard cells from LSG are applied to an analysis methodology to assess their hotspot severity by assigning a score according to their optical image parameters - NILS, MEEF, %PV band and thus potential hotspots can be defined by determining their ranking. This flow is demonstrated on Samsung 7nm technology optimizing OPC recipe and early enough in the process avoiding using problematic patterns.

Anticipating and controlling mask costs within EDA physical design

NASA Astrophysics Data System (ADS)

Rieger, Michael L.; Mayhew, Jeffrey P.; Melvin, Lawrence S.; Lugg, Robert M.; Beale, Daniel F.

2003-08-01

For low k1 lithography, more aggressive OPC is being applied to critical layers, and the number of mask layers with OPC treatments is growing rapidly. The 130 nm, process node required, on average, 8 layers containing rules- or model-based OPC. The 90 nm node will have 16 OPC layers, of which 14 layers contain aggressive model-based OPC. This escalation of mask pattern complexity, coupled with the predominant use of vector-scan e-beam (VSB) mask writers contributes to the rising costs of advanced mask sets. Writing times for OPC layouts are several times longer than for traditional layouts, making mask exposure the single largest cost component for OPC masks. Lower mask yields, another key factor in higher mask costs, is also aggravated by OPC. Historical mask set costs are plotted below. The initial cost of a 90 nm-node mask set will exceed one million dollars. The relative impact of mask cost on chip depends on how many total wafers are printed with each mask set. For many foundry chips, where unit production is often well below 1000 wafers, mask costs are larger than wafer processing costs. Further increases in NRE may begin to discourage these suppliers' adoption to 90 nm and smaller nodes. In this paper we will outline several alternatives for reducing mask costs by strategically leveraging dimensional margins. Dimensional specifications for a particular masking layer usually are applied uniformly to all features on that layer. As a practical matter, accuracy requirements on different features in the design may vary widely. Take a polysilicon layer, for example: global tolerance specifications for that layer are driven by the transistor-gate requirements; but these parameters over-specify interconnect feature requirements. By identifying features where dimensional accuracy requirements can be reduced, additional margin can be leveraged to reduce OPC complexity. Mask writing time on VSB tools will drop in nearly direct proportion to reduce shot count. By inspecting masks with reference to feature-dependent margins, instead of uniform specifications, mask yield can be effectively increased further reducing delivered mask expense.

Developing a PLC-friendly state machine model: lessons learned

NASA Astrophysics Data System (ADS)

Pessemier, Wim; Deconinck, Geert; Raskin, Gert; Saey, Philippe; Van Winckel, Hans

2014-07-01

Modern Programmable Logic Controllers (PLCs) have become an attractive platform for controlling real-time aspects of astronomical telescopes and instruments due to their increased versatility, performance and standardization. Likewise, vendor-neutral middleware technologies such as OPC Unified Architecture (OPC UA) have recently demonstrated that they can greatly facilitate the integration of these industrial platforms into the overall control system. Many practical questions arise, however, when building multi-tiered control systems that consist of PLCs for low level control, and conventional software and platforms for higher level control. How should the PLC software be structured, so that it can rely on well-known programming paradigms on the one hand, and be mapped to a well-organized OPC UA interface on the other hand? Which programming languages of the IEC 61131-3 standard closely match the problem domains of the abstraction levels within this structure? How can the recent additions to the standard (such as the support for namespaces and object-oriented extensions) facilitate a model based development approach? To what degree can our applications already take advantage of the more advanced parts of the OPC UA standard, such as the high expressiveness of the semantic modeling language that it defines, or the support for events, aggregation of data, automatic discovery, ... ? What are the timing and concurrency problems to be expected for the higher level tiers of the control system due to the cyclic execution of control and communication tasks by the PLCs? We try to answer these questions by demonstrating a semantic state machine model that can readily be implemented using IEC 61131 and OPC UA. One that does not aim to capture all possible states of a system, but rather one that attempts to organize the course-grained structure and behaviour of a system. In this paper we focus on the intricacies of this seemingly simple task, and on the lessons that we've learned during the development process of such a "PLC-friendly" state machine model.

Improving reticle defect disposition via fully automated lithography simulation

NASA Astrophysics Data System (ADS)

Mann, Raunak; Goodman, Eliot; Lao, Keith; Ha, Steven; Vacca, Anthony; Fiekowsky, Peter; Fiekowsky, Dan

2016-03-01

Most advanced wafer fabs have embraced complex pattern decoration, which creates numerous challenges during in-fab reticle qualification. These optical proximity correction (OPC) techniques create assist features that tend to be very close in size and shape to the main patterns as seen in Figure 1. A small defect on an assist feature will most likely have little or no impact on the fidelity of the wafer image, whereas the same defect on a main feature could significantly decrease device functionality. In order to properly disposition these defects, reticle inspection technicians need an efficient method that automatically separates main from assist features and predicts the resulting defect impact on the wafer image. Analysis System (ADAS) defect simulation system[1]. Up until now, using ADAS simulation was limited to engineers due to the complexity of the settings that need to be manually entered in order to create an accurate result. A single error in entering one of these values can cause erroneous results, therefore full automation is necessary. In this study, we propose a new method where all needed simulation parameters are automatically loaded into ADAS. This is accomplished in two parts. First we have created a scanner parameter database that is automatically identified from mask product and level names. Second, we automatically determine the appropriate simulation printability threshold by using a new reference image (provided by the inspection tool) that contains a known measured value of the reticle critical dimension (CD). This new method automatically loads the correct scanner conditions, sets the appropriate simulation threshold, and automatically measures the percentage of CD change caused by the defect. This streamlines qualification and reduces the number of reticles being put on hold, waiting for engineer review. We also present data showing the consistency and reliability of the new method, along with the impact on the efficiency of in-fab reticle qualification.

EM calibration based on Post OPC layout analysis

NASA Astrophysics Data System (ADS)

Sreedhar, Aswin; Kundu, Sandip

2010-03-01

Design for Manufacturability (DFM) involves changes to the design and CAD tools to help increase pattern printability and improve process control. Design for Reliability (DFR) performs the same to improve reliability of devices from failures such as Electromigration (EM), gate-oxide break down, hot carrier injection (HCI), Negative Bias Temperature Insatiability (NBTI) and mechanical stress effects. Electromigration (EM) occurs due to migration or displacement of atoms as a result of the movement of electrons through a conducting medium. The rate of migration determines the Mean Time to Failure (MTTF) which is modeled as a function of temperature and current density. The model itself is calibrated through failure analysis (FA) of parts that are deemed to have failed due to EM against design parameters such as linewidth. Reliability Verification (RV) of a design involves verifying that every conducting line in a design meets certain MTTF threshold. In order to perform RV, current density for each wire must be computed. Current itself is a function of the parasitics that are determined through RC extraction. The standard practice is to perform the RC extraction and current density calculation on drawn, pre-OPC layouts. If a wire fails to meet threshold for MTTF, it may be resized. Subsequently, mask preparation steps such as OPC and PSM introduce extra features such as SRAFs, jogs,hammerheads and serifs that change their resistance, capacitance and current density values. Hence, calibrating EM model based on pre-OPC layouts will lead to different results compared to post-OPC layouts. In this work, we compare EM model calibration and reliability check based on drawn layout versus predicted layout, where the drawn layout is pre-OPC layout and predicted layout is based on litho simulation of post-OPC layout. Results show significant divergence between these two approaches, making a case for methodology based on predicted layout.

Manufacturing an advanced process characterization reticle incorporating halftone biasing

NASA Astrophysics Data System (ADS)

Nakagawa, Kent H.; Van Den Broeke, Douglas J.; Chen, J. Fung; Laidig, Thomas L.; Wampler, Kurt E.; Caldwell, Roger F.

1999-04-01

As the semiconductor roadmap continues to require imaging of smaller feature son wafers, we continue to explore new approaches in OPC strategies to extend the lifespan of existing technology. In this paper, we study a new OPC technology, called halftone biasing, and its application on an OPC characterization reticle, designed by MicroUnity Systems Engineering, Inc. The RTP9 test reticle is the latest in a series of 'LineSweeper' characterization reticles. Each reticle contains a wide range of line width sand pitches, each with several alternative OPC treatments, including references cases, scattering bars, and fine biasing. One of RTP9's design requirements was to support very fine, incremental biases for densely-pitched lines. Ordinarily, this would dictate a reduced address unit and with it the costly penalty of a square-law increase in e- beam write time. RTP9 incorporates a new OPC strategy, called halftone biasing, which has been proposed to address this problem. Taking advantage of optical reduction printing, this technique applies a sub-resolution halftone screen to the edges of figures to accomplish fine biasing equivalent to using an address unit one-fourth of the size of the actual e-beam writing grid. The resulting edge structure has some of the characteristics of aggressive OPC structures, but can be used in areas where traditional scattering bars cannot be placed. The trade-off between the faster write times achieved and the inflation of pattern file size is examined. The manufacturability and inspectability of halftone-biased lines on the RTP9 test reticle are explored. Pattern fidelity is examined using both optical and SEM tools. Printed 0.18 micrometers DUV resist line edge profiles are compared for both halftone and non- halftone feature edges. The CD uniformity of the OPC features, and result of die-to-database inspection are reported. The application of halftone biasing to real circuits, including the impact of data volume and saved write time, is also discussed.

Dysfunctional oligodendrocyte progenitor cell (OPC) populations may inhibit repopulation of OPC depleted tissue.

PubMed

Chari, D M; Huang, W L; Blakemore, W F

2003-09-15

We have attempted to extend a previously described rat model of focal oligodendrocyte progenitor cell (OPC) depletion, using 40 Gy X-irradiation (Chari and Blakemore [2002] Glia 37:307-313), to the adult mouse spinal cord, to examine the ability of OPCs present in adjacent normal areas to colonise areas of progenitor depletion. In contrast to rat, OPCs in the mouse spinal cord appeared to be a comparatively radiation-resistant population, as 30-35% of OPCs survived in X-irradiated tissue (whereas <1% of OPCs survive in X-irradiated rat spinal cord). The numbers of surviving OPCs remained constant with time indicating that this population was incapable of regenerating itself in response to OPC loss. Additionally, these OPCs did not contribute to remyelination of axons when demyelinating lesions were placed in X-irradiated tissue, suggesting that the surviving cells are functionally impaired. Importantly, the length of the OPC-depleted area did not diminish with time, as would be expected if progressive repopulation of OPC-depleted areas by OPCs from normal areas was occurring. Our findings therefore raise the possibility that the presence of a residual dysfunctional OPC population may inhibit colonisation of such areas by normal OPCs. Copyright 2003 Wiley-Liss, Inc.

EVALUATION OF OPTICALLY ACQUIRED ZOOPLANKTON SIZE-SPECTRUM DATA AS A POTENTIAL TOOL FOR ASSESSMENT OF CONDITION IN THE GREAT LAKES

EPA Science Inventory

An optical zooplankton counter (OPC) potentially provides as assessment tool for zooplankton condition in ecosystems that is rapid, economical, and spatially extensive. We collected zooplankton data with an optical zooplankton counter in 20 near-shore regions of four of the Laure...

Towards a flexible array control and operation framework for CTA

NASA Astrophysics Data System (ADS)

Birsin, E.; Colomé, J.; Hoffmann, D.; Koeppel, H.; Lamanna, G.; Le Flour, T.; Lopatin, A.; Lyard, E.; Melkumyan, D.; Oya, I.; Panazol, J.-L.; Schlenstedt, S.; Schmidt, T.; Schwanke, U.; Stegmann, C.; Walter, R.; Wegner, P.; CTA Consortium

2012-12-01

The Cherenkov Telescope Array (CTA) [1] will be the successor to current Imaging Atmospheric Cherenkov Telescopes (IACT) like H.E.S.S., MAGIC and VERITAS. CTA will improve in sensitivity by about an order of magnitude compared to the current generation of IACTs. The energy range will extend from well below 100 GeV to above 100 TeV. To accomplish these goals, CTA will consist of two arrays, one in each hemisphere, consisting of 50-80 telescopes and composed of three different telescope types with different mirror sizes. It will be the first open observatory for very high energy γ-ray astronomy. The Array Control working group of CTA is currently evaluating existing technologies which are best suited for a project like CTA. The considered solutions comprise the ALMA Common Software (ACS), the OPC Unified Architecture (OPC UA) and the Data Distribution Service (DDS) for bulk data transfer. The first applications, like an automatic observation scheduler and the control software for some prototype instrumentation have been developed.

SU-E-T-398: Feasibility of Automated Tools for Robustness Evaluation of Advanced Photon and Proton Techniques in Oropharyngeal Cancer

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

Liu, H; Liang, X; Kalbasi, A

2014-06-01

Purpose: Advanced radiotherapy (RT) techniques such as proton pencil beam scanning (PBS) and photon-based volumetric modulated arc therapy (VMAT) have dosimetric advantages in the treatment of head and neck malignancies. However, anatomic or alignment changes during treatment may limit robustness of PBS and VMAT plans. We assess the feasibility of automated deformable registration tools for robustness evaluation in adaptive PBS and VMAT RT of oropharyngeal cancer (OPC). Methods: We treated 10 patients with bilateral OPC with advanced RT techniques and obtained verification CT scans with physician-reviewed target and OAR contours. We generated 3 advanced RT plans for each patient: protonmore » PBS plan using 2 posterior oblique fields (2F), proton PBS plan using an additional third low-anterior field (3F), and a photon VMAT plan using 2 arcs (Arc). For each of the planning techniques, we forward calculated initial (Ini) plans on the verification scans to create verification (V) plans. We extracted DVH indicators based on physician-generated contours for 2 target and 14 OAR structures to investigate the feasibility of two automated tools (contour propagation (CP) and dose deformation (DD)) as surrogates for routine clinical plan robustness evaluation. For each verification scan, we compared DVH indicators of V, CP and DD plans in a head-to-head fashion using Student's t-test. Results: We performed 39 verification scans; each patient underwent 3 to 6 verification scan. We found no differences in doses to target or OAR structures between V and CP, V and DD, and CP and DD plans across all patients (p > 0.05). Conclusions: Automated robustness evaluation tools, CP and DD, accurately predicted dose distributions of verification (V) plans using physician-generated contours. These tools may be further developed as a potential robustness screening tool in the workflow for adaptive treatment of OPC using advanced RT techniques, reducing the need for physician-generated contours.« less

Examining Students' Use of Online Annotation Tools in Support of Argumentative Reading

ERIC Educational Resources Information Center

Lu, Jingyan; Deng, Liping

2013-01-01

This study examined how students in a Hong Kong high school used Diigo, an online annotation tool, to support their argumentative reading activities. Two year 10 classes, a high-performance class (HPC) and an ordinary-performance class (OPC), highlighted passages of text and wrote and attached sticky notes to them to clarify argumentation…

OPC-28326, a selective femoral arterial vasodilator, augments ischemia induced angiogenesis.

PubMed

Sumi, Makoto; Sata, Masataka; Hashimoto, Ayako; Imaizumi, Takashi; Yanaga, Katsuhiko; Ohki, Takao; Mori, Toyoki; Nagai, Ryozo

2007-05-01

OPC-28326, 4-(N-methyl-2-phenylethylamino)-1-(3,5-dimethyl-4-propionyl-aminobenzoyl) piperidine hydrochloride monohydrate, is a newly developed selective peripheral vasodilator and increases blood flow to lower extremities with alpha2-adrenergic antagonist property. Here, we investigated the effect of OPC-28326 on ischemia-induced angiogenesis. OPC-28326 enhanced tube formation by human aortic endothelial cells (HAECs). Moreover, OPC-28326 enhanced the number of microvessels sprouting from aortic rings embedded in collagen gel. OPC-28326 markedly induced phosphorylation of endothelial nitric oxide synthase (eNOS) in HAECs via phosphatidylinositol-3 kinase PI3K/Akt (PI3K/Akt) pathway. Next, the angiogenic effect of OPC-28326 was evaluated in a mouse hindlimb ischemia model. Blood flow recovery to the ischemic leg was significantly enhanced by OPC-28326. Furthermore, anti-CD31 immunostaining revealed that OPC-28326 increased capillary density in the ischemic muscle. However, OPC-28326 failed to promote blood flow recovery in ischemic hindlimb in eNOS-deficient mice. These results suggest that OPC-28326 promotes angiogenesis, which was associated with activation of eNOS via PI3K/Akt pathway. OPC-28326 might be promising to treat patients with ischemic vascular diseases.

Emerging insights into recurrent and metastatic human papillomavirus‐related oropharyngeal squamous cell carcinoma

PubMed Central

Faraji, Farhoud; Eisele, David W.

2017-01-01

ABSTRACT Objective To review recent literature on human papillomavirus‐related (HPV‐positive) oropharyngeal squamous cell carcinoma (OPC) and focus on implications of recurrent and metastatic disease. Methods Primary articles from 1990 to 2016 indexed in MEDLINE (1) pertaining to the epidemiology of HPV‐positive OPC and (2) providing clinical insight into recurrent and metastatic OPC. Results The incidence of HPV‐positive OPC is increasing globally. HPV‐positive OPC is a subtype with distinct molecular and clinical features including enhanced treatment response and improved overall survival. While disease recurrence is less common in patients with HPV‐positive OPC, up to 36% of patients experience treatment failure within eight years. Recurrent and metastatic OPC has historically signified poor prognosis, however recent data are challenging this dogma. Here, we discuss recurrent and metastatic OPC in the context of HPV tumor status. Conclusion HPV‐positive OPC exhibits distinct genetic, cellular, epidemiological, and clinical features from HPV‐negative OPC. HPV tumor status is emerging as a marker indicative of improved prognosis after disease progression in both locoregionally recurrent and distant metastatic OPC. Level of Evidence N/A. PMID:28894817

A comparison of dehydration effects of V2-antagonist (OPC-31260) on the inner ear between systemic and round window applications.

PubMed

Takeda, Taizo; Takeda, Setsuko; Kakigi, Akinobu; Okada, Teruhiko; Nishioka, Rie; Taguchi, Daizo

2006-08-01

V2-antagonist (OPC-31260 (OPC)) application to the scala tympani reduced endolymphatic hydrops. In the present study, we investigated whether systemic administration or local infusion via the round window (RW application) of OPC would be more suitable for clinical use. In Experiment 1, the increase ratios of the cross-sectional area of the scala media of experimentally induced endolymphatic hydrops were quantitatively assessed among four groups of non-OPC application, RW application of xanthan gum, systemic application of OPC and RW application of OPC. In Experiment 2, the effects of systemic and RW applications of OPC on plasma vasopressin (p-VP) concentrations and plasma osmolality (p-OSM) were investigated. In Experiment 3, endocochlear DC potential (EP) was measured in guinea pigs with the RW application of OPC. Electron microscopic observations of the stria vascularis and the hair cells were also made. Both systemic and RW applications of OPC significantly reduced endolymphatic hydrops. However, systemic application resulted in the distension of the Reissner's membrane in the non-operated ear, which seemed to be caused by elevated p-VP levels resulting from the systemic application of OPC. In contrast, RW application of OPC produced no apparent toxic effects in the inner ear, as indicated electrophysiological or morphological changes. Thus, drug delivery via the round window is more useful for the clinical application of OPC for medical decompression.

Cluster tool solution for fabrication and qualification of advanced photomasks

NASA Astrophysics Data System (ADS)

Schaetz, Thomas; Hartmann, Hans; Peter, Kai; Lalanne, Frederic P.; Maurin, Olivier; Baracchi, Emanuele; Miramond, Corinne; Brueck, Hans-Juergen; Scheuring, Gerd; Engel, Thomas; Eran, Yair; Sommer, Karl

2000-07-01

The reduction of wavelength in optical lithography, phase shift technology and optical proximity correction (OPC), requires a rapid increase in cost effective qualification of photomasks. The knowledge about CD variation, loss of pattern fidelity especially for OPC pattern and mask defects concerning the impact on wafer level is becoming a key issue for mask quality assessment. As part of the European Community supported ESPRIT projection 'Q-CAP', a new cluster concept has been developed, which allows the combination of hardware tools as well as software tools via network communication. It is designed to be open for any tool manufacturer and mask hose. The bi-directional network access allows the exchange of all relevant mask data including grayscale images, measurement results, lithography parameters, defect coordinates, layout data, process data etc. and its storage to a SQL database. The system uses SEMI format descriptions as well as standard network hardware and software components for the client server communication. Each tool is used mainly to perform its specific application without using expensive time to perform optional analysis, but the availability of the database allows each component to share the full data ste gathered by all components. Therefore, the cluster can be considered as one single virtual tool. The paper shows the advantage of the cluster approach, the benefits of the tools linked together already, and a vision of a mask house in the near future.

Dehydration effects of a V2 antagonist on endolymphatic hydrops in guinea pigs.

PubMed

Egami, Naoya; Kakigi, Akinobu; Takeda, Taizo; Yamasoba, Tatsuya

2016-02-01

We investigated the influence of vasopressin type 2 receptor antagonist (OPC-41061; Tolvaptan) on experimentally induced endolymphatic hydrops (EH) in guinea pigs. In the first series, the endolymphatic sac (ES) of the left ear of all animals was electrocauterized. Four weeks after surgery, the animals were allocated to four groups: three systemic applications groups (saline, OPC 10 and 100 mg/kg) and a local round window (RW) OPC 1 mg/body application group. We examined the histopathology of the temporal bones and assessed volumetric changes of the endolymphatic space in the cochlea and saccule. In the second series, we investigated the effects of systemic and topical applications of OPC on plasma vasopressin (p-VP) concentrations and plasma osmolality (p-OSM). In the first series, we found that EH was reduced in the OPC 10 mg/kg systemic and OPC RW application groups. In contrast, EH increased in the OPC 100 mg/kg systemic application group. In the second series, neither p-VP levels nor p-OSM were significantly different among the non-OPC, OPC 10 mg/kg systemic, and OPC RW application groups. However, in the OPC 100 mg/kg systemic application group, the p-VP level was significantly higher than that in other groups, and p-OSM was higher than that in the non-OPC group. The systemic application of a low dose of OPC and topical application of OPC resulted in reduced EH in the face of minimal systemic effects (p-VP and p-OSM). These findings suggest that OPC-41061 may be one useful treatment option for EH. Copyright © 2015 Elsevier B.V. All rights reserved.

A novel method to fast fix the post OPC weak-points through Calibre eqDRC application

NASA Astrophysics Data System (ADS)

Jin, YaDong; Lyu, Shizhi; Deng, ZeXi; Lu, Cong

2018-03-01

With shrinking nodes, as the layout patterns are becoming more and more complicated, OPC accuracy and performance is becoming increasingly challenging. While we are trying to perfect our OPC script to have a clean output without weak points, in a real urgent tape-out scenario, often there will be weak points and we cannot afford the cost to run the OPC again with an updated OPC recipe. Naturally the post OPC repair becomes the only cost-effective choice. The paper studies and compares a few methods for the post OPC weak-points repair: the manual OPC repair flow and traditional repair flow based on the DRC commands. Here, we introduce a novel method based on the eqDRC commands, which are widely used in the design house but have never been used in the post OPC flow. We discuss how to apply the eqDRC into the post OPC repairs and demonstrate its advantages over the traditional methods.

A different regional response by mouse oligodendrocyte progenitor cells (OPCs) to high-dose X-irradiation has consequences for repopulating OPC-depleted normal tissue.

PubMed

Irvine, Karen-Amanda; Blakemore, William F

2007-01-01

This study was designed to investigate whether the residual, dysfunctional oligodendrocyte progenitor cells (OPCs) observed following X-irradiation of the mouse spinal cord [D. M. Chari et al. (2003) Exp. Neurol., 198, 145-153], the presence of which prevented the endogenous repopulation of these areas from normal tissue, reflects a general response of OPCs in the mouse central nervous system (CNS) to X-irradiation. The brains of adult mice were exposed to 40 Gy of X-irradiation and the effect of X-irradiation on the OPCs was assessed up to 4 weeks post-irradiation using anti-NG2 antibodies. X-irradiation resulted in almost complete depletion of OPCs within the telencephalon (cortex, corpus callosum and hippocampus) by 7 days post-irradiation, which was followed by progressive repopulation of OPCs from non-irradiated areas of the cortex. By contrast, within the lower brain centres (the diencephalon and mesencephalon) OPC loss occurred much more slowly so that 26% of the OPCs still remained 4 weeks after X-irradiation. The consequence of this heterogeneous response to X-irradiation was that whereas transplanted and endogenous OPCs rapidly established themselves in the OPC-depleted telencephalon this did not occur in the areas where there was incomplete depletion of endogenous OPCs. Our findings confirm not only the requirement for almost complete OPC depletion in order to establish transplanted OPCs in normal tissue but also highlight a heterogeneity of progenitor populations in different areas of the mouse CNS.

Optical phase conjugation: principles, techniques, and applications

NASA Astrophysics Data System (ADS)

He, Guang S.

2002-05-01

Over the last three decades, optical phase conjugation (OPC) has been one of the major research subjects in the field of nonlinear optics and quantum electronics. OPC defines usually a special relationship between two coherent optical beams propagating in opposite directions with reversed wave front and identical transverse amplitude distributions. The unique feature of a pair of phase-conjugate beams is that the aberration influence imposed on the forward beam passed through an inhomogeneous or disturbing medium can be automatically removed for the backward beam passed through the same disturbing medium. To date there have been three major technical approaches that can efficiently produce the backward phase-conjugate beam. The first approach is based on the degenerate (or partially degenerate) four-wave mixing processes, the second is based on various backward simulated (Brillouin, Raman, Rayleigh-wing or Kerr) scattering processes, and the third is based on one-photon or multi-photon pumped backward stimulated emission (lasing) processes. Among these three different approaches, there is a common physical mechanism that plays the same essential role in generating a backward phase-conjugate beam, which is the formation of the induced holographic grating and the subsequent wave-front restoration via a backward reading beam. In most experimental studies, certain types of resonance enhancements of induced refractive-index changes are desirable for obtaining higher grating-refraction efficiency. The momentum of OPC studies has recently become even stronger because there are more prospective potentials and achievements for applications. OPC-associated techniques can be successfully utilized in many different application areas: such as high-brightness laser oscillator/amplifier systems, cavity-less lasing devices, laser target-aiming systems, aberration correction for coherent-light transmission and reflection through disturbing media, long distance optical fiber communications with ultra-high bit-rate, optical phase locking and coupling systems, and novel optical data storage and processing systems.

Ba2+- and bupivacaine-sensitive background K+ conductances mediate rapid EPSP attenuation in oligodendrocyte precursor cells

PubMed Central

Chan, Chu-Fang; Kuo, Tzu-Wei; Weng, Ju-Yun; Lin, Yen-Chu; Chen, Ting-Yu; Cheng, Jen-Kun; Lien, Cheng-Chang

2013-01-01

Glutamatergic transmission onto oligodendrocyte precursor cells (OPCs) may regulate OPC proliferation, migration and differentiation. Dendritic integration of excitatory postsynaptic potentials (EPSPs) is critical for neuronal functions, and mechanisms regulating dendritic propagation and summation of EPSPs are well understood. However, little is known about EPSP attenuation and integration in OPCs. We developed realistic OPC models for synaptic integration, based on passive membrane responses of OPCs obtained by simultaneous dual whole-cell patch-pipette recordings. Compared with neurons, OPCs have a very low value of membrane resistivity, which is largely mediated by Ba2+- and bupivacaine-sensitive background K+ conductances. The very low membrane resistivity not only leads to rapid EPSP attenuation along OPC processes but also sharpens EPSPs and narrows the temporal window for EPSP summation. Thus, background K+ conductances regulate synaptic responses and integration in OPCs, thereby affecting activity-dependent neuronal control of OPC development and function. PMID:23940377

Oligodendrocyte progenitor cell (OPC) transplantation is unlikely to offer a means of preventing X-irradiation induced damage in the CNS.

PubMed

Chari, Divya M; Gilson, Jennifer M; Franklin, Robin J M; Blakemore, William F

2006-03-01

Oligodendrocyte lineage cells [oligodendrocytes and their parent cells, the oligodendrocyte progenitor cells (OPCs)] are depleted by X-irradiation and progenitor cell transplantation has been proposed as a therapeutic strategy to counteract radiation induced myelopathy. Previous studies have demonstrated that oligodendrocyte progenitor cell (OPC) depletion is a prerequisite for establishing transplanted OPCs in normal tissue. One can therefore predict that the extent and timing of OPC depletion and regeneration following X-irradiation will be crucial factors in determining the feasibility of this therapeutic approach. To address this issue, we have examined the time course of OPC depletion and regeneration following a range of X-irradiation doses (5 to 40 Gy), and its relationship to establishing transplanted OPCs in X-irradiated tissue. Doses above 10 Gy resulted in rapid death of OPCs. With doses up to 20 Gy, surviving X-irradiated OPCs were capable of robust regeneration, restoring normal densities within 6 weeks. Transplanted OPCs could only be established in tissue that had been exposed to > or =20 Gy. Since 20 Gy is close to the ED50 for radiation necrosis, our findings demonstrate the limitation of OPC replacement strategies.

Fibronectin on extracellular vesicles from microvascular endothelial cells is involved in the vesicle uptake into oligodendrocyte precursor cells

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

Osawa, Sho; Department of Molecular and Cellular Neurobiology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511; Kurachi, Masashi

We previously reported transplantation of brain microvascular endothelial cells (MVECs) into cerebral white matter infarction model improved the animal's behavioral outcome by increasing the number of oligodendrocyte precursor cells (OPCs). We also revealed extracellular vesicles (EVs) derived from MVECs promoted survival and proliferation of OPCs in vitro. In this study, we investigated the mechanism how EVs derived from MVECs contribute to OPC survival and proliferation. Protein mass spectrometry and enzyme-linked immunosorbent assay revealed fibronectin was abundant on the surface of EVs from MVECs. As fibronectin has been reported to promote OPC survival and proliferation via integrin signaling pathway, we blocked themore » binding between fibronectin and integrins using RGD sequence mimics. Blocking the binding, however, did not attenuate the survival and proliferation promoting effect of EVs on OPCs. Flow cytometric and imaging analyses revealed fibronectin on EVs mediates their internalization into OPCs by its binding to heparan sulfate proteoglycan on OPCs. OPC survival and proliferation promoted by EVs were attenuated by blocking the internalization of EVs into OPCs. These lines of evidence suggest that fibronectin on EVs mediates their internalization into OPCs, and the cargo of EVs promotes survival and proliferation of OPCs, independent of integrin signaling pathway. - Highlights: • Fibronectin exists on the surface of extracellular vesicles from endothelial cells. • Integrin signaling is not involved in effects of extracellular vesicles on OPCs. • Fibronectin on the surface of extracellular vesicles mediates their uptake into OPCs.« less

Chd7 Collaborates with Sox2 to Regulate Activation of Oligodendrocyte Precursor Cells after Spinal Cord Injury.

PubMed

Doi, Toru; Ogata, Toru; Yamauchi, Junji; Sawada, Yasuhiro; Tanaka, Sakae; Nagao, Motoshi

2017-10-25

Oligodendrocyte precursor cells (OPCs) act as a reservoir of new oligodendrocytes (OLs) in homeostatic and pathological conditions. OPCs are activated in response to injury to generate myelinating OLs, but the underlying mechanisms remain poorly understood. Here, we show that chromodomain helicase DNA binding protein 7 (Chd7) regulates OPC activation after spinal cord injury (SCI). Chd7 is expressed in OPCs in the adult spinal cord and its expression is upregulated with a concomitant increase in Sox2 expression after SCI. OPC-specific ablation of Chd7 in injured mice leads to reduced OPC proliferation, the loss of OPC identity, and impaired OPC differentiation. Ablation of Chd7 or Sox2 in cultured OPCs shows similar phenotypes to those observed in Chd7 knock-out mice. Chd7 and Sox2 form a complex in OPCs and bind to the promoters or enhancers of the regulator of cell cycle ( Rgcc ) and protein kinase C θ ( PKC θ) genes, thereby inducing their expression. The expression of Rgcc and PKCθ is reduced in the OPCs of the injured Chd7 knock-out mice. In cultured OPCs, overexpression and knock-down of Rgcc or PKCθ promote and suppress OPC proliferation, respectively. Furthermore, overexpression of both Rgcc and PKCθ rescues the Chd7 deletion phenotypes. Chd7 is thus a key regulator of OPC activation, in which it cooperates with Sox2 and acts via direct induction of Rgcc and PKCθ expression. SIGNIFICANCE STATEMENT Spinal cord injury (SCI) leads to oligodendrocyte (OL) loss and demyelination, along with neuronal death, resulting in impairment of motor or sensory functions. Oligodendrocyte precursor cells (OPCs) activated in response to injury are potential sources of OL replacement and are thought to contribute to remyelination and functional recovery after SCI. However, the molecular mechanisms underlying OPC activation, especially its epigenetic regulation, remain largely unclear. We demonstrate here that the chromatin remodeler chromodomain helicase DNA binding protein 7 (Chd7) regulates the proliferation and identity of OPCs after SCI. We have further identified regulator of cell cycle (Rgcc) and protein kinase Cθ (PKCθ) as novel targets of Chd7 for OPC activation. Copyright © 2017 the authors 0270-6474/17/3710290-20$15.00/0.

An optimized OPC and MDP flow for reducing mask write time and mask cost

NASA Astrophysics Data System (ADS)

Yang, Ellyn; Li, Cheng He; Park, Se Jin; Zhu, Yu; Guo, Eric

2010-09-01

In the process of optical proximity correction, layout edge or fragment is migrating to proper position in order to minimize edge placement error (EPE). During this fragment migration, several factors other than EPE can be also taken into account as a part of cost function for optimal fragment displacement. Several factors are devised in favor of OPC stability, which can accommodate room for high mask error enhancement factor (MEEF), lack of process window, catastrophic pattern failure such as pinch/bridge and improper fragmentation. As technology node becomes finer, there happens conflict between OPC accuracy and stability. Especially for metal layers, OPC has focused on the stability by loss of accurate OPC results. On this purpose, several techniques have been introduced, which are target smoothing, process window aware OPC, model-based retargeting and adaptive OPC. By utilizing those techniques, OPC enables more stabilized patterning, instead of realizing design target exactly on wafer. Inevitably, post-OPC layouts become more complicated because those techniques invoke additional edge, or fragments prior to correction or during OPC iteration. As a result, jogs of post OPC layer can be dramatically increased, which results in huge number of shot count after data fracturing. In other words, there is trade-off relationship between data complexity and various methods for OPC stability. In this paper, those relationships have been investigated with respect to several technology nodes. The mask shot count reduction is achieved by reducing the number of jogs with which EPE difference are within pre-specified value. The effect of jog smoothing on OPC output - in view of OPC performance and mask data preparation - was studied quantitatively for respective technology nodes.

Digestion products of the PH20 hyaluronidase inhibit remyelination.

PubMed

Preston, Marnie; Gong, Xi; Su, Weiping; Matsumoto, Steven G; Banine, Fatima; Winkler, Clayton; Foster, Scott; Xing, Rubing; Struve, Jaime; Dean, Justin; Baggenstoss, Bruce; Weigel, Paul H; Montine, Thomas J; Back, Stephen A; Sherman, Larry S

2013-02-01

Oligodendrocyte progenitor cells (OPCs) recruited to demyelinating lesions often fail to mature into oligodendrocytes (OLs) that remyelinate spared axons. The glycosaminoglycan hyaluronan (HA) accumulates in demyelinating lesions and has been implicated in the failure of OPC maturation and remyelination. We tested the hypothesis that OPCs in demyelinating lesions express a specific hyaluronidase, and that digestion products of this enzyme inhibit OPC maturation. Mouse OPCs grown in vitro were analyzed for hyaluronidase expression and activity. Gain of function studies were used to define the hyaluronidases that blocked OPC maturation. Mouse and human demyelinating lesions were assessed for hyaluronidase expression. Digestion products from different hyaluronidases and a hyaluronidase inhibitor were tested for their effects on OPC maturation and functional remyelination in vivo. OPCs demonstrated hyaluronidase activity in vitro and expressed multiple hyaluronidases, including HYAL1, HYAL2, and PH20. HA digestion by PH20 but not other hyaluronidases inhibited OPC maturation into OLs. In contrast, inhibiting HA synthesis did not influence OPC maturation. PH20 expression was elevated in OPCs and reactive astrocytes in both rodent and human demyelinating lesions. HA digestion products generated by the PH20 hyaluronidase but not another hyaluronidase inhibited remyelination following lysolecithin-induced demyelination. Inhibition of hyaluronidase activity lead to increased OPC maturation and promoted increased conduction velocities through lesions. We determined that PH20 is elevated in demyelinating lesions and that increased PH20 expression is sufficient to inhibit OPC maturation and remyelination. Pharmacological inhibition of PH20 may therefore be an effective way to promote remyelination in multiple sclerosis and related conditions. Copyright © 2012 American Neurological Association.

The Role of NG2 Glial Cells in ALS Pathogenesis

DTIC Science & Technology

2014-12-01

NG2+ glial cells ( OPCs ), NPCs were further differentiated to pre- OPCs and OPCs , outlined in Figure 2, which showed reliable cell morphology and cell...marker expression. Pre- OPCs were determined by their expression of Olig2 and NKX2.2 (Figure 1). The majority of colonies showed Olig2+, NKX2.2...and Olig2+/NKX2.2+ cells, however the percentage of each marker expression varied among colonies. To further differentiate pre- OPCs to OPCs , the

Human papillomavirus-associated oropharynx cancer (HPV-OPC): treatment options.

PubMed

Chau, Nicole G; Rabinowits, Guilherme; Haddad, Robert I

2014-12-01

Human papillomavirus-associated oropharynx cancer (HPV-OPC) is growing in incidence and has distinct clinical, pathologic, molecular, and epidemiologic features. However, the management of HPV-OPC does not presently differ from HPV-negative OPC based on the current evidence and requires complex multidisciplinary approaches. The superior prognosis of HPV-OPC and the toxicities of current multimodality treatment in a young population serve as the impetus to evaluate de-intensification treatment regimens aimed at reducing toxicity while maintaining therapeutic efficacy. Clinical trials are underway to evaluate reduced doses of radiation or less toxic systemic therapy regimens in HPV-OPC. Minimally invasive surgical approaches in the HPV-OPC population with early tumor stage also are being investigated. De-intensification strategies should only be employed in the context of clinical trials, and HPV-OPC patients should be offered clinical trials' participation. Appropriate patient selection is critical to the development of de-intensification regimens, and this requires greater understanding of risk factors within the HPV-OPC population, HPV-OPC biology, and how HPV modulates response to specific therapies. Smoking history and bulky nodal disease have been shown to impact negatively the favorable prognosis of HPV association. Validated biomarkers within the HPV-OPC population are lacking, although alterations in the PI3K pathway and markers of immune response may emerge as important considerations in the future. Novel therapeutic strategies are desperately needed particularly for HPV-OPC patients who fail definitive therapy, and select patients with recurrent or metastatic disease may benefit from aggressive approaches.

Off-target model based OPC

NASA Astrophysics Data System (ADS)

Lu, Mark; Liang, Curtis; King, Dion; Melvin, Lawrence S., III

2005-11-01

Model-based Optical Proximity correction has become an indispensable tool for achieving wafer pattern to design fidelity at current manufacturing process nodes. Most model-based OPC is performed considering the nominal process condition, with limited consideration of through process manufacturing robustness. This study examines the use of off-target process models - models that represent non-nominal process states such as would occur with a dose or focus variation - to understands and manipulate the final pattern correction to a more process robust configuration. The study will first examine and validate the process of generating an off-target model, then examine the quality of the off-target model. Once the off-target model is proven, it will be used to demonstrate methods of generating process robust corrections. The concepts are demonstrated using a 0.13 μm logic gate process. Preliminary indications show success in both off-target model production and process robust corrections. With these off-target models as tools, mask production cycle times can be reduced.

Framework for SEM contour analysis

NASA Astrophysics Data System (ADS)

Schneider, L.; Farys, V.; Serret, E.; Fenouillet-Beranger, C.

2017-03-01

SEM images provide valuable information about patterning capability. Geometrical properties such as Critical Dimension (CD) can be extracted from them and are used to calibrate OPC models, thus making OPC more robust and reliable. However, there is currently a shortage of appropriate metrology tools to inspect complex two-dimensional patterns in the same way as one would work with simple one-dimensional patterns. In this article we present a full framework for the analysis of SEM images. It has been proven to be fast, reliable and robust for every type of structure, and particularly for two-dimensional structures. To achieve this result, several innovative solutions have been developed and will be presented in the following pages. Firstly, we will present a new noise filter which is used to reduce noise on SEM images, followed by an efficient topography identifier, and finally we will describe the use of a topological skeleton as a measurement tool that can extend CD measurements on all kinds of patterns.

Outplacement Services for Displaced Employees: Attitudes of Human Resource Managers Based on Differences in Internal and External Delivery

ERIC Educational Resources Information Center

Kilcrease, Kelly M.

2013-01-01

The results from a survey of 238 human resources executives from organizations that offer outplacement counseling (OPC) internally and 168 that offer it externally suggest that internal OPC delivery is inferior to external OPC delivery. The author found that most internal OPC organizations did not offer the 13 traditional OPC services, even when…

Rat astrocytes are more supportive for mouse OPC self-renewal than mouse astrocytes in culture.

PubMed

Cheng, Xuejun; Xie, Binghua; Qi, Jiajun; Zhao, Xiaofeng; Zhang, Zunyi; Qiu, Mengsheng; Yang, Junlin

2017-09-01

Mouse primary oligodendrocyte precursor cells (OPCs) are increasingly used to study the molecular mechanisms underlying the phenotype changes in oligodendrocyte differentiation and axonal myelination observed in transgenic or mutant mouse models. However, mouse OPCs are much more difficult to be isolated by the simple dissociation culture of brain tissues than their rat counterparts. To date, the mechanisms underlying the species difference in OPC preparation remain obscure. In this study, we showed that astrocytes from rats have a stronger effect than those from mouse in promoting OPC proliferation and survival in vitro. Mouse astrocytes displayed significantly weaker viability in culture and reduced potential in maintaining OPC self-renewal, as confirmed by culturing OPCs with conditioned media from rat or mouse astrocytes. These results explained the reason for why stratified cultures of OPCs and astrocytes are difficult to be achieved in mouse CNS tissues. Based on these findings, we adopted inactivated rat astrocytes as feeder cells to support the self-renewal of mouse cortical OPCs and preparation of high-purity mouse OPCs. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 907-916, 2017. © 2016 Wiley Periodicals, Inc.

Designing high-performance cost-efficient embedded SRAM in deep-submicron era

NASA Astrophysics Data System (ADS)

Kobozeva, Olga; Venkatraman, Ramnath; Castagnetti, Ruggero; Duan, Franklin; Kamath, Arvind; Ramesh, Shiva

2004-05-01

We have previously presented the smallest and fastest 6 Transistor (6T)-Static Random Access Memories (SRAM) bitcells for System-on-Chip (SoC) high-density (HD) memories in 0.18 μm and 0.13 μm technologies. Our 1.87 μm2 6TSRAM bitcell with cell current of 47 μA and industry lowest soft error rate (0.35 FIT/Kbit) is used to assemble memory blocks embedded into SoC designs in 0.13 μm process technology. Excellent performance is achieved at a low overall cost, as our bitcells are based on standard CMOS process and demonstrate high yields in manufacturing. This paper discusses our methodology of embedded SRAM bitcell design. The key aspects of our approach are: 1) judicious selection of tightest achievable yet manufacturable design rules to build the cell; 2) compatibility with standard Optical Proximity Correction (OPC) flow; 3) use of parametric testing and yield analysis to achieve excellent design robustness and manufacturability. A thorough understanding of process limitations, particularly those related to photolithography was critical to the successful design and manufacturing of our aggressive, yet robust SRAM bitcells. The patterning of critical layers, such as diffusion, poly gate, contact and metal 1 has profound implications on functionality, electrical performance and manufacturability of memories. We have conducted the development of SRAM bitcells using two approaches for OPC: a) "manual" OPC, wherein the bitcell layout of each of the critical layers is achieved using iterative improvement of layout & aerial image simulation and b) automated OPC-compatible design, wherein the drawn bitcell layout becomes a subject of a full chip OPC. While manual-OPC remains a popular option, automated OPC-compatible bitcell design is very attractive, as it does not require additional development costs to achieve fab-to-fab portability. In both cases we have obtained good results with respect to patterning of the critical layers, electrical performance of the bitcell and memory yields. A critical part of our memory technology development effort is the design of memory-specific test structures that are used for: a) verifying electrical characteristics of SRAM transistors and b) confirming the robustness of the design rules used within the SRAM cell. In addition to electrical test structures, we have a fully functional SRAM test chip called RAMPCM that is composed of sub-blocks each designated to evaluate the robustness of a specific critical design rule used within the bitcells. The results from the electrical testing and RAMPCM yield analysis are used to identify opportunities for improvements in the layout design. The paper will also suggest some techniques that can result in more design friendly OPC solutions. Our work indicates that future IC designs can benefit from an automated OPC tool that can intelligently handle layout modifications according to design priorities.

Relationships of obesity and diabetes mellitus to other primary cancers in surgically treated gastric cancer patients.

PubMed

Takeuchi, Daisuke; Koide, Naohiko; Komatsu, Daisuke; Okumura, Motohiro; Suzuki, Akira; Miyagawa, Shinichi

2014-01-01

Other primary cancers (OPC) have been reported in gastric cancer (GC) patients. Recent studies have shown relationships of obesity and diabetes mellitus to cancer development in several organs. The purpose of this study was to investigate the relationships of obesity and diabetes mellitus (DM) to the prevalence of OPC in GC patients. We reviewed 435 GC patients who were treated surgically and followed their outcomes after surgery. Patients with body mass index (BMI) ≥ 25 kg/m(2) were defined as obese. Fasting plasma glucose (FPG) and HbA1c levels were examined before surgery. OPC was observed in 109 GC patients (25.1%): 40 (9.2%) with synchronous OPC and 76 (18.2%) with metachronous OPC. The most common OPC was colorectal cancer (22.8%). OPC was frequently observed in patients with DM (p = 0.0022), and DM was an independent risk factor for the occurrence of OPC (odds ratio, 2.215; 95% confidence interval, 1.2007-4.0850; p = 0.011). Synchronous OPC was frequently observed in patients with obesity (p = 0.025), and obesity was an independent risk factor for the occurrence of synchronous OPC (odds ratio, 2.354; 95% confidence interval, 1.1246-4.9279; p = 0.023). Metachronous OPC was frequently observed in patients with DM (p = 0.0071), and DM was an independent risk factor for the occurrence of OPC (odds ratio, 2.680; 95% confidence interval, 1.0291-6.9780; p = 0.044). There is a need to be aware of the possibility of OPC in GC patients with DM/obesity. They should undergo intensive screening for OPC before and after gastrectomy. Copyright © 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

PDGF is Required for Remyelination-Promoting IgM Stimulation of Oligodendrocyte Progenitor Cell Proliferation

PubMed Central

Watzlawik, Jens O.; Warrington, Arthur E.; Rodriguez, Moses

2013-01-01

Background Promotion of remyelination is a major goal in treating demyelinating diseases such as multiple sclerosis (MS). The recombinant human monoclonal IgM, rHIgM22, targets myelin and oligodendrocytes (OLs) and promotes remyelination in animal models of MS. It is unclear whether rHIgM22-mediated stimulation of lesion repair is due to promotion of oligodendrocyte progenitor cell (OPC) proliferation and survival, OPC differentiation into myelinating OLs or protection of mature OLs. It is also unknown whether astrocytes or microglia play a functional role in IgM-mediated lesion repair. Methods We assessed the effect of rHIgM22 on cell proliferation in mixed CNS glial and OPC cultures by tritiated-thymidine uptake and by double-label immunocytochemistry using the proliferation marker, Ki-67. Antibody-mediated signaling events, OPC differentiation and OPC survival were investigated and quantified by Western blots. Results rHIgM22 stimulates OPC proliferation in mixed glial cultures but not in purified OPCs. There is no proliferative response in astrocytes or microglia. rHIgM22 activates PDGFαR in OPCs in mixed glial cultures. Blocking PDGFR-kinase inhibits rHIgM22-mediated OPC proliferation in mixed glia. We confirm in isolated OPCs that rHIgM22-mediated anti-apoptotic signaling and inhibition of OPC differentiation requires PDGF and FGF-2. We observed no IgM-mediated effect in mature OLs in the absence of PDGF and FGF-2. Conclusion Stimulation of OPC proliferation by rHIgM22 depends on co-stimulatory astrocytic and/or microglial factors. We demonstrate that rHIgM22-mediated activation of PDGFαR is required for stimulation of OPC proliferation. We propose that rHIgM22 lowers the PDGF threshold required for OPC proliferation and protection, which can result in remyelination of CNS lesions. PMID:23383310

Oligodendrocyte progenitor cells proliferate and survive in an immature state following treatment with an axolemma-enriched fraction

PubMed Central

Becker-Catania, Sara G; Nelson, Julie K; Olivares, Shantel; Chen, Shu-Jen; DeVries, George H

2011-01-01

The ability of an AEF (axolemma-enriched fraction) to influence the proliferation, survival and differentiation of OPC (oligodendrocyte progenitor cells) was evaluated. Following addition of AEF to cultured OPC, the AEF associated with the outer surface of OPC so that subsequent metabolic events were likely mediated by direct AEF-OPC contact. Addition of AEF to the cultured OPC resulted in a dose- and time-dependent increase in proliferation that was partially dependent on Akt (protein kinase B) and MAPK (mitogen-activated protein kinase) activation. The major mitogen in an AEF-SE (soluble 2.0 M NaCl extract of the AEF) was identified as aFGF (acidic fibroblast growth factor) and accounted for 50% of the mitogenicity. The remaining 50% of the mitogenicity had properties consistent with bFGF (basic fibroblast growth factor) but was not unequivocally identified. Under conditions that limit the survival of OPC in culture, AEF treatment prolonged the survival of the OPC. Antigenic and morphological examination of the AEF-treated OPC indicated that the AEF treatment helped the OPC survive in a more immature state. The potential downstream metabolic pathways potentially activated in OPC by AEF and the consequences of these activated pathways are discussed. The results of these studies are consistent with the view that direct contact of axons with OPC stimulates their proliferation and survival while preventing their differentiation. PMID:21345173

Multiple Modes of Communication between Neurons and Oligodendrocyte Precursor Cells.

PubMed

Maldonado, Paloma P; Angulo, María Cecilia

2015-06-01

The surprising discovery of bona fide synapses between neurons and oligodendrocytes precursor cells (OPCs) 15 years ago placed these progenitors as real partners of neurons in the CNS. The role of these synapses has not been established yet, but a main hypothesis is that neuron-OPC synaptic activity is a signaling pathway controlling OPC proliferation/differentiation, influencing the myelination process. However, new evidences describing non-synaptic mechanisms of communication between neurons and OPCs have revealed that neuron-OPC interactions are more complex than expected. The activation of extrasynaptic receptors by ambient neurotransmitter or local spillover and the ability of OPCs to sense neuronal activity through a potassium channel suggest that distinct modes of communication mediate different functions of OPCs in the CNS. This review discusses different mechanisms used by OPCs to interact with neurons and their potential roles during postnatal development and in brain disorders. © The Author(s) 2014.

Adult oligodendrocyte progenitor cells - multifaceted regulators of the CNS in health and disease

PubMed Central

Fernandez-Castaneda, Anthony; Gaultier, Alban

2016-01-01

Oligodendrocyte progenitor cells (OPCs) are the often-overlooked fourth glial cell type in the central nervous system (CNS), comprising about 5% of the CNS. For a long time, our vision of OPC function was limited to the generation of mature oligodendrocytes. However, new studies have highlighted the multifaceted nature of the OPCs. During homeostatic and pathological conditions, OPCs are the most proliferative cell type in the CNS, a property not consistent with the need to generate new oligodendrocytes. Indeed, OPCs modulate neuronal activity and OPC depletion in the brain can trigger depressive-like behavior. More importantly, OPCs are actively recruited to injury sites, where they orchestrate glial scar formation and contribute to the immune response. The following is a comprehensive analysis of the literature on OPC function beyond myelination, in the context of the healthy and diseased adult CNS. PMID:26796621

Evaluation of the Alphasense Optical Particle Counter (OPC-N2) and the Grimm Portable Aerosol Spectrometer (PAS-1.108)

PubMed Central

Sousan, Sinan; Koehler, Kirsten; Hallett, Laura; Peters, Thomas M.

2017-01-01

We compared the performance of a low-cost (∼$500), compact optical particle counter (OPC, OPC-N2, Alphasense) to another OPC (PAS-1.108, Grimm Technologies) and reference instruments. We measured the detection efficiency of the OPCs by size from 0.5 to 5 μm for monodispersed, polystyrene latex (PSL) spheres. We then compared number and mass concentrations measured with the OPCs to those measured with reference instruments for three aerosols: salt, welding fume and Arizona road dust. The OPC-N2 detection efficiency for monodispersed was similar to the PAS-1.108 for particles larger than 0.8 μm (minimum of 79% at 1 μm and maximum of 101% at 3 μm). For 0.5-μm particles, the detection efficiency of OPCN2 was underestimated at 78%, whereas PAS-1.108 overestimated concentrations by 183%. The mass concentrations from the OPCs were linear (r ≥ 0.97) with those from the reference instruments for all aerosols, although the slope and intercept were different. The mass concentrations were overestimated for dust (OPC-N2, slope = 1.6; PAS-1.108, slope = 2.7) and underestimated for welding fume (OPC-N2, slope = 0.05; PAS-1.108, slope = 0.4). The coefficient of variation (CV, precision) for OPC-N2 for all experiments was between 4.2% and 16%. These findings suggest that, given site-specific calibrations, the OPC-N2 can provide number and mass concentrations similar to the PAS-1.108 for particles larger than 1 μm. PMID:28871213

Evaluation of the Alphasense Optical Particle Counter (OPC-N2) and the Grimm Portable Aerosol Spectrometer (PAS-1.108).

PubMed

Sousan, Sinan; Koehler, Kirsten; Hallett, Laura; Peters, Thomas M

2016-01-01

We compared the performance of a low-cost (∼$500), compact optical particle counter (OPC, OPC-N2, Alphasense) to another OPC (PAS-1.108, Grimm Technologies) and reference instruments. We measured the detection efficiency of the OPCs by size from 0.5 to 5 μm for monodispersed, polystyrene latex (PSL) spheres. We then compared number and mass concentrations measured with the OPCs to those measured with reference instruments for three aerosols: salt, welding fume and Arizona road dust. The OPC-N2 detection efficiency for monodispersed was similar to the PAS-1.108 for particles larger than 0.8 μm (minimum of 79% at 1 μm and maximum of 101% at 3 μm). For 0.5-μm particles, the detection efficiency of OPCN2 was underestimated at 78%, whereas PAS-1.108 overestimated concentrations by 183%. The mass concentrations from the OPCs were linear (r ≥ 0.97) with those from the reference instruments for all aerosols, although the slope and intercept were different. The mass concentrations were overestimated for dust (OPC-N2, slope = 1.6; PAS-1.108, slope = 2.7) and underestimated for welding fume (OPC-N2, slope = 0.05; PAS-1.108, slope = 0.4). The coefficient of variation (CV, precision) for OPC-N2 for all experiments was between 4.2% and 16%. These findings suggest that, given site-specific calibrations, the OPC-N2 can provide number and mass concentrations similar to the PAS-1.108 for particles larger than 1 μm.

Characterization of human papillomavirus antibodies in individuals with head and neck cancer

PubMed Central

Lang Kuhs, Krystle A.; Pawlita, Michael; Gibson, Sandra P.; Schmitt, Nicole C.; Trivedi, Sumita; Argiris, Athanassios; Kreimer, Aimée R.; Ferris, Robert L.; Waterboer, Tim

2016-01-01

BACKGROUND Human papillomavirus type 16 (HPV16) E6 antibodies are a promising biomarker of oropharyngeal cancer (OPC); however, seropositivity among non-OPC cases is not well characterized. METHODS Pre-treatment sera from 260 (38 OPC, 222 non-OPC) incident head and neck cancers diagnosed at the University of Pittsburgh between 2003 and 2006 were tested for HPV16 (L1,E1,E2,E4,E6,E7) and non-HPV16 E6 (HPV6,11,18,33) antibodies. Sensitivity and specificity of HPV16 E6 antibodies for HPV-driven tumors was evaluated among tumors with known HPV status (n=25). RESULTS 63.2% of OPC versus 27.5% of non-OPC cases were HPV16 seropositive; HPV16 E6 seroprevalence was 60.5% and 6.3% respectively, odds ratio 22.8 (95% confidence interval [CI] 9.8–53.1). Sensitivity and specificity of HPV16 E6 antibodies for HPV-driven OPC was 100% [95%CI:50%–100%; n=6] and 100% [95%CI:60%–100%, n=4] compared to 0% (n=2) and 0% (n=13) for non-OPC cases. CONCLUSIONS HPV16 antibodies were significantly more common in OPC versus non-OPC cases, particularly HPV16 E6 antibodies. PMID:27010729

Characterization of human papillomavirus antibodies in individuals with head and neck cancer.

PubMed

Lang Kuhs, Krystle A; Pawlita, Michael; Gibson, Sandra P; Schmitt, Nicole C; Trivedi, Sumita; Argiris, Athanassios; Kreimer, Aimée R; Ferris, Robert L; Waterboer, Tim

2016-06-01

Human papillomavirus type 16 (HPV16) E6 antibodies are a promising biomarker of oropharyngeal cancer (OPC); however, seropositivity among non-OPC cases is not well characterized. Pre-treatment sera from 260 (38 OPC, 222 non-OPC) incident head and neck cancers diagnosed at the University of Pittsburgh between 2003 and 2006 were tested for HPV16 (L1,E1,E2,E4,E6,E7) and non-HPV16 E6 (HPV6,11,18,33) antibodies. Sensitivity and specificity of HPV16 E6 antibodies for HPV-driven tumors was evaluated among tumors with known HPV status (n=25). 63.2% of OPC versus 27.5% of non-OPC cases were HPV16 seropositive; HPV16 E6 seroprevalence was 60.5% and 6.3% respectively, odds ratio 22.8 (95% confidence interval [CI] 9.8-53.1). Sensitivity and specificity of HPV16 E6 antibodies for HPV-driven OPC was 100% [95% CI: 50-100%; n=6] and 100% [95% CI: 60-100%, n=4] compared to 0% (n=2) and 0% (n=13) for non-OPC cases. HPV16 antibodies were significantly more common in OPC versus non-OPC cases, particularly HPV16 E6 antibodies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Outpatient Palliative Care and Aggressiveness of End-of-Life Care in Patients with Metastatic Colorectal Cancer.

PubMed

Lee, Si Won; Jho, Hyun Jung; Baek, Ji Yeon; Shim, Eun Kyung; Kim, Hyun Mi; Ku, Ji Yeon; Nam, Eun Jung; Chang, Yoon-Jung; Choi, Hye Jin; Kim, Sun Young

2018-01-01

Palliative care in outpatient setting has been shown to promote better symptom management and transition to hospice care among patients with advanced cancer. Nevertheless, specialized palliative care is rarely provided at cancer centers in Korea. Herein, we aimed to assess aggressiveness of end-of-life care for patients with metastatic colorectal cancer according to the use of outpatient palliative care (OPC) at a single cancer center in Korea. We performed a retrospective medical record review for 132 patients with metastatic colorectal cancer who died between 2011 and 2014. Fifty patients used OPC (OPC group), while 82 patients did not (non-OPC group). Indicators of aggressiveness of end-of-life care including chemotherapy use, emergency department visits, hospitalization, and utilization of hospice care were analyzed according to the use of OPC. More patients in the OPC group were admitted to hospice than those in the non-OPC group (32% vs 17%, P = .047). The mean of inpatient days within 30 days of death was shorter for the OPC group than the non-OPC group (4.02 days vs 7.77 days, respectively, P = .032). There were no differences in the proportions of patients who received chemotherapy and visited the emergency department within 30 days from death. Among patients with metastatic colorectal cancer, OPC was associated with shorter inpatient days near death and greater hospice utilization. Further prospective studies are needed to evaluate the impact of OPC on end-of-life care in Korea.

Prevalence of human papillomavirus in cancer of the oropharynx by gender.

PubMed

Combes, Jean-Damien; Chen, Alyce A; Franceschi, Silvia

2014-12-01

Oropharyngeal cancer (OPC) is more frequent in men than women mainly due to the heavier and longer duration of smoking in men. Human papillomavirus (HPV) has a role in the rising incidence of OPC in the United States and other high-income countries. To determine whether there is a difference in the proportion of HPV-attributable OPC between men and women, we systematically retrieved HPV prevalence data from 63 studies reporting separately on OPC by gender. The male/female (M/F) ratios of HPV prevalence in OPC across different countries and the corresponding M/F ratios of cumulative lung cancer risk (a proxy for smoking) were compared. The United States had the highest M/F ratios of HPV prevalence in OPC (1.5). The lowest M/F ratios (≤0.7) were found in Asia and some European countries (e.g., France). The countries in which the M/F ratio of HPV prevalence in OPC was ≥1.0 had the most similar lung cancer risks for men and women. When HPV prevalence data were applied to age-standardized OPC incidence rates in the United States, Australia, the United Kingdom, and France, the M/F ratio for the HPV-positive OPC incidence rates was rather stable (around 4) in all countries. In contrast, the M/F ratio for the HPV-negative OPC incidence rates reached 10.2 in France versus <3 elsewhere. We showed that HPV prevalence in OPC differs by gender and country mainly as a consequence of the vast international variation in male smoking habits. Nevertheless, HPV-positive OPC may affect men more heavily than women in different populations for reasons that are unclear. ©2014 American Association for Cancer Research.

Alteration of synaptic connectivity of oligodendrocyte precursor cells following demyelination

PubMed Central

Sahel, Aurélia; Ortiz, Fernando C.; Kerninon, Christophe; Maldonado, Paloma P.; Angulo, María Cecilia; Nait-Oumesmar, Brahim

2015-01-01

Oligodendrocyte precursor cells (OPCs) are a major source of remyelinating oligodendrocytes in demyelinating diseases such as Multiple Sclerosis (MS). While OPCs are innervated by unmyelinated axons in the normal brain, the fate of such synaptic contacts after demyelination is still unclear. By combining electrophysiology and immunostainings in different transgenic mice expressing fluorescent reporters, we studied the synaptic innervation of OPCs in the model of lysolecithin (LPC)-induced demyelination of corpus callosum. Synaptic innervation of reactivated OPCs in the lesion was revealed by the presence of AMPA receptor-mediated synaptic currents, VGluT1+ axon-OPC contacts in 3D confocal reconstructions and synaptic junctions observed by electron microscopy. Moreover, 3D confocal reconstructions of VGluT1 and NG2 immunolabeling showed the existence of glutamatergic axon-OPC contacts in post-mortem MS lesions. Interestingly, patch-clamp recordings in LPC-induced lesions demonstrated a drastic decrease in spontaneous synaptic activity of OPCs early after demyelination that was not caused by an impaired conduction of compound action potentials. A reduction in synaptic connectivity was confirmed by the lack of VGluT1+ axon-OPC contacts in virtually all rapidly proliferating OPCs stained with EdU (50-ethynyl-20-deoxyuridine). At the end of the massive proliferation phase in lesions, the proportion of innervated OPCs rapidly recovers, although the frequency of spontaneous synaptic currents did not reach control levels. In conclusion, our results demonstrate that newly-generated OPCs do not receive synaptic inputs during their active proliferation after demyelination, but gain synapses during the remyelination process. Hence, glutamatergic synaptic inputs may contribute to inhibit OPC proliferation and might have a physiopathological relevance in demyelinating disorders. PMID:25852473

Diagnostic accuracy of serum antibodies to human papillomavirus type 16 early antigens in the detection of human papillomavirus-related oropharyngeal cancer.

PubMed

Dahlstrom, Kristina R; Anderson, Karen S; Field, Matthew S; Chowell, Diego; Ning, Jing; Li, Nan; Wei, Qingyi; Li, Guojun; Sturgis, Erich M

2017-12-15

Because of the current epidemic of human papillomavirus (HPV)-related oropharyngeal cancer (OPC), a screening strategy is urgently needed. The presence of serum antibodies to HPV-16 early (E) antigens is associated with an increased risk for OPC. The purpose of this study was to evaluate the diagnostic accuracy of antibodies to a panel of HPV-16 E antigens in screening for OPC. This case-control study included 378 patients with OPC, 153 patients with nonoropharyngeal head and neck cancer (non-OPC), and 782 healthy control subjects. The tumor HPV status was determined with p16 immunohistochemistry and HPV in situ hybridization. HPV-16 E antibody levels in serum were identified with an enzyme-linked immunosorbent assay. A trained binary logistic regression model based on the combination of all E antigens was predefined and applied to the data set. The sensitivity and specificity of the assay for distinguishing HPV-related OPC from controls were calculated. Logistic regression analysis was used to calculate odds ratios with 95% confidence intervals for the association of head and neck cancer with the antibody status. Of the 378 patients with OPC, 348 had p16-positive OPC. HPV-16 E antibody levels were significantly higher among patients with p16-positive OPC but not among patients with non-OPC or among controls. Serology showed high sensitivity and specificity for HPV-related OPC (binary classifier: 83% sensitivity and 99% specificity for p16-positive OPC). A trained binary classification algorithm that incorporates information about multiple E antibodies has high sensitivity and specificity and may be advantageous for risk stratification in future screening trials. Cancer 2017;123:4886-94. © 2017 American Cancer Society. © 2017 American Cancer Society.

Effects of OPC-14523, a combined sigma and 5-HT1a ligand, on pre- and post-synaptic 5-HT1a receptors.

PubMed

Bermack, Jordanna E; Debonnel, Guy

2007-01-01

OPC-14523 (OPC) is a novel compound with high affinity for sigma and 5-HT1A receptors that shows 'antidepressant-like' effects in animal models of depression. We have previously demonstrated that OPC produces an increase in 5-HT neurotransmission and a decreased response of 5-HT neurons to the acute administration of paroxetine in the DRN, an effect that appears to be mediated by OPC's 5-HT1A receptor affinity. The current study sets out to investigate more specifically the effects of OPC on 5-HT1A pre- and post-synaptic receptors, to assess whether it acts as an agonist or antagonist. Using an electrophysiological model of in vivo extracellular recordings in anaesthetized rats, the effects of OPC was assessed on pre-synaptic DRN 5-HT1A autoreceptors and post-synaptically on hippocampal 5-HT1A receptors of CA3 pyramidal neurons. OPC applied by microiontophoresis, produced a significant decrease in the firing activity of 5-HT neurons of the DRN and of quisqualate-activated CA3 pyramidal neurons of the dorsal hippocampus. The effects of OPC on 5-HT1A receptors were significantly reduced by the co-application of the 5-HT1A antagonist WAY-100635. In addition, the effects of OPC were not blocked by the injection of the sigma antagonists NE-100 or haloperidol. Therefore, OPC is acting as an agonist on both pre- and post-synaptic 5-HT1A receptors. The current findings combined with previous data on OPC suggest a pharmacological profile that warrants further investigation.

Rab10 Disruption Results in Delayed OPC Maturation.

PubMed

Zhang, Zhao-Huan; Zhao, Wei-Qian; Ma, Fan-Fei; Zhang, Hui; Xu, Xiao-Hui

2017-10-01

Oligodendrocyte precursor cell (OPC) maturation requires membrane addition for myelin sheath formation. Since the Rab system has been shown to contribute to membrane addition in other cell types, in this study, we explored the role of Rab in OPC maturation. SiRNA and shRNA techniques and conditional knockout mice provided in vitro and in vivo evidence that Rab10 is involved in OPC maturation and may affect myelination during OPC development.

Primary Spinal OPC Culture System from Adult Zebrafish to Study Oligodendrocyte Differentiation In Vitro.

PubMed

Kroehne, Volker; Tsata, Vasiliki; Marrone, Lara; Froeb, Claudia; Reinhardt, Susanne; Gompf, Anne; Dahl, Andreas; Sterneckert, Jared; Reimer, Michell M

2017-01-01

Endogenous oligodendrocyte progenitor cells (OPCs) are a promising target to improve functional recovery after spinal cord injury (SCI) by remyelinating denuded, and therefore vulnerable, axons. Demyelination is the result of a primary insult and secondary injury, leading to conduction blocks and long-term degeneration of the axons, which subsequently can lead to the loss of their neurons. In response to SCI, dormant OPCs can be activated and subsequently start to proliferate and differentiate into mature myelinating oligodendrocytes (OLs). Therefore, researchers strive to control OPC responses, and utilize small molecule screening approaches in order to identify mechanisms of OPC activation, proliferation, migration and differentiation. In zebrafish, OPCs remyelinate axons of the optic tract after lysophosphatidylcholine (LPC)-induced demyelination back to full thickness myelin sheaths. In contrast to zebrafish, mammalian OPCs are highly vulnerable to excitotoxic stress, a cause of secondary injury, and remyelination remains insufficient. Generally, injury induced remyelination leads to shorter internodes and thinner myelin sheaths in mammals. In this study, we show that myelin sheaths are lost early after a complete spinal transection injury, but are re-established within 14 days after lesion. We introduce a novel, easy-to-use, inexpensive and highly reproducible OPC culture system based on dormant spinal OPCs from adult zebrafish that enables in vitro analysis. Zebrafish OPCs are robust, can easily be purified with high viability and taken into cell culture. This method enables to examine why zebrafish OPCs remyelinate better than their mammalian counterparts, identify cell intrinsic responses, which could lead to pro-proliferating or pro-differentiating strategies, and to test small molecule approaches. In this methodology paper, we show efficient isolation of OPCs from adult zebrafish spinal cord and describe culture conditions that enable analysis up to 10 days in vitro . Finally, we demonstrate that zebrafish OPCs differentiate into Myelin Basic Protein (MBP)-expressing OLs when co-cultured with human motor neurons differentiated from induced pluripotent stem cells (iPSCs). This shows that the basic mechanisms of oligodendrocyte differentiation are conserved across species and that understanding the regulation of zebrafish OPCs can contribute to the development of new treatments to human diseases.

Detrimental effects of cement mortar and fly ash mortar on asthma progression.

PubMed

Cho, Ara; Jang, Hong-Seok; Roh, Yoon Seok; Park, Hee Jin; Talha, A F S M; So, Seung-Young; Lim, Chae Woong; Kim, Bumseok

2013-11-01

Currently, concrete additive materials are used worldwide to improve properties of concrete production and to reduce the total cost of the materials used in the concrete. However, the effects of exposure to various gases emitted from mortar mixed with additive materials are poorly understood. To evaluate the pattern of gas emission from cement mortar and additives, the emission levels of gas including ammonia (NH3) and volatile organic compounds (VOCs) were measured from two different mortar types, Ordinary Portland Cement (OPC), and OPC with fly ash on various time points after manufacture. On days 1, 3, 10 and 30 after manufacture, moderate concentrations of NH3 (4, 9, 12 and 5 ppm) were measured in OPC mortar (24h, 150 mm × 150 mm × 50 mm), whereas higher concentrations of NH3 (73, 55, 20 and 5 ppm) were measured in OPC mortar with fly ash (24h, 150 mm × 150 mm × 50 mm). Furthermore, the concentration of VOCs was more than 10 ppm on 1, 3, and 10 days of age in OPC and OPC with fly ash mortars. To examine the mortars' allergic effects on the respiratory system, mice were sensitized with ovalbumin (OVA) and divided into four groups: normal, asthma control, OPC mortar and OPC mortar with fly ash. The mice were housed in corresponding group cage for 10 days with OVA challenges to induce asthma. Histopathologically, increased infiltration of lymphocytes was observed in the lung perivascular area of mice housed in OPC mortar and OPC mortar with fly ash cages compared to lungs of asthma control mice. Moreover, severe bronchial lumen obstruction and increased hypertrophy of bronchial epithelial cells (p<0.05) were observed in the OPC mortar with fly ash group compared to OPC mortar or asthma control groups. Lungs of the two mortar groups generally expressed higher levels of genes related with asthma, including IL-4, eotaxin and epidermal growth factor (EGF) compared to lungs of asthma control mice. Additionally, the OPC mortar with fly ash group showed higher expression of IL-5, 13 and monocyte chemoattractant protein-1 (MCP-1) compared to the asthma control group. These results indicate that OPC mortar and OPC mortar with fly ash might exacerbate asthma. Copyright © 2013 Elsevier B.V. All rights reserved.

Leptin sustains spontaneous remyelination in the adult central nervous system

PubMed Central

Matoba, Ken; Muramatsu, Rieko; Yamashita, Toshihide

2017-01-01

Demyelination is a common feature of many central nervous system (CNS) diseases and is associated with neurological impairment. Demyelinated axons are spontaneously remyelinated depending on oligodendrocyte development, which mainly involves molecules expressed in the CNS environment. In this study, we found that leptin, a peripheral hormone secreted from adipocytes, promoted the proliferation of oligodendrocyte precursor cells (OPCs). Leptin increased the OPC proliferation via in vitro phosphorylation of extracellular signal regulated kinase (ERK); whereas leptin neutralization inhibited OPC proliferation and remyelination in a mouse model of toxin-induced demyelination. The OPC-specific leptin receptor long isoform (LepRb) deletion in mice inhibited both OPC proliferation and remyelination in the response to demyelination. Intrathecal leptin administration increased OPC proliferation. These results demonstrated a novel molecular mechanism by which leptin sustained OPC proliferation and remyelination in a pathological CNS. PMID:28091609

Insufficient OPC migration into demyelinated lesions is a cause of poor remyelination in MS and mouse models.

PubMed

Boyd, Amanda; Zhang, Hui; Williams, Anna

2013-06-01

Failure of remyelination of multiple sclerosis (MS) lesions contributes to neurodegeneration that correlates with chronic disability in patients. Currently, there are no available treatments to reduce neurodegeneration, but one therapeutic approach to fill this unmet need is to promote remyelination. As many demyelinated MS lesions contain plentiful oligodendrocyte precursor cells (OPCs), but no mature myelinating oligodendrocytes, research has previously concentrated on promoting OPC maturation. However, some MS lesions contain few OPCs, and therefore, remyelination failure may also be secondary to OPC recruitment failure. Here, in a series of MS samples, we determined how many lesions contained few OPCs, and correlated this to pathological subtype and expression of the chemotactic molecules Semaphorin (Sema) 3A and 3F. 37 % of MS lesions contained low numbers of OPCs, and these were mostly chronic active lesions, in which cells expressed Sema3A (chemorepellent). To test the hypothesis that differential Sema3 expression in demyelinated lesions alters OPC recruitment and the efficiency of subsequent remyelination, we used a focal myelinotoxic mouse model of demyelination. Adding recombinant (r)Sema3A (chemorepellent) to demyelinated lesions reduced OPC recruitment and remyelination, whereas the addition of rSema3F (chemoattractant), or use of transgenic mice with reduced Sema3A expression increased OPC recruitment and remyelination. We conclude that some MS lesions fail to remyelinate secondary to reduced OPC recruitment, and that chemotactic molecules are involved in the mechanism, providing a new group of drug targets to improve remyelination, with a specific target in the Sema3A receptor neuropilin-1.

Oligodendrocyte Precursor Cells Synthesize Neuromodulatory Factors

PubMed Central

Sakry, Dominik; Yigit, Hatice; Dimou, Leda; Trotter, Jacqueline

2015-01-01

NG2 protein-expressing oligodendrocyte progenitor cells (OPC) are a persisting and major glial cell population in the adult mammalian brain. Direct synaptic innervation of OPC by neurons throughout the brain together with their ability to sense neuronal network activity raises the question of additional physiological roles of OPC, supplementary to generating myelinating oligodendrocytes. In this study we investigated whether OPC express neuromodulatory factors, typically synthesized by other CNS cell types. Our results show that OPC express two well-characterized neuromodulatory proteins: Prostaglandin D2 synthase (PTGDS) and neuronal Pentraxin 2 (Nptx2/Narp). Expression levels of the enzyme PTGDS are influenced in cultured OPC by the NG2 intracellular region which can be released by cleavage and localizes to glial nuclei upon transfection. Furthermore PTGDS mRNA levels are reduced in OPC from NG2-KO mouse brain compared to WT cells after isolation by cell sorting and direct analysis. These results show that OPC can contribute to the expression of these proteins within the CNS and suggest PTGDS expression as a downstream target of NG2 signaling. PMID:25966014

Effectiveness of vasopressin V2 receptor antagonists OPC-31260 and OPC-41061 on polycystic kidney disease development in the PCK rat.

PubMed

Wang, Xiaofang; Gattone, Vincent; Harris, Peter C; Torres, Vicente E

2005-04-01

cAMP plays a major role in cystogenesis. Recent in vitro studies suggested that cAMP stimulates B-Raf/ERK activation and proliferation of cyst-derived cells in a Ca(2+) inhibitable, Ras-dependent manner. OPC-31260, a vasopressin V2 receptor (VPV2) antagonist, was shown to lower renal cAMP and inhibit renal disease development and progression in models orthologous to human cystic diseases. Here it is shown that OPC-41061, an antagonist chosen for its potency and selectivity for human VPV2, is effective in PCK rats. PCK kidneys have increased Ras-GTP and phosphorylated ERK levels and 95-kD/68-kD B-Raf ratios, changes that are corrected by the administration of OPC-31260 or OPC-41061. These results support the importance of cAMP in the pathogenesis of polycystic kidney disease, confirm the effectiveness of a VPV2 antagonist to be used in clinical trials for this disease, and suggest that OPC-31260 and OPC-41061 inhibit Ras/mitogen-activated protein kinase signaling in polycystic kidneys.

Boundary-based cellwise OPC for standard-cell layouts

NASA Astrophysics Data System (ADS)

Pawlowski, David M.; Deng, Liang; Wong, Martin D. F.

2007-03-01

Model based optical proximity correction (OPC) has become necessary at 90nm technology node. Cellwise OPC is an attractive technique to reduce the mask data size as well as the prohibitive runtime of full-chip OPC. As feature dimensions have gotten smaller, the radius of influence for edge features has extended further into neighboring cells such that it is no longer sufficient to perform cellwise OPC independent of neighboring cells, especially for the critical layers. The methodology described in this work accounts for features in neighboring cells and allows a cellwise approach to be applied to cells with a printed gate length of 45nm with the projection that it can also be applied to future technology nodes. OPC-ready cells are generated at library creation (independent of placement) using a boundary-based technique. Each cell has a tractable number of OPC-ready versions due to an intelligent characterization of standard cell layout features. Results are very promising: the average edge placement error (EPE) for all metal1 features in 100 layouts is 0.731nm which is less than 1% of metal1 width; the maximum EPE for poly features reduced to 1/3, compared to cellwise OPC without considering boundaries, creating similar levels of lithographic accuracy while obviating any of the drawbacks inherent in layout specific full-chip model-based OPC.

Inhibitory effect of OPC-15161, a component of fungus Thielavia minor, on proliferation and extracellular matrix production of rat cultured hepatic stellate cells.

PubMed

Sugawara, H; Ueno, T; Torimura, T; Inuzuka, S; Tanikawa, K

1998-03-01

A component of fungus Thielavia minor, OPC-15161, has been shown to inhibit the proliferation and extracellular matrix production of extracellular matrix-producing mesangial cells in the kidney in vivo. In this study, we examined the effects of OPC-15161 on the proliferation and extracellular matrix production of rat cultured hepatic stellate cells (HSCs). To determine the effect of OPC-15161 on proliferation of HSCs, the cell number and the uptake of [3H]thymidine were investigated in the presence and absence of interleukin-1beta (IL-1beta). IL-1beta significantly increased the uptake of [3H]thymidine in the HSCs, and the addition of OPC-15161 inhibited the uptake in a dose-dependent manner. The cell number of HSCs was also increased by IL-1beta, which was inhibited by OPC-15161. Production of extracellular matrix by OPC-15161 was studied by the production of [3H]-hydroxyproline in the presence and absence of transforming growth factor-beta1 (TGF-beta1). TGF-beta1 significantly increased the production of [3H]-hydroxyproline in the cells, whereas the addition of OPC-15161 inhibited this effect dose dependently. We also investigated the effects of OPC-15161 on Ca2+ mobilization and measured D-myo-inositol 1,4,5-triphosphate (IP3) in the HSCs. IL-1beta induced the increase of intracellular Ca2+ and IP3 concentrations in the HSCs, which were decreased by OPC-15161. Based on these results, we conclude that OPC-1 5161 inhibited the proliferation and production of hydroxyproline in cultured rat HSCs, and thus, it may have a role in prevention of liver fibrosis in vivo.

Effect of the cardiac inotropic drug, OPC 8212, on pituitary-thyroid function in the rat.

PubMed

Lueprasitsakul, W; Fang, S L; Alex, S; Braverman, L E

1991-06-01

3,4-Dihydro-6-[4-(3,4-dimethoxybenzoyl)-1 piperaznyl]-2(1H)-quinolinone (OPC 8212) is a new synthetic quinolinone with potent cardiac inotropic action in man. Long term oral administration of OPC induces goiter and thyroid tumor formation in rats, associated with decreases in serum T4 and increases in serum TSH concentrations. Studies were carried out to explore the mechanisms responsible for these drug induced abnormalities. OPC 8212, administered for 1 week at doses of 500 and 2000 mg/kg.day mixed with the diet, resulted in an increase in thyroid weight, a decrease in circulating T4 and free T4 concentrations and an increase in serum TSH concentrations. OPC decreased the 5'-deiodinase (5'-D) activity in liver homogenates and increased the 5'-D activity in pituitary homogenates, consistent with hypothyroidism. OPC 8212 did not affect thyroid iodine metabolism and hormone synthesis or the binding of T4 to serum binding proteins. The hepatic uptake of 125 I-T4 4 h after T4 administration was significantly increased in OPC 8212 treated rats. The biliary excretion of administered 125 I-T4 was increased in OPC 8212-treated rats and most of the increase was due to an increase in the excretion of T4-glucuronide. Hepatic T4-glucuronyltransferase activity measured in vitro in OPC 8212 treated rats was increased as compared to that of controls. It is concluded that the effect of OPC 8212 on lowering serum T4 with a compensatory rise in TSH leading to goiter formation is due to a drug-induced increase in hepatic T4 disposal. The induction of T4-glucuronyl-transferase appears to play an important role in the increased biliary excretion of T4 in OPC 8212-treated rats.

Pharmacokinetics of a new positive inotropic agent, 3, 4-dihydro-6-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl]-2(1H)-qu inolinone (OPC-8212), in the rat, rabbit, beagle dog and rhesus monkey.

PubMed

Miyamoto, G; Sasabe, H

1984-01-01

The pharmacokinetics of 3, 4-dihydro-6-[4-(3,4- dimethoxybenzoyl )-1-piperazinyl]-2(1H)- quin olinone ( OPC -8212) were studied after the administration of 14C- OPC -8212 or OPC -8212 to animals of different species. After oral doses of 10 mg/kg of 14C- OPC -8212 to rats and beagle dogs, the Tmax, Cmax and T1/2 values of OPC -8212 were 4 h, 2995 ng eq/ml, and 3-4 h in rats and 1 h, 2244 ng eq/ml and 5-6 h in beagle dogs, respectively. After oral doses of 10 mg/kg of 14C- OPC -8212 to rats, the radioactivity was distributed comparatively widely in the tissues. However, there was no evidence of accumulation of radioactivity in the tissues due to repeated oral doses of 10 mg/kg of 14C- OPC -8212 once a day for 21 days. After oral doses of 10 mg/kg of 14C- OPC -8212, the amounts of radioactivity excreted in the urine and feces in the first 72 h accounted for 29.25% and 60.24% of the dose in rats and 35.53% and 63.18% of the dose in beagle dogs, respectively. There were no apparent changes in the urinary and fecal excretions of radioactivity due to repeated oral doses of 10 mg/kg of 14C- OPC -8212 once a day for 21 days in rats. Biliary excretion of radioactivity was 22.41% of the dose after oral doses of 10 mg/kg 14C- OPC -8212 in rats. Enterohepatic circulation was 22.04% of the dose after an intraduodenal dose in rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Dianionic Titanyl and Vanadyl (Cation+ )2 [MIV O(Pc4- )]2- Phthalocyanine Salts Containing Pc4- Macrocycles.

PubMed

Konarev, Dmitri V; Kuzmin, Alexey V; Khasanov, Salavat S; Litvinov, Alexey L; Otsuka, Akihiro; Yamochi, Hideki; Kitagawa, Hiroshi; Lyubovskaya, Rimma N

2018-06-18

In this study, the titanyl and vanadyl phthalocyanine (Pc) salts (Bu 4 N + ) 2 [M IV O(Pc 4- )] 2- (M=Ti, V) and (Bu 3 MeP + ) 2 [M IV O(Pc 4- )] 2- (M=Ti, V) with [M IV O(Pc 4- )] 2- dianions were synthesized and characterized. Reduction of M IV O(Pc 2- ) carried out with an excess of sodium fluorenone ketyl in the presence of Bu 4 N + or Bu 3 MeP + is exclusive to the phthalocyanine centers, forming Pc 4- species. During reduction, the metal +4 charge did not change, implying that Pc is an non-innocent ligand. The Pc negative charge increase caused the C-N(pyr) bonds to elongate and the C-N(imine) bonds to alternate, thus increasing the distortion of Pc. Jahn-Teller effects are significant in the [eg(π*)] 2 dianion ground state and can additionally distort the Pc macrocycles. Blueshifts of the Soret and Q-bands were observed in the UV/Vis/NIR when M IV O(Pc 2- ) was reduced to [M IV O(Pc . 3- )] . - and [M IV O(Pc 4- )] 2- . From magnetic measurements, [Ti IV O(Pc 4- )] 2- was found to be diamagnetic and (Bu 4 N + ) 2 [V IV O(Pc 4- )] 2- and (Bu 3 MeP + ) 2 [V IV O(Pc 4- )] 2- were found to have magnetic moments of 1.72-1.78 μ B corresponding to an S=1/2 spin state owing to V IV electron spin. As a result, two latter salts show EPR signals with V IV hyperfine coupling. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Occupational therapists' and physiotherapists' perceptions of implementing Occupational Performance Coaching.

PubMed

Graham, Fiona; Boland, Pauline; Ziviani, Jenny; Rodger, Sylvia

2018-06-01

Occupational Performance Coaching (OPC) has been proposed as an intervention for working with caregivers towards achievement of goals for themselves and their children. Preliminary studies indicate the effectiveness of OPC; however, translation into practice requires an understanding of therapists' perceptions of applying OPC in their service delivery settings. This study explored physio- and occupational-therapists' experiences of using OPC and their perceptions of the contextual factors which influence its implementation. Interviews and a focus group were used to gather physio- (n = 4) and occupational- (n = 12) therapists' perspectives of applying OPC in their work with caregivers of children with disabilities. Data were analysed thematically. One overarching theme and three major themes emerged. The overarching theme, "Listening better" pervaded all other themes. Three major themes, each with subthemes, were: (1) Sharing power, (2) Reprioritising processes, and (3) Liberating but challenging. Implementing OPC drew on skills that were familiar to therapists and aligned with existing values when working with families but challenged some aspects of their practice. From physio- and occupational-therapists' perspectives, OPC is applicable in a range of paediatric service environments. However, therapist and service-level flexibility appeared to be key contextual factors in adhering to intervention principles. Implications for Rehabilitation Occupational Performance Coaching (OPC) is a strengths-focused intervention in which caregiver engagement and active involvement is prioritised. Therapists reported distinct changes to the process of therapy and outcomes achieved following OPC training and implementation. Most therapists indicated that OPC enabled them to operationalisation person-centred principles to a greater extent which they perceived enhanced the way therapy was delivered and the benefit to services users. Some flexibility in service structures may be needed to implement OPC in the way it was intended.

Antidepressant-like responses to the combined sigma and 5-HT1A receptor agonist OPC-14523.

PubMed

Tottori, K; Miwa, T; Uwahodo, Y; Yamada, S; Nakai, M; Oshiro, Y; Kikuchi, T; Altar, C A

2001-12-01

The antidepressant-like activity of a novel compound, OPC-14523, was investigated in comparison with the conventional antidepressants, fluoxetine and imipramine. OPC-14523 bound with nanomolar affinities to sigma receptors (IC(50)=47-56 nM), the 5-HT(1A) receptor (IC(50)=2.3 nM), and the 5-HT transporter (IC(50)=80 nM). OPC-14523 inhibited the in vitro reuptake of 3H-5-HT (IC(50)=27 nM), but it showed very weak inhibitory activity on 3H-NE and 3H-DA reuptake. OPC-14523 did not inhibit MAO A or B activities or muscarinic receptors. A single oral administration of OPC-14523 produced a marked antidepressant-like effect in the forced swimming test (FST) with rats (ED(50)=27 mg/kg) and mice (ED(50)=20mg/kg) without affecting the general locomotor activity. In contrast, fluoxetine and imipramine each required at least four days of repeated dosing to show this activity. The acute activity of OPC-14523 was blocked by pretreatment with the sigma receptor antagonist NE-100 or the selective 5-HT(1A) receptor antagonist WAY-100635. The induction of flat body posture by OPC-14523 was blocked by the selective 5-HT(1A) receptor antagonist NAN-190, and forebrain 5-HT biosynthesis was attenuated by OPC-14523 at behaviorally effective doses. In contrast, OPC-14523, unlike fluoxetine, failed to inhibit 5-HT reuptake at oral doses below 100mg/kg. Thus, the acute antidepressant-like action of OPC-14523 is achieved by the combined stimulation of sigma and 5-HT(1A) receptors without inhibition of 5-HT reuptake in vivo.

Myelin Proteolipid Protein Complexes with αv Integrin and AMPA Receptors In Vivo and Regulates AMPA-Dependent Oligodendrocyte Progenitor Cell Migration through the Modulation of Cell-Surface GluR2 Expression

PubMed Central

Harlow, Danielle E.; Saul, Katherine E.; Komuro, Hitoshi

2015-01-01

In previous studies, stimulation of ionotropic AMPA/kainate glutamate receptors on cultured oligodendrocyte cells induced the formation of a signaling complex that includes the AMPA receptor, integrins, calcium-binding proteins, and, surprisingly, the myelin proteolipid protein (PLP). AMPA stimulation of cultured oligodendrocyte progenitor cells (OPCs) also caused an increase in OPC migration. The current studies focused primarily on the formation of the PLP–αv integrin–AMPA receptor complex in vivo and whether complex formation impacts OPC migration in the brain. We found that in wild-type cerebellum, PLP associates with αv integrin and the calcium-impermeable GluR2 subunit of the AMPA receptor, but in mice lacking PLP, αv integrin did not associate with GluR2. Live imaging studies of OPC migration in ex vivo cerebellar slices demonstrated altered OPC migratory responses to neurotransmitter stimulation in the absence of PLP and GluR2 or when αv integrin levels were reduced. Chemotaxis assays of purified OPCs revealed that AMPA stimulation was neither attractive nor repulsive but clearly increased the migration rate of wild-type but not PLP null OPCs. AMPA receptor stimulation of wild-type OPCs caused decreased cell-surface expression of the GluR2 AMPA receptor subunit and increased intracellular Ca2+ signaling, whereas PLP null OPCs did not reduce GluR2 at the cell surface or increase Ca2+ signaling in response to AMPA treatment. Together, these studies demonstrate that PLP is critical for OPC responses to glutamate signaling and has important implications for OPC responses when levels of glutamate are high in the extracellular space, such as following demyelination. SIGNIFICANCE STATEMENT After demyelination, such as occurs in multiple sclerosis, remyelination of axons is often incomplete, leading to loss of neuronal function and clinical disability. Remyelination may fail because oligodendrocyte precursor cells (OPCs) do not completely migrate into demyelinated areas or OPCs in lesions may not mature into myelinating oligodendrocytes. We have found that the myelin proteolipid protein is critical to regulating OPC migratory responses to the neurotransmitter glutamate through modulation of cell-surface expression of the calcium-impermeable GluR2 subunit of the AMPA glutamate receptor and increased intercellular Ca2+ signaling. Altered glutamate homeostasis has been reported in demyelinated lesions. Therefore, understanding how OPCs respond to glutamate has important implications for treatment after white matter injury and disease. PMID:26311781

Effect of OPC-12759 on EGF receptor activation, p44/p42 MAPK activity, and secretion in conjunctival goblet cells.

PubMed

Ríos, J David; Shatos, Marie A; Urashima, Hiroki; Dartt, Darlene A

2008-04-01

The purpose of the study was to determine if OPC-12759 stimulates secretion from conjunctival goblet cells in culture and if it activates the EGF receptor (EGFR) and p44/p42 mitogen-activated protein kinase (MAPK) to cause mucin secretion. Conjunctival goblet cells were cultured from pieces of male rat conjunctiva. OPC-12759 was added at increasing concentrations and for varying times to the cultured cells. The cholinergic agonist carbachol was used as a positive control. In selected experiments an inhibitor of the EGFR, AG1478, or an inhibitor of the kinase that activates MAPK, U0126, were added before OPC-12759. Goblet cell secretion of high molecular weight glycoconjugates was measured by an enzyme-linked lectin assay using the lectin UEA-1. Activation of the EGFR and MAPK were determined with Western blotting analysis using antibodies specific to the phosphorylated and the total amounts of these proteins. We found that OPC-12759 induced goblet cell secretion in a time- and concentration-dependent manner. Inhibition of the EGFR with AG1478 blocked secretion stimulated by OPC-12759. Inhibition of MAPK with U0126 also blocked secretion stimulated by OPC-12759. OPC-12759 increased the phosphorylation of the EGFR and MAPK in a time-dependent manner. We concluded that OPC-12759 stimulates secretion from cultured conjunctival goblet cells by activating the EGFR, which then induces MAPK activity.

WNK1 is involved in Nogo66 inhibition of OPC differentiation.

PubMed

Zhang, Zhao-Huan; Li, Jiao-Jiao; Wang, Qing-Jin; Zhao, Wei-Qian; Hong, Jiang; Lou, Shu-jie; Xu, Xiao-Hui

2015-03-01

LINGO-1 is a transmembrane receptor expressed primarily in the central nervous system (CNS) and plays an important role in myelination. Recent studies have indicated that it is also involved in oligodendrocyte precursor cell (OPC) survival and differentiation; however, the downstream signaling pathway underlying OPC development is unknown. In our previous study, we found that LINGO-1 is associated with WNK1 in mediating Nogo-induced neurite extension inhibition by RhoA activation. In an effort to identify the role of LINGO-1-WNK1 in OPCs, we first confirmed that WNK1 is also expressed in OPCs and co-localized with LINGO-1, which suppresses WNK1 expression by RNA interference-attenuated Nogo66-induced inhibition of OPC differentiation. Furthermore, we mapped the WNK1 kinase domain using several fragmented peptides to identify the key region of interaction with LINGO-1. We found that a sequence corresponding to the D6 peptide is necessary for the interaction. Finally, we found that using the TAT-D6 peptide to introduce D6 peptide into primary cultured OPC inhibits the association between LINGO-1 and WNK1 and significantly attenuates Nogo66-induced inhibition of OPC differentiation. Taken together, our results show that WNK1, via a specific region on WNK1 kinase domain, interacts with LINGO-1, thus mediating Nogo66-inhibited OPC differentiation. Copyright © 2015 Elsevier Inc. All rights reserved.

Improvement in circulation and in cardiovascular risk factors with a proprietary isotonic bioflavonoid formula OPC-3.

PubMed

Cesarone, Maria R; Di Renzo, Andrea; Errichi, Silvia; Schönlau, Frank; Wilmer, James L; Blumenfeld, Julian

2008-01-01

This study investigated the efficacy of isotonic bioflavonoid supplementation, OPC-3 on 61 individuals presenting with risk factors meeting the criteria for metabolic syndrome. Subjects were supplemented with a proprietary isotonic bioflavonoid OPC-3 or placebo over 2 months. Plasma oxidative stress status was significantly lowered by 10.1% with OPC-3. All major cardiovascular risk factors were improved with blood pressure, total cholesterol, and fasting blood glucose lowered. OPC-3 significantly improved endothelial function as evaluated by increased vasorelaxation in reactive hyperemia and enhanced diastolic carotid artery flow. Cardiac ultrasound scanning revealed a significant increase of left ventricular ejection fraction. Skin microcirculation was enhanced, and better tissue perfusion led to significantly increased transcutaneous oxygen partial pressure and decreased pCO(2). With OPC-3 a dramatic and significant plasma C-reactive protein decrease by 52.1% occurred. Individuals may improve key cardiovascular risk factors by daily supplementation with the bioflavonoid OPC-3 as an important part of a healthier lifestyle.

Cardiomyocyte-released factors stimulate oligodendrocyte precursor cells proliferation

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

Kuroda, Mariko; Muramatsu, Rieko; Precursory Research for Embryonic Science and Technology

The heart produces multiple diffusible factors that are involved in a number of physiological processes, but the action of these factors on the central nervous system is not well understood. In this study, we found that one or more factors released by cardiomyocytes promote oligodendrocyte precursor cell (OPC) proliferation in vitro. Mouse OPCs co-cultured with mouse cardiomyocytes showed higher proliferative ability than OPCs cultured alone. In addition, cardiomyocyte-conditioned media was sufficient to promote OPC proliferation. The phosphorylation of phosphatidylinositol (PI) 3-kinase and extracellular signal-regulated kinase (ERK) in OPCs is necessary for the enhancement of OPC proliferation by cardiomyocyte-conditioned media. These datamore » indicate that heart-derived factors have the ability to directly regulate the function of central nervous system (CNS) cells.« less

Remyelinating Oligodendrocyte Precursor Cell miRNAs from the Sfmbt2 Cluster Promote Cell Cycle Arrest and Differentiation

PubMed Central

Kuypers, Nicholas J.; Bankston, Andrew N.; Howard, Russell M.; Beare, Jason E.

2016-01-01

Oligodendrocyte (OL) loss contributes to the functional deficits underlying diseases with a demyelinating component. Remyelination by oligodendrocyte progenitor cells (OPCs) can restore these deficits. To understand the role that microRNAs (miRNAs) play in remyelination, 2′,3′-cyclic-nucleotide 3′-phosphodiesterase-EGFP+ mice were treated with cuprizone, and OPCs were sorted from the corpus callosum. Microarray analysis revealed that Sfmbt2 family miRNAs decreased during cuprizone treatment. One particular Sfmbt2 miRNA, miR-297c-5p, increased during mouse OPC differentiation in vitro and during callosal development in vivo. When overexpressed in both mouse embryonic fibroblasts and rat OPCs (rOPCs), cell cycle analysis revealed that miR-297c-5p promoted G1/G0 arrest. Additionally, miR-297c-5p transduction increased the number of O1+ rOPCs during differentiation. Luciferase reporter assays confirmed that miR-297c-5p targets cyclin T2 (CCNT2), the regulatory subunit of positive transcription elongation factor b, a complex that inhibits OL maturation. Furthermore, CCNT2-specific knockdown promoted rOPC differentiation while not affecting cell cycle status. Together, these data support a dual role for miR-297c-5p as both a negative regulator of OPC proliferation and a positive regulator of OL maturation via its interaction with CCNT2. SIGNIFICANCE STATEMENT This work describes the role of oligodendrocyte progenitor cell (OPC) microRNAs (miRNAs) during remyelination and development in vivo and differentiation in vitro. This work highlights the importance of miRNAs to OPC biology and describes miR-297c-5p, a novel regulator of OPC function. In addition, we identified CCNT2 as a functional target, thus providing a mechanism by which miR-297c-5p imparts its effects on differentiation. These data are important, given our lack of understanding of OPC miRNA regulatory networks and their potential clinical value. Therefore, efforts to understand the role of miR-297c-5p in pathological conditions and its potential for facilitating repair may provide future therapeutic strategies to treat demyelination. PMID:26843650

Proposed Staging System for Patients With HPV-Related Oropharyngeal Cancer Based on Nasopharyngeal Cancer N Categories

PubMed Central

Dahlstrom, Kristina R.; Garden, Adam S.; William, William N.; Lim, Ming Yann

2016-01-01

Purpose Patients with human papillomavirus (HPV)–related oropharyngeal cancer (OPC) generally present with more advanced disease but have better survival than patients with HPV-unrelated OPC. The current American Joint Commission on Cancer (AJCC)/Union for International Cancer Control (UICC) TNM staging system for OPC was developed for HPV-unrelated OPC. A new staging system is needed to adequately predict outcomes of patients with HPV-related OPC. Patients and Methods Patients with newly diagnosed HPV-positive OPC (by p16 immunohistochemistry or in situ hybridization) treated at our institution from January 2003 through December 2012 were included. By using recursive partitioning analysis (RPA), we developed new stage groupings with both traditional OPC regional lymph node (N) categories and nasopharyngeal carcinoma (NPC) N categories. Survival was estimated by the Kaplan-Meier method, and the relationship between stage and survival was examined by using Cox proportional hazards regression analysis. Results A total of 661 patients with HPV-positive OPC met the inclusion criteria. With the traditional TNM staging system, there was no difference in survival between stages (P = .141). RPA with NPC N categories resulted in more balanced stage groups and better separation between groups for 5-year survival than RPA with traditional OPC N categories. With the stage groupings that were based in part on NPC N categories, the risk of death increased with increasing stage (P for trend < .001), and patients with stage III disease had five times the risk of death versus patients with stage IA disease. Conclusion New stage groupings that are based on primary tumor (T) categories and NPC N categories better separate patients with HPV-positive OPC with respect to survival than does the current AJCC/UICC TNM staging system. Although confirmation of our findings in other patient populations is needed, we propose consideration of NPC N categories as an alternative to the traditional OPC N categories in the new AJCC/UICC TNM staging system that is currently being developed. PMID:26884553

A retrospective study of 606 cases of nasopharyngeal carcinoma with or without oropharyngeal candidiasis during radiotherapy

PubMed Central

Xia, Wei-Xiong; Yang, Jing; Yu, Ya-Hui; Liang, Hu; Huang, Xin-Jun; Liu, Guo-Ying; Li, Wang-Zhong; Xiang, Yan-Qun; Guo, Xiang; Lv, Xing

2017-01-01

Background To evaluate the clinical characteristics, treatment-related toxicities and survival in patients with nasopharyngeal carcinoma (NPC) with or without oropharyngealcandidiasis (OPC) during radiotherapy. Methods The current study was conducted with NPC patients undergoing radiotherapy at Sun Yat-Sen University Cancer Center between June 2011 and May 2012. A clinical diagnosis of candidiasis was determined on the basis of a positive potassium hydroxide (KOH) test and the presence of pseudomembranous (white) form of candidal overgrowth. The Cox proportional hazard regression model was used to test the association of OPC and related survival rates. Results Compared with the non-OPC group, the OPC group had significantly increased occurrence rates of grade 3–4 mucositis (14.5% vs. 7.4%, P = 0.049), anaemia (11.3% vs. 4.4%, P = 0.020), hepatotoxicity (4.8% vs. 1.1%, P = 0.021) and critical weight loss (85.5% vs. 56.6%, P<0.001) during radiotherapy. The OPC group had a significantly lower disease-free survival (DFS) (70.9% vs. 82.6%, P = 0.012), mainly as a result of a reduction in locoregional relapse-free survival (LRFS) (87.0%vs. 94.9%, P = 0.025). After stratification by T stage, the 5-year DFS in T3-4 patients were 82.0% and 68.8% in non-OPC and OPC groups, respectively (P = 0.022). Multivariate analyses indicated that OPC was a prognostic factor for LRFS and DFS. Conclusions OPC during radiotherapy may worsen the nutritional status of NPC patients according to weight loss and anaemia, leading to a negative impact on 5-year locoregional relapse-free survival and disease-specific survival. Further investigations are needed to explore whether prevention and treatment of OPC during radiotherapy will be useful. PMID:28797119

On the accuracy of stratospheric aerosol extinction derived from in situ size distribution measurements and surface area density derived from remote SAGE II and HALOE extinction measurements

DOE PAGES

Kovilakam, Mahesh; Deshler, Terry

2015-08-26

In situ stratospheric aerosol measurements, from University of Wyoming optical particle counters (OPCs), are compared with Stratospheric Aerosol Gas Experiment (SAGE) II (versions 6.2 and 7.0) and Halogen Occultation Experiment (HALOE) satellite measurements to investigate differences between SAGE II/HALOE-measured extinction and derived surface area and OPC-derived extinction and surface area. Coincident OPC and SAGE II measurements are compared for a volcanic (1991-1996) and nonvolcanic (1997-2005) period. OPC calculated extinctions agree with SAGE II measurements, within instrumental uncertainty, during the volcanic period, but have been a factor of 2 low during the nonvolcanic period. Three systematic errors associated with the OPCmore » measurements, anisokineticity, inlet particle evaporation, and counting efficiency, were investigated. An overestimation of the OPC counting efficiency is found to be the major source of systematic error. With this correction OPC calculated extinction increases by 15-30% (30-50%) for the volcanic (nonvolcanic) measurements. These changes significantly improve the comparison with SAGE II and HALOE extinctions in the nonvolcanic cases but slightly degrade the agreement in the volcanic period. These corrections have impacts on OPC-derived surface area density, exacerbating the poor agreement between OPC and SAGE II (version 6.2) surface areas. Furthermore, this disparity is reconciled with SAGE II version 7.0 surface areas. For both the volcanic and nonvolcanic cases these changes in OPC counting efficiency and in the operational SAGE II surface area algorithm leave the derived surface areas from both platforms in significantly better agreement and within the ± 40% precision of the OPC moment calculations.« less

On the accuracy of stratospheric aerosol extinction derived from in situ size distribution measurements and surface area density derived from remote SAGE II and HALOE extinction measurements

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

Kovilakam, Mahesh; Deshler, Terry

In situ stratospheric aerosol measurements, from University of Wyoming optical particle counters (OPCs), are compared with Stratospheric Aerosol Gas Experiment (SAGE) II (versions 6.2 and 7.0) and Halogen Occultation Experiment (HALOE) satellite measurements to investigate differences between SAGE II/HALOE-measured extinction and derived surface area and OPC-derived extinction and surface area. Coincident OPC and SAGE II measurements are compared for a volcanic (1991-1996) and nonvolcanic (1997-2005) period. OPC calculated extinctions agree with SAGE II measurements, within instrumental uncertainty, during the volcanic period, but have been a factor of 2 low during the nonvolcanic period. Three systematic errors associated with the OPCmore » measurements, anisokineticity, inlet particle evaporation, and counting efficiency, were investigated. An overestimation of the OPC counting efficiency is found to be the major source of systematic error. With this correction OPC calculated extinction increases by 15-30% (30-50%) for the volcanic (nonvolcanic) measurements. These changes significantly improve the comparison with SAGE II and HALOE extinctions in the nonvolcanic cases but slightly degrade the agreement in the volcanic period. These corrections have impacts on OPC-derived surface area density, exacerbating the poor agreement between OPC and SAGE II (version 6.2) surface areas. Furthermore, this disparity is reconciled with SAGE II version 7.0 surface areas. For both the volcanic and nonvolcanic cases these changes in OPC counting efficiency and in the operational SAGE II surface area algorithm leave the derived surface areas from both platforms in significantly better agreement and within the ± 40% precision of the OPC moment calculations.« less

Oligomeric proanthocyanidin complexes (OPC) exert anti-proliferative and pro-apoptotic effects on prostate cancer cells.

PubMed

Neuwirt, Hannes; Arias, Mercedes Cedeno; Puhr, Martin; Hobisch, Alfred; Culig, Zoran

2008-11-01

Oligomeric proanthocyanidin complexes (OPC) are extracted from grape seeds or maritime pine bark and have been used for enhancement of capillary stability and lymphatic drainage. Since a role for OPC in cancer prevention was postulated, we asked whether they have an effect on prostate cancer cells. Cell proliferation was determined by (3)H-thymidine assay and cell cycle status was analyzed on a flow cytometer. Expression of regulators of proliferation and apoptosis was determined by Western blot. We found that androgen-responsive cells LNCaP are more sensitive to OPC in terms of inhibition of proliferation in comparison to androgen receptor-negative PC3 or DU145 cells. Treatment with OPC resulted in a decrease in the percentage of LNCaP cells in the S phase and an increase in the percentage of cells in sub G1 phase. The anti-proliferative and pro-apoptotic effect of OPC in the LNCaP cell line was associated with down-regulation of expression of the androgen receptor. Interestingly, similar regulatory effects of OPC, such as inhibition of expression of cyclin-dependent kinases and cyclins and stimulation of tumor suppressors p21 and p27, were seen in LNCaP and PC3 cells. Favorable changes in the Bcl-2/Bax ratio were observed in LNCaP and PC3 cells after the treatment with OPC. OPC caused an increase of phosphorylated mitogen-activated protein kinase p44 and p42, thus suggesting induction of cellular differentiation. We conclude that OPC is a candidate that fulfills criteria for chemopreventive strategies in prostate cancer that might be established in following in vivo studies. (c) 2008 Wiley-Liss, Inc.

Effects of antioxidant, OPC-14117, on secondary cellular damage and behavioral deficits following cortical contusion in the rat.

PubMed

Aoyama, Naoki; Katayama, Yoichi; Kawamata, Tatsuro; Maeda, Takeshi; Mori, Tatsuro; Yamamoto, Takamitsu; Kikuchi, Tetsuro; Uwahodo, Yasuhumi

2002-05-03

In the present study, we examined the effects of OPC-14117, a superoxide radical scavenger, on the secondary cellular damage and cognitive dysfunction occurring in a rat model of cerebral contusion induced by a controlled cortical impact (CCI). Histological examinations revealed that the contusion necrosis volume reached 13.6+/-5.3 mm(3) in non-treated animals and declined to 1.9+/-0.6 mm(3) in OPC-14117-treated animals (P<0.01). The cell number of the CA3 region was 120.0+/-12.4 cells/mm in the normal controls, 73.6+/-9.9 cells/mm in the non-treated animals, and 111.2+/-10.2 cells/mm in the OPC-14117-treated animals, indicating that CCI-induced selective neuronal cell death in the CA3 region was attenuated by the OPC-14117 administration (P<0.01). The tissue osmolality, as determined with a vapor pressure osmometer, was 314.5+/-15.4 mmol/kg in the normal brain and increased to 426.0+/-20.1 mmol/kg at 12 h following CCI. The increase in tissue osmolality was significantly attenuated by OPC-14117 administration (P<0.01). The OPC-14117 administration also attenuated the CCI-induced cognitive deficits. The OPC-14117-treated animals showed a tendency to improve on the Morris water maze performance test. The impairment of the habituation of exploratory activity elicited by CCI was significantly attenuated by OPC-14117 administration (P<0.05). In conclusion, OPC-14117 may have a potential for decreasing secondary cellular damage due to traumatic brain injury since it is as efficacious as any other compound tested in this model.

A retrospective study of 606 cases of nasopharyngeal carcinoma with or without oropharyngeal candidiasis during radiotherapy.

PubMed

Qiu, Wen-Ze; Ke, Liang-Ru; Xia, Wei-Xiong; Yang, Jing; Yu, Ya-Hui; Liang, Hu; Huang, Xin-Jun; Liu, Guo-Ying; Li, Wang-Zhong; Xiang, Yan-Qun; Guo, Xiang; Lv, Xing

2017-01-01

To evaluate the clinical characteristics, treatment-related toxicities and survival in patients with nasopharyngeal carcinoma (NPC) with or without oropharyngealcandidiasis (OPC) during radiotherapy. The current study was conducted with NPC patients undergoing radiotherapy at Sun Yat-Sen University Cancer Center between June 2011 and May 2012. A clinical diagnosis of candidiasis was determined on the basis of a positive potassium hydroxide (KOH) test and the presence of pseudomembranous (white) form of candidal overgrowth. The Cox proportional hazard regression model was used to test the association of OPC and related survival rates. Compared with the non-OPC group, the OPC group had significantly increased occurrence rates of grade 3-4 mucositis (14.5% vs. 7.4%, P = 0.049), anaemia (11.3% vs. 4.4%, P = 0.020), hepatotoxicity (4.8% vs. 1.1%, P = 0.021) and critical weight loss (85.5% vs. 56.6%, P<0.001) during radiotherapy. The OPC group had a significantly lower disease-free survival (DFS) (70.9% vs. 82.6%, P = 0.012), mainly as a result of a reduction in locoregional relapse-free survival (LRFS) (87.0%vs. 94.9%, P = 0.025). After stratification by T stage, the 5-year DFS in T3-4 patients were 82.0% and 68.8% in non-OPC and OPC groups, respectively (P = 0.022). Multivariate analyses indicated that OPC was a prognostic factor for LRFS and DFS. OPC during radiotherapy may worsen the nutritional status of NPC patients according to weight loss and anaemia, leading to a negative impact on 5-year locoregional relapse-free survival and disease-specific survival. Further investigations are needed to explore whether prevention and treatment of OPC during radiotherapy will be useful.

OPC-28326, a selective peripheral vasodilator with angiogenic activity, mitigates postinfarction cardiac remodeling.

PubMed

Ogino, Atsushi; Takemura, Genzou; Hashimoto, Ayako; Kanamori, Hiromitsu; Okada, Hideshi; Nakagawa, Munehiro; Tsujimoto, Akiko; Goto, Kazuko; Kawasaki, Masanori; Nagashima, Kenshi; Miyakoda, Goro; Fujiwara, Takako; Yabuuchi, Youichi; Fujiwara, Hisayoshi; Minatoguchi, Shinya

2015-07-01

Although OPC-28326, 4-(N-methyl-2-phenylethylamino)-1-(3,5-dimethyl-4-propionyl-aminobenzoyl) piperidine hydrochloride monohydrate, was developed as a selective peripheral vasodilator with α2-adrenergic antagonist properties, it also reportedly exhibits angiogenic activity in an ischemic leg model. The purpose of this study was to examine the effect of OPC-28326 on the architectural dynamics and function of the infarcted left ventricle during the chronic stage of myocardial infarction. Myocardial infarction was induced in male C3H/He mice, after which the mice were randomly assigned into two groups: a control group receiving a normal diet and an OPC group whose diet contained 0.05% OPC-28326. The survival rate among the mice (n = 18 in each group) 4 wk postinfarction was significantly greater in the OPC than control group (83 vs. 44%; P < 0.05), and left ventricular remodeling and dysfunction were significantly mitigated. Histologically, infarct wall thickness was significantly greater in the OPC group, due in part to an abundance of nonmyocyte components, including blood vessels and myofibroblasts. Five days postinfarction, Ki-67-positive proliferating cells were more abundant in the granulation tissue in the OPC group, and there were fewer apoptotic cells. These effects were accompanied by activation of myocardial Akt and endothelial nitric oxide synthase. Hypoxia within the infarct issue, assessed using pimonidazole staining, was markedly attenuated in the OPC group. In summary, OPC-28326 increased the nonmyocyte population in infarct tissue by increasing proliferation and reducing apoptosis, thereby altering the tissue dynamics such that wall stress was reduced, which might have contributed to a mitigation of postinfarction cardiac remodeling and dysfunction. Copyright © 2015 the American Physiological Society.

Dynamic mapping of EDDL device descriptions to OPC UA

NASA Astrophysics Data System (ADS)

Atta Nsiah, Kofi; Schappacher, Manuel; Sikora, Axel

2017-07-01

OPC UA (Open Platform Communications Unified Architecture) is already a well-known concept used widely in the automation industry. In the area of factory automation, OPC UA models the underlying field devices such as sensors and actuators in an OPC UA server to allow connecting OPC UA clients to access device-specific information via a standardized information model. One of the requirements of the OPC UA server to represent field device data using its information model is to have advanced knowledge about the properties of the field devices in the form of device descriptions. The international standard IEC 61804 specifies EDDL (Electronic Device Description Language) as a generic language for describing the properties of field devices. In this paper, the authors describe a possibility to dynamically map and integrate field device descriptions based on EDDL into OPCUA.

Characterization of a novel non-peptide vasopressin V1 receptor antagonist (OPC-21268) in the rat.

PubMed

Burrell, L M; Phillips, P A; Stephenson, J; Risvanis, J; Hutchins, A M; Johnston, C I

1993-08-01

A non-peptide, orally effective, vasopressin (AVP) V1 receptor antagonist 1-(1-[4-(3-acetylaminopropoxy) benzoyl]-4-piperidyl)-3,4-dihydro-2(1H)-quinolinone (OPC-21268) has recently been described. This paper reports the in-vitro and in-vivo characterization of OPC-21268 binding to vasopressin receptors in rat liver and kidney. OPC-21268 caused a concentration-dependent displacement of the selective V1 receptor antagonist radioligand, 125I-labelled [d(CH2)5,sarcosine7]AVP to V1 receptors in both rat liver and kidney medulla membranes. The concentration of OPC-21268 that displaced 50% of specific AVP binding (IC50) was 40 +/- 3 nmol/l for liver V1 and 15 +/- 2 nmol/l for kidney V1 receptors (mean +/- S.E.M.; n = 3). OPC-21268 had little effect on the selective V2 antagonist radioligand [3H]desGly-NH2(9)]d(CH2)5,D-Ile2,Ile4] AVP binding to V2 receptors in renal medulla membranes (IC50 > 0.1 mmol/l). After oral administration to rats, OPC-21268 was an effective V1 antagonist in a time- and dose-dependent manner. Binding kinetic studies showed that OPC-21268 acted as a competitive antagonist at the liver V1 receptor in vitro and in vivo, in addition to its in-vitro competitive effects at the renal V1 receptor. OPC-21268 shows promise as an orally active V1 antagonist.

Involuntary Outpatient Commitment and the Elusive Pursuit of Violence Prevention.

PubMed

Swartz, Marvin S; Bhattacharya, Sayanti; Robertson, Allison G; Swanson, Jeffrey W

2017-02-01

Involuntary outpatient commitment (OPC)-also referred to as 'assisted outpatient treatment' or 'community treatment orders'-are civil court orders whereby persons with serious mental illness and repeated hospitalisations are ordered to adhere to community-based treatment. Increasingly, in the United States, OPC is promoted to policy makers as a means to prevent violence committed by persons with mental illness. This article reviews the background and context for promotion of OPC for violence prevention and the empirical evidence for the use of OPC for this goal. Relevant publications were identified for review in PubMed, Ovid Medline, PsycINFO, personal communications, and relevant Internet searches of advocacy and policy-related publications. Most research on OPC has focussed on outcomes such as community functioning and hospital recidivism and not on interpersonal violence. As a result, research on violence towards others has been limited but suggests that low-level acts of interpersonal violence such as minor, noninjurious altercations without weapon use and arrests can be reduced by OPC, but there is no evidence that OPC can reduce major acts of violence resulting in injury or weapon use. The impact of OPC on major violence, including mass shootings, is difficult to assess because of their low base rates. Effective implementation of OPC, when combined with intensive community services and applied for an adequate duration to take effect, can improve treatment adherence and related outcomes, but its promise as an effective means to reduce serious acts of violence is unknown.

Induced Accelerated Aging in Induced Pluripotent Stem Cell Lines from Patients with Parkinson’s Disease

DTIC Science & Technology

2014-07-01

after manipulation of the cells prohibited this approach. 2. Differentiation into oligoprecursor cells ( OPCs ) and oligodendrocytes As we have...Jing Bian, PhD and Birgitt Schuele, MD 18 Development of expandable OPCs from human iPSC derived...Neri et al., 2010) + + + + Human iPSC derived OPCs and Oligos (Wang et al., 2013) + + + + mEpsc derived OPCs and Oligos (Najm et al

Overexpression of Polysialylated Neural Cell Adhesion Molecule Improves the Migration Capacity of Induced Pluripotent Stem Cell-Derived Oligodendrocyte Precursors

PubMed Central

Czepiel, Marcin; Leicher, Lasse; Becker, Katja; Boddeke, Erik

2014-01-01

Cell replacement therapy aiming at the compensation of lost oligodendrocytes and restoration of myelination in acquired or congenital demyelination disorders has gained considerable interest since the discovery of induced pluripotent stem cells (iPSCs). Patient-derived iPSCs provide an inexhaustible source for transplantable autologous oligodendrocyte precursors (OPCs). The first transplantation studies in animal models for demyelination with iPSC-derived OPCs demonstrated their survival and remyelinating capacity, but also revealed their limited migration capacity. In the present study, we induced overexpression of the polysialylating enzyme sialyltransferase X (STX) in iPSC-derived OPCs to stimulate the production of polysialic acid-neuronal cell adhesion molecules (PSA-NCAMs), known to promote and facilitate the migration of OPCs. The STX-overexpressing iPSC-derived OPCs showed a normal differentiation and maturation pattern and were able to downregulate PSA-NCAMs when they became myelin-forming oligodendrocytes. After implantation in the demyelinated corpus callosum of cuprizone-fed mice, STX-expressing iPSC-derived OPCs demonstrated a significant increase in migration along the axons. Our findings suggest that the reach and efficacy of iPSC-derived OPC transplantation can be improved by stimulating the OPC migration potential via specific gene modulation. PMID:25069776

Wafer hotspot prevention using etch aware OPC correction

NASA Astrophysics Data System (ADS)

Hamouda, Ayman; Power, Dave; Salama, Mohamed; Chen, Ao

2016-03-01

As technology development advances into deep-sub-wavelength nodes, multiple patterning is becoming more essential to achieve the technology shrink requirements. Recently, Optical Proximity Correction (OPC) technology has proposed simultaneous correction of multiple mask-patterns to enable multiple patterning awareness during OPC correction. This is essential to prevent inter-layer hot-spots during the final pattern transfer. In state-of-art literature, multi-layer awareness is achieved using simultaneous resist-contour simulations to predict and correct for hot-spots during mask generation. However, this approach assumes a uniform etch shrink response for all patterns independent of their proximity, which isn't sufficient for the full prevention of inter-exposure hot-spot, for example different color space violations post etch or via coverage/enclosure post etch. In this paper, we explain the need to include the etch component during multiple patterning OPC. We also introduce a novel approach for Etch-aware simultaneous Multiple-patterning OPC, where we calibrate and verify a lumped model that includes the combined resist and etch responses. Adding this extra simulation condition during OPC is suitable for full chip processing from a computation intensity point of view. Also, using this model during OPC to predict and correct inter-exposures hot-spots is similar to previously proposed multiple-patterning OPC, yet our proposed approach more accurately corrects post-etch defects too.

Isolation of proanthocyanidins from red wine, and their inhibitory effects on melanin synthesis in vitro.

PubMed

Fujimaki, Takahiro; Mori, Shoko; Horikawa, Manabu; Fukui, Yuko

2018-05-15

The red wines made from Vitis vinifera were identified as skin-whitening effectors by using in vitro assays. OPCs in the wine were evaluated for tyrosinase activity and melanogenesis. Strong tyrosinase inhibitory activity was observed in fractions with high oligomeric proanthocyanidin (OPC) content. Among OPC dimers, a strong inhibitory effect on tyrosinase was observed with OPCs which contain (+)-catechin as an upper unit. Melanogenesis inhibitory effect was observed with OPCs which have (-)-epicatechin as upper units. Also, OPC trimers, upper and middle units joined with 4 → 8 bonds, showed stronger effects compared to trimers with 4 → 6 linkages. Interestingly, (-)-epicatechin-(4β → 8)-(-)-epicatechin 3-O-gallate, which is a unique component of grapes has potent inhibitory effects on both tyrosinase and melanogenesis. Our data provide structural information about such active compounds. These results suggest that red wines containing OPC, have high melanogenesis inhibitory effect and are supposed to have skin-whitening effect. Copyright © 2017 Elsevier Ltd. All rights reserved.

Transplantation of PDGF-AA-Overexpressing Oligodendrocyte Precursor Cells Promotes Recovery in Rat Following Spinal Cord Injury.

PubMed

Yao, Zong-Feng; Wang, Ying; Lin, Yu-Hong; Wu, Yan; Zhu, An-You; Wang, Rui; Shen, Lin; Xi, Jin; Qi, Qi; Jiang, Zhi-Quan; Lü, He-Zuo; Hu, Jian-Guo

2017-01-01

Our previous study showed that Schwann cells (SCs) promote survival, proliferation and migration of co-transplanted oligodendrocyte progenitor cells (OPCs) and neurological recovery in rats with spinal cord injury (SCI). A subsequent in vitro study confirmed that SCs modulated OPC proliferation and migration by secreting platelet-derived growth factor (PDGF)-AA and fibroblast growth factor-2 (FGF)-2. We also found that PDGF-AA stimulated OPC proliferation and their differentiation into oligodendrocytes (OLs) at later stages. We therefore speculated that PDGF-AA administration can exert the same effect as SC co-transplantation in SCI repair. To test this hypothesis, in this study we investigated the effect of transplanting PDGF-AA-overexpressing OPCs in a rat model of SCI. We found that PDGF-AA overexpression in OPCs promoted their survival, proliferation, and migration and differentiation into OLs in vivo . OPCs overexpressing PDGF-AA were also associated with increased myelination and tissue repair after SCI, leading to the recovery of neurological function. These results indicate that PDGF-AA-overexpressing OPCs may be an effective treatment for SCI.

Optimized distributed computing environment for mask data preparation

NASA Astrophysics Data System (ADS)

Ahn, Byoung-Sup; Bang, Ju-Mi; Ji, Min-Kyu; Kang, Sun; Jang, Sung-Hoon; Choi, Yo-Han; Ki, Won-Tai; Choi, Seong-Woon; Han, Woo-Sung

2005-11-01

As the critical dimension (CD) becomes smaller, various resolution enhancement techniques (RET) are widely adopted. In developing sub-100nm devices, the complexity of optical proximity correction (OPC) is severely increased and applied OPC layers are expanded to non-critical layers. The transformation of designed pattern data by OPC operation causes complexity, which cause runtime overheads to following steps such as mask data preparation (MDP), and collapse of existing design hierarchy. Therefore, many mask shops exploit the distributed computing method in order to reduce the runtime of mask data preparation rather than exploit the design hierarchy. Distributed computing uses a cluster of computers that are connected to local network system. However, there are two things to limit the benefit of the distributing computing method in MDP. First, every sequential MDP job, which uses maximum number of available CPUs, is not efficient compared to parallel MDP job execution due to the input data characteristics. Second, the runtime enhancement over input cost is not sufficient enough since the scalability of fracturing tools is limited. In this paper, we will discuss optimum load balancing environment that is useful in increasing the uptime of distributed computing system by assigning appropriate number of CPUs for each input design data. We will also describe the distributed processing (DP) parameter optimization to obtain maximum throughput in MDP job processing.

Comparison of binary mask defect printability analysis using virtual stepper system and aerial image microscope system

NASA Astrophysics Data System (ADS)

Phan, Khoi A.; Spence, Chris A.; Dakshina-Murthy, S.; Bala, Vidya; Williams, Alvina M.; Strener, Steve; Eandi, Richard D.; Li, Junling; Karklin, Linard

1999-12-01

As advanced process technologies in the wafer fabs push the patterning processes toward lower k1 factor for sub-wavelength resolution printing, reticles are required to use optical proximity correction (OPC) and phase-shifted mask (PSM) for resolution enhancement. For OPC/PSM mask technology, defect printability is one of the major concerns. Current reticle inspection tools available on the market sometimes are not capable of consistently differentiating between an OPC feature and a true random defect. Due to the process complexity and high cost associated with the making of OPC/PSM reticles, it is important for both mask shops and lithography engineers to understand the impact of different defect types and sizes to the printability. Aerial Image Measurement System (AIMS) has been used in the mask shops for a number of years for reticle applications such as aerial image simulation and transmission measurement of repaired defects. The Virtual Stepper System (VSS) provides an alternative method to do defect printability simulation and analysis using reticle images captured by an optical inspection or review system. In this paper, pre- programmed defects and repairs from a Defect Sensitivity Monitor (DSM) reticle with 200 nm minimum features (at 1x) will be studied for printability. The simulated resist lines by AIMS and VSS are both compared to SEM images of resist wafers qualitatively and quantitatively using CD verification.Process window comparison between unrepaired and repaired defects for both good and bad repair cases will be shown. The effect of mask repairs to resist pattern images for the binary mask case will be discussed. AIMS simulation was done at the International Sematech, Virtual stepper simulation at Zygo and resist wafers were processed at AMD-Submicron Development Center using a DUV lithographic process for 0.18 micrometer Logic process technology.

Inhibition of endogenous phosphodiesterase 7 promotes oligodendrocyte precursor differentiation and survival.

PubMed

Medina-Rodríguez, E M; Arenzana, F J; Pastor, J; Redondo, M; Palomo, V; García de Sola, R; Gil, C; Martínez, A; Bribián, A; de Castro, F

2013-09-01

During the development of the central nervous system (CNS), oligodendrocyte precursors (OPCs) are generated in specific sites within the neural tube and then migrate to colonize the entire CNS, where they differentiate into myelin-forming oligodendrocytes. Demyelinating diseases such as multiple sclerosis (MS) are characterized by the death of these cells. The CNS reacts to demyelination and by promoting spontaneous remyelination, an effect mediated by endogenous OPCs, cells that represent approximately 5-7 % of the cells in the adult brain. Numerous factors influence oligodendrogliogenesis and oligodendrocyte differentiation, including morphogens, growth factors, chemotropic molecules, extracellular matrix proteins, and intracellular cAMP levels. Here, we show that during development and in early adulthood, OPCs in the murine cerebral cortex contain phosphodiesterase-7 (PDE7) that metabolizes cAMP. We investigated the effects of different PDE7 inhibitors (the well-known BRL-50481 and two new ones, TC3.6 and VP1.15) on OPC proliferation, survival, and differentiation. While none of the PDE7 inhibitors analyzed altered OPC proliferation, TC3.6 and VP1.15 enhanced OPC survival and differentiation, processes in which ERK intracellular signaling played a key role. PDE7 expression was also observed in OPCs isolated from adult human brains and the differentiation of these OPCs into more mature oligodendroglial phenotypes was accelerated by treatment with both new PDE7 inhibitors. These findings reveal new roles for PDE7 in regulating OPC survival and differentiation during brain development and in adulthood, and they may further our understanding of myelination and facilitate the development of therapeutic remyelination strategies for the treatment of MS.

OPC-28326, a selective femoral vasodilator, is an alpha2C-adrenoceptor-selective antagonist.

PubMed

Sun, B; Lockyer, S; Li, J; Chen, R; Yoshitake, M; Kambayashi, J I

2001-11-01

OPC-28326 has been reported to selectively increase femoral blood flow in open-chest dogs and autoperfused canine femoral artery preparations. Preliminary data indicated that OPC-28326 has a high affinity at the alpha2-adrenoceptor. In the present study, we tested OPC-28326 in isoflurane anesthetized rats at a dose of 3 mg/kg of body weight, given intraduodenally. OPC-28326 significantly increased femoral blood flow, by 44.7 +/- 13.8%, 45 min after drug administration, whereas carotid blood flow increased by only 3.6 +/- 5.5% (n = 6). Chinese hamster ovary cell lines overexpressing rat alpha2D-, alpha2B-, or alpha2C-adrenoceptor were established. These cells also coexpress luciferase, driven by cAMP elevation. In radioligand binding assays using cell membrane preparations, OPC-28326 dose dependently competed with [3H]RX821002 binding, with calculated K(i) values of 3840 +/- 887, 633 +/- 46, and 13.7 +/- 1.9 nM on alpha2D-, alpha2B-, and alpha2C-adrenoceptor, respectively. A similar affinity and rank order of potency were also found for OPC-28326 on the alpha2-subtypes using epinephrine as agonist in luciferase assays. No agonistic effect of OPC-28326 was detected on any of the alpha2-adrenoceptors. Finally, in situ hybridization performed on skeletal muscle tissue sections collected from rat hind limb (musculus gastrocnemius) demonstrated a high level expression of alpha2C in the vascular tissues. Thus, the abundance of alpha2C in the skeletal muscle may account for the selective effect of OPC-28326 in increasing femoral blood flow.

OPC-compounds prevent oxidant-induced carbonylation and depolymerization of the F-actin cytoskeleton and intestinal barrier hyperpermeability.

PubMed

Banan, A; Fitzpatrick, L; Zhang, Y; Keshavarzian, A

2001-02-01

Rebamipide (OPC-12759), a quinolone derivative, and OPC-6535, a thiazol-carboxylic acid derivative, are compounds with ability to protect gastrointestinal (GI) mucosal integrity against reactive oxygen metabolites (ROM). The underlying mechanism of OPC-mediated protection remains poorly understood. It is now established that ROM can injure the mucosa by disruption of the cytoskeletal network, a key component of mucosal barrier integrity. We, therefore, investigated whether OPC compounds prevent the oxidation, disassembly, and instability of the cytoskeletal protein actin and, in turn, protect intestinal barrier function against ROM. Human intestinal (Caco-2) cell monolayers were pretreated with OPC (-12759 or -6535) prior to incubation with ROM (H2O2) or HOCl). Effects on cell integrity (ethidium homodimer-1), epithelial barrier function (fluorescein sulfonic acid clearance), and actin cytoskeletal integrity (high-resolution laser confocal) were then determined. Cells were also processed for quantitative immunoblotting of G- and F-actin to measure oxidation (carbonylation) and disassembly of actin. In monolayers exposed to ROM, preincubation with OPC compounds prevented actin oxidation, decreased depolymerized G-actin, and enhanced the stable F-actin. Concomitantly, OPC agents abolished both actin cytoskeletal disruption and monolayer barrier dysfunction. Data suggest for the first time that OPC drugs prevent oxidation of actin and lead to the protection of actin cytoskeleton and intestinal barrier integrity against oxidant insult. Accordingly, these compounds may be used as novel therapeutic agents for the treatment of a variety of oxidative inflammatory intestinal disorders with an abnormal mucosal barrier such as inflammatory bowel disease.

Realignment of the Army Government Purchase Card Program in Japan

DTIC Science & Technology

2014-06-01

REDUNDANCIES .........................................................................................28  1.  A/ OPC Bank Setup...28  2.  A/ OPC Training Records ..................................................................29...Air Force instructions AIM Authorization, Issuance, and Maintenance A/ OPC agency/organizational program coordinator AO approving official BO

Biological half-life and organ distribution of [3H]8-arginine vasopressin following administration of vasopressin receptor antagonist OPC-31260.

PubMed

Molnár, Andor H; Varga, Csaba; Janáky, Tamás; Tóth, Gábor; Tóth, Géza; Farkas, Judit; László, Ferenc; László, Ferenc A

2007-06-07

The effects of the antidiuretic (V(2)) non-peptide receptor antagonist OPC-31260 on the plasma vasopressin level and the biological half-life and organ distribution of radiochemically pure, biologically active [(3)H]8-arginine vasopressin [spec. act.: 15.9 mCi/mmol (588 GBq/mmol)] were studied in Wistar rats. The plasma vasopressin level increased significantly throughout the whole experimental period (24 h). There was no change in the fast phase of the curves of total radioactivity disappearance from the plasma after the administration of [(3)H]arginine vasopressin (control: 1.51+/-0.17 min, OPC-31260-treated: 1.42+/-0.12 min, n=10). The fast phase of the disappearance curves of intact [(3)H]arginine vasopressin did not change either following the administration of OPC-31260 in a dose of 30 mg/kg p.o. (control: 1.06+/-0.19 min, OPC-31260-treated: 1.00+/-0.15 min, n=6). The slow phase of the biological half-life, which is characteristic for the examined compound, proved to be significantly longer (total radioactivity control: 9.29+/-0.61 min, OPC-31260-treated: 12.33+/-0.42 min, P<0.05, n=10; [(3)H]arginine vasopressin radioactivity: control: 5.96+/-0.58 min, OPC-31260-treated: 8.90+/-0.37 min, P<0.05, n=6). In the control rats, the radioactivity was accumulated to the greatest extent in the neurohypophysis, adenohypophysis and kidney. Following OPC-31260 administration, significantly more radioactive compounds accumulated in the kidney (control: 0.30+/-0.052 total radioactivity %/100 mg organ weight, OPC-31260-treated: 0.50+/-0.133 total radioactivity %/100 mg organ weight, P<0.05, n=10) and neurohypophysis (control: 0.37+/-0.053 total radioactivity %/100 mg organ weight, OPC-31260-treated: 0.52+/-0.076 total radioactivity %/100 mg organ weight, P<0.05, n=10). Our results permit the conclusion that the antidiuretic antagonist OPC-31260 not only blocks the V(2) receptors, but also increases the biological half-life of vasopressin. The longer biological half-life of vasopressin following OPC-31260 administration may play a role in the elevation of the plasma vasopressin level.

[Mechanism of action for oligomeric proanthocyaniclins in pava qnat-induced acute lung injury].

PubMed

Liu, P; Zhou, Y S; Qin, Y L; Li, L; Liu, Y; Xu, B; Huang, K; Ji, C C; Lin, F; Wang, Y G; Li, K; Chen, S H; Shao, L F; Mu, J S

2017-11-20

Objective: The present study was designed to evaluate the protective effects of oligomeric proanthocyanidins (OPC) in mice exposed to paraquat (PQ) , and to explore the molecular mechanism. Methods: Four experimental groups were designed. 10 BALB/c mice were intraperitoneally injected with normal saline) . PQ group: 10 BALB/c mice were intraperitoneally injected with PQ (100 mg/kg) . PQ+OPC group: 10 BALB/c mice were administered with OPC (100 mg/kg) for 1 h before PQ (100 mg/kg) expo-sure. OPC group: 10 BALB/c mice were intraperitoneally injected with OPC (100 mg/kg) . The peripheral blood samples or lung tissue samples were collected at the designed time points for measuring the levels of oxi-dative stress indicators, the related protein levels of nuclear factor-kappa B (NF-κB) pathway and nuclear fac-tor erythroid related factor-2 (Nrf2) pathway. Results: Compared with the control group, the level of reactive oxygen species (ROS) , the content of malondialdehyde (MDA) in the PQ group were significantly induced, and the activity of superoxide dismutase (SOD) in the PQ group was decreased in the peripheral blood. As com-pared with the PQ group, the level of ROS and the content of MDA in the PQ+OPC group were significantly re-duced, the activity SOD in the PQ+OPC group was increased in the peripheral blood; the level of ROS and the content of MDA were also reduced in lung tissues in the PQ+OPC group. Moreover, compared with the con-trol group, the phosphorylation of IκBα and the expression of NF-κB p65 were increased in lung tissues in the PQ group. The phosphorylation of IκBα and the expression of NF-κB p65 were decreased in lung tissues in the PQ+OPC group as compared with the PQ group. In addition, compared with the control group, the expressions of HO-1 and Nrf2 were increased in lung tissues in OPC group, and these were decreased in lung tissues in PQ groups. Furthermore, the expressions of HO-1 and Nrf2 were also increased in lung tissues in PQ+OPC as com-pared with the PQ group. Conclusion: OPC could alleviate PQ-induced systemic toxicity in mice by regulating oxidative stress via NF-κB and Nrf2 pathway.

In vitro-microenvironment directs preconditioning of human chorion derived MSC promoting differentiation of OPC-like cells.

PubMed

Periasamy, Ramesh; Surbek, Daniel V; Schoeberlein, Andreina

2018-06-01

The loss of oligodendrocyte progenitor cells (OPC) is a hallmark of perinatal brain injury. Our aim was to develop an in vitro culture condition for human chorion-derived mesenchymal stem cells (MSC) that enhances their stem cell properties and their capability to differentiate towards OPC-like cells. MSC were grown either in serum replacement medium (SRM) or serum-containing medium (SM) and tested for their morphology, proliferation, secretome, migration, protein expression and differentiation into OPC-like cells. MSC cultured in SRM condition have distinct morphology/protein expression profile, increased cell proliferation/migration and capacity to differentiate into OPC-like cells. Copyright © 2018 Elsevier Ltd. All rights reserved.

Anticancer effects of oligomeric proanthocyanidins on human colorectal cancer cell line, SNU-C4

PubMed Central

Kim, Youn-Jung; Park, Hae-Jeong; Yoon, Seo-Hyun; Kim, Mi-Ja; Leem, Kang-Hyun; Chung, Joo-Ho; Kim, Hye-Kyung

2005-01-01

AIM: Oligomeric proanthocyanidins (OPC), natural polyphenolic compounds found in plants, are known to have antioxidant and anti-cancer effects. We investigated whether the anti-cancer effects of the OPC are induced by apoptosis on human colorectal cancer cell line, SNU-C4. METHODS: Colorectal cancer cell line, SNU-C4 was cultured in RPMI 1640 medium supplemented with 10% fetal bovine serum. The cytotoxic effect of OPC was assessed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenylt-etrazolium bromide (MTT) assay. To find out the apoptotic cell death, 4, 6-diamidino-2-phenylindole (DAPI) staining, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay, reverse transcription-polymerase chain reaction (RT-PCR), and caspase-3 enzyme assay were performed. RESULTS: In this study, cytotoxic effect of OPC on SNU-C4 cells appeared in a dose-dependent manner. OPC treatment (100 µg/mL) revealed typical morphological apoptotic features. Additionally OPC treatment (100 µg/mL) increased level of BAX and CASPASE-3, and decreased level of BCL-2 mRNA expression. Caspase-3 enzyme activity was also significantly increased by treatment of OPC (100 µg/mL) compared with control. CONCLUSION: These data indicate that OPC caused cell death by apoptosis through caspase pathways on human colorectal cancer cell line, SNU-C4. PMID:16094708

CD8 T-cells and E-cadherin in host responses against oropharyngeal candidiasis

PubMed Central

Quimby, K.; Lilly, E.A.; Zacharek, M.; McNulty, K.; Leigh, J.E.; Vazquez, J.E.; Fidel, P.L.

2011-01-01

Oropharyngeal candidiasis (OPC) is the most common oral infection in HIV+ persons. Previous studies suggest a role for CD8+ T-cells against OPC when CD4+ T-cells are lost, but enhanced susceptibility to infection occurs when CD8+ T-cell migration is inhibited by reduced tissue E-cadherin. Objective Conduct a longitudinal study of tissue CD8+ T-cells and E-cadherin expression before, during, and after episodes of OPC. Methods Oral fungal burden was monitored and tissue was evaluated for CD8+ T-cells and E-cadherin over a one-year period in HIV+ persons with a history of, or an acute episode of OPC. Results While longitudinal analyses precluded formal interpretations, point prevalence analyses of the dataset revealed that when patients experiencing OPC were successfully treated, tissue E-cadherin expression was similar to patients who had not experienced OPC, and higher numbers of CD8+ T-cells were distributed throughout OPC− tissue under normal expression of E-cadherin. Conclusion These results suggest that 1) reduction in tissue E-cadherin expression in OPC+ patients is not permanent, and 2) high numbers of CD8+ T-cells can be distributed throughout OPC− tissue under normal E-cadherin expression. Together these results extend our previous studies and continue to support a role for CD8+ T-cells in host defense against OPC. PMID:21958417

Optimization of optical proximity correction to reduce mask write time using genetic algorithm

NASA Astrophysics Data System (ADS)

Dick, Gregory J.; Cao, Liang; Asthana, Abhishek; Cheng, Jing; Power, David N.

2018-03-01

The ever increasing pattern densities and design complexities make the tuning of optical proximity correction (OPC) recipes very challenging. One known method for tuning is genetic algorithm (GA). Previously GA has been demonstrated to fine tune OPC recipes in order to achieve better results for possible 1D and 2D geometric concerns like bridging and pinching. This method, however, did not take into account the impact of excess segmentation on downstream operations like fracturing and mask writing. This paper introduces a general methodology to significantly reduce the number of excess edges in the OPC output, thus reducing the number of flashes generated at fracture and subsequently the write time at mask build. GA is used to reduce the degree of unwarranted segmentation while ensuring good OPC quality. An Objective Function (OF) is utilized to ensure quality convergence and process-variation (PV) plus an additional weighed factor to reduce clustered edge count. The technique is applied to 14nm metal layer OPC recipes in order to identify excess segmentation and to produce a modified recipe that significantly reduces these segments. OPC output file sizes is shown to be reduced by 15% or more and overall edge count is shown to be reduced by 10% or more. At the same time overall quality of the OPC recipe is shown to be maintained via OPC Verification (OPCV) results.

Empirical OPC rule inference for rapid RET application

NASA Astrophysics Data System (ADS)

Kulkarni, Anand P.

2006-10-01

A given technological node (45 nm, 65 nm) can be expected to process thousands of individual designs. Iterative methods applied at the node consume valuable days in determining proper placement of OPC features, and manufacturing and testing mask correspondence to wafer patterns in a trial-and-error fashion for each design. Repeating this fabrication process for each individual design is a time-consuming and expensive process. We present a novel technique which sidesteps the requirement to iterate through the model-based OPC analysis and pattern verification cycle on subsequent designs at the same node. Our approach relies on the inference of rules from a correct pattern at the wafer surface it relates to the OPC and pre-OPC pattern layout files. We begin with an offline phase where we obtain a "gold standard" design file that has been fab-tested at the node with a prepared, post-OPC layout file that corresponds to the intended on-wafer pattern. We then run an offline analysis to infer rules to be used in this method. During the analysis, our method implicitly identifies contextual OPC strategies for optimal placement of RET features on any design at that node. Using these strategies, we can apply OPC to subsequent designs at the same node with accuracy comparable to the original design file but significantly smaller expected runtimes. The technique promises to offer a rapid and accurate complement to existing RET application strategies.

A morphological and electrophysiological study on the postnatal development of oligodendrocyte precursor cells in the rat brain.

PubMed

Chen, Peng-hui; Cai, Wen-qin; Wang, Li-yan; Deng, Qi-yue

2008-12-03

A widespread population of cells in CNS is identified by specific expression of the NG2 chondroitin sulphate proteoglycan and named as oligodendrocyte precursor cell (OPC). OPCs may possess stem cell-like characteristics, including multipotentiality in vitro and in vivo. It was proposed that OPCs in the CNS parenchyma comprise a unique population of glia, distinct from oligodendrocytes and astrocytes. This study confirmed that NG2 immunoreactive OPCs were continuously distributed in cerebral cortex and hippocampus during different postnatal developmental stages. These cells rapidly increased in number over the postnatal 7 days and migrate extensively to populate with abundant processes both in developing cortex and hippocampus. The morphology of OPCs exhibited extremely complex changes with the distribution of long distance primary process gradually increased from neonatal to adult CNS. Immunohistochemical studies showed that OPCs exhibited the morphological properties that can be distinguished from astrocytes. The electrophysiological properties showed that OPCs expressed a small amount of inward Na(+) currents which was distinguished from Na(+) currents in neurons owing to their lower Na-to-K conductance ratio and higher command voltage step depolarized maximum Na(+) current amplitude. These observations suggest that OPCs can be identified as the third type of macroglia because of their distribution in the CNS, the morphological development in process diversity and the electrophysiological difference from astrocyte.

Socioeconomic characteristics of patients with oropharyngeal carcinoma according to tumor HPV status, patient smoking status, and sexual behavior.

PubMed

Dahlstrom, Kristina R; Bell, Diana; Hanby, Duncan; Li, Guojun; Wang, Li-E; Wei, Qingyi; Williams, Michelle D; Sturgis, Erich M

2015-09-01

Patients with oropharyngeal cancer (OPC) have distinct risk factor profiles reflected in the human papillomavirus (HPV) status of their tumor, and these profiles may also be influenced by factors related to socioeconomic status (SES). The goal of this study was to describe the socioeconomic characteristics of a large cohort of patients with OPC according to HPV status, smoking status, and sexual behavior. Patients with OPC prospectively provided information about their smoking and alcohol use, socioeconomic characteristics, and sexual behaviors. HPV status was determined by a composite of immunohistochemistry for p16 expression, HPV in situ hybridization, and PCR assay in 356 patients. Standard descriptive statistics and logistic regression were used to compare socioeconomic characteristics between patient subgroups. Patients with HPV-positive OPC had higher levels of education, income, and overall SES. Among patients with HPV-positive OPC, never/light smokers had more than 5 times the odds of having at least a bachelor's degree and being in the highest level of SES compared with smokers. Patients with HPV-positive OPC and those with higher levels of education and SES had higher numbers of lifetime any and oral sex partners, although not all of these differences were significant. Socioeconomic differences among subgroups of OPC patients have implications for OPC prevention efforts, including tobacco cessation, behavior modification, and vaccination programs. Copyright © 2015 Elsevier Ltd. All rights reserved.

OPC-41061, a highly potent human vasopressin V2-receptor antagonist: pharmacological profile and aquaretic effect by single and multiple oral dosing in rats.

PubMed

Yamamura, Y; Nakamura, S; Itoh, S; Hirano, T; Onogawa, T; Yamashita, T; Yamada, Y; Tsujimae, K; Aoyama, M; Kotosai, K; Ogawa, H; Yamashita, H; Kondo, K; Tominaga, M; Tsujimoto, G; Mori, T

1998-12-01

The pharmacological profile and the acute and chronic aquaretic effects of OPC-41061, a novel nonpeptide human arginine vasopressin (AVP) V2-receptor antagonist, were respectively characterized in HeLa cells expressing cloned human AVP receptors and in conscious male rats. OPC-41061 antagonized [3H]-AVP binding to human V2-receptors (Ki = 0.43 +/- 0.06 nM) more potently than AVP (Ki = 0. 78 +/- 0.08 nM) or OPC-31260 (Ki = 9.42 +/- 0.90 nM). OPC-41061 also inhibited [3H]-AVP binding to human V1a-receptors (Ki = 12.3 +/- 0.8 nM) but not to human V1b-receptors, indicating that OPC-41061 was 29 times more selective for V2-receptors than for V1a-receptors. OPC-41061 inhibited cAMP production induced by AVP with no intrinsic agonist activity. In rats, OPC-41061 inhibited [3H]-AVP binding to V1a-receptors (Ki = 325 +/- 41 nM) and V2-receptors (Ki = 1.33 +/- 0. 30 nM), showing higher receptor selectivity (V1a/V2 = 244) than with human receptors. A single oral administration of OPC-41061 in rats clearly produced dose-dependent aquaresis. In treatment by multiple OPC-41061 dosing for 28 days at 1 and 10 mg/kg p.o. in rats, significant aquaretic effects were seen throughout the study period. As the result of aquaresis, hemoconcentration was seen at 4 hr postdosing although, no differences were seen in serum osmolality, sodium, creatinine and urea nitrogen concentrations at 24 hr postdosing. Furthermore, there was no difference in serum AVP concentration, pituitary AVP content or the number and affinity of AVP receptors in the kidney and liver at trough throughout the study period. These results demonstrate that OPC-41061 is a highly potent human AVP V2-receptor antagonist and produces clear aquaresis after single and multiple dosing, suggesting the usefulness in the treatment of various water retaining states.

Kinetics of the Human Papillomavirus Type 16 E6 Antibody Response Prior to Oropharyngeal Cancer

PubMed Central

Kreimer, Aimée R.; Johansson, Mattias; Yanik, Elizabeth L.; Katki, Hormuzd A.; Check, David P.; Lang Kuhs, Krystle A.; Willhauck-Fleckenstein, Martina; Holzinger, Dana; Hildesheim, Allan; Pfeiffer, Ruth; Williams, Craig; Freedman, Neal D.; Huang, Wen-Yi; Purdue, Mark P.; Michel, Angelika; Pawlita, Michael; Brennan, Paul; Waterboer, Tim

2017-01-01

Abstract Background: In a European cohort, it was previously reported that 35% of oropharyngeal cancer (OPC) patients were human papillomavirus type-16 (HPV16) seropositive up to 10 years before diagnosis vs 0.6% of cancer-free controls. Here, we describe the kinetics of HPV16-E6 antibodies prior to OPC diagnosis. Methods: We used annual serial prediagnostic blood samples from the PLCO Cancer Screening Trial. Antibodies to HPV were initially assessed in prediagnostic blood drawn at study enrollment from 198 incident head and neck cancer patients (median years to cancer diagnosis = 6.6) and 924 matched control subjects using multiplex serology, and subsequently in serial samples (median = 5/individual). Available tumor samples were identified and tested for HPV16 RNA to define HPV-driven OPC. Results: HPV16-E6 antibodies were present at baseline in 42.3% of 52 OPC patients and 0.5% of 924 control subjects. HPV16-E6 antibody levels were highly elevated and stable across serial blood samples for 21 OPC patients who were seropositive at baseline, as well as for one OPC patient who seroconverted closer to diagnosis. All five subjects with HPV16-driven OPC tumors were HPV16-E6-seropositive, and the four subjects with HPV16-negative OPC tumors were seronegative. The estimated 10-year cumulative risk of OPC was 6.2% (95% confidence interval [CI] = 1.8% to 21.5%) for HPV16-E6-seropositive men, 1.3% (95% CI = 0.1% to 15.3%) for HPV16-E6-seropositive women, and 0.04% (95% CI = 0.03% to 0.06%) among HPV16-E6-seronegative individuals. Conclusions: Forty-two percent of subjects diagnosed with OPC between 1994 and 2009 in a US cohort were HPV16-E6 seropositive, with stable antibody levels during annual follow-up for up to 13 years prior to diagnosis. Tumor analysis indicated that the sensitivity and specificity of HPV16-E6 antibodies were exceptionally high in predicting HPV-driven OPC. PMID:28376197

Kinetics of the Human Papillomavirus Type 16 E6 Antibody Response Prior to Oropharyngeal Cancer.

PubMed

Kreimer, Aimée R; Johansson, Mattias; Yanik, Elizabeth L; Katki, Hormuzd A; Check, David P; Lang Kuhs, Krystle A; Willhauck-Fleckenstein, Martina; Holzinger, Dana; Hildesheim, Allan; Pfeiffer, Ruth; Williams, Craig; Freedman, Neal D; Huang, Wen-Yi; Purdue, Mark P; Michel, Angelika; Pawlita, Michael; Brennan, Paul; Waterboer, Tim

2017-08-01

In a European cohort, it was previously reported that 35% of oropharyngeal cancer (OPC) patients were human papillomavirus type-16 (HPV16) seropositive up to 10 years before diagnosis vs 0.6% of cancer-free controls. Here, we describe the kinetics of HPV16-E6 antibodies prior to OPC diagnosis. We used annual serial prediagnostic blood samples from the PLCO Cancer Screening Trial. Antibodies to HPV were initially assessed in prediagnostic blood drawn at study enrollment from 198 incident head and neck cancer patients (median years to cancer diagnosis = 6.6) and 924 matched control subjects using multiplex serology, and subsequently in serial samples (median = 5/individual). Available tumor samples were identified and tested for HPV16 RNA to define HPV-driven OPC. HPV16-E6 antibodies were present at baseline in 42.3% of 52 OPC patients and 0.5% of 924 control subjects. HPV16-E6 antibody levels were highly elevated and stable across serial blood samples for 21 OPC patients who were seropositive at baseline, as well as for one OPC patient who seroconverted closer to diagnosis. All five subjects with HPV16-driven OPC tumors were HPV16-E6-seropositive, and the four subjects with HPV16-negative OPC tumors were seronegative. The estimated 10-year cumulative risk of OPC was 6.2% (95% confidence interval [CI] = 1.8% to 21.5%) for HPV16-E6-seropositive men, 1.3% (95% CI = 0.1% to 15.3%) for HPV16-E6-seropositive women, and 0.04% (95% CI = 0.03% to 0.06%) among HPV16-E6-seronegative individuals. Forty-two percent of subjects diagnosed with OPC between 1994 and 2009 in a US cohort were HPV16-E6 seropositive, with stable antibody levels during annual follow-up for up to 13 years prior to diagnosis. Tumor analysis indicated that the sensitivity and specificity of HPV16-E6 antibodies were exceptionally high in predicting HPV-driven OPC. Published by Oxford University Press 2017. This work is written by US Government employees and is in the public domain in the US.

Classification and printability of EUV mask defects from SEM images

NASA Astrophysics Data System (ADS)

Cho, Wonil; Price, Daniel; Morgan, Paul A.; Rost, Daniel; Satake, Masaki; Tolani, Vikram L.

2017-10-01

Classification and Printability of EUV Mask Defects from SEM images EUV lithography is starting to show more promise for patterning some critical layers at 5nm technology node and beyond. However, there still are many key technical obstacles to overcome before bringing EUV Lithography into high volume manufacturing (HVM). One of the greatest obstacles is manufacturing defect-free masks. For pattern defect inspections in the mask-shop, cutting-edge 193nm optical inspection tools have been used so far due to lacking any e-beam mask inspection (EBMI) or EUV actinic pattern inspection (API) tools. The main issue with current 193nm inspection tools is the limited resolution for mask dimensions targeted for EUV patterning. The theoretical resolution limit for 193nm mask inspection tools is about 60nm HP on masks, which means that main feature sizes on EUV masks will be well beyond the practical resolution of 193nm inspection tools. Nevertheless, 193nm inspection tools with various illumination conditions that maximize defect sensitivity and/or main-pattern modulation are being explored for initial EUV defect detection. Due to the generally low signal-to-noise in the 193nm inspection imaging at EUV patterning dimensions, these inspections often result in hundreds and thousands of defects which then need to be accurately reviewed and dispositioned. Manually reviewing each defect is difficult due to poor resolution. In addition, the lack of a reliable aerial dispositioning system makes it very challenging to disposition for printability. In this paper, we present the use of SEM images of EUV masks for higher resolution review and disposition of defects. In this approach, most of the defects detected by the 193nm inspection tools are first imaged on a mask SEM tool. These images together with the corresponding post-OPC design clips are provided to KLA-Tencor's Reticle Decision Center (RDC) platform which provides ADC (Automated Defect Classification) and S2A (SEM-to-Aerial printability) analysis of every defect. First, a defect-free or reference mask SEM is rendered from the post-OPC design, and the defective signature is detected from the defect-reference difference image. These signatures help assess the true nature of the defect as evident in e-beam imaging; for example, excess or missing absorber, line-edge roughness, contamination, etc. Next, defect and reference contours are extracted from the grayscale SEM images and fed into the simulation engine with an EUV scanner model to generate corresponding EUV defect and reference aerial images. These are then analyzed for printability and dispositioned using an Aerial Image Analyzer (AIA) application to automatically measure and determine the amount of CD errors. Thus by integrating EUV ADC and S2A applications together, every defect detection is characterized for its type and printability which is essential for not only determining which defects to repair, but also in monitoring the performance of EUV mask process tools. The accuracy of the S2A print modeling has been verified with other commercially-available simulators, and will also be verified with actual wafer print results. With EUV lithography progressing towards volume manufacturing at 5nm technology, and the likelihood of EBMI inspectors approaching the horizon, the EUV ADC-S2A system will continue serving an essential role of dispositioning defects off e-beam imaging.

Evaluation of a low-cost optical particle counter (Alphasense OPC-N2) for ambient air monitoring

NASA Astrophysics Data System (ADS)

Crilley, Leigh R.; Shaw, Marvin; Pound, Ryan; Kramer, Louisa J.; Price, Robin; Young, Stuart; Lewis, Alastair C.; Pope, Francis D.

2018-02-01

A fast-growing area of research is the development of low-cost sensors for measuring air pollutants. The affordability and size of low-cost particle sensors makes them an attractive option for use in experiments requiring a number of instruments such as high-density spatial mapping. However, for these low-cost sensors to be useful for these types of studies their accuracy and precision need to be quantified. We evaluated the Alphasense OPC-N2, a promising low-cost miniature optical particle counter, for monitoring ambient airborne particles at typical urban background sites in the UK. The precision of the OPC-N2 was assessed by co-locating 14 instruments at a site to investigate the variation in measured concentrations. Comparison to two different reference optical particle counters as well as a TEOM-FDMS enabled the accuracy of the OPC-N2 to be evaluated. Comparison of the OPC-N2 to the reference optical instruments shows some limitations for measuring mass concentrations of PM1, PM2.5 and PM10. The OPC-N2 demonstrated a significant positive artefact in measured particle mass during times of high ambient RH (> 85 %) and a calibration factor was developed based upon κ-Köhler theory, using average bulk particle aerosol hygroscopicity. Application of this RH correction factor resulted in the OPC-N2 measurements being within 33 % of the TEOM-FDMS, comparable to the agreement between a reference optical particle counter and the TEOM-FDMS (20 %). Inter-unit precision for the 14 OPC-N2 sensors of 22 ± 13 % for PM10 mass concentrations was observed. Overall, the OPC-N2 was found to accurately measure ambient airborne particle mass concentration provided they are (i) correctly calibrated and (ii) corrected for ambient RH. The level of precision demonstrated between multiple OPC-N2s suggests that they would be suitable devices for applications where the spatial variability in particle concentration was to be determined.

Immunological and epidemiological factors affecting candidiasis in HIV patients beginning antiretroviral therapy in an Asian clinic.

PubMed

Wulandari, Endah A T; Saraswati, Henny; Adawiyah, Robiatul; Djauzi, Samsuridjal; Wahyuningsih, Retno; Price, Patricia

2017-10-01

Oropharyngeal candidiasis (OPC) is common in HIV patients beginning antiretroviral therapy (ART). Here we address the response to ART, and the roles of poor oral hygiene and defects in local innate immunity with a focus on salivary β-defensins, as they are implicated in control of candidiasis but have not been investigated in this context. ART naïve HIV-infected adults (n=82) with <200 CD4 + T-cells/mm 3 attending clinics at Cipto Mangunkusumo Hospital, Jakarta, were examined at the commencement of ART, and 73 were re-examined after 3 months. OPC was detected by clinical examination, and Candida albicans and fungal burdens were determined following culture on CHROMagar and saboroud-dextrose agar (resp). Salivary β-defensins (-2 and -3) were quantified by ELISA. Healthy control subjects (n=40) matched the patients by age and gender. OPC was evident in 47 patients before ART, and associated with greater fingal burdens. No OPC was detected in healthy controls and culture positivity was rare. ART decreased the prevalence of OPC to 8/73 HIV patients re-examined after 3 months, with reduced total fungal and C. albicans burdens. The incidence of OPC was independent of oral hygiene. Hyposalivation was more common in untreated HIV patients (16%) than after 3 months on ART and was rare in healthy controls. HIV patients were also more likely to have acidic saliva. Salivary β-defensin-2 was elevated in the presence of C. albicans pseudohyphae and OPC after 3 months on ART, but β-defensin-3 was not affected by OPC or ART. ART reduces the prevalence of OPC, and the total fungal and C. albicans burden. Levels of salivary β-defensin-2 may associate with OPC in HIV patients responding to ART. Copyright © 2017 Elsevier Ltd. All rights reserved.

Self-regulation workshop and Occupational Performance Coaching with teachers: A pilot study.

PubMed

Hui, Caroline; Snider, Laurie; Couture, Mélanie

2016-04-01

Teachers' occupational role and performance can be undermined when working with students with disruptive classroom behaviours. This pilot study aimed to explore the impact of school-based occupational therapy intervention on teachers' classroom management self-efficacy and perceived performance/satisfaction in their management of students with disruptive behaviours. This pilot study used a multiple-case replication study design. A cohort of regular classroom elementary school teachers (n = 11) participated in a 1-day workshop on sensorimotor strategies for supporting student self-regulation followed by eight individual sessions of Occupational Performance Coaching (OPC). Measurement tools were the Canadian Occupational Performance Measure, Goal Attainment Scaling (GAS), and Teachers' Self-Efficacy Scale-Classroom Management. Improvement in teachers' perception of performance, satisfaction, and classroom management was seen. GAS showed clinically significant improvement. Improvements were sustained at 7 weeks follow-up. Preliminary results support the use of sensorimotor education combined with OPC to enable teachers' occupational performance. © CAOT 2016.

Automated mask and wafer defect classification using a novel method for generalized CD variation measurements

NASA Astrophysics Data System (ADS)

Verechagin, V.; Kris, R.; Schwarzband, I.; Milstein, A.; Cohen, B.; Shkalim, A.; Levy, S.; Price, D.; Bal, E.

2018-03-01

Over the years, mask and wafers defects dispositioning has become an increasingly challenging and time consuming task. With design rules getting smaller, OPC getting complex and scanner illumination taking on free-form shapes - the probability of a user to perform accurate and repeatable classification of defects detected by mask inspection tools into pass/fail bins is reducing. The critical challenging of mask defect metrology for small nodes ( < 30 nm) was reviewed in [1]. While Critical Dimension (CD) variation measurement is still the method of choice for determining a mask defect future impact on wafer, the high complexity of OPCs combined with high variability in pattern shapes poses a challenge for any automated CD variation measurement method. In this study, a novel approach for measurement generalization is presented. CD variation assessment performance is evaluated on multiple different complex shape patterns, and is benchmarked against an existing qualified measurement methodology.

Protein kinase C activation is required for the lead-induced inhibition of proliferation and differentiation of cultured oligodendroglial progenitor cells.

PubMed

Deng, Wenbin; Poretz, Ronald D

2002-03-01

Lead (Pb) is a common neurotoxicant of major public health concern. Previous studies revealed that cultured oligodendrocyte progenitor cells (OPCs) are highly vulnerable to Pb toxicity. The present study examines the effect of Pb on the survival, proliferation and differentiation of OPCs in vitro. Dose-response studies showed that> or = l5-10 microM Pb is cytotoxic to OPCs within 24 h. However, 1 microM of Pb was found to inhibit the proliferation and differentiation of OPCs without affecting cell viability. Pb markedly decreased the proliferative capability of OPCs and inhibited cell-intrinsic lineage progression of OPCs at a late progenitor stage. The Pb-induced decrease of proliferation and differentiation was abolished by inhibition of protein kinase C (PKC) with bisindolylmaleimide I, while the effect of the PKC-activating agent phorbol-12,13-didecanoate was potentiated by Pb. Furthermore, Pb exposure of OPCs caused the translocation of PKC from the cytoplasm to membrane without an increase in total cellular PKC enzymic activity. These results indicate that Pb inhibits the proliferation and differentiation of oligodendrocyte lineage cells in vitro through a mechanism requiring PKC activation.

Thread scheduling for GPU-based OPC simulation on multi-thread

NASA Astrophysics Data System (ADS)

Lee, Heejun; Kim, Sangwook; Hong, Jisuk; Lee, Sooryong; Han, Hwansoo

2018-03-01

As semiconductor product development based on shrinkage continues, the accuracy and difficulty required for the model based optical proximity correction (MBOPC) is increasing. OPC simulation time, which is the most timeconsuming part of MBOPC, is rapidly increasing due to high pattern density in a layout and complex OPC model. To reduce OPC simulation time, we attempt to apply graphic processing unit (GPU) to MBOPC because OPC process is good to be programmed in parallel. We address some issues that may typically happen during GPU-based OPC simulation in multi thread system, such as "out of memory" and "GPU idle time". To overcome these problems, we propose a thread scheduling method, which manages OPC jobs in multiple threads in such a way that simulations jobs from multiple threads are alternatively executed on GPU while correction jobs are executed at the same time in each CPU cores. It was observed that the amount of GPU peak memory usage decreases by up to 35%, and MBOPC runtime also decreases by 4%. In cases where out of memory issues occur in a multi-threaded environment, the thread scheduler was used to improve MBOPC runtime up to 23%.

Comparison of solidification/stabilization effects of calcite between Australian and South Korean cements

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

Lee, Dongjin; Waite, T. David; Swarbrick, Gareth

2005-11-15

The differences in the effect of calcite on the strength and stability of Pb-rich wastes solidified and stabilized using Australian and South Korean ordinary Portland cements are examined in this study. Pb-rich waste stabilized using Australian OPC has been shown to possess both substantially higher unconfined compressive strength and lead immobilization ability than South Korean OPC as a result of its higher C{sub 3}S content and the associated enhanced degree of precipitation of lead on the surfaces of silicate phases present. Calcite addition is observed to have an accelerating effect on the OPC-induced solidification/stabilization of Pb-rich wastes as gauged bymore » the unconfined compressive strength and leachability of the solids formed. This effect is observed to be far more dramatic for South Korean OPC than for Australian OPC. Using scanning electron microscopy, waste stabilized with cement and calcite was observed to develop significantly greater proportions of hydrated crystals than wastes stabilized with cement alone. The results of X-ray diffraction studies have shown that the presence of calcite in South Korean OPC results in greater acceleration in the formation of portlandite than is the case for Australian OPC.« less

Retinal determination genes coordinate neuroepithelial specification and neurogenesis modes in the Drosophila optic lobe

PubMed Central

Apitz, Holger

2016-01-01

Differences in neuroepithelial patterning and neurogenesis modes contribute to area-specific diversifications of neural circuits. In the Drosophila visual system, two neuroepithelia, the outer (OPC) and inner (IPC) proliferation centers, generate neuron subtypes for four ganglia in several ways. Whereas neuroepithelial cells in the medial OPC directly convert into neuroblasts, in an IPC subdomain they generate migratory progenitors by epithelial-mesenchymal transition that mature into neuroblasts in a second proliferative zone. The molecular mechanisms that regulate the identity of these neuroepithelia, including their neurogenesis modes, remain poorly understood. Analysis of Polycomblike revealed that loss of Polycomb group-mediated repression of the Hox gene Abdominal-B (Abd-B) caused the transformation of OPC to IPC neuroepithelial identity. This suggests that the neuroepithelial default state is IPC-like, whereas OPC identity is derived. Ectopic Abd-B blocks expression of the highly conserved retinal determination gene network members Eyes absent (Eya), Sine oculis (So) and Homothorax (Hth). These factors are essential for OPC specification and neurogenesis control. Finally, eya and so are also sufficient to confer OPC-like identity, and, in parallel with hth, the OPC-specific neurogenesis mode on the IPC. PMID:27381228

Inhibition of TROY Promotes OPC Differentiation and Increases Therapeutic Efficacy of OPC Graft for Spinal Cord Injury

PubMed Central

Sun, Liang; Liu, Shengliang; Sun, Qi; Li, Zhuying; Xu, Fengyan; Hou, Chunmei; Harada, Toshihide; Chu, Ming; Xu, Kun; Feng, Xiaoling

2014-01-01

Endogenous or graft-derived oligodendrocytes promote myelination and aid in the recovery from central nervous system (CNS) injury. Regulatory mechanisms underlying neural myelination and remyelination in response to injury, including spinal cord injury (SCI), are unclear. In the present study, we demonstrated that TROY serves as an important negative regulator of oligodendrocyte development and that TROY inhibition augments the repair potential of oligodendrocyte precursor cell (OPC) graft for SCI. TROY expression was detected by reverse transcriptase–polymerase chain reaction in OPCs as well as in differentiated premature and mature oligodendrocytes of postnatal mice. Pharmacological inhibition or RNAi-induced knockdown of TROY promotes OPC differentiation, whereas overexpression of TROY dampens oligodendrocyte maturation. Further, treatment of cocultures of DRG neurons and OPCs with TROY inhibitors promotes myelination and myelin-sheath-like structures. Mechanically, protein kinase C (PKC) signaling is involved in the regulation of the inhibitory effects of TROY. Moreover, in situ transplantation of OPCs with TROY knockdown leads to notable remyelination and neurological recovery in rats with SCI. Our results indicate that TROY negatively modulates remyelination in the CNS, and thus may be a suitable target for improving the therapeutic efficacy of cell transplantation for CNS injury. PMID:24749558

Inhibition of TROY promotes OPC differentiation and increases therapeutic efficacy of OPC graft for spinal cord injury.

PubMed

Sun, Liang; Liu, Shengliang; Sun, Qi; Li, Zhuying; Xu, Fengyan; Hou, Chunmei; Harada, Toshihide; Chu, Ming; Xu, Kun; Feng, Xiaoling; Duan, Yongshun; Zhang, Yafang; Wu, Shuliang

2014-09-01

Endogenous or graft-derived oligodendrocytes promote myelination and aid in the recovery from central nervous system (CNS) injury. Regulatory mechanisms underlying neural myelination and remyelination in response to injury, including spinal cord injury (SCI), are unclear. In the present study, we demonstrated that TROY serves as an important negative regulator of oligodendrocyte development and that TROY inhibition augments the repair potential of oligodendrocyte precursor cell (OPC) graft for SCI. TROY expression was detected by reverse transcriptase-polymerase chain reaction in OPCs as well as in differentiated premature and mature oligodendrocytes of postnatal mice. Pharmacological inhibition or RNAi-induced knockdown of TROY promotes OPC differentiation, whereas overexpression of TROY dampens oligodendrocyte maturation. Further, treatment of cocultures of DRG neurons and OPCs with TROY inhibitors promotes myelination and myelin-sheath-like structures. Mechanically, protein kinase C (PKC) signaling is involved in the regulation of the inhibitory effects of TROY. Moreover, in situ transplantation of OPCs with TROY knockdown leads to notable remyelination and neurological recovery in rats with SCI. Our results indicate that TROY negatively modulates remyelination in the CNS, and thus may be a suitable target for improving the therapeutic efficacy of cell transplantation for CNS injury.

The effect of glia-glia interactions on oligodendrocyte precursor cell biology during development and in demyelinating diseases

PubMed Central

Clemente, Diego; Ortega, María Cristina; Melero-Jerez, Carolina; de Castro, Fernando

2013-01-01

Oligodendrocyte precursor cells (OPCs) originate in specific areas of the developing central nervous system (CNS). Once generated, they migrate towards their destinations where they differentiate into mature oligodendrocytes. In the adult, 5–8% of all cells in the CNS are OPCs, cells that retain the capacity to proliferate, migrate, and differentiate into oligodendrocytes. Indeed, these endogenous OPCs react to damage in demyelinating diseases, like multiple sclerosis (MS), representing a key element in spontaneous remyelination. In the present work, we review the specific interactions between OPCs and other glial cells (astrocytes, microglia) during CNS development and in the pathological scenario of MS. We focus on: (i) the role of astrocytes in maintaining the homeostasis and spatial distribution of different secreted cues that determine OPC proliferation, migration, and differentiation during CNS development; (ii) the role of microglia and astrocytes in the redistribution of iron, which is crucial for myelin synthesis during CNS development and for myelin repair in MS; (iii) how microglia secrete different molecules, e.g., growth factors, that favor the recruitment of OPCs in acute phases of MS lesions; and (iv) how astrocytes modify the extracellular matrix in MS lesions, affecting the ability of OPCs to attempt spontaneous remyelination. Together, these issues demonstrate how both astroglia and microglia influence OPCs in physiological and pathological situations, reinforcing the concept that both development and neural repair are complex and global phenomena. Understanding the molecular and cellular mechanisms that control OPC survival, proliferation, migration, and differentiation during development, as well as in the mature CNS, may open new opportunities in the search for reparative therapies in demyelinating diseases like MS. PMID:24391545

In Vitro and In Vivo Antibacterial Activities of OPC-20011, a Novel Parenteral Broad-Spectrum 2-Oxaisocephem Antibiotic

PubMed Central

Matsumoto, Makoto; Tamaoka, Hisashi; Ishikawa, Hiroshi; Kikuchi, Mikio

1998-01-01

OPC-20011, a new parenteral 2-oxaisocephem antibiotic, has an oxygen atom at the 2- position of the cephalosporin frame. OPC-20011 had the best antibacterial activities against gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), Enterococcus faecalis, and penicillin-resistant Streptococcus pneumoniae: MICs at which 90% of the isolates were inhibited were 6.25, 6.25, and 0.05 μg/ml, respectively. Its activity is due to a high affinity of the penicillin-binding protein 2′ in MRSA, an affinity which was approximately 1,050 times as high as that for flomoxef. Against gram-negative bacteria, OPC-20011 also showed antibacterial activities similar to those of ceftazidime. The in vivo activities of OPC-20011 were comparable to or greater than those of reference compounds in murine models of systemic infection caused by gram-positive and -negative pathogens. OPC-20011 was up to 10 times as effective as vancomycin against MRSA infections in mice. This better in vivo efficacy is probably due to the bactericidal activity of OPC-20011, while vancomycin showed bacteriostatic activity against MRSA. OPC-20011 produced a significant decrease of viable counts in lung tissue at a dose of 2.5 mg/kg of body weight, an efficacy similar to that of ampicillin at a dose of 10 to 20 mg/kg on an experimental murine model of respiratory tract infection caused by non-ampicillin-susceptible S. pneumoniae T-0005. The better therapeutic efficacy of OPC-20011 was considered to be due to its potent antibacterial activity and low affinity for serum proteins of experimental animals (29% in mice and 6.4% in rats). PMID:9797230

The quantitative determination of cilostazol and its four metabolites in human liver microsomal incubation mixtures by high-performance liquid chromatography.

PubMed

Tata, P N; Fu, C H; Browder, N J; Chow, P C; Bramer, S L

1998-11-01

A high-performance liquid chromatography-ultraviolet (HPLC-UV) method for the quantitation of cilostazol and four of its principal metabolites (i.e. OPC-13015, OPC-13213, OPC-13217 and OPC-13326) in human liver microsomal solutions was developed and validated. Cilostazol, its metabolites, and the internal standard (OPC-3930), were analyzed by protein precipitation followed by reverse-phase HPLC separation on a TSK-Gel ODS-80TM (150 x 4.6 mm, 5 microm) column and a Cosmil C-18 column (150 x 4.6 mm, 5 microm) in tandem and UV detection at 254 nm. An 80 min gradient elution of mobile phase acetonitrile in acetate buffer (pH = 6.50) was used to obtain quality chromatography and peak resolution. All the analytes were separated from each other, with the resolution being 2.43-17.59. The components of liver microsomal incubation mixture and five metabolic inhibitor probes (quinidine sulfate, diethyl dithiocarbamate (DEDTC), omeprazole, ketoconazole and furafylline) did not interfere with this analytical method. The LOQ was 1000 ng ml(-1) for cilostazol and 100 ng ml(-1) for each of the metabolites. This method has been validated for linear ranges of 100-4000 ng ml(-1) for OPC-13213, OPC-13217 and OPC-13326; 100-2000 ng ml(-1) for OPC-13015; and 1000-20000 ng ml(-1) for cilostazol. The percent relative recovery of this method was established to be 81.2-101.0% for analytes, with the precision (% coefficient of variation (CV)) being 2.8-7.7%. The autosampler stability of the analytes was evaluated and it was found that all analytes were stable at room temperature for a period of at least 17 h. This assay has been shown to be precise, accurate and reproducible.

Professional education and hospital development for organ donation.

PubMed

Fukushima, N; Konaka, S; Kato, O; Ashikari, J

2012-05-01

Because of the strict Organ Transplantation Act, only 81 brain dead (BD) organ donations had been performed in Japan for 13 years since 1997. The Act was revised on July 17, 2010, allowing, organs to be donated after BD with consent from the family, if the subject had not denied organ donation previously. This act has lead to an expectation of a 6-7-fold increase in BD donation. The 82 organ procurement coordinators (OPC) in Japan include 32 belonging to the Japanese Organ Network (JOT) and the others to each administrative division. JOT has guideline manuals of standard roles and procedures of OPC during organ procurement from BD and cardiac death donors. To manage the increased organ donations after the revision of the act, we have modified the education system. First, we modified the guideline manuals for OPC to correspond to the revised Transplant Act and governmental guidelines. Second, all OPC gathered in a meeting room to learn the new organ procurement system to deal with the revised Transplant Act and guidelines. Third, a special education program for 2 months was provided for the 10 newcomers. Last, the practical training in each donor case for newcomers was performed by older OPC. Topics of the education program were the revised transplant act and guidelines, family approach to organ donation, BD diagnosis, donor evaluation and management, organ procurement and preservation, allocation system, hospital development and family care. In the future, each OPC will be divided into special categories, such as the donor family OPC, the donor management OPC, and the operating room OPC. Therefore, we need to construct separate special education programs for each category. Copyright © 2012 Elsevier Inc. All rights reserved.

Effect of opicapone multiple-dose regimens on levodopa pharmacokinetics.

PubMed

Rocha, José-Francisco; Sicard, Éric; Fauchoux, Nicolas; Falcão, Amílcar; Santos, Ana; Loureiro, Ana I; Pinto, Roberto; Bonifácio, Maria João; Nunes, Teresa; Almeida, Luís; Soares-da-Silva, Patrício

2017-03-01

To compare the levodopa/carbidopa (LC) and levodopa/benserazide (LB) pharmacokinetic profiles following repeated doses of opicapone (OPC) administered apart from levodopa. Two randomized, double blind, sex-balanced, placebo-controlled studies in four groups of 12 or 18 healthy subjects each. In each group, enrolled subjects received a once-daily morning (5, 15 and 30 mg) or evening (5, 15 and 50 mg) administration of OPC or placebo for up to 28 days. On the morning of Day 11, 12 h after the OPC or placebo evening dose, or the morning of Day 21, 1 h after the OPC or placebo dose, a single dose of immediate-release 100/25 mg LC was administered. Similarly, on Day 18 morning, 12 h after the OPC or placebo evening dose, or Day 28 morning, 1 h after the OPC or placebo dose, a single dose of immediate-release 100/25 mg LB was administered. All OPC treatments, in relation to the placebo group, presented a higher extent of exposure (AUC) to levodopa following either LC or LB doses. A relevant but not dose-dependent increase in the levodopa AUC occurred with all OPC dose groups in relation to placebo. All active treatments significantly inhibited both peak (E max ) and extent (AUEC) of the catechol-O-methyltransferase activity in relation to placebo. The tolerability profile was favourable. Opicapone, as once-daily oral evening regimen and/or 1 h apart from levodopa therapy, increases the bioavailability of levodopa associated with its pronounced, long-lasting and sustained catechol-O-methyltransferase inhibition. The tolerability profile was favourable and similar between OPC and placebo. © 2016 The British Pharmacological Society.

Early age compressive strength, porosity, and sorptivity of concrete using peat water to produce and cure concrete

NASA Astrophysics Data System (ADS)

Olivia, Monita; Ismeddiyanto, Wibisono, Gunawan; Sitompul, Iskandar R.

2017-09-01

Construction in peatland has faced scarce water sources for mixing and curing concrete. It is known that peat water has high organic content and low pH that can be harmful to concrete in the environment. In some remote areas in Riau Province, contractors used peat water directly without sufficient treatments to comply with SKSNI requirements of concrete mixing water. This paper presents a study of compressive strength, porosity and sorptivity of Ordinary Portland Cement (OPC) and blended OPC-Palm Oil Fuel Ash (OPC-POFA) concrete. The specimens were mixed using natural water and peat water, then some of them were cured in fresh water and peat water. Six mixtures were investigated using a variation of cement, mixing water and curing water. Tap water is used as control mixing and curing water for all specimens. The compressive strength, porosity and sorptivity were calculated at seven and 28 days. Results indicate that the use of peat water will cause low compressive strength, high porosity and sorptivity for both OPC and OPC-POFA concrete. Using peat water and curing the specimens in tap water could improve the early strength, porosity and sorptivity of OPC concrete; however, it has an adverse effect on OPC-POFA specimens. The properties of early age concrete of both types (OPC and OPC-POFA) using peat water were as good as those with tap water. Therefore, it is suggested that peat water should be considered as mixing and curing water for concrete where tap water resources are scarce. Investigation of its long-term properties, as well as extending the observed age of concrete is recommended before any use of peat water.

Effect of opicapone multiple‐dose regimens on levodopa pharmacokinetics

PubMed Central

Rocha, José‐Francisco; Sicard, Éric; Fauchoux, Nicolas; Falcão, Amílcar; Santos, Ana; Loureiro, Ana I.; Pinto, Roberto; Bonifácio, Maria João; Nunes, Teresa; Almeida, Luís

2016-01-01

Aims To compare the levodopa/carbidopa (LC) and levodopa/benserazide (LB) pharmacokinetic profiles following repeated doses of opicapone (OPC) administered apart from levodopa. Methods Two randomized, double blind, sex‐balanced, placebo‐controlled studies in four groups of 12 or 18 healthy subjects each. In each group, enrolled subjects received a once‐daily morning (5, 15 and 30 mg) or evening (5, 15 and 50 mg) administration of OPC or placebo for up to 28 days. On the morning of Day 11, 12 h after the OPC or placebo evening dose, or the morning of Day 21, 1 h after the OPC or placebo dose, a single dose of immediate‐release 100/25 mg LC was administered. Similarly, on Day 18 morning, 12 h after the OPC or placebo evening dose, or Day 28 morning, 1 h after the OPC or placebo dose, a single dose of immediate‐release 100/25 mg LB was administered. Results All OPC treatments, in relation to the placebo group, presented a higher extent of exposure (AUC) to levodopa following either LC or LB doses. A relevant but not dose‐dependent increase in the levodopa AUC occurred with all OPC dose groups in relation to placebo. All active treatments significantly inhibited both peak (Emax) and extent (AUEC) of the catechol‐O‐methyltransferase activity in relation to placebo. The tolerability profile was favourable. Conclusion Opicapone, as once‐daily oral evening regimen and/or 1 h apart from levodopa therapy, increases the bioavailability of levodopa associated with its pronounced, long‐lasting and sustained catechol‐O‐methyltransferase inhibition. The tolerability profile was favourable and similar between OPC and placebo. PMID:27763682

Distress levels in patients with oropharyngeal vs. non-oropharyngeal squamous cell carcinomas of the head and neck over 1 year after diagnosis: a retrospective cohort study.

PubMed

Schorr, Melissa; Carlson, Linda E; Lau, Harold Y; Zhong, Lihong; Bultz, Barry D; Waller, Amy; Groff, Shannon L; Hao, Desiree

2017-10-01

Human papillomavirus (HPV)-related cancers have been associated with different demographic profiles and disease characteristics than HPV-unrelated cancers in head and neck patients, but distress and other symptoms have not been compared. The aim of this study was to assess whether distress levels, fatigue, pain, anxiety, depression, and common psychological and practical problems differ between head and neck cancer patients with HPV-related vs. HPV-unrelated carcinomas (using oropharyngeal carcinoma (OPC) and non-OPC cancers as surrogates for HPV status). Distress, depression, anxiety, fatigue, pain, and common problems were examined in 56 OPC and 90 non-OPC patients at 4 timepoints during the first year following diagnosis. Two-level hierarchical linear modeling was used to examine effects. The HPV-related OPC group was more likely to be younger (p = 0.05), Caucasian (p = 0.001), non-smokers (p = 0.01), earn more (p = 0.04), and present with more advanced stage (p < 0.0001). At baseline, OPC patients reported only higher pain scores (p = 0.01) than non-OPC patients. Total problems decreased more in the OPC group (p = 0.08) than the non-OPC group from baseline to 12-month follow-up. In both groups, scores on distress, depression, psychosocial problems, and practical problems decreased similarly over time. Despite a difference in the clinico-demographic characteristics of HPV-related vs. HPV-unrelated patients, only baseline pain levels and total problems over time differed between the two groups.

Oligomeric proanthocyanidins inhibit apoptosis of chondrocytes induced by interleukin-1β.

PubMed

Yin, Meng-Hong; Wang, Yi-Teng; Li, Qing; Lv, Guo-Feng

2017-10-01

Oligomeric proanthocyanidin (OPC) is a water-soluble plant polyphenolic compound known for its cytoprotective effects in various tissue types. However, its effect on chondrocytes has not been well characterized. The present study aimed to investigate the effect of OPC on interleukin‑1β (IL‑1β)‑induced apoptosis in chondrocytes, and to determine the mechanisms underlying the protective effects of OPC. Knee articular chondrocytes obtained from 6‑week‑old SPF Kunming mice were cultured and serially passaged. First‑generation chondrocytes were selected for subsequent experiments following toluidine blue staining. Subsequent to IL‑1β and OPC administration, an MTT assay was performed to examine the viability rate of chondrocytes, and the optimal drug concentration was determined. The fluorescence dye 2',7'-dichlorofluorescein diacetate was used to determine the intracellular content of reactive oxygen species (ROS). Mitochondrial membrane potential (MMP) was measured using a 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl-benzimidazolylcarbocyanine iodide (JC‑1) assay. The apoptosis rate of chondrocytes was assessed using an Annexin V‑FITC/PI assay and ultrastructural changes were observed under an electron microscope. The results demonstrated that OPC increased the survival rate of chondrocytes against IL‑1β‑induced apoptosis. The most significant protective effect of OPC was observed at the concentration of 0.050 mg/ml. OPC reversed the increased ROS content and MMP levels, and inhibited IL‑1β‑induced apoptosis in chondrocytes. In addition, OPC was revealed to protect the ultrastructural integrity of chondrocytes. Taken together, the results of the present study suggest that OPC protects chondrocytes against IL‑1β‑induced damage by decreasing ROS content and MMP levels.

Rising population of survivors of oral squamous cell cancer in the United States.

PubMed

Patel, Mira A; Blackford, Amanda L; Rettig, Eleni M; Richmon, Jeremy D; Eisele, David W; Fakhry, Carole

2016-05-01

The incidence of oropharyngeal cancer (OPC) and a subset of oral cavity cancer (OCC) is increasing in the United States. To the authors' knowledge, the presumed growing prevalence of survivors of OPC and OCC has not been investigated to date. Retrospective analysis of Surveillance, Epidemiology, and End Results data (1975-2012) estimated changes in incidence, 5-year cause-specific survival, and prevalence for OPC and OCC. Changes in incidence, cause-specific survival and prevalence were estimated by linear regression and expressed as the percentage change (B). Differences in incidence trends over time were determined by joinpoint analysis. The incidence of OPC increased by 62.6% from 1975 through 2012. Notable increases in OPC incidence were observed among men, white individuals, and those of younger ages. The 5-year survival for OPC increased significantly for all sexes, races, and individuals aged >30 years, with white individuals and males experiencing the largest increase in survival. By contrast, the incidence of OCC declined by 22.3% during the same time period. OCC incidence decreased across all groups but increased among individuals aged 30 to 39 years. Significant increases in survival were observed for OCC, except for those who were female, black, and aged <40 years. The prevalence of survivors of OPC increased from 2000 to 2012 (B, 115.1 per 100,000 individuals per year; P<.0001), whereas the prevalence of survivors of OCC significantly decreased (B, -15.8 per 100,000 individuals per year; P<.0001). The prevalence of survivors of OPC is increasing, whereas the prevalence of survivors of OCC is declining. These data portend significant implications for long-term care planning for survivors of OPC and OCC. Cancer 2016;122:1380-1387. © 2016 American Cancer Society. © 2016 American Cancer Society.

Ordinary portland cement based solidification of toxic wastes: The role of OPC reviewed

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

Hills, C.D.; Sollars, C.J.; Perry, R.

1993-01-01

A mixed waste stream, which is commercially solidified, has been solidified in the laboratory using OPC and PFA (pulverized fly ash) in a variety of mix proportions. The solidified products have been subjected to calorimetric, physical and microstructural analysis. The heat of hydration for OPC/waste mixes showed that a progressive poisoning of normal hydration reactions occurred with increasing waste addition. Once poisoned OPC failed to act as a cement and was substituted by PFA and other products in this role. Strength development was found to be related to the heat of hydration; this suggests that conduction calorimetry could be usedmore » to determine the suitability of a particular waste for OPC based solidification.« less

Accelerated generation of oligodendrocyte progenitor cells from human induced pluripotent stem cells by forced expression of Sox10 and Olig2.

PubMed

Li, Pengyan; Li, Mo; Tang, Xihe; Wang, Shuyan; Zhang, Y Alex; Chen, Zhiguo

2016-11-01

Oligodendrocyte progenitor cells (OPCs) hold great promise for treatment of dysmyelinating disorders, such as multiple sclerosis and cerebral palsy. Recent studies on generation of human OPCs mainly use human embryonic stem cells (hESCs) or neural stem cells (NSCs) as starter cell sources for the differentiation process. However, NSCs are restricted in availability and the present method for generation of oligodendrocytes (OLs) from ESCs often requires a lengthy period of time. Here, we demonstrated a protocol to efficiently derive OPCs from human induced pluripotent stem cells (hiPSCs) by forced expression of two transcription factors (2TFs), Sox10 and Olig2. With this method, PDGFRα + OPCs can be obtained in 14 days and O4 + OPCs in 56 days. Furthermore, OPCs may be able to differentiate to mature OLs that could ensheath axons when co-cultured with rat cortical neurons. The results have implications in the development of autologous cell therapies.

Asking the difficult questions: message strategies used by organ procurement coordinators in requesting familial consent to organ donation.

PubMed

Anker, Ashley E; Feeley, Thomas Hugh

2011-07-01

The present study provides an in-depth examination of the messages used by organ procurement coordinators (OPCs) in shaping familial requests for organ donation. OPCs (N = 102), recruited from a national sample of 16 organ procurement organizations, participated in a structured interview designed to uncover the communication strategies used in obtaining familial consent for donation. Analysis of interviews indicates OPCs' messages cover 4 domain areas. Specifically, OPCs report use of messages intended to (a) provide education, (b) discuss the benefits to donation, (c) learn about potential donor families, and (d) persuade families to engage in donation. Within the 4 domain areas, OPCs report use of 15 specific messages (e.g., "positively framing the donor," "social proof," "discuss the benefit of donation to grieving") in requesting consent. The present study provides a detailed examination of strategies and offers recommendations for using message strategies to explore the effectiveness of the consent process from the perspective of OPCs in approaching donor families.

Characterization of titanyl phthalocyanine (TiOPc) thin films by microscopic and spectroscopic method

NASA Astrophysics Data System (ADS)

Skonieczny, R.; Makowiecki, J.; Bursa, B.; Krzykowski, A.; Szybowicz, M.

2018-02-01

The titanyl phthalocyanine (TiOPc) thin film deposited on glass, silicon and gold substrate have been studied using Raman spectroscopy, atomic force microscopy (AFM), absorption and profilometry measurements. The TiOPc thin layers have been deposited at room temperature by the quasi-molecular beam evaporation technique. The Raman spectra have been recorded using micro Raman system equipped with a confocal microscope. Using surface Raman mapping techni que with polarized Raman spectra the polymorphic forms of the TiOPc thin films distribution have been obtained. The AFM height and phase image were examined in order to find surface features and morphology of the thin films. Additionally to compare experimental results, structure optimization and vibrational spectra calculation of single TiOPc molecule were performed using DFT calculations. The received results showed that the parameters like polymorphic form, grain size, roughness of the surface in TiOPc thin films can well characterize the obtained organic thin films structures in terms of their use in optoelectronics and photovoltaics devices.

Corrosion of aluminium metal in OPC- and CAC-based cement matrices

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

Kinoshita, Hajime, E-mail: h.kinoshita@sheffield.ac.uk; Swift, Paul; Utton, Claire

Corrosion of aluminium metal in ordinary Portland cement (OPC) based pastes produces hydrogen gas and expansive reaction products causing problems for the encapsulation of aluminium containing nuclear wastes. Although corrosion of aluminium in cements has been long known, the extent of aluminium corrosion in the cement matrices and effects of such reaction on the cement phases are not well established. The present study investigates the corrosion reaction of aluminium in OPC, OPC-blast furnace slag (BFS) and calcium aluminate cement (CAC) based systems. The total amount of aluminium able to corrode in an OPC and 4:1 BFS:OPC system was determined, andmore » the correlation between the amount of calcium hydroxide in the system and the reaction of aluminium obtained. It was also shown that a CAC-based system could offer a potential matrix to incorporate aluminium metal with a further reduction of pH by introduction of phosphate, producing a calcium phosphate cement.« less

Scale-up of recombinant Opc protein production in Escherichia coli for a meningococcal vaccine.

PubMed

Pérez, Raúl Espinosa; Lasa, Alexis Musacchio; Rodríguez, Ricardo Silva; Menéndez, Evelin Caballero; Suárez, José García; Balaguer, Héctor Díaz

2006-12-15

Opc is an outer membrane protein from Neisseria meningitidis present in meningococcal vaccine preparations. The opc gene, codifying for this protein, was cloned in to Escherichia coli and the Opc protein was expressed under the control of a tryptophan promoter. The recombinant strain was grown in batch cultures. Opc was expressed as inclusion bodies at about 32% of the total cellular protein. We examined the scale-up culture conditions for the production of the recombinant Opc. The scale-up process was performed from 1.5 l to 50 l culture, using first, the constant power per unit of volume (P/V) as main scaling criteria, and then the oxygen mass transfer coefficient (K(L)a) scaling criteria to adjust the optimal aeration conditions. A final productivity of 52 mgl(-1)h(-1) was obtained at the 50l culture scale compared with the 49 mgl(-1)h(-1) productivity at 1.5l laboratory scale.

The Effects of Social Anxiety and Online Privacy Concern on Individual Differences in Internet-Based Interaction Anxiety and Communication Preferences.

PubMed

Shaughnessy, Krystelle; Rocheleau, Jessica N; Kamalou, Somayyeh; Moscovitch, David A

2017-04-01

Social anxiety (SA) and online privacy concerns (OPCs) are conceptually distinct fears, but both may be activated by Internet-based social contexts. Whereas SA is focused on being the object of interpersonal evaluation, OPC is focused on preventing others from gaining unauthorized access to private personal information. No research to date has investigated how SA and OPCs may uniquely or interactively predict individual differences in online interaction anxiety or attitudes and preferences about online communication. Participants (N = 374) completed the Social Phobia Inventory and measures of OPCs, online interaction anxiety, and attitudes related to online communication. The results revealed that SA and OPCs were not correlated with one another; however, they each uniquely predicted significant variance in particular outcomes, with no interactive effects. Findings help to illuminate the ways in which online communication preferences may be differentially shaped by people's levels of SA and OPCs, respectively. Theoretical implications and applications are discussed.

Diffusion in cementitious materials. 2: Further investigations of chloride and oxygen diffusion in well-cured OPC and OPC/30%PFA pastes

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

Ngala, V.T.; Page, C.L.; Parrott, L.J.

1995-05-01

Steady-state diffusion of dissolved oxygen and chloride ions in hydrated OPC and OPC/30%PFA pastes, hydrated for 2 weeks at 20 C and 10 weeks at 38 C, was studied at water/binder (w/s) ratios 0.4, 0.5, 0.6 and 0.7. Total porosity and a simple measure of capillary porosity, the volume fractions of the water lost in specimens from a saturated surface dry condition to a near-constant weight at 90.7% relative humidity, were also determined. The diffusion rate of chloride ions diminished markedly, to very low values, as the capillary porosity approached zero. For a given w/s ratio or capillary porosity themore » chloride ion diffusion coefficient for OPC/30%PFA pastes was about one order of magnitude smaller than that to OPC pastes. The rate of diffusion of dissolved oxygen also diminished as the capillary porosity reduced but it was still significant as the capillary porosity approached zero. For a given capillary porosity the oxygen diffusion coefficient for OPC/30%PFA pastes was about 30% smaller than that for OPC pastes. The results support the view that chloride ion diffusion in pastes of low capillary porosity is retarded by the surface charge of the hydrated cement gel. In contrast, the hydrated cement gel is much more permeable to the similarly-sized, neutral oxygen molecule.« less

UAF: a generic OPC unified architecture framework

NASA Astrophysics Data System (ADS)

Pessemier, Wim; Deconinck, Geert; Raskin, Gert; Saey, Philippe; Van Winckel, Hans

2012-09-01

As an emerging Service Oriented Architecture (SOA) specically designed for industrial automation and process control, the OPC Unied Architecture specication should be regarded as an attractive candidate for controlling scientic instrumentation. Even though an industry-backed standard such as OPC UA can oer substantial added value to these projects, its inherent complexity poses an important obstacle for adopting the technology. Building OPC UA applications requires considerable eort, even when taking advantage of a COTS Software Development Kit (SDK). The OPC Unied Architecture Framework (UAF) attempts to reduce this burden by introducing an abstraction layer between the SDK and the application code in order to achieve a better separation of the technical and the functional concerns. True to its industrial origin, the primary requirement of the framework is to maintain interoperability by staying close to the standard specications, and by expecting the minimum compliance from other OPC UA servers and clients. UAF can therefore be regarded as a software framework to quickly and comfortably develop and deploy OPC UA-based applications, while remaining compatible to third party OPC UA-compliant toolkits, servers (such as PLCs) and clients (such as SCADA software). In the rst phase, as covered by this paper, only the client-side of UAF has been tackled in order to transparently handle discovery, session management, subscriptions, monitored items etc. We describe the design principles and internal architecture of our open-source software project, the rst results of the framework running at the Mercator Telescope, and we give a preview of the planned server-side implementation.

OPC model data collection for 45-nm technology node using automatic CD-SEM offline recipe creation

NASA Astrophysics Data System (ADS)

Fischer, Daniel; Talbi, Mohamed; Wei, Alex; Menadeva, Ovadya; Cornell, Roger

2007-03-01

Optical and Process Correction in the 45nm node is requiring an ever higher level of characterization. The greater complexity drives a need for automation of the metrology process allowing more efficient, accurate and effective use of the engineering resources and metrology tool time in the fab, helping to satisfy what seems an insatiable appetite for data by lithographers and modelers charged with development of 45nm and 32nm processes. The scope of the work referenced here is a 45nm design cycle "full-loop automation", starting with gds formatted target design layout and ending with the necessary feedback of one and two dimensional printed wafer metrology. In this paper the authors consider the key elements of software, algorithmic framework and Critical Dimension Scanning Electron Microscope (CDSEM) functionality necessary to automate its recipe creation. We evaluate specific problems with the methodology of the former art, "on-tool on-wafer" recipe construction, and discuss how the implementation of the design based recipe generation improves upon the overall metrology process. Individual target-by-target construction, use of a one pattern recognition template fits all approach, a blind navigation to the desired measurement feature, lengthy sessions on tool to construct recipes and limited ability to determine measurement quality in the resultant data set are each discussed as to how the state of the art Design Based Metrology (DBM) approach is implemented. The offline created recipes have shown pattern recognition success rates of up to 100% and measurement success rates of up to 93% for line/space as well as for 2D Minimum/Maximum measurements without manual assists during measurement.

[Procyanidins enhance the chemotherapeutic sensitivity of laryngeal carcinoma cells to cisplatin through autophagy pathway].

PubMed

Yu, Feng; Liu, Wei; Gong, Xiao Rong; Zhou, Yi Bo; Lin, Ying

2018-03-01

To investigate the effect of Procyanidins (OPCs) on the autophagy of laryngeal cancer cell line TU686 and to explore the effect of OPCs on the chemosensitivity of laryngeal cancer cells to DDP in terms of autophagy and apoptosis. CCK-8 was used to detected the effect of different concentrations of OPC and DDP on TU686 cell viability. Experimental grouping: Both kinds of cells were divided into CON group, DDP group, OPC group and MIX group. Annexin-V-FITC/PI double staining of flow cytometry was used to detect the effect of each experimental group on the apoptosis. Cell immunofluorescence staining was used to detect the formation of autophagy. Western blot was used to detect the expression of autophagy-related and apoptosis-related proteins. Autophagy inhibitors (3-MA) were used to study the effect of autophagy on apoptosis. The results of CCK-8 showed that TU686 cells were inhibited by OPC and DDP in a concentration-dependent manner for 24 hours. LC3-Ⅱ protein staining showed that compared with CON group, DDP group and OPC group, MIX group significantly induced autophagy formation in TU686 cells ( P <0.05). Flow cytometry showed that compared with CON group, apoptosis of TU686 cells was induced in DDP group, OPC group and MIX group. And the effect of MIX on apoptosis was significantly higher than that of OPC and DDP groups ( P <0.05). After pretreatment with 3-MA, the apoptotic effect of OPC group and MIX group on TU686 cells was significantly decreased ( P <0.05). Western blot results showed that the expression of LC3-Ⅱ and Caspase-3 in DDP, OPC and MIX groups was significantly higher than that in CON group ( P <0.05). In MIX group, the expression of LC3-Ⅱ and Caspase-3 also had significant difference ( P <0.05) compared with single drug group. After using 3-MA to inhibit autophagy, the expression of LC3-Ⅱ was significantly decreased ( P <0.05), and the expression of Caspase-3 was decreased along with LC3-Ⅱ, but the decrease of Caspase-3 expression was only significant in OPC and MIX group ( P <0.05). OPC can induce autophagy in laryngeal carcinoma TU686 cells and promote its apoptosis, which in turn enhances sensitivity of laryngeal cancer cells to cisplatin chemotherapy. Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.

Neisseria meningitidis Opc invasin binds to the cytoskeletal protein alpha-actinin.

PubMed

Sa E Cunha, Claudia; Griffiths, Natalie J; Murillo, Isabel; Virji, Mumtaz

2009-03-01

Neisseria meningitidis Opc protein is an effective invasin for human endothelial cells. We have investigated novel human endothelial receptors targeted by Opc and observed that Opc-expressing bacteria interacted with a 100 kDa protein in whole-cell lysates of human endothelial and epithelial cells. The identity of the protein was established as alpha-actinin by mass spectrometry. Opc expression was essential for the recognition of alpha-actinin whether provided in a purified form or in cell extracts. The interaction of the two proteins did not involve intermediate molecules. As there was no demonstrable expression of alpha-actinin on the surfaces of any of the eight cell lines studied, the likelihood of the interactions after meningococcal internalization was examined. Confocal imaging demonstrated considerable colocalization of N. meningitidis with alpha-actinin especially after a prolonged period of internalization. This may imply that bacteria and alpha-actinin initially occur in separate compartments and co-compartmentalization occurs progressively over the 8 h infection period used. In conclusion, these studies have identified a novel and an intracellular target for the N. meningitidis Opc invasin. Since alpha-actinin is a modulator of a variety of signalling pathways and of cytoskeletal functions, its targeting by Opc may enable bacteria to survive/translocate across endothelial barriers.

Inhibitory effect of vasopressin receptor antagonist OPC-31260 on experimental brain oedema induced by global cerebral ischaemia.

PubMed

Molnár, A H; Varga, C; Berkó, A; Rojik, I; Párducz, A; László, F; László, F A

2008-03-01

The effects of the non-peptide vasopressin V(2) receptor antagonist 5-dimethylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine hydrochloride (OPC-31260) on the cerebral oedema induced by general cerebral hypoxia were studied in rats. The general cerebral hypoxia was produced by bilateral common carotid ligation in Sprague-Dawley rats of the CFY strain. By 6 h after the ligation, half of the rats had died, but the survival rate was significantly higher following OPC-31260 administration. Electron microscopic examinations revealed typical ischaemic changes after the carotid ligation. The carotid ligation increased the brain contents of water and Na(+) and enhanced the plasma vasopressin level. The increased brain water and Na(+) accumulation was prevented by OPC-31260 administration, but the plasma vasopressin level was further enhanced by OPC-31260. These results demonstrate the important role of vasopressin in the development of the disturbances in brain water and electrolyte balance in response to general cerebral hypoxia. The carotid ligation-induced cerebral oedema was significantly reduced following oral OPC-31260 administration. The protective mechanism exerted by OPC-31260 stems from its influence on the renal vasopressin V(2) receptors. These observations might suggest an effective approach to the treatment of global hypoxia-induced cerebral oedema in humans.

Myt1L Promotes Differentiation of Oligodendrocyte Precursor Cells and is Necessary for Remyelination After Lysolecithin-Induced Demyelination.

PubMed

Shi, Yanqing; Shao, Qi; Li, Zhenghao; Gonzalez, Ginez A; Lu, Fengfeng; Wang, Dan; Pu, Yingyan; Huang, Aijun; Zhao, Chao; He, Cheng; Cao, Li

2018-04-01

The differentiation and maturation of oligodendrocyte precursor cells (OPCs) is essential for myelination and remyelination in the CNS. The failure of OPCs to achieve terminal differentiation in demyelinating lesions often results in unsuccessful remyelination in a variety of human demyelinating diseases. However, the molecular mechanisms controlling OPC differentiation under pathological conditions remain largely unknown. Myt1L (myelin transcription factor 1-like), mainly expressed in neurons, has been associated with intellectual disability, schizophrenia, and depression. In the present study, we found that Myt1L was expressed in oligodendrocyte lineage cells during myelination and remyelination. The expression level of Myt1L in neuron/glia antigen 2-positive (NG2 + ) OPCs was significantly higher than that in mature CC1 + oligodendrocytes. In primary cultured OPCs, overexpression of Myt1L promoted, while knockdown inhibited OPC differentiation. Moreover, Myt1L was potently involved in promoting remyelination after lysolecithin-induced demyelination in vivo. ChIP assays showed that Myt1L bound to the promoter of Olig1 and transcriptionally regulated Olig1 expression. Taken together, our findings demonstrate that Myt1L is an essential regulator of OPC differentiation, thereby supporting Myt1L as a potential therapeutic target for demyelinating diseases.

Astrocytes Promote Oligodendrogenesis after White Matter Damage via Brain-Derived Neurotrophic Factor.

PubMed

Miyamoto, Nobukazu; Maki, Takakuni; Shindo, Akihiro; Liang, Anna C; Maeda, Mitsuyo; Egawa, Naohiro; Itoh, Kanako; Lo, Evan K; Lok, Josephine; Ihara, Masafumi; Arai, Ken

2015-10-14

Oligodendrocyte precursor cells (OPCs) in the adult brain contribute to white matter homeostasis. After white matter damage, OPCs compensate for oligodendrocyte loss by differentiating into mature oligodendrocytes. However, the underlying mechanisms remain to be fully defined. Here, we test the hypothesis that, during endogenous recovery from white matter ischemic injury, astrocytes support the maturation of OPCs by secreting brain-derived neurotrophic factor (BDNF). For in vitro experiments, cultured primary OPCs and astrocytes were prepared from postnatal day 2 rat cortex. When OPCs were subjected to chemical hypoxic stress by exposing them to sublethal CoCl2 for 7 d, in vitro OPC differentiation into oligodendrocytes was significantly suppressed. Conditioned medium from astrocytes (astro-medium) restored the process of OPC maturation even under the stressed conditions. When astro-medium was filtered with TrkB-Fc to remove BDNF, the BDNF-deficient astro-medium no longer supported OPC maturation. For in vivo experiments, we analyzed a transgenic mouse line (GFAP(cre)/BDNF(wt/fl)) in which BDNF expression is downregulated specifically in GFAP(+) astrocytes. Both wild-type (GFAP(wt)/BDNF(wt/fl) mice) and transgenic mice were subjected to prolonged cerebral hypoperfusion by bilateral common carotid artery stenosis. As expected, compared with wild-type mice, the transgenic mice exhibited a lower number of newly generated oligodendrocytes and larger white matter damage. Together, these findings demonstrate that, during endogenous recovery from white matter damage, astrocytes may promote oligodendrogenesis by secreting BDNF. The repair of white matter after brain injury and neurodegeneration remains a tremendous hurdle for a wide spectrum of CNS disorders. One potentially important opportunity may reside in the response of residual oligodendrocyte precursor cells (OPCs). OPCs may serve as a back-up for generating mature oligodendrocytes in damaged white matter. However, the underlying mechanisms are still mostly unknown. Here, we use a combination of cell biology and an animal model to report a new pathway in which astrocyte-derived BDNF supports oligodendrogenesis and regeneration after white matter damage. These findings provide new mechanistic insight into white matter physiology and pathophysiology, which would be broadly and clinically applicable to CNS disease. Copyright © 2015 the authors 0270-6474/15/3514002-07$15.00/0.

Potent aquaretic agent. A novel nonpeptide selective vasopressin 2 antagonist (OPC-31260) in men.

PubMed Central

Ohnishi, A; Orita, Y; Okahara, R; Fujihara, H; Inoue, T; Yamamura, Y; Yabuuchi, Y; Tanaka, T

1993-01-01

Solute-free water diuretics (aquaretics) by antagonizing hydrosmotic vasopressin receptors (V2) may be useful in treating water-retaining diseases. The effects of intravenous administration of a newly developed nonpeptide, selective V2 antagonist, OPC-31260, at doses ranging from 0.017 to 1.0 mg/kg to groups of healthy, normally hydrated men were compared with those of 0.33 mg/kg furosemide and placebo. OPC-31260 increased the hypotonic urine volume dose dependently for the first 4 h, while furosemide induced sodium diuresis for 2 h. The absolute increase in the cumulative response in the urine to the highest doses of OPC-31260 was not significantly different from that to furosemide. The higher doses of OPC-31260 rapidly lowered urine osmolality for 2 h, particularly between minutes 15 and 45 (e.g., 1.0-mg/kg dose: 63 +/- 2 mOsm/kg in urine collected between minutes 30 and 45). In a marked hypotonic diuresis, mean free water clearance of the 4-h urine increased dose proportionally into the positive range, reaching 1.80 +/- 0.21 ml/min at 1.0 mg/kg. Whereas furosemide induced marked Na and K diuresis, OPC-31260 increased urinary Na excretion only slightly. At 4 h, 0.75 and 1.0 mg/kg of OPC-31260 almost doubled the plasma arginine vasopressin; and the higher doses increased plasma osmolality and plasma Na slightly, but did not alter plasma K, blood pressure, or heart rate. OPC-31260 thus safely induced a potent aquaretic effect in men. Images PMID:8254021

Results of the combined U.S. Multicenter Pivotal Study and the Continuing Access Study of the Nit-Occlud PDA device for percutaneous closure of patent ductus arteriosus.

PubMed

Moore, John W; Greene, Jessica; Palomares, Salvadore; Javois, Alexander; Owada, Carl Y; Cheatham, John P; Hoyer, Mark H; Jones, Thomas K; Levi, Daniel S

2014-12-01

This study aimed to compare the efficacy and safety of the Nit-Occlud PDA device (PFM Medical, Cologne, Germany) to benchmarks designed as objective performance criteria (OPC). The Nit-Occlud PDA is a nitinol coil-type patent ductus arteriosus (PDA) occluder with a reverse cone configuration, which is implanted using a controlled delivery system. Patients with <4-mm minimum diameter PDA were prospectively enrolled in the Pivotal and the Continuing Access Studies from 15 sites in the United States and were followed up for 12 months post-procedure. Investigator-reported outcomes were compared to OPC including a composite success criterion, efficacy criteria of successful closure (clinical and echocardiographic), and safety criteria incidence of adverse events (serious and of total). The Pivotal Study enrolled patients between November 1, 2002 and October 31, 2005, and the Continuing Access Study enrolled additional patients between September 1, 2006 and October 31, 2007. A total of 357 patients were enrolled, and 347 had successful device implantations. After 12 months, 96.8% had complete echocardiographic closure (OPC = 85%) and 98.1% had clinical closure (OPC = 95%). There were no deaths or serious adverse events (OPC = 1%). The total adverse event rate was 4.7% (OPC = 6%). Composite success was 95.1% in the study patients (OPC = 80%). Closure of small- and medium-sized PDA with the Nit-Occlud PDA is effective and safe when compared with OPC. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Protocol to Isolate a Large Amount of Functional Oligodendrocyte Precursor Cells from the Cerebral Cortex of Adult Mice and Humans

PubMed Central

Medina-Rodríguez, Eva María; Arenzana, Francisco Javier; Bribián, Ana; de Castro, Fernando

2013-01-01

During development, oligodendrocytes are generated from oligodendrocyte precursor cells (OPCs), a cell type that is a significant proportion of the total cells (3-8%) in the adult central nervous system (CNS) of both rodents and humans. Adult OPCs are responsible for the spontaneous remyelination that occurs in demyelinating diseases like Multiple Sclerosis (MS) and they constitute an interesting source of cells for regenerative therapy in such conditions. However, there is little data regarding the neurobiology of adult OPCs isolated from mice since an efficient method to isolate them has yet to be established. We have designed a protocol to obtain viable adult OPCs from the cerebral cortex of different mouse strains and we have compared its efficiency with other well-known methods. In addition, we show that this protocol is also useful to isolate functional OPCs from human brain biopsies. Using this method we can isolate primary cortical OPCs in sufficient quantities so as to be able to study their survival, maturation and function, and to facilitate an evaluation of their utility in myelin repair. PMID:24303061

Protocol to isolate a large amount of functional oligodendrocyte precursor cells from the cerebral cortex of adult mice and humans.

PubMed

Medina-Rodríguez, Eva María; Arenzana, Francisco Javier; Bribián, Ana; de Castro, Fernando

2013-01-01

During development, oligodendrocytes are generated from oligodendrocyte precursor cells (OPCs), a cell type that is a significant proportion of the total cells (3-8%) in the adult central nervous system (CNS) of both rodents and humans. Adult OPCs are responsible for the spontaneous remyelination that occurs in demyelinating diseases like Multiple Sclerosis (MS) and they constitute an interesting source of cells for regenerative therapy in such conditions. However, there is little data regarding the neurobiology of adult OPCs isolated from mice since an efficient method to isolate them has yet to be established. We have designed a protocol to obtain viable adult OPCs from the cerebral cortex of different mouse strains and we have compared its efficiency with other well-known methods. In addition, we show that this protocol is also useful to isolate functional OPCs from human brain biopsies. Using this method we can isolate primary cortical OPCs in sufficient quantities so as to be able to study their survival, maturation and function, and to facilitate an evaluation of their utility in myelin repair.

Retrovirus-mediated conditional immortalization and analysis of established cell lines of osteoclast precursor cells

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

Kawata, Shigehisa; Suzuki, Jun; Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871

2006-11-10

Osteoclast precursor cells (OPCs) have previously been established from bone marrow cells of SV40 temperature-sensitive T antigen-expressing transgenic mice. Here, we use retrovirus-mediated gene transfer to conditionally immortalize OPCs by expressing temperature-sensitive large T antigen (tsLT) from wild type bone marrow cells. The immortalized OPCs proliferated at the permissive temperature of 33.5 deg. C, but stopped growing at the non-permissive temperature of 39 deg. C. In the presence of receptor activator of NF{kappa}B ligand (RANKL), the OPCs differentiated into tartrate-resistant acid phosphatase (TRAP)-positive cells and formed multinucleate osteoclasts at 33.5 deg. C. From these OPCs, we cloned two types ofmore » cell lines. Both differentiated into TRAP-positive cells, but one formed multinucleate osteoclasts while the other remained unfused in the presence of RANKL. These results indicate that the established cell lines are useful for analyzing mechanisms of differentiation, particularly multinucleate osteoclast formation. Retrovirus-mediated conditional immortalization should be a useful method to immortalize OPCs from primary bone marrow cells.« less

Sirt1 regulates glial progenitor proliferation and regeneration in white matter after neonatal brain injury

PubMed Central

Jablonska, Beata; Gierdalski, Marcin; Chew, Li-Jin; Hawley, Teresa; Catron, Mackenzie; Lichauco, Arturo; Cabrera-Luque, Juan; Yuen, Tracy; Rowitch, David; Gallo, Vittorio

2016-01-01

Regenerative processes in brain pathologies require the production of distinct neural cell populations from endogenous progenitor cells. We have previously demonstrated that oligodendrocyte progenitor cell (OPC) proliferation is crucial for oligodendrocyte (OL) regeneration in a mouse model of neonatal hypoxia (HX) that reproduces diffuse white matter injury (DWMI) of premature infants. Here we identify the histone deacetylase Sirt1 as a Cdk2 regulator in OPC proliferation and response to HX. HX enhances Sirt1 and Sirt1/Cdk2 complex formation through HIF1α activation. Sirt1 deacetylates retinoblastoma (Rb) in the Rb/E2F1 complex, leading to dissociation of E2F1 and enhanced OPC proliferation. Sirt1 knockdown in culture and its targeted ablation in vivo suppresses basal and HX-induced OPC proliferation. Inhibition of Sirt1 also promotes OPC differentiation after HX. Our results indicate that Sirt1 is an essential regulator of OPC proliferation and OL regeneration after neonatal brain injury. Therefore, enhancing Sirt1 activity may promote OL recovery after DWMI. PMID:27991597

Antidiuretic effects of a nonpeptide vasopressin V(2)-receptor agonist, OPC-51803, administered orally to rats.

PubMed

Nakamura, S; Hirano, T; Tsujimae, K; Aoyama, M; Kondo, K; Yamamura, Y; Mori, T; Tominaga, M

2000-12-01

OPC-51803 is the first nonpeptide vasopressin (AVP) V(2)-receptor-selective agonist. Its pharmacological profile, including antidiuretic action and receptor binding, was characterized using conscious Brattleboro rats with hereditary diabetes insipidus and Sprague-Dawley rats. In membrane preparations from the liver and kidney, OPC-51803 displaced the [(3)H]AVP binding to V(2)-receptors (K(i) = 49.8 +/- 8.1 nM) more greatly than that to V(1a)-receptors (K(i) = 1061 +/- 60 nM), showing a 21 times higher affinity for V(2)-receptors. At single oral doses of 0.003 to 0.3 mg/kg in female Brattleboro rats, OPC-51803 decreased urine volume (from 10.8 +/- 1.1 to 0.5 +/- 0.2 ml during 0-2 h postdosing) and increased urinary osmolality (from 114 +/- 9 to 432 +/- 114 mOsm/kg) in a dose-dependent manner. During the period of 4-week treatment with OPC-51803, significant and constant antidiuresis was observed. In male Sprague-Dawley rats with normal plasma AVP levels, OPC-51803 at 0.03 to 0.3 mg/kg also produced a dose-dependent antidiuretic action (urine volume: from 2.6 +/- 0.6 to 1.1 +/- 0.2 ml at 0-4 h postdosing). Few changes in urinary parameters, serum parameters, or plasma hormone levels were observed. OPC-51803 did not change blood pressure or heart rate, or inhibit AVP-induced pressor response even at 30 mg/kg p.o. These results demonstrate that OPC-51803 is a V(2)-selective agonist that produces a significant antidiuretic action after single and multiple oral dosing in AVP-deficient and normal AVP states. The data suggest that OPC-51803 is a useful therapeutic drug in the treatment of hypothalamic diabetes insipidus, nocturnal enuresis, and some kinds of urinary incontinence.

Interaction of organophosphorus compounds with carboxylesterases in the rat.

PubMed

Jokanović, M; Kosanović, M; Maksimović, M

1996-01-01

Carboxylesterases (CarbE) are involved in detoxication of organophosphorus compounds (OPC) through two mechanisms: hydrolysis of ester bonds in OPC which contain them and binding of OPC at the active site of CarbE which reduces the amount of OPC available for acetylcholinesterase inhibition. This study of the interaction of rat plasma and liver CarbE with dichlorvos, soman and sarin in vitro and in vivo was undertaken in order to contribute to better understanding of the role of CarbE in detoxication of OPC. The results obtained have shown that inhibitory potency (I50) of dichlorvos, sarin and soman towards rat liver CarbE was 0.2 microM, 0.5 microM and 4.5 microM, respectively, for 20-min incubation at 25 degrees C. Second-order rate constants (k(a)) for liver CarbE inhibition were 2.3 x 10(5) M-1 min-1, 6.9 x 10(4) M-1 min-1 and 1.1 x 10(4) M-1 min-1 for dichlorvos, sarin and soman, respectively. The corresponding values for plasma CarbE could not be calculated because of dominant spontaneous reactivation of inhibited CarbE. CarbE inhibited with these OPC in vitro spontaneously reactivate with half-times of 18, 143 and 497 min for sarin, dichlorvos and soman in plasma and 111, 163 and 297 min for sarin, soman and dichlorvos in liver, respectively. These results were also confirmed in experiments in vivo in which rats were subcutaneously treated with 0.5 LD50 of these agents. The half-times of spontaneous reactivation of rat plasma CarbE in vivo were 1.2, 2.0 and 2.7 h for dichlorvos, sarin and soman, respectively. These findings have changed current understanding of the mechanism of interaction of CarbE with OPC and involvement of the enzymes in detoxication of OPC, suggesting an active and important role of the enzymes in metabolic conversions of OPC to their less toxic metabolites.

Review of the Complications Associated with Treatment of Oropharyngeal Cancer: A Guide to the Dental Practitioner

PubMed Central

Turner, Lena; Mupparapu, Muralidhar; Akintoye, Sunday O

2013-01-01

Objectives Oropharyngeal cancer (OPC) is the 6th most common cancer worldwide. Focus on risk factors, improved diagnostic methods and effective management strategies have made it possible to successfully treat OPC. However, the 5-year survival rate has not improved for several years due to multiple treatment complications, tissue morbidity, loss of function and diminished quality of life. Survivors are faced with complications like oral mucositis, hyposalivation, osteoradionecrosis; tissue fibrosis, morbidity from jaw resection; disfigurement and loss of function that further diminish quality of life. The aim of this review is to highlight major complications associated with treatment of OPC via a literature search and review of available options for identification and management of these complications. Data Sources Relevant publications on oral complications of OPC therapy were thoroughly reviewed from the literature published between the years 1988 and 2012. Material and Method We evaluated reported incidence, prevalence and risk factors for oral complications of chemotherapy and radiotherapy for OPC. The authors conducted electronic search using English language databases namely PubMed Plus, Medline (Pre-Medline and Medline), Cochrane Database of systematic reviews (evidence-based medicine), Dentistry & Oral sciences source, AccessScience, Embase, Evidence-Based Medicine Reviews Multifile, Google Scholar, ISI Journal Citation Reports, Ovid Multi-Database. Conclusion We identified the most common complications associated with the treatment of oral cancers. Based on the information gathered, there is evidence that survival of OPC extends beyond eradication of the diseased tissue. Understanding the potential treatment complications and utilizing available resources to prevent and minimize them are important. Caring for OPC survivors should be a multidisciplinary team approach involving the dentist, oncologist, internist and social worker to improve the currently stagnant 5-year survival rate of OPC. More emphasis on improved quality of life after elimination of the cancer will ultimately improve OPC survivorship. PMID:23444208

The effects of V2 antagonist (OPC-31260) on endolymphatic hydrops.

PubMed

Takeda, Taizo; Sawada, Shoichi; Takeda, Setsuko; Kitano, Hiroya; Suzuki, Mikio; Kakigi, Akinobu; Takeuchi, Shunji

2003-08-01

In the present study, two experiments were performed to investigate the influence of OPC-31260 on experimentally induced endolymphatic hydrops in guinea pigs and the regulation of aquaporin-2 (AQP2) mRNA expression in the rat inner ear. In morphological studies, the increases in the ratios of the length of Reissner's membrane (IR-L) and the cross-sectional area of the scala media (IR-S) were quantitatively assessed among normal guinea pigs (normal ears) and three groups with hydropic ears: hydropic ears with no infusion (non-infusion hydropic ears), hydropic ears with an infusion of physiological saline into the scala tympani (saline-infused hydropic ears) and hydropic ears with infusion of 0.3% OPC-31260 into the scala tympani (OPC-infused hydropic ears). IR-Ls in the experimental groups were markedly larger than in the normal ear group, but there was no significant difference among the groups of non-infusion hydropic ears, saline-infused hydropic ears and OPC-infused hydropic ears. The IR-Ss of non-infusion hydropic ears and saline-infused hydropic ears (48.8-49.3%) were statistically different from that of normal ears (6.5%) (Dunnet multiple comparison test, P<0.01). However, IR-S of the OPC-infused hydropic ears (-14.8%) was significantly smaller than those of non-infusion hydropic ears and saline-infused hydropic ears (one-way ANOVA, P<0.01). In the quantitative polymerase chain reaction study, a comparison of the ratio of AQP2 and beta-actin mRNA (MAQP2/Mbeta-actin) was made between water-injected and OPC-31260-injected rats. An intravenous injection of OPC-31260 resulted in a significant decrease in MAQP2/Mbeta-actin both in the cochlea and in the endolymphatic sac (t-test, P<0.001). These results indicate that water homeostasis in the inner ear is regulated via the vasopressin-AQP2 system, and that the vasopressin type-2 antagonist OPC-31260 is a promising drug in the treatment of Meniere's disease.

Comparative performance of conventional OPC concrete and HPC designed by densified mixture design algorithm

NASA Astrophysics Data System (ADS)

Huynh, Trong-Phuoc; Hwang, Chao-Lung; Yang, Shu-Ti

2017-12-01

This experimental study evaluated the performance of normal ordinary Portland cement (OPC) concrete and high-performance concrete (HPC) that were designed by the conventional method (ACI) and densified mixture design algorithm (DMDA) method, respectively. Engineering properties and durability performance of both the OPC and HPC samples were studied using the tests of workability, compressive strength, water absorption, ultrasonic pulse velocity, and electrical surface resistivity. Test results show that the HPC performed good fresh property and further showed better performance in terms of strength and durability as compared to the OPC.

The First 2 Years of Activity of a Specialized Organ Procurement Center: Report of an Innovative Approach to Improve Organ Donation.

PubMed

Marsolais, P; Durand, P; Charbonney, E; Serri, K; Lagacé, A-M; Bernard, F; Albert, M

2017-06-01

The number of patients requiring organ transplants continues to outgrow the number of organs donated each year. In an attempt to improve the organ donation process and increase the number of organs available, we created a specialized multidisciplinary team within a specialized organ procurement center (OPC) with dedicated intensive care unit (ICU) beds and operating rooms. The OPC was staffed with ICU nurses, operating room nurses, organ donor management ICU physicians, and multidisciplinary staff. All organ donors within a designated geographic area were transferred to and managed within the OPC. During the first 2 years of operation, 126 patients were referred to the OPC. The OPC was in use for a total of 3527 h and involved 253 health workers. We retrieved 173 kidneys, 95 lungs, 68 livers, 37 hearts, and 13 pancreases for a total of 386 organs offered for transplantation. This translates to a total of 124.6 persons transplanted per million population, which compares most favorably to recently published numbers in developed countries. The OPC clearly demonstrates potential to increase the number of deceased donor organs available for transplant. Further studies are warranted to better understand the exact influence of the different components of the OPC on organ procurement. © 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

Antidiuretic effects of a novel nonpeptide vasopressin V(2)-receptor agonist, OPC-51803, administered orally to dogs.

PubMed

Nakamura, Shigeki; Hirano, Takahiro; Onogawa, Toshiyuki; Itoh, Shuji; Hashimoto, Ayako; Yamamura, Yoshitaka; Kondo, Kazumi; Mori, Toyoki; Kambe, Toshimi

2004-04-01

We elucidated the pharmacological properties of a novel nonpeptide vasopressin V(2)-receptor agonist, OPC-51803 ((5R)-2-[1-(2-chloro-4-(1-pyrrolidinyl)benzoyl-2,3,4,5-tetrahydro-1H-1-benzazepine-5-yl]-N-isopropylacetamide), via both in vitro binding experiments incorporating canine kidney and platelet membrane fractions and in vivo experiments that would determine the compound's antidiuretic effects after oral administration to water-loaded dogs. OPC-51803 displaced [(3)H]arginine vasopressin (AVP) binding to canine V(2) and V(1a) receptors, as determined by resulting K(i) values of 15.2 +/- 0.6 nM (n = 4) and 653 +/- 146 nM (n = 4), respectively. These data indicate that OPC-51803 was about 43 times more selective for V(2) receptors than for V(1a) receptors. Antidiuretic studies showed that orally administered doses of OPC-51803 (0.03 to 0.3 mg x kg(-1)) decreased urine volume and increased urinary osmolality in a dose-dependent manner in water-loaded dogs. Intravenous OPC-51803 infusions (0.3 and 3 microg x kg(-1) x min(-1)) did not affect renal or systemic hemodynamics in anesthetized dogs. Since these results confirm that OPC-51803 shows antidiuretic action in dogs, the compound may be useful for treating AVP-deficient pathophysiological states.

Bactericidal activity of OPC-67683 against drug-tolerant Mycobacterium tuberculosis.

PubMed

Saliu, Oluwabunmi Y; Crismale, Catina; Schwander, Stephan K; Wallis, Robert S

2007-11-01

There is an urgent need for drugs that hasten sterilization in tuberculosis; however, we presently lack indicators of this activity to guide early drug development. We previously described a novel in vitro assay to study mycobacterial phenotypic drug tolerance, in which sterilizing activity could be assessed. OPC-67,683 is a novel imidazooxazole that accelerates sterilization in the mouse tuberculosis model. The present study was conducted to determine the activity of OPC-67,683 in the in vitro tolerance model using drug-tolerant clinical Mycobacterium tuberculosis strains. Tolerance was assessed in Bactec radiometric culture as: (i) delayed decline in growth index during 14 days of drug exposure; (ii) shorter time to positivity of subcultures following drug exposure. Four isolates were selected from among 16 surveyed, based on delayed killing by isoniazid and OPC-67,683. Unlike isoniazid and rifampicin, whose rates of killing were concentration-independent, OPC-67,683 showed concentration-dependent effects that, at the highest dose levels tested (1.0 microg/mL), were superior to isoniazid and equal to rifampicin. The sterilizing activity of OPC-67683 against drug-tolerant M. tuberculosis in the Bactec model is consistent with its activity in mice. Further studies are warranted to examine the effects of OPC-67683 on mycobacterial persistence in tuberculous patients and to determine the biological basis of tolerance in the model.

Suppression of phosphate liberation from eutrophic lake sediment by using fly ash and ordinary Portland cement

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

Heng-Peng Ye; Fan-Zhong Chen; Yan-Qing Sheng

2006-08-15

In this study, the effect of suppression on phosphate liberation from eutrophic lake sediment by using fly ash and ordinary Portland cement (OPC) was investigated by small scale experiment. A system including sediment, lake water, and several kinds of capping materials was designed to clarify the suppression of phosphate liberation from sediment under the anaerobic condition. The suppression efficiencies of fly ash, OPC and glass bead used as control material were also determined, and these effects were discussed. The suppression efficiency of glass bead was 44.4%, and those of fly ash and OPC were 84.4%, 94.9%, respectively. The suppression bymore » fly ash and OPC was mainly carried out by the adsorption effect, in addition to the covering effect. The suppression efficiency depended on the amounts of the material used, and about 90% of liberated phosphate was suppressed by fly ash of 10.0 Kg m{sup -2}, and OPC of 6.0 Kg m{sup -2}. The concentrations of heavy metals, such as mercury, cadmium, lead, copper, zinc, chromium, silver, arsenic and nickel, in fly ash and OPC were lower than those in the environmental materials. And it was considered that the concentrations of heavy metals in fly ash and OPC were too low to influence the ecosystem in natural water region.« less

Racial and ethnic differences in pediatric obesity-prevention counseling: national prevalence of clinician practices.

PubMed

Branner, Christopher M; Koyama, Tatsuki; Jensen, Gordon L

2008-03-01

To assess the frequency of clinician-reported delivery of obesity-prevention counseling (OPC) at well-child visits; evaluating for racial/ethnic discrepancies. Combined, weighted well-child visit data from the National Ambulatory Medical Care Survey (NAMCS) and National Hospital Ambulatory Medical Care Survey (NHAMCS) from 2001 to 2004 were analyzed for patients aged 4-18 years. Obesity-prevention counseling was defined as the combined delivery of diet/nutrition and exercise counseling. Patients receiving over- or underweight related diagnoses were excluded. Counseling frequencies were calculated. Multivariate logistic regression models examined the relationship of OPC with race, ethnicity, region, provider, sex, age, and payor type. Of 55,695,554 (weighted) visits, 24.4% included OPC (90.8% of these from NAMCS). 15.4% of Hispanic patients received OPC compared to 28.8% of non-Hispanics. Frequencies were similar between Whites and Blacks (25.0 and 27.1%). Patients with private insurance received more counseling (26.9%) than Medicaid (19.1%) or self-pay (15.1%). In logistic regression models, non-Hispanics were more likely to receive OPC (odds ratio (OR) = 1.94; confidence interval (CI) = 1.13-3.32), and patients in the West were less likely to receive OPC (OR = 0.39; CI = 0.18-0.85). Payor type was not predictive in regression analysis. Patients in hospital-based practices received less OPC (11.9% vs. 25.7% with OR = 0.40; CI =0.22-0.74). Obesity prevention, like treatment, is a complex and multifactorial process. With the documented racial and ethnic disparities in rates of pediatric obesity, reasons for discrepancies in the provision of OPC must be further investigated as preventive strategies are formulated.

Identification of Bax-interacting proteins in oligodendrocyte progenitors during glutamate excitotoxicity and perinatal hypoxia–ischemia

PubMed Central

Simonishvili, Sopio; Jain, Mohit Raja; Li, Hong; Levison, Steven W.; Wood, Teresa L.

2013-01-01

OPC (oligodendrocyte progenitor cell) death contributes significantly to the pathology and functional deficits following hypoxic-ischemic injury in the immature brain and to deficits resulting from demyelinating diseases, trauma and degenerative disorders in the adult CNS. Glutamate toxicity is a major cause of oligodendroglial death in diverse CNS disorders, and previous studies have demonstrated that AMPA/kainate receptors require the pro-apoptotic protein Bax in OPCs undergoing apoptosis. The goal of the present study was to define the pro-apoptotic and anti-apoptotic effectors that regulate Bax in healthy OPCs and after exposure to excess glutamate in vitro and following H–I (hypoxia–ischemia) in the immature rat brain. We show that Bax associates with a truncated form of Bid, a BH3-only domain protein, subsequent to glutamate treatment. Furthermore, glutamate exposure reduces Bax association with the anti-apoptotic Bcl family member, Bcl-xL. Cell fractionation studies demonstrated that both Bax and Bid translocate from the cytoplasm to mitochondria during the early stages of cell death consistent with a role for Bid as an activator, whereas Bcl-xL, which normally complexes with both Bax and Bid, disassociates from these complexes when OPCs are exposed to excess glutamate. Bax remained unactivated in the presence of insulin-like growth factor-1, and the Bcl-xL complexes were protected. Our data similarly demonstrate loss of Bcl-xL–Bax association in white matter following H–I and implicate active Bad in Bax-mediated OPC death. To identify other Bax-binding partners, we used proteomics and identified cofilin as a Bax-associated protein in OPCs. Cofilin and Bax associated in healthy OPCs, whereas the Bax–cofilin association was disrupted during glutamate-induced OPC apoptosis. PMID:24195677

pERK1/2 Peripheral Recruitment and Filopodia Protrusion Augment Oligodendrocyte Progenitor Cell Migration: Combined Effects of PDGF-A and Fibronectin.

PubMed

Tripathi, Ashutosh; Parikh, Zalak S; Vora, Parvez; Frost, Emma E; Pillai, Prakash P

2017-03-01

Oligodendrocyte progenitor cell (OPC) migration is critical for effective myelination of the central nervous system. Not only during normal myelination but also during remyelination, the growth factors (GFs) and extracellular matrix (ECM) protein affect the OPC migration. Studies showed the altered levels of GFs and ECM in the demyelinating lesions. In our earlier studies, we have shown that the effect of platelet-derived growth factor alpha (PDGF-A) on OPC migration is dose- and time-dependent. In that we have shown that the physiological concentration (1 ng/ml) of PDGF-A was unable to induce OPC migration at transient exposure (30 min). However, the involvement of ECM in the regulation of PDGF-A mediated OPC migration was not clear. In the present study, we have used fibronectin (FN) as ECM. PDGF-A and FN have similar and overlapping intracellular signaling pathways including the extracellular regulated kinases 1 and 2 (ERK1/2). Here we demonstrate how physiological concentration of PDGF-A combines with FN to augment OPC migration in vitro. The present study is first of its kind to show the importance of the synergistic effects of PDGF-A and FN on peripheral recruitment of phosphorylated/activated ERK1/2 (pERK1/2), actin-pERK1/2 co-localization, and filopodia formation, which are essential for the enhanced OPC migration. These findings were further confirmed by ERK1/2 inhibition studies, using the pharmacological inhibitor U0126. An understanding of these complex interactions may lead to additional strategies for transplanting genetically modified OPCs to repair widespread demyelinated lesions.

Attenuation of scopolamine-induced and age-associated memory impairments by the sigma and 5-hydroxytryptamine(1A) receptor agonist OPC-14523 (1-[3-[4-(3-chlorophenyl)-1-piperazinyl]propyl]-5-methoxy-3,4-dihydro-2[1H]-quinolinone monomethanesulfonate).

PubMed

Tottori, Katsura; Nakai, Masami; Uwahodo, Yasufumi; Miwa, Takashi; Yamada, Sakiko; Oshiro, Yasuo; Kikuchi, Tetsuro; Altar, C Anthony

2002-04-01

Sigma and 5-HT(1A) receptor stimulation can increase acetylcholine (ACh) release in the brain. Because ACh release facilitates learning and memory, we evaluated the degree to which OPC-14523 (1-[3-[4-(3-chlorophenyl)-1-piperazinyl]propyl]-5-methoxy-3,4-dihydro-2[1H]-quinolinone monomethane sulfonate), a novel sigma and 5-HT(1A) receptor agonist, can augment ACh release and improve learning impairments in rats due to cholinergic- or age-related deficits. Single oral administration of OPC-14523 improved scopolamine-induced learning impairments in the passive-avoidance task and memory impairment in the Morris water maze. The chronic oral administration of OPC-14523 attenuated age-associated impairments of learning acquisition in the water maze and in the conditioned active-avoidance response test. OPC-14523 did not alter basal locomotion or inhibit acetylcholinesterase (AChE) activity at concentrations up to 100 microM and, unlike AChE inhibitors, did not cause peripheral cholinomimetic responses. ACh release in the dorsal hippocampus of freely moving rats increased after oral delivery of OPC-14523 and after local delivery of OPC-14523 into the hippocampus. The increases in hippocampal ACh release were blocked by the sigma receptor antagonist NE-100 (N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)-phenyl]-ethylamine). Thus, OPC-14523 improves scopolamine-induced and age-associated learning and memory impairments by enhancing ACh release, due to a stimulation of sigma and probably 5-HT(1A) receptors. Combined sigma/5-HT(1A) receptor agonism may be a novel approach to ameliorate cognitive disorders associated with age-associated cholinergic deficits.

Prevention of hypoxic brain oedema by the administration of vasopressin receptor antagonist OPC-31260.

PubMed

Molnár, Andor H; Varga, Csaba; Berkó, Anikó; Rojik, Imre; Párducz, Arpád; László, Ferenc; László, Ferenc A

2008-01-01

The numerous situations which can result in cerebral hypoxic damage occur in newborn infants and in the elderly. In research aimed at more effective therapeutic intervention in ischaemic disorders of the brain, the animal model used and the principles of the causal therapy should be better outlined. The effects of the non-peptide AVPR (V2) antagonist 5-dimethylamino-1-[4-(2-methylbenzoylamino) benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine hydrochloride (OPC-31260) on the cerebral oedema induced by general cerebral hypoxia were studied in rats. The general cerebral hypoxia was produced by bilateral common carotid ligation in Sprague-Dawley rats of the CFY strain. By 6h after the ligation, half of the rats had died, but the survival rate was significantly higher following OPC-31260 administration. Electron microscopic examinations revealed typical ischaemic changes after the carotid ligation, and OPC-31260 treatment did not significantly reduce the hypoxic signs in the brain cortex; only a certain decrease in the pericapillary oedema was observed. The carotid ligation increased the brain contents of water and Na(+) and enhanced the plasma AVP level. The increased brain water and Na(+) accumulation was prevented by OPC-31260 administration, but the plasma AVP level was further enhanced by OPC-31260. These results demonstrate the important role of AVP in the development of the disturbances in brain water and electrolyte balance in response to general cerebral hypoxia. The carotid ligation-induced cerebral oedema was significantly reduced following oral OPC-31260 administration. The protective mechanism exerted by OPC-31260 stems from its influence on the renal AVPR (V2). These observations might suggest an effective approach to the treatment of global hypoxia-induced cerebral oedema in humans.

The applicability of new TNM classification for humanpapilloma virus-related oropharyngeal cancer in the 8th edition of the AJCC/UICC TNM staging system in Japan: A single-centre study.

PubMed

Sano, Daisuke; Yabuki, Kenichiro; Arai, Yasuhiro; Tanabe, Teruhiko; Chiba, Yoshihiro; Nishimura, Goshi; Takahashi, Hideaki; Yamanaka, Shoji; Oridate, Nobuhiko

2018-06-01

The purpose of this study is to validate the applicability of new TNM classification for human papillomavirus (HPV)-related oropharyngeal cancer (OPC) in the 8th edition of the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) TNM staging system in Japan. A total of 91 OPC patients treated with radiation-based therapy between November 2001 and July 2015 were analyzed retrospectively in this study. HPV infection status was evaluated using tumor p16 expression. 40 OPC patients (44.0%) had HPV-positive disease in this study. The distribution of disease stage of HPV-positive OPC patients dramatically changed from the 7th edition to the 8th edition of AJCC/UICC TNM classification. However, neither the 8th edition nor the 7th edition of the AJCC/UICC TNM staging system could adequately predict outcomes of HPV-positive OPC patients in our patient series. On the other hand, our multivariate analysis indicated that matted nodes and age ≥63 were independent prognostic factors for progression-free survival. In addition, HPV-positive OPC patients with stage I without matted nodes showed significantly better overall and progression-free survival compared with those with stage I with matted nodes and stages II and III in the 8th edition of the AJCC/UICC TNM staging system (P=0.008, and P=0.043, respectively). Our results suggested that matted nodes of HPV-positive OPC patients might be additionally examined to apply the 8th edition of AJCC/UICC TNM classification for more adequate predicting outcomes of HPV-positive OPC patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Diosgenin promotes oligodendrocyte progenitor cell differentiation through estrogen receptor-mediated ERK1/2 activation to accelerate remyelination.

PubMed

Xiao, Lin; Guo, Dazhi; Hu, Chun; Shen, Weiran; Shan, Lei; Li, Cui; Liu, Xiuyun; Yang, Wenjing; Zhang, Weidong; He, Cheng

2012-07-01

Differentiation of oligodendrocyte progenitor cells (OPCs) into mature oligodendrocytes is a prerequisite for remyelination after demyelination, and impairment of this process is suggested to be a major reason for remyelination failure. Diosgenin, a plant-derived steroid, has been implicated for therapeutic use in many diseases, but little is known about its effect on the central nervous system. In this study, using a purified rat OPC culture model, we show that diosgenin significantly and specifically promotes OPC differentiation without affecting the viability, proliferation, or migration of OPC. Interestingly, the effect of diosgenin can be blocked by estrogen receptor (ER) antagonist ICI 182780 but not by glucocorticoid and progesterone receptor antagonist RU38486, nor by mineralocorticoid receptor antagonist spirolactone. Moreover, it is revealed that both ER-alpha and ER-beta are expressed in OPC, and diosgenin can activate the extracellular signal-regulated kinase 1/2 (ERK1/2) in OPC via ER. The pro-differentiation effect of diosgenin can also be obstructed by the ERK inhibitor PD98059. Furthermore, in the cuprizone-induced demyelination model, it is demonstrated that diosgenin administration significantly accelerates/enhances remyelination as detected by Luxol fast blue stain, MBP immunohistochemistry and real time RT-PCR. Diosgenin also increases the number of mature oligodendrocytes in the corpus callosum while it does not affect the number of OPCs. Taking together, our results suggest that diosgenin promotes the differentiation of OPC into mature oligodendrocyte through an ER-mediated ERK1/2 activation pathway to accelerate remyelination, which implicates a novel therapeutic usage of this steroidal natural product in demyelinating diseases such as multiple sclerosis (MS). Copyright © 2012 Wiley Periodicals, Inc.

Neuronal expression of pathological tau accelerates oligodendrocyte progenitor cell differentiation

PubMed Central

Ossola, Bernardino; Zhao, Chao; Compston, Alastair; Pluchino, Stefano; Franklin, Robin J. M.

2015-01-01

Oligodendrocyte progenitor cell (OPC) differentiation is an important therapeutic target to promote remyelination in multiple sclerosis (MS). We previously reported hyperphosphorylated and aggregated microtubule‐associated protein tau in MS lesions, suggesting its involvement in axonal degeneration. However, the influence of pathological tau‐induced axonal damage on the potential for remyelination is unknown. Therefore, we investigated OPC differentiation in human P301S tau (P301S‐htau) transgenic mice, both in vitro and in vivo following focal demyelination. In 2‐month‐old P301S‐htau mice, which show hyperphosphorylated tau in neurons, we found atrophic axons in the spinal cord in the absence of prominent axonal degeneration. These signs of early axonal damage were associated with microgliosis and an upregulation of IL‐1β and TNFα. Following in vivo focal white matter demyelination we found that OPCs differentiated more efficiently in P301S‐htau mice than wild type (Wt) mice. We also found an increased level of myelin basic protein within the lesions, which however did not translate into increased remyelination due to higher susceptibility of P301S‐htau axons to demyelination‐induced degeneration compared to Wt axons. In vitro experiments confirmed higher differentiation capacity of OPCs from P301S‐htau mice compared with Wt mice‐derived OPCs. Because the OPCs from P301S‐htau mice do not ectopically express the transgene, and when isolated from newborn mice behave like Wt mice‐derived OPCs, we infer that their enhanced differentiation capacity must have been acquired through microenvironmental priming. Our data suggest the intriguing concept that damaged axons may signal to OPCs and promote their differentiation in the attempt at rescue by remyelination. GLIA 2016;64:457–471 PMID:26576485

Human embryonic stem cell-derived oligodendrocyte progenitor cell transplants remyelinate and restore locomotion after spinal cord injury.

PubMed

Keirstead, Hans S; Nistor, Gabriel; Bernal, Giovanna; Totoiu, Minodora; Cloutier, Frank; Sharp, Kelly; Steward, Oswald

2005-05-11

Demyelination contributes to loss of function after spinal cord injury, and thus a potential therapeutic strategy involves replacing myelin-forming cells. Here, we show that transplantation of human embryonic stem cell (hESC)-derived oligodendrocyte progenitor cells (OPCs) into adult rat spinal cord injuries enhances remyelination and promotes improvement of motor function. OPCs were injected 7 d or 10 months after injury. In both cases, transplanted cells survived, redistributed over short distances, and differentiated into oligodendrocytes. Animals that received OPCs 7 d after injury exhibited enhanced remyelination and substantially improved locomotor ability. In contrast, when OPCs were transplanted 10 months after injury, there was no enhanced remyelination or locomotor recovery. These studies document the feasibility of predifferentiating hESCs into functional OPCs and demonstrate their therapeutic potential at early time points after spinal cord injury.

Vitamin D receptor–retinoid X receptor heterodimer signaling regulates oligodendrocyte progenitor cell differentiation

PubMed Central

de la Fuente, Alerie Guzman; Errea, Oihana; van Wijngaarden, Peter; Gonzalez, Ginez A.; Kerninon, Christophe; Jarjour, Andrew A.; Lewis, Hilary J.; Jones, Clare A.; Nait-Oumesmar, Brahim; Zhao, Chao; Huang, Jeffrey K.; ffrench-Constant, Charles

2015-01-01

The mechanisms regulating differentiation of oligodendrocyte (OLG) progenitor cells (OPCs) into mature OLGs are key to understanding myelination and remyelination. Signaling via the retinoid X receptor γ (RXR-γ) has been shown to be a positive regulator of OPC differentiation. However, the nuclear receptor (NR) binding partner of RXR-γ has not been established. In this study we show that RXR-γ binds to several NRs in OPCs and OLGs, one of which is vitamin D receptor (VDR). Using pharmacological and knockdown approaches we show that RXR–VDR signaling induces OPC differentiation and that VDR agonist vitamin D enhances OPC differentiation. We also show expression of VDR in OLG lineage cells in multiple sclerosis. Our data reveal a role for vitamin D in the regenerative component of demyelinating disease and identify a new target for remyelination medicines. PMID:26644513

Universal lab on a smartphone: a research of TiOPc thin film as a light dependence electrode

NASA Astrophysics Data System (ADS)

Lin, PoHan; Hsu, Y. H.; Lee, C. K.

2014-02-01

In this paper, we study the photoconductivity of a polymer-based TiOPc (Titanium Oxide Phthalocyanine) thin-film for the development of a multi-opto-piezoelectric-valve-array. Using a polymer-based TiOPc thin film to serve as the electrode and a structural layer of a piezoelectric polymer, P(VDF-TrFE) poly[(vinylidenefluoride-co-trifluoroethylene], an optical control valve-array could be developed for manipulating multiple microdroplets for the application of digital microfluidic. In this ongoing project, the dependency of the light intensity, thickness, and composition of spin-coated polymer-based TiOPc thin-film was studied. The experimental finding suggested that a 14 to 55 times resistivity change could be achieved by controlling the film thickness to be between 0.9 μm and 1.5 μm with TiOPc concentration of 20% and 30% w/w compositions.

Aerial image metrology for OPC modeling and mask qualification

NASA Astrophysics Data System (ADS)

Chen, Ao; Foong, Yee Mei; Thaler, Thomas; Buttgereit, Ute; Chung, Angeline; Burbine, Andrew; Sturtevant, John; Clifford, Chris; Adam, Kostas; De Bisschop, Peter

2017-06-01

As nodes become smaller and smaller, the OPC applied to enable these nodes becomes more and more sophisticated. This trend peaks today in curve-linear OPC approaches that are currently starting to appear on the roadmap. With this sophistication of OPC, the mask pattern complexity increases. CD-SEM based mask qualification strategies as they are used today are starting to struggle to provide a precise forecast of the printing behavior of a mask on wafer. An aerial image CD measurement performed on ZEISS Wafer-Level CD system (WLCD) is a complementary approach to mask CD-SEMs to judge the lithographical performance of the mask and its critical production features. The advantage of the aerial image is that it includes all optical effects of the mask such as OPC, SRAF, 3D mask effects, once the image is taken under scanner equivalent illumination conditions. Additionally, it reduces the feature complexity and analyzes the printing relevant CD.

Extracellular Acidic pH Inhibits Oligodendrocyte Precursor Viability, Migration, and Differentiation

PubMed Central

Jagielska, Anna; Wilhite, Kristen D.; Van Vliet, Krystyn J.

2013-01-01

Axon remyelination in the central nervous system requires oligodendrocytes that produce myelin. Failure of this repair process is characteristic of neurodegeneration in demyelinating diseases such as multiple sclerosis, and it remains unclear how the lesion microenvironment contributes to decreased remyelination potential of oligodendrocytes. Here, we show that acidic extracellular pH, which is characteristic of demyelinating lesions, decreases the migration, proliferation, and survival of oligodendrocyte precursor cells (OPCs), and reduces their differentiation into oligodendrocytes. Further, OPCs exhibit directional migration along pH gradients toward acidic pH. These in vitro findings support a possible in vivo scenario whereby pH gradients attract OPCs toward acidic lesions, but resulting reduction in OPC survival and motility in acid decreases progress toward demyelinated axons and is further compounded by decreased differentiation into myelin-producing oligodendrocytes. As these processes are integral to OPC response to nerve demyelination, our results suggest that lesion acidity could contribute to decreased remyelination. PMID:24098762

Reticles, write time, and the need for speed

NASA Astrophysics Data System (ADS)

Ackmann, Paul W.; Litt, Lloyd C.; Ning, Guo Xiang

2014-10-01

Historical data indicates reticle write times are increasing node-to-node. The cost of mask sets is increasing driven by the tighter requirements and more levels. The regular introduction of new generations of mask patterning tools with improved performance is unable to fully compensate for the increased data and complexity required. Write time is a primary metric that drives mask fabrication speed. Design (Raw data) is only the first step in the process and many interactions between mask and wafer technology such as OPC used, OPC efficiency for writers, fracture engines, and actual field size used drive total write time. Yield, technology, and inspection rules drive the remaining raw cycle time. Yield can be even more critical for speed of delivery as it drives re-writes and wasted time. While intrinsic process yield is important, repair capability is the reason mask delivery is still able to deliver 100% good reticles to the fab. Advanced nodes utilizing several layers of multiple patterning may require mask writer tool dedication to meet image placement specifications. This will increase the effective mask cycle time for a layer mask set and drive the need for additional mask write capability in order to deliver masks at the rate required by the wafer fab production schedules.

The Value of a Checklist for Child Abuse in Out-of-Hours Primary Care: To Screen or Not to Screen.

PubMed

Schouten, Maartje Cm; van Stel, Henk F; Verheij, Theo Jm; Houben, Michiel L; Russel, Ingrid Mb; Nieuwenhuis, Edward Es; van de Putte, Elise M

2017-01-01

To assess the diagnostic value of the screening instrument SPUTOVAMO-R2 (checklist, 5 questions) for child abuse at Out-of-hours Primary Care locations (OPC), by comparing the test outcome with information from Child Protection Services (CPS). Secondary, to determine whether reducing the length of the checklist compromises diagnostic value. All children (<18 years) attending one of the participating OPCs in the region of Utrecht, the Netherlands, in a year time, were included. The checklist is an obligatory field in the electronic patient file. CPS provided data on all checklist positives and a sample of 5500 checklist negatives (dataset). The checklist outcome was compared with a report to CPS in 10 months follow up after the OPC visit. The checklist was filled in for 50671 children; 108 (0.2%) checklists were positive. Within the dataset, 61 children were reported to CPS, with emotional neglect as the most frequent type of abuse (32.8%). The positive predictive value (PPV) of the checklist for child abuse was 8.3 (95% CI 3.9-15.2). The negative predictive value (NPV) was 99.1 (98.8-99.3), with 52 false negatives. When the length of the checklist was reduced to two questions closely related to the medical process (SPUTOVAMO-R3), the PPV was 9.1 (3.7-17.8) and the NPV 99.1 (98.7-99.3). These two questions are on the injury in relation to the history, and the interaction between child and parents. The checklist SPUTOVAMO-R2 has a low detection rate of child abuse within the OPC setting, and a high false positive rate. Therefore, we recommend to use the shortened checklist only as a tool to increase the awareness of child abuse and not as a diagnostic instrument.

The Value of a Checklist for Child Abuse in Out-of-Hours Primary Care: To Screen or Not to Screen

PubMed Central

van Stel, Henk F.; Verheij, Theo JM; Houben, Michiel L.; Russel, Ingrid MB; Nieuwenhuis, Edward ES; van de Putte, Elise M.

2017-01-01

Objectives To assess the diagnostic value of the screening instrument SPUTOVAMO-R2 (checklist, 5 questions) for child abuse at Out-of-hours Primary Care locations (OPC), by comparing the test outcome with information from Child Protection Services (CPS). Secondary, to determine whether reducing the length of the checklist compromises diagnostic value. Methods All children (<18 years) attending one of the participating OPCs in the region of Utrecht, the Netherlands, in a year time, were included. The checklist is an obligatory field in the electronic patient file. CPS provided data on all checklist positives and a sample of 5500 checklist negatives (dataset). The checklist outcome was compared with a report to CPS in 10 months follow up after the OPC visit. Results The checklist was filled in for 50671 children; 108 (0.2%) checklists were positive. Within the dataset, 61 children were reported to CPS, with emotional neglect as the most frequent type of abuse (32.8%). The positive predictive value (PPV) of the checklist for child abuse was 8.3 (95% CI 3.9–15.2). The negative predictive value (NPV) was 99.1 (98.8–99.3), with 52 false negatives. When the length of the checklist was reduced to two questions closely related to the medical process (SPUTOVAMO-R3), the PPV was 9.1 (3.7–17.8) and the NPV 99.1 (98.7–99.3). These two questions are on the injury in relation to the history, and the interaction between child and parents. Conclusions The checklist SPUTOVAMO-R2 has a low detection rate of child abuse within the OPC setting, and a high false positive rate. Therefore, we recommend to use the shortened checklist only as a tool to increase the awareness of child abuse and not as a diagnostic instrument. PMID:28045904

Quantitation of Human Papillomavirus DNA in Plasma of Oropharyngeal Carcinoma Patients

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

Cao Hongbin; Banh, Alice; Kwok, Shirley

Purpose: To determine whether human papillomavirus (HPV) DNA can be detected in the plasma of patients with HPV-positive oropharyngeal carcinoma (OPC) and to monitor its temporal change during radiotherapy. Methods and Materials: We used polymerase chain reaction to detect HPV DNA in the culture media of HPV-positive SCC90 and VU147T cells and the plasma of SCC90 and HeLa tumor-bearing mice, non-tumor-bearing controls, and those with HPV-negative tumors. We used real-time quantitative polymerase chain reaction to quantify the plasma HPV DNA in 40 HPV-positive OPC, 24 HPV-negative head-and-neck cancer patients and 10 non-cancer volunteers. The tumor HPV status was confirmed bymore » p16{sup INK4a} staining and HPV16/18 polymerase chain reaction or HPV in situ hybridization. A total of 14 patients had serial plasma samples for HPV DNA quantification during radiotherapy. Results: HPV DNA was detectable in the plasma samples of SCC90- and HeLa-bearing mice but not in the controls. It was detected in 65% of the pretreatment plasma samples from HPV-positive OPC patients using E6/7 quantitative polymerase chain reaction. None of the HPV-negative head-and-neck cancer patients or non-cancer controls had detectable HPV DNA. The pretreatment plasma HPV DNA copy number correlated significantly with the nodal metabolic tumor volume (assessed using {sup 18}F-deoxyglucose positron emission tomography). The serial measurements in 14 patients showed a rapid decline in HPV DNA that had become undetectable at radiotherapy completion. In 3 patients, the HPV DNA level had increased to a discernable level at metastasis. Conclusions: Xenograft studies indicated that plasma HPV DNA is released from HPV-positive tumors. Circulating HPV DNA was detectable in most HPV-positive OPC patients. Thus, plasma HPV DNA might be a valuable tool for identifying relapse.« less

Accelerated ageing of blended OPC cements

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

Quillin, K.C.; Duerden, S.L.; Majumdar, A.J.

1994-12-31

An accelerated experimental technique using high water:cement ratios has been developed to study the long term hydration of blended cements that may be used in a repository for the disposal of radioactive waste. This technique has been used to investigate the hydration reactions of Ordinary Portland Cement (OPC) blended with ground granulated blastfurnace slag (ggbs) or pulverised fuel ash (pfa). The effects of high sulphate-bearing and high carbonate-bearing ground waters on the compounds formed on hydration were investigated. Solid/solution compositional data were collected during the course of the hydration process for periods up to 2 years. Thomsonite, thaumasite, afwillite andmore » a tobermorite-like phase were found in addition to the expected cement hydration products. The pH of the aqueous solution in contact with 60 pfa:40 OPC blends hydrated at 90{degrees}C fell to below 8. This is lower than the value required to inhibit the corrosion of steel canisters in a repository. The pH of the aqueous solution in contact with OPC and 75 ggbs:25 OPC blends remained above 11, although if the ground waters in contact with the OPC/ggbs blends were periodically replaced the pH eventually fell below 10.« less

Controlling bridging and pinching with pixel-based mask for inverse lithography

NASA Astrophysics Data System (ADS)

Kobelkov, Sergey; Tritchkov, Alexander; Han, JiWan

2016-03-01

Inverse Lithography Technology (ILT) has become a viable computational lithography candidate in recent years as it can produce mask output that results in process latitude and CD control in the fab that is hard to match with conventional OPC/SRAF insertion approaches. An approach to solving the inverse lithography problem as a nonlinear, constrained minimization problem over a domain mask pixels was suggested in the paper by Y. Granik "Fast pixel-based mask optimization for inverse lithography" in 2006. The present paper extends this method to satisfy bridging and pinching constraints imposed on print contours. Namely, there are suggested objective functions expressing penalty for constraints violations, and their minimization with gradient descent methods is considered. This approach has been tested with an ILT-based Local Printability Enhancement (LPTM) tool in an automated flow to eliminate hotspots that can be present on the full chip after conventional SRAF placement/OPC and has been applied in 14nm, 10nm node production, single and multiple-patterning flows.

Autologous adipose tissue-derived stromal cells for treatment of spinal cord injury.

PubMed

Kang, Soo-Kyung; Shin, Myung-Joo; Jung, Jin Sup; Kim, Yong Geun; Kim, Cheul-Hong

2006-08-01

Isolated rat adipose tissue-derived stromal cells (rATSCs) contain pluripotent cells that can be differentiated into a variety of cell lineages, including neural cells. Recent work has shown that ATSCs can make neurosphere-like clumps and differentiate into neuron-like cells expressing neuronal markers, but their therapeutic effect is unclear. Here we report that intravenous infusion of oligodendrocyte precursor cells (OPCs) derived from rATSC autograft cells sources improve motor function in rat models of spinal cord injury (SCI). After 4-5 weeks, transplanted rATSC-OPC cells survived and migrated into the injured region of SCI very efficiently (30-35%) and migrated cells were partially differentiated into neurons and oligodendrocyte. Also, we found some of the engrafted OPCs migrated and integrated in the kidney, brain, lung, and liver through the intravenous system. Behavioral analysis revealed the locomotor functions of OPC-autografted SCI rats were significantly restored. Efficient migration of intravenously engrafted rATSC-OPCs cells into SCI lesion suggests that SCI-induced chemotaxic factors facilitate migration of rATSC-OPCs. Here, we verified that engrafted rATSCs and SCI-induced chemotaxic factors indeed play an important role in proliferation, migration, and differentiation of endogeneous spinal cord-derived neural progenitor cells in the injured region. In transplantation paradigms, the interaction between engrafted rATSC-OPCs and endogeneous spinal cord-derived neuronal progenitor cells will be important in promoting healing through fate decisions, resulting in coordinated induction of cell migration and differentiation.

Improvement on post-OPC verification efficiency for contact/via coverage check by final CD biasing of metal lines and considering their location on the metal layout

NASA Astrophysics Data System (ADS)

Kim, Youngmi; Choi, Jae-Young; Choi, Kwangseon; Choi, Jung-Hoe; Lee, Sooryong

2011-04-01

As IC design complexity keeps increasing, it is more and more difficult to ensure the pattern transfer after optical proximity correction (OPC) due to the continuous reduction of layout dimensions and lithographic limitation by k1 factor. To guarantee the imaging fidelity, resolution enhancement technologies (RET) such as off-axis illumination (OAI), different types of phase shift masks and OPC technique have been developed. In case of model-based OPC, to cross-confirm the contour image versus target layout, post-OPC verification solutions continuously keep developed - contour generation method and matching it to target structure, method for filtering and sorting the patterns to eliminate false errors and duplicate patterns. The way to detect only real errors by excluding false errors is the most important thing for accurate and fast verification process - to save not only reviewing time and engineer resource, but also whole wafer process time and so on. In general case of post-OPC verification for metal-contact/via coverage (CC) check, verification solution outputs huge of errors due to borderless design, so it is too difficult to review and correct all points of them. It should make OPC engineer to miss the real defect, and may it cause the delay time to market, at least. In this paper, we studied method for increasing efficiency of post-OPC verification, especially for the case of CC check. For metal layers, final CD after etch process shows various CD bias, which depends on distance with neighbor patterns, so it is more reasonable that consider final metal shape to confirm the contact/via coverage. Through the optimization of biasing rule for different pitches and shapes of metal lines, we could get more accurate and efficient verification results and decrease the time for review to find real errors. In this paper, the suggestion in order to increase efficiency of OPC verification process by using simple biasing rule to metal layout instead of etch model application is presented.

Strong sonic hedgehog signaling in the mouse ventral spinal cord is not required for oligodendrocyte precursor cell (OPC) generation but is necessary for correct timing of its generation.

PubMed

Hashimoto, Hirokazu; Jiang, Wen; Yoshimura, Takeshi; Moon, Kyeong-Hye; Bok, Jinwoong; Ikenaka, Kazuhiro

2017-11-06

In the mouse neural tube, sonic hedgehog (Shh) secreted from the floor plate (FP) and the notochord (NC) regulates ventral patterning of the neural tube, and later is essential for the generation of oligodendrocyte precursor cells (OPCs). During early development, the NC is adjacent to the neural tube and induces ventral domains in it, including the FP. In the later stage of development, during gliogenesis in the spinal cord, the pMN domain receives strong Shh signaling input. While this is considered to be essential for the generation of OPCs, the actual role of this strong input in OPC generation remains unclear. Here we studied OPC generation in bromi mutant mice which show abnormal ciliary structure. Shh signaling occurs within cilia and has been reported to be weak in bromi mutants. At E11.5, accumulation of Patched1 mRNA, a Shh signaling reporter, is observed in the pMN domain of wild type but not bromi mutants, whereas expression of Gli1 mRNA, another Shh reporter, disappeared. Thus, Shh signaling input to the pMN domain at E12.5 was reduced in bromi mutant mice. In these mutants, induction of the FP structure was delayed and its size was reduced compared to wild type mice. Furthermore, while the p3 and pMN domains were induced, the length of the Nkx2.2-positive region and the number of Olig2-positive cells decreased. The number of OPCs was also significantly decreased in the E12.5 and E14.5 bromi mutant spinal cord. In contrast, motor neuron (MN) production, detected by HB9 expression, significantly increased. It is likely that the transition from MN production to OPC generation in the pMN domain is impaired in bromi mutant mice. These results suggest that strong Shh input to the pMN domain is not required for OPC generation but is essential for producing a sufficient number of OPCs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Comprehensive Identification of Long Non-coding RNAs in Purified Cell Types from the Brain Reveals Functional LncRNA in OPC Fate Determination.

PubMed

Dong, Xiaomin; Chen, Kenian; Cuevas-Diaz Duran, Raquel; You, Yanan; Sloan, Steven A; Zhang, Ye; Zong, Shan; Cao, Qilin; Barres, Ben A; Wu, Jia Qian

2015-12-01

Long non-coding RNAs (lncRNAs) (> 200 bp) play crucial roles in transcriptional regulation during numerous biological processes. However, it is challenging to comprehensively identify lncRNAs, because they are often expressed at low levels and with more cell-type specificity than are protein-coding genes. In the present study, we performed ab initio transcriptome reconstruction using eight purified cell populations from mouse cortex and detected more than 5000 lncRNAs. Predicting the functions of lncRNAs using cell-type specific data revealed their potential functional roles in Central Nervous System (CNS) development. We performed motif searches in ENCODE DNase I digital footprint data and Mouse ENCODE promoters to infer transcription factor (TF) occupancy. By integrating TF binding and cell-type specific transcriptomic data, we constructed a novel framework that is useful for systematically identifying lncRNAs that are potentially essential for brain cell fate determination. Based on this integrative analysis, we identified lncRNAs that are regulated during Oligodendrocyte Precursor Cell (OPC) differentiation from Neural Stem Cells (NSCs) and that are likely to be involved in oligodendrogenesis. The top candidate, lnc-OPC, shows highly specific expression in OPCs and remarkable sequence conservation among placental mammals. Interestingly, lnc-OPC is significantly up-regulated in glial progenitors from experimental autoimmune encephalomyelitis (EAE) mouse models compared to wild-type mice. OLIG2-binding sites in the upstream regulatory region of lnc-OPC were identified by ChIP (chromatin immunoprecipitation)-Sequencing and validated by luciferase assays. Loss-of-function experiments confirmed that lnc-OPC plays a functional role in OPC genesis. Overall, our results substantiated the role of lncRNA in OPC fate determination and provided an unprecedented data source for future functional investigations in CNS cell types. We present our datasets and analysis results via the interactive genome browser at our laboratory website that is freely accessible to the research community. This is the first lncRNA expression database of collective populations of glia, vascular cells, and neurons. We anticipate that these studies will advance the knowledge of this major class of non-coding genes and their potential roles in neurological development and diseases.

Predictable turn-around time for post tape-out flow

NASA Astrophysics Data System (ADS)

Endo, Toshikazu; Park, Minyoung; Ghosh, Pradiptya

2012-03-01

A typical post-out flow data path at the IC Fabrication has following major components of software based processing - Boolean operations before the application of resolution enhancement techniques (RET) and optical proximity correctin (OPC), the RET and OPC step [etch retargeting, sub-resolution assist feature insertion (SRAF) and OPC], post-OPCRET Boolean operations and sometimes in the same flow simulation based verification. There are two objectives that an IC Fabrication tapeout flow manager wants to achieve with the flow - predictable completion time and fastest turn-around time (TAT). At times they may be competing. There have been studies in the literature modeling the turnaround time from historical data for runs with the same recipe and later using that to derive the resource allocation for subsequent runs. [3]. This approach is more feasible in predominantly simulation dominated tools but for edge operation dominated flow it may not be possible especially if some processing acceleration methods like pattern matching or hierarchical processing is involved. In this paper, we suggest an alternative method of providing target turnaround time and managing the priority of jobs while not doing any upfront resource modeling and resource planning. The methodology then systematically either meets the turnaround time need and potentially lets the user know if it will not as soon as possible. This builds on top of the Calibre Cluster Management (CalCM) resource management work previously published [1][2]. The paper describes the initial demonstration of the concept.

Microstructural and Microanalytical Study on Concrete Exposed to the Sulfate Environment

NASA Astrophysics Data System (ADS)

Qing, Fang; Beixing, Li; Jiangang, Yin; Xiaolu, Yuan

2017-11-01

Microstructural properties have been examined to investigate the effect of mineral admixtures on the sulfate resistance of concrete. Concrete and cement paste specimens made with ordinary Portland cement (OPC) or ordinary Portland cement incorporating 20% fly ash (FA) or 30% ground blast furnace slag (GBFS), were made and exposed to 250 cycles of the cyclic sulfate environment. Microstructural and Microanalytical study was conducted by means of x-ray diffraction (XRD), scanning electron microscope (SEM), energy dispersive spectroscopy (EDS) and mercury intrusion porosimetry (MIP). Results indicate that the pore structure of concrete after sulfate exposure possesses the fractal feature. The OPC concrete presents more complex pore internal surface, higher porosity and less micro-pores than the concrete incorporating fly ash and GBFS. Portlandite in OPC concrete and OPC-FA concrete is mainly converted to gypsum; while for OPC-GBFS concrete, both gypsum and ettringite are formed. In the cyclic sulfate environment, repeated hydration and dehydration of sulfates produce the expansive stress in pores, aggravating the demolishment of concrete structure.

Relation between speckle decorrelation and optical phase conjugation (OPC)-based turbidity suppression through dynamic scattering media: a study on in vivo mouse skin.

PubMed

Jang, Mooseok; Ruan, Haowen; Vellekoop, Ivo M; Judkewitz, Benjamin; Chung, Euiheon; Yang, Changhuei

2015-01-01

Light scattering in biological tissue significantly limits the accessible depth for localized optical interrogation and deep-tissue optical imaging. This challenge can be overcome by exploiting the time-reversal property of optical phase conjugation (OPC) to reverse multiple scattering events or suppress turbidity. However, in living tissue, scatterers are highly movable and the movement can disrupt time-reversal symmetry when there is a latency in the OPC playback. In this paper, we show that the motion-induced degradation of the OPC turbidity-suppression effect through a dynamic scattering medium shares the same decorrelation time constant as that determined from speckle intensity autocorrelation - a popular conventional measure of scatterer movement. We investigated this decorrelation characteristic time through a 1.5-mm-thick dorsal skin flap of a living mouse and found that it ranges from 50 ms to 2.5 s depending on the level of immobilization. This study provides information on relevant time scales for applying OPC to living tissues.

A calorimetric and microstructural study of solidified toxic wastes. Part 1: A classification of OPC/waste interference effects

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

Hills, C.D.; Sollars, C.J.; Perry, R.

1994-01-01

Ordinary Portland cement (OPC) has been used to solidify hazardous waste for about 25 years. The effects of waste components on the hydraulic activity of his binder have been subject to increasing research. Under certain circumstances, as yet to be defined, the hydration reactions thought responsible for solidification can be poisoned and appear to be retarded indefinitely. In this study, a number of wastes known to be capable of poisoning hydration were added to OPC and the effects were examined by conduction calorimetry and microstructural analysis techniques. A comparison of results showed that it was possible to classify waste/OPC interactionsmore » by phase development and the heat of hydration evolved. During the second part of this work, which is reported separately, the individual wastes were characterized, and the individual components identified as significant were added to OPC in single and combined additions. A comparison of results showed that it was possible to reproduce the poisoning effects observed.« less

Comparison of OPC job prioritization schemes to generate data for mask manufacturing

NASA Astrophysics Data System (ADS)

Lewis, Travis; Veeraraghavan, Vijay; Jantzen, Kenneth; Kim, Stephen; Park, Minyoung; Russell, Gordon; Simmons, Mark

2015-03-01

Delivering mask ready OPC corrected data to the mask shop on-time is critical for a foundry to meet the cycle time commitment for a new product. With current OPC compute resource sharing technology, different job scheduling algorithms are possible, such as, priority based resource allocation and fair share resource allocation. In order to maximize computer cluster efficiency, minimize the cost of the data processing and deliver data on schedule, the trade-offs of each scheduling algorithm need to be understood. Using actual production jobs, each of the scheduling algorithms will be tested in a production tape-out environment. Each scheduling algorithm will be judged on its ability to deliver data on schedule and the trade-offs associated with each method will be analyzed. It is now possible to introduce advance scheduling algorithms to the OPC data processing environment to meet the goals of on-time delivery of mask ready OPC data while maximizing efficiency and reducing cost.

Focusing light through biological tissue and tissue-mimicking phantoms up to 9.6 cm in thickness with digital optical phase conjugation

NASA Astrophysics Data System (ADS)

Shen, Yuecheng; Liu, Yan; Ma, Cheng; Wang, Lihong V.

2016-08-01

Optical phase conjugation (OPC)-based wavefront shaping techniques focus light through or within scattering media, which is critically important for deep-tissue optical imaging, manipulation, and therapy. However, to date, the sample thickness in OPC experiments has been limited to only a few millimeters. Here, by using a laser with a long coherence length and an optimized digital OPC system that can safely deliver more light power, we focused 532-nm light through tissue-mimicking phantoms up to 9.6 cm thick, as well as through ex vivo chicken breast tissue up to 2.5 cm thick. Our results demonstrate that OPC can be achieved even when photons have experienced on average 1000 scattering events. The demonstrated penetration of nearly 10 cm (˜100 transport mean free paths) has never been achieved before by any optical focusing technique, and it shows the promise of OPC for deep-tissue noninvasive optical imaging, manipulation, and therapy.

Prevalence and Treatment Management of Oropharyngeal Candidiasis in Cancer Patients: Results of the French Candidoscope Study

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

Gligorov, Joseph; Bastit, Laurent; Gervais, Honorine

2011-06-01

Purpose: The aim of this pharmaco-epidemiological study was to evaluate the prevalence of oropharyngeal candidiasis (OPC) in cancer patients treated with chemotherapy and/or radiotherapy. Methods and Materials: Signs and symptoms of OPC were noted for all patients. Antifungal therapeutic management was recorded in OPC patients. Patients receiving local antifungal treatments were monitored until the end of treatment. Results: Enrolled in the study were 2,042 patients with solid tumor and/or lymphoma treated with chemotherapy and/or another systemic cancer treatment and/or radiotherapy. The overall prevalence of OPC was 9.6% (95% confidence interval, 8.4%-11.0%]in this population. It was most frequent in patients treatedmore » with combined chemoradiotherapy (22.0%) or with more than two cytotoxic agents (16.9%). Local antifungal treatments were prescribed in 75.0% of OPC patients as recommended by guidelines. The compliance to treatment was higher in patients receiving once-daily miconazole mucoadhesive buccal tablet (MBT; 88.2%) than in those treated with several daily mouthwashes of amphotericin B (40%) or nystatin (18.8%). Conclusion: OPC prevalence in treated cancer patients was high. Local treatments were usually prescribed as per guidelines. Compliance to local treatments was better with once-daily drugs.« less

Comparison of composition and absorption of sugarcane policosanols.

PubMed

Marinangeli, Christopher P F; Kassis, Amira N; Jain, Deepak; Ebine, Naoyuki; Cunnane, Stephen C; Jones, Peter J H

2007-02-01

Policosanols (PC) exist as very-long-chain alcohols derived from sugarcane currently used in many countries as a cholesterol-lowering therapy. PC purity and relative percentage composition have been suggested as primary reasons why the original Cuban PC (OPC) supplements possess lipid-lowering efficacy. The purpose of the present study was, first, to compare the relative percentage purity and PC composition of both OPC and alternative sources of PC (APC). A second objective was to feed Syrian hamsters a diet containing 0.275 mg PC/g of either the OPC or an APC product (APC1) and compare subsequent tissue, plasma and faecal PC levels. Five animals from the APC1 dietary group received a diet containing ten times the original amount of PC. Results indicate that the APC formulations have a composition that is highly consistent with the OPC supplement, with octacosanol being present within the cited 60-70 % range. PC were undetectable in the small intestine, liver, adipose or plasma in animals fed either source. Hamsters fed OPC excreted octacosanol (C28) more rapidly (P < 0.05) than hamsters receiving APC1. If the cholesterol-lowering efficacy of PC mixtures is dependent on their purity and composition, then sugarcane-derived APC products should possess similar therapeutic properties as the OPC supplement.

Effect of Industrial By-Products on Unconfined Compressive Strength of Solidified Organic Marine Clayey Soils

PubMed Central

Park, Chan-Gi; Yun, Sung-Wook; Baveye, Phillippe C.; Yu, Chan

2015-01-01

The use of industrial by-products as admixture to ASTM Type I cement (ordinary Portland cement (OPC)) was investigated with the objective of improving the solidification of organic marine clayey soils. The industrial by-products considered in this paper were oyster-shell powder (OSP), steelmaking slag dust (SMS) and fuel-gas-desulfurized (FGD) gypsum. The industrial by-products were added to OPC at a ratio of 5% based on dry weight to produce a mixture used to solidify organic marine clayey soils. The dosage ratios of mixtures to organic marine clayey soils were 5, 10 and 15% on a dry weight basis. Unconfined compressive strength (UCS) test after 28 days revealed that the highest strength was obtained with the OPC + SMS 15% mixing ratio. The UCS of specimens treated with this mixture was >500 kPa, compared with 300 kPa for specimens treated with a 15% OPC + OSP mixture and 200 kPa when 15% of OPC was used alone. These results were attributed to the more active hydration and pozzolanic reaction of the OPC + SMS mixture. This hypothesis was verified through X-ray diffraction (XRD) and scanning electron microscopy (SEM) analyses, and was confirmed by variations in the calcium carbonate (CaCO3) content of the materials during curing. PMID:28793493

Quality design of belite–melilite clinker

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

Kurokawa, Daisuke, E-mail: daisuke_kurokawa@taiheiyo-cement.co.jp; Department of Materials Science and Engineering, Nagoya Institute of Technology, Nagoya 466-8555; Honma, Kenichi

2013-12-15

We have developed a new cement clinker, consisting mainly of belite and melilite, which is capable of increasing the amount of recycled waste as a part of its raw materials. We analyzed clinkers with a wide range of compositions, and clarified the quantitative relationship between the chemical and mineral compositions. Clinkers consisting mostly of belite and melilite were successfully obtained at the CaO/SiO{sub 2} mass ratio of 1.7 to 1.9. Test cements were prepared using these clinkers and mixed with OPC for the evaluation of fluidity and strength. The belite–melilite cement was found to have good fluidity, and the belite–melilitemore » cement mixed with OPC at up to 30% exhibited a satisfactory long term strength equivalent to the OPC, demonstrating the potential as an alternative to OPC. Electron probe microanalysis revealed the relatively high concentration of diphosphorus pentaoxide in belite, suggesting this component might contribute to the strength enhancement of the cement. -- Highlights: •A new cement clinker consisting mainly of belite and melilite was designed. •The clinker enables the use of various recycled wastes as part of its raw materials. •The relationship between the chemical and mineral compositions was clarified. •This cement mixed with OPC at up to 30% exhibited a good quality equivalent to OPC.« less

Quercetin promotes proliferation and differentiation of oligodendrocyte precursor cells after oxygen/glucose deprivation-induced injury.

PubMed

Wu, Xiuxiang; Qu, Xuebin; Zhang, Qiang; Dong, Fuxing; Yu, Hongli; Yan, Chen; Qi, Dashi; Wang, Meng; Liu, Xuan; Yao, Ruiqin

2014-04-01

The aim of this study was to investigate quercetin's (Qu) ability to promote proliferation and differentiation of oligodendrocyte precursor cells (OPCs) under oxygen/glucose deprivation (OGD)-induced injury in vitro. The results showed that after OGD, OPCs survival rate was significantly increased by Qu as measured by Cell Counting Kit-8. Furthermore, Qu treatment reduced apoptosis of OPCs surveyed by Hoechst 33258 nuclear staining. Qu at 9 and 27 μM promoted the proliferation of OPCs the most by Brdu and Olig2 immunocytochemical staining after OGD 3 days. Also, Qu treatment for 8 days after OGD, the differentiation of OPCs to oligodendrocyte was detected by immunofluorescence staining showing that O4, Olig2, and myelin basic protein (MBP) positive cells were significantly increased compared to control group. Additionally, the protein levels of Olig2 and MBP of OPCs were quantified using western blot and mRNA levels of Olig2 and Inhibitor of DNA binding 2 (Id2) were measured by RT-PCR. Western blot showed a significant increase in Olig2 and MBP expression levels compared with controls after OGD and Qu treatment with a linear does-response curve from 3 to 81 μM. After treatment with Qu compared to its control group, Olig2 mRNA level was significantly up-regulated, whereas Id2 mRNA level was down-regulated. In conclusion, Qu at 3-27 μM can promote the proliferation and differentiation of OPCs after OGD injury and may regulate the activity of Olig2 and Id2.

Rapid generation of OPC-like cells from human pluripotent stem cells for treating spinal cord injury.

PubMed

Kim, Dae-Sung; Jung, Se Jung; Lee, Jae Souk; Lim, Bo Young; Kim, Hyun Ah; Yoo, Jeong-Eun; Kim, Dong-Wook; Leem, Joong Woo

2017-07-28

Remyelination via the transplantation of oligodendrocyte precursor cells (OPCs) has been considered as a strategy to improve the locomotor deficits caused by traumatic spinal cord injury (SCI). To date, enormous efforts have been made to derive OPCs from human pluripotent stem cells (hPSCs), and significant progress in the transplantation of such cells in SCI animal models has been reported. The current methods generally require a long period of time (>2 months) to obtain transplantable OPCs, which hampers their clinical utility for patients with SCI. Here we demonstrate a rapid and efficient method to differentiate hPSCs into neural progenitors that retain the features of OPCs (referred to as OPC-like cells). We used cell sorting to select A2B5-positive cells from hPSC-derived neural rosettes and cultured the selected cells in the presence of signaling cues, including sonic hedgehog, PDGF and insulin-like growth factor-1. This method robustly generated neural cells positive for platelet-derived growth factor receptor-α (PDGFRα) and NG2 (~90%) after 4 weeks of differentiation. Behavioral tests revealed that the transplantation of the OPC-like cells into the spinal cords of rats with contusive SCI at the thoracic level significantly improved hindlimb locomotor function. Electrophysiological assessment revealed enhanced neural conduction through the injury site. Histological examination showed increased numbers of axon with myelination at the injury site and graft-derived myelin formation with no evidence of tumor formation. Our method provides a cell source from hPSCs that has the potential to recover motor function following SCI.

Oligodendrocyte progenitor programming and reprogramming: Toward myelin regeneration.

PubMed

Lopez Juarez, Alejandro; He, Danyang; Richard Lu, Q

2016-05-01

Demyelinating diseases such as multiple sclerosis (MS) are among the most disabling and cost-intensive neurological disorders. The loss of myelin in the central nervous system, produced by oligodendrocytes (OLs), impairs saltatory nerve conduction, leading to motor and cognitive deficits. Immunosuppression therapy has a limited efficacy in MS patients, arguing for a paradigm shift to strategies that target OL lineage cells to achieve myelin repair. The inhibitory microenvironment in MS lesions abrogates the expansion and differentiation of resident OL precursor cells (OPCs) into mature myelin-forming OLs. Recent studies indicate that OPCs display a highly plastic ability to differentiate into alternative cell lineages under certain circumstances. Thus, understanding the mechanisms that maintain and control OPC fate and differentiation into mature OLs in a hostile, non-permissive lesion environment may open new opportunities for regenerative therapies. In this review, we will focus on 1) the plasticity of OPCs in terms of their developmental origins, distribution, and differentiation potentials in the normal and injured brain; 2) recent discoveries of extrinsic and intrinsic factors and small molecule compounds that control OPC specification and differentiation; and 3) therapeutic potential for motivation of neural progenitor cells and reprogramming of differentiated cells into OPCs and their likely impacts on remyelination. OL-based therapies through activating regenerative potentials of OPCs or cell replacement offer exciting opportunities for innovative strategies to promote remyelination and neuroprotection in devastating demyelinating diseases like MS. This article is part of a Special Issue entitled SI:NG2-glia(Invited only). Copyright © 2015 Elsevier B.V. All rights reserved.

Gender- and ethnicity-specific survival trends of oral cavity and oropharyngeal cancers in British Columbia.

PubMed

Auluck, Ajit; Hislop, Greg; Bajdik, Chris; Hay, John; Bottorff, Joan L; Zhang, Lewei; Rosin, Miriam P

2012-12-01

A shift in etiology of oral cancers has been associated with a rise in incidence for oropharyngeal cancers (OPC) and decrease for oral cavity cancers (OCC); however, there is limited information about population-based survival trends. We report epidemiological transitions in survival for both OPC and OCC from a population-based cancer registry, focusing upon gender and ethnic differences. All primary oral cancers diagnosed between 1980 and 2005 were identified from the British Columbia Cancer Registry and regrouped into OPC and OCC by topographical subsites, time periods (1980-1993 and 1994-2005), stage at diagnosis, and ethnicity. Cases were then followed up to December 2009. Using gender-based analysis, actuarial life tables were used to calculate survival rates, which were compared using Kaplan-Meier curves and log-rank tests. For OPC, survival improved, significant for tonsil and base of tongue in men and marginally significant at base of tongue in women. This improvement occurred in spite of an increase in late-stage diagnosis for OPC in both genders. Interestingly, there was no difference in survival for early- and late-stage disease for OPC in men. For OCC, there was a decrease in survival for floor of mouth cancers in both genders although significant in women only. South Asians had the poorest survival for OCC in both genders. Survival for OPC improved, more dramatically in men than women, in spite of late-stage diagnosis and increasing nodal involvement. Given the poor survival rates and need for early detection, targeted OCC screening programs are required for South Asians.

Rapid generation of OPC-like cells from human pluripotent stem cells for treating spinal cord injury

PubMed Central

Kim, Dae-Sung; Jung, Se Jung; Lee, Jae Souk; Lim, Bo Young; Kim, Hyun Ah; Yoo, Jeong-Eun; Kim, Dong-Wook; Leem, Joong Woo

2017-01-01

Remyelination via the transplantation of oligodendrocyte precursor cells (OPCs) has been considered as a strategy to improve the locomotor deficits caused by traumatic spinal cord injury (SCI). To date, enormous efforts have been made to derive OPCs from human pluripotent stem cells (hPSCs), and significant progress in the transplantation of such cells in SCI animal models has been reported. The current methods generally require a long period of time (>2 months) to obtain transplantable OPCs, which hampers their clinical utility for patients with SCI. Here we demonstrate a rapid and efficient method to differentiate hPSCs into neural progenitors that retain the features of OPCs (referred to as OPC-like cells). We used cell sorting to select A2B5-positive cells from hPSC-derived neural rosettes and cultured the selected cells in the presence of signaling cues, including sonic hedgehog, PDGF and insulin-like growth factor-1. This method robustly generated neural cells positive for platelet-derived growth factor receptor-α (PDGFRα) and NG2 (~90%) after 4 weeks of differentiation. Behavioral tests revealed that the transplantation of the OPC-like cells into the spinal cords of rats with contusive SCI at the thoracic level significantly improved hindlimb locomotor function. Electrophysiological assessment revealed enhanced neural conduction through the injury site. Histological examination showed increased numbers of axon with myelination at the injury site and graft-derived myelin formation with no evidence of tumor formation. Our method provides a cell source from hPSCs that has the potential to recover motor function following SCI. PMID:28751784

Does Your Optical Particle Counter Measure What You Think it Does? Calibration and Refractive Index Correction Methods.

NASA Astrophysics Data System (ADS)

Rosenberg, Phil; Dean, Angela; Williams, Paul; Dorsey, James; Minikin, Andreas; Pickering, Martyn; Petzold, Andreas

2013-04-01

Optical Particle Counters (OPCs) are the de-facto standard for in-situ measurements of airborne aerosol size distributions and small cloud particles over a wide size range. This is particularly the case on airborne platforms where fast response is important. OPCs measure scattered light from individual particles and generally bin particles according to the measured peak amount of light scattered (the OPC's response). Most manufacturers provide a table along with their instrument which indicates the particle diameters which represent the edges of each bin. It is important to correct the particle size reported by OPCs for the refractive index of the particles being measured, which is often not the same as for those used during calibration. However, the OPC's response is not a monotonic function of particle diameter and obvious problems occur when refractive index corrections are attempted, but multiple diameters correspond to the same OPC response. Here we recommend that OPCs are calibrated in terms of particle scattering cross section as this is a monotonic (usually linear) function of an OPC's response. We present a method for converting a bin's boundaries in terms of scattering cross section into a bin centre and bin width in terms of diameter for any aerosol species for which the scattering properties are known. The relationship between diameter and scattering cross section can be arbitrarily complex and does not need to be monotonic; it can be based on Mie-Lorenz theory or any other scattering theory. Software has been provided on the Sourceforge open source repository for scientific users to implement such methods in their own measurement and calibration routines. As a case study data is presented showing data from Passive Cavity Aerosol Spectrometer Probe (PCASP) and a Cloud Droplet Probe (CDP) calibrated using polystyrene latex spheres and glass beads before being deployed as part of the Fennec project to measure airborne dust in the inaccessible regions of the Sahara.

Effects of an oral vasopressin receptor antagonist (OPC-31260) in a dog with syndrome of inappropriate secretion of antidiuretic hormone.

PubMed

Fleeman, L M; Irwin, P J; Phillips, P A; West, J

2000-12-01

The syndrome of inappropriate secretion of antidiuretic hormone is a rare disorder in dogs characterised by hypo-osmolality and persistent arginine vasopressin production in the absence of hypovolaemia and/or hypotension. The study describes the efficacy and safety of the nonpeptide selective arginine vasopressin V2 receptor antagonist OPC-31260 in a dog with the naturally occurring syndrome. The detailed case history of a dog with spontaneous syndrome of inappropriate secretion of antidiuretic hormone that received long-term therapy with oral OPC-31260 is presented. Effects of the first dose of OPC-31260 and of a dose administered after a continuous dosing period of 12 days are reported. Packed cell volume, plasma sodium, total protein, arginine vasopressin, renin activity, atrial natriuretic peptide, urine specific gravity, urine output, heart rate and body weight were monitored for 2 h before, and for 4 h after, the first dose of OPC-31260. The same parameters plus plasma osmolality and urine osmolality were monitored when an identical dose was administered after 12 days of therapy. Oral administration of OPC-31260 at 3 mg/kg body weight resulted in marked aquaresis with increased urine output and decline in urine specific gravity within 1 h. Corresponding increases in concentrations of plasma sodium, plasma osmolality and plasma renin activity were recorded over a 4 h period. Arginine vasopressin concentration remained inappropriately elevated throughout the study. Results were similar when the trial procedure was repeated after a stabilisation period of 12 days. Long-term therapy with OPC-31260 at a dose of 3 mg/kg body weight orally every 12 h resulted in good control of clinical signs with no deleterious effects detected during a 3-year follow-up period. Despite sustained clinical benefits observed in this case, plasma sodium did not normalise with continued administration of the drug. Treatment of a dog with naturally occurring syndrome of inappropriate secretion of antidiuretic hormone with OPC-31260 at 3 mg/kg body weight orally every 12 h resulted in marked aquaresis and significant palliation of clinical signs with no discernible side-effects detected over a 3-year period. Thus, OPC-31260 appears to offer a feasible medical alternative to water restriction for treatment of dogs with syndrome of inappropriate secretion of antidiuretic hormone. Higher doses of OPC-31260 may be required to achieve and maintain normal plasma sodium in dogs with this syndrome.

alpha(2)-adrenoceptor antagonist properties of OPC-28326, a novel selective peripheral vasodilator.

PubMed

Orito, K; Kishi, M; Imaizumi, T; Nakazawa, T; Hashimoto, A; Mori, T; Kambe, T

2001-10-01

1. Antagonistic properties of OPC-28326 ([4-(N-methyl-2-phenylethylamino)-1-(3,5-dimethyl-4-propionyl-aminobenzoyl)] piperidine hydrochloride monohydrate), a selective peripheral vasodilator, were investigated by analysing the data from functional studies in various tissues from the rat and binding studies of the drug to alpha(2)-adrenoceptor subtypes. 2. Using a human recombinant receptor and rat kidney cortex, we found that OPC-28326 displays affinities to alpha(2A)-, alpha(2B)- and alpha(2C)-adrenoceptors with K(i) values of 2040, 285, and 55 nM, respectively. The K(i) values of yohimbine for alpha(2A)-, alpha(2B)-, and alpha(2C)-adrenoceptors were 3.0, 2.0 and 11.0 nM, respectively. 3. B-HT 920, an alpha(2)-adrenoceptor agonist, produced a pressor response via peripheral postsynaptic alpha(2)-adrenoceptor stimulation (thought to be an alpha(2B)-subtype) in a reserpine-pretreated pithed rat preparation. OPC-28326 (3 - 30 mg kg(-1), i.v.) and yohimbine (0.3 - 3 mg kg(-1), i.v.) caused dose-dependent rightward shift in the pressor dose-response curve induced by B-HT 920. The apparent pA(2) values were 1.55 (0.87 - 2.75, 95% confidence interval) and 0.11 (0.06 - 0.21) mg kg(-1), respectively. The potency of OPC-28326 was about 14 times less than that of yohimbine. 4. Clonidine inhibited the tension developed by electrical stimulation, of the rat vas deferens, by its peripheral presynaptic alpha(2A/D)-adrenoceptor action. OPC-28326 (1 - 100 microM) and yohimbine (10 - 1000 nM) caused a rightward shift in the concentration-response curve of clonidine. The pA(2) values were 5.73 (5.54 - 5.91) and 7.92 (7.84 - 8.01), respectively, providing evidence for a potency of OPC-28326 of about 155 times less than that of yohimbine. 5. Mydriasis was induced by brimonidine via stimulation of central alpha(2A/D)-adrenoceptors in anaesthetized rats. Intravenous OPC-28326 had no effect on this action, even at a very high dose of 10 mg kg(-1) i.v., while yohimbine (0.1 - 0.3 mg kg(-1) i.v.) inhibited mydriasis in a dose-dependent manner, indicating that OPC-28326 was at least 100 times less potent than yohimbine in regard to the anti-mydriatic effect. 6. These data suggest that OPC-28326 preferentially exerts peripheral and postsynaptic antagonistic actions on the alpha(2B)- and alpha(2C)-adrenoceptor subtypes.

A Methodology for Multidisciplinary Decision Making for a Surface Combatant Main Engine Selection Problem

DTIC Science & Technology

2014-06-01

nautical miles per hour ONR Office of Naval Research OPC overall propulsive coefficient RS repairable at sea SFC specific fuel consumption SHP shaft...fmSFC SHP hp =  (2.3) Overall Propulsive Coefficient ( OPC ) The overall propulsive coefficient is equal to the ratio between the effective...horsepower (EHP), and the total installed shaft horsepower (SHP) delivered by the main engine [6]. OPC can be determined using the following relationship

Role of phosphoinositide 3-kinase IA (PI3K-IA) activation in cardioprotection induced by ouabain preconditioning.

PubMed

Duan, Qiming; Madan, Namrata D; Wu, Jian; Kalisz, Jennifer; Doshi, Krunal Y; Haldar, Saptarsi M; Liu, Lijun; Pierre, Sandrine V

2015-03-01

Acute myocardial infarction, the clinical manifestation of ischemia-reperfusion (IR) injury, is a leading cause of death worldwide. Like ischemic preconditioning (IPC) induced by brief episodes of ischemia and reperfusion, ouabain preconditioning (OPC) mediated by Na/K-ATPase signaling protects the heart against IR injury. Class I PI3K activation is required for IPC, but its role in OPC has not been investigated. While PI3K-IB is critical to IPC, studies have suggested that ouabain signaling is PI3K-IA-specific. Hence, a pharmacological approach was used to test the hypothesis that OPC and IPC rely on distinct PI3K-I isoforms. In Langendorff-perfused mouse hearts, OPC was initiated by 4 min of ouabain 10 μM and IPC was triggered by 4 cycles of 5 min ischemia and reperfusion prior to 40 min of global ischemia and 30 min of reperfusion. Without affecting PI3K-IB, ouabain doubled PI3K-IA activity and Akt phosphorylation at Ser(473). IPC and OPC significantly preserved cardiac contractile function and tissue viability as evidenced by left ventricular developed pressure and end-diastolic pressure recovery, reduced lactate dehydrogenase release, and decreased infarct size. OPC protection was blunted by the PI3K-IA inhibitor PI-103, but not by the PI3K-IB inhibitor AS-604850. In contrast, IPC-mediated protection was not affected by PI-103 but was blocked by AS-604850, suggesting that PI3K-IA activation is required for OPC while PI3K-IB activation is needed for IPC. Mechanistically, PI3K-IA activity is required for ouabain-induced Akt activation but not PKCε translocation. However, in contrast to PKCε translocation which is critical to protection, Akt activity was not required for OPC. Further studies shall reveal the identity of the downstream targets of this new PI3K IA-dependent branch of OPC. These findings may be of clinical relevance in patients at risk for myocardial infarction with underlying diseases and/or medication that could differentially affect the integrity of cardiac PI3K-IA and IB pathways. Copyright © 2015 Elsevier Ltd. All rights reserved.

Comprehensive Identification of Long Non-coding RNAs in Purified Cell Types from the Brain Reveals Functional LncRNA in OPC Fate Determination

PubMed Central

Dong, Xiaomin; Chen, Kenian; Cuevas-Diaz Duran, Raquel; You, Yanan; Sloan, Steven A.; Zhang, Ye; Zong, Shan; Cao, Qilin; Barres, Ben A.; Wu, Jia Qian

2015-01-01

Long non-coding RNAs (lncRNAs) (> 200 bp) play crucial roles in transcriptional regulation during numerous biological processes. However, it is challenging to comprehensively identify lncRNAs, because they are often expressed at low levels and with more cell-type specificity than are protein-coding genes. In the present study, we performed ab initio transcriptome reconstruction using eight purified cell populations from mouse cortex and detected more than 5000 lncRNAs. Predicting the functions of lncRNAs using cell-type specific data revealed their potential functional roles in Central Nervous System (CNS) development. We performed motif searches in ENCODE DNase I digital footprint data and Mouse ENCODE promoters to infer transcription factor (TF) occupancy. By integrating TF binding and cell-type specific transcriptomic data, we constructed a novel framework that is useful for systematically identifying lncRNAs that are potentially essential for brain cell fate determination. Based on this integrative analysis, we identified lncRNAs that are regulated during Oligodendrocyte Precursor Cell (OPC) differentiation from Neural Stem Cells (NSCs) and that are likely to be involved in oligodendrogenesis. The top candidate, lnc-OPC, shows highly specific expression in OPCs and remarkable sequence conservation among placental mammals. Interestingly, lnc-OPC is significantly up-regulated in glial progenitors from experimental autoimmune encephalomyelitis (EAE) mouse models compared to wild-type mice. OLIG2-binding sites in the upstream regulatory region of lnc-OPC were identified by ChIP (chromatin immunoprecipitation)-Sequencing and validated by luciferase assays. Loss-of-function experiments confirmed that lnc-OPC plays a functional role in OPC genesis. Overall, our results substantiated the role of lncRNA in OPC fate determination and provided an unprecedented data source for future functional investigations in CNS cell types. We present our datasets and analysis results via the interactive genome browser at our laboratory website that is freely accessible to the research community. This is the first lncRNA expression database of collective populations of glia, vascular cells, and neurons. We anticipate that these studies will advance the knowledge of this major class of non-coding genes and their potential roles in neurological development and diseases. PMID:26683846

Brain-Derived Neurotrophic Factor Deficiency Restricts Proliferation of Oligodendrocyte Progenitors Following Cuprizone-Induced Demyelination

PubMed Central

Tsiperson, Vladislav; Huang, Yangyang; Bagayogo, Issa; Song, Yeri; VonDran, Melissa W; DiCicco-Bloom, Emanuel

2015-01-01

Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family of growth factors that through its neurotrophic tyrosine kinase, receptor, type 2 (TrkB) receptor, increases 5-bromo-2-deoxyuridine incorporation in oligodendrocyte progenitor cells (OPCs) in culture. Roles in vivo are less well understood; however, increases in numbers of OPCs are restricted in BDNF+/− mice following cuprizone-elicited demyelination. Here, we investigate whether these blunted increases in OPCs are associated with changes in proliferation. BDNF+/+ and BDNF+/− mice were fed cuprizone-containing or control feed. To assess effects on OPC numbers, platelet-derived growth factor receptor alpha (PDGFRα)+ or NG2+ cells were counted. To monitor DNA synthesis, 5-ethynyl-2′-deoxyuridine (EdU) was injected intraperitoneally and colocalized with PDGFRα+ cells. Alternatively, proliferating cell nuclear antigen (PCNA) was colocalized with PDGFRα or NG2. Labeling indices were determined in the BDNF+/+ and BDNF+/− animals. After 4 or 5 weeks of control feed, BDNF+/− mice exhibit similar numbers of OPCs compared with BDNF+/+ animals. The labeling indices for EdU and PCNA also were not significantly different, suggesting that neither the DNA synthesis phase (S phase) nor the proliferative pool size was different between genotypes. In contrast, when mice were challenged by cuprizone for 4 or 5 weeks, increases in OPCs observed in BDNF+/+ mice were reduced in the BDNF+/− mice. This difference in elevations in cell number was accompanied by decreases in EdU labeling and PCNA labeling without changes in cell death, indicating a reduction in the DNA synthesis and the proliferative pool. Therefore, levels of BDNF influence the proliferation of OPCs resulting from a demyelinating lesion. PMID:25586993

Effects of electroacupuncture and the retinoid X receptor (RXR) signalling pathway on oligodendrocyte differentiation in the demyelinated spinal cord of rats

PubMed Central

Yang, Xiao-Hua; Ding, Ying; Li, Wen; Zhang, Rong-Yi; Wu, Jin-Lang; Ling, Eng-Ang; Wu, Wutian

2017-01-01

Objectives In spinal cord demyelination, some oligodendrocyte precursor cells (OPCs) remain in the demyelinated region but have a reduced capacity to differentiate into oligodendrocytes. This study investigated whether ‘Governor Vessel’ (GV) electroacupuncture (EA) would promote the differentiation of endogenous OPCs into oligodendrocytes by activating the retinoid X receptor γ (RXR-γ)-mediated signalling pathway. Methods Adult rats were microinjected with ethidium bromide (EB) into the T10 spinal cord to establish a model of spinal cord demyelination. EB-injected rats remained untreated (EB group, n=26) or received EA treatment (EB+EA group, n=26). A control group (n=26) was also included that underwent dural exposure without EB injection. After euthanasia at 7 days (n=5 per group), 15 days (n=8 per group) or 30 days (n=13 per group), protein expression of RXR-γ in the demyelinated spinal cord was evaluated by immunohistochemistry and Western blotting. In addition, OPCs derived from rat embryonic spinal cord were cultured in vitro, and exogenous 9-cis-RA (retinoic acid) and RXR-γ antagonist HX531 were administered to determine whether RA could activate RXR-γ and promote OPC differentiation. Results EA was found to increase the numbers of both OPCs and oligodendrocytes expressing RXR-γ and RALDH2, and promote remyelination in the remyelinated spinal cord. Exogenous 9-cis-RA enhanced the differentiation of OPCs into mature oligodendrocytes by activating RXR-γ. Conclusions The results suggest that EA may activate RXR signalling to promote the differentiation of OPCs into oligodendrocytes in spinal cord demyelination. PMID:27841975

Co-Ultramicronized Palmitoylethanolamide/Luteolin Facilitates the Development of Differentiating and Undifferentiated Rat Oligodendrocyte Progenitor Cells.

PubMed

Skaper, Stephen D; Barbierato, Massimo; Facci, Laura; Borri, Mila; Contarini, Gabriella; Zusso, Morena; Giusti, Pietro

2018-01-01

Oligodendrocytes, the myelin-producing cells of the central nervous system (CNS), have limited capability to bring about repair in chronic CNS neuroinflammatory demyelinating disorders such as multiple sclerosis (MS). MS lesions are characterized by a compromised pool of undifferentiated oligodendrocyte progenitor cells (OPCs) unable to mature into myelin-producing oligodendrocytes. An attractive strategy may be to replace lost OLs and/or promote their maturation. N-palmitoylethanolamine (PEA) is an endogenous fatty acid amide signaling molecule with anti-inflammatory and neuroprotective actions. Recent studies show a co-ultramicronized composite of PEA and the flavonoid luteolin (co-ultraPEALut) to be more efficacious than PEA in improving outcome in CNS injury models. Here, we examined the effects of co-ultraPEALut on development of OPCs from newborn rat cortex cultured under conditions favoring either differentiation (Sato medium) or proliferation (fibroblast growth factor-2 and platelet-derived growth factor (PDGF)-AA-supplemented serum-free medium ("SFM")). OPCs in SFM displayed high expression of PDGF receptor alpha gene and the proliferation marker Ki-67. In Sato medium, in contrast, OPCs showed rapid decreases in PDGF receptor alpha and Ki-67 expression with a concomitant rise in myelin basic protein (MBP) expression. In these conditions, co-ultraPEALut (10 μM) enhanced OPC morphological complexity and expression of MBP and the transcription factor TCF7l2. Surprisingly, co-ultraPEALut also up-regulated MBP mRNA expression in OPCs in SFM. MBP expression in all cases was sensitive to inhibition of mammalian target of rapamycin. Within the context of strategies to promote endogenous remyelination in MS which focus on enhancing long-term survival of OPCs and stimulating their differentiation into remyelinating oligodendrocytes, co-ultraPEALut may represent a novel pharmacological approach.

Human Papillomavirus-associated oropharyngeal cancer: an observational study of diagnosis, prevalence and prognosis in a UK population

PubMed Central

2013-01-01

Background The incidence of Human Papillomavirus (HPV) associated oropharyngeal cancer (OPC) is increasing. HPV-associated OPC appear to have better prognosis than HPV-negative OPC. The aim of this study was to robustly determine the prevalence of HPV-positive OPC in an unselected UK population and correlate HPV positivity with clinical outcome. Methods HPV testing by GP5+/6+ PCR, In Situ Hybridisation (ISH) and p16 immunohistochemistry (IHC) was performed on 138 OPCs diagnosed in South Wales (UK) between 2001–06. Kaplan-Meier analysis was used to correlate HPV status with clinical outcome. Results Using a composite definition of HPV positivity (HPV DNA and p16 overexpression), HPV was detected in 46/83 (55%) samples where DNA quality was assured. Five year overall survival was 75.4% (95% CI: 65.2 to 85.5) in HPV-positives vs 25.3% (95% CI: 14.2 to 36.4) in HPV negatives, corresponding to a 78% reduction in death rate (HR 0.22, p < 0.001). HPV-positives had less locoregional recurrence but second HPV-positive Head and Neck primaries occurred. Poor quality DNA in fixed pathological specimens reduced both HPV prevalence estimates and the prognostic utility of DNA-based HPV testing methods. As a single marker, p16 was least affected by sample quality and correlated well with prognosis, although was not sufficient on its own for accurate HPV prevalence reporting. Conclusions This study highlights the significant burden of OPC associated with HPV infection. HPV positive cases are clinically distinct from other OPC, and are associated with significantly better clinical outcomes. A composite definition of HPV positivity should be used for accurate prevalence reporting and up-front DNA quality assessment is recommended for any DNA-based HPV detection strategy. PMID:23634887

Comparison of oropharyngeal and oral cavity squamous cell cancer incidence and trends in New Zealand and Queensland, Australia.

PubMed

Elwood, J Mark; Youlden, Danny R; Chelimo, Carol; Ioannides, Sally J; Baade, Peter D

2014-02-01

Increases in the incidence of squamous cell oropharyngeal cancer (OPC) have been reported from some countries, but have not been assessed in Australia or New Zealand. This study examines trends for squamous cell OPC and squamous cell oral cavity cancer (OCC) in two similarly sized populations, New Zealand and Queensland, Australia. Incidence data for 1982-2010 were obtained from the respective population-based cancer registries for squamous cell OPC and OCC, by subsite, sex, and age. Time trends and annual percentage changes (APCs) were assessed by joinpoint regression. The incidence rates of squamous cell OPC in males in New Zealand since 2005 and Queensland since 2006 have increased rapidly, with APCs of 11.9% and 10.6% respectively. The trends were greatest at ages 50-69 and followed more gradual increases previously. In females, rates increased by 2.1% per year in New Zealand from 1982, but by only 0.9% (not significant) in Queensland. In contrast, incidence rates for OCC decreased by 1.2% per year in males in Queensland since 1982, but remained stable for females in Queensland and for both sexes in New Zealand. Overall, incidence rates for both OCC and OPC were substantially higher in Queensland than in New Zealand. In males in both areas, OPC incidence is now higher than that of OCC. Incidence rates of squamous cell OPC have increased rapidly in men, while rates of OCC have been stable or reducing, showing distinct etiologies. This has both clinical and public health importance, including implications for the extension of human papilloma virus (HPV) vaccination to males. Copyright © 2014 Elsevier Ltd. All rights reserved.

Synthesis, metabolism and systemic transport of a fluorinated mimic of the endogenous jasmonate precursor OPC-8:0.

PubMed

Jimenez-Aleman, Guillermo H; Scholz, Sandra S; Heyer, Monika; Reichelt, Michael; Mithöfer, Axel; Boland, Wilhelm

2015-12-01

Jasmonates (JAs) are fatty acid derivatives that mediate many developmental processes and stress responses in plants. Synthetic jasmonate derivatives (commonly isotopically labeled), which mimic the action of the endogenous compounds are often employed as internal standards or probes to study metabolic processes. However, stable-isotope labeling of jasmonates does not allow the study of spatial and temporal distribution of these compounds in real time by positron emission tomography (PET). In this study, we explore whether a fluorinated jasmonate could mimic the action of the endogenous compound and therefore, be later employed as a tracer to study metabolic processes by PET. We describe the synthesis and the metabolism of (Z)-7-fluoro-8-(3-oxo-2-(pent-2-en-1-yl)cyclopentyl)octanoic acid (7F-OPC-8:0), a fluorinated analog of the JA precursor OPC-8:0. Like endogenous jasmonates, 7F-OPC-8:0 induces the transcription of marker jasmonate responsive genes (JRG) and the accumulation of jasmonates after its application to Arabidopsis thaliana plants. By using UHPLC-MS/MS, we could show that 7F-OPC-8:0 is metabolized in vivo similarly to the endogenous OPC-8:0. Furthermore, the fluorinated analog was successfully employed as a probe to show its translocation to undamaged systemic leaves when it was applied to wounded leaves. This result suggests that OPC-8:0 - and maybe other oxylipins - may contribute to the mobile signal which triggers systemic defense responses in plants. We highlight the potential of fluorinated oxylipins to study the mode of action of lipid-derived molecules in planta, either by conventional analytical methods or fluorine-based detection techniques. Copyright © 2015 Elsevier B.V. All rights reserved.

OPC-12759 increases proliferation of cultured rat conjunctival goblet cells.

PubMed

Ríos, José D; Shatos, Marie; Urashima, Hiroki; Tran, Hao; Dartt, Darlene A

2006-06-01

To determine if the gastroprotective drug OPC-12759 increased proliferation of rat conjunctival goblet cells in culture. Cultured goblet cells were incubated with 10(-12) to 10(-8) M OPC-12759 for 1 to 7 days. Fetal bovine serum (FBS) was used as a positive control. Cell proliferation was determined by a MTT [3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide] colorimetric assay and by immunohistochemical staining with anti-Ki-67, a marker of cell division. Goblet cells were identified by double-labeling with anti-Ki-67, a marker of cell division, and Ulex europaeus agglutinin I lectin, anti-MUC5AC and anticytokeratin 7. Stratified squamous cells were identified by using Griffonia (Bandeiraea) simplicifolia lectin and anticytokeratin 4 antibody. As determined by MTT conversion to formazan, OPC-12579 at 10(-11) M induced an almost 2-fold increase in goblet cell proliferation on Days 1 and 3 of incubation but not on Days 5 and 7. The FBS at 10% increased cell proliferation by 2- to 3-fold at each time point. Daily replenishment of OPC-12579 for 3 consecutive days induced cell proliferation at all concentrations. Proliferation as determined by the number of Ki-67 positive cells increased by 4- and 3-fold at Days 1 and 3, respectively with addition of 10(-11) M OPC-12579. The FBS at 10% induced a 10-fold increase in goblet cell proliferation on Days 1, 3, and 5. Colocalization of Ulex europaeus agglutinin I, MUC5AC and anticytokeratin 7 with Ki-67 indicated that proliferating cells were goblet cells. Proliferating cells were negative for the nongoblet cell markers Bandeiraea lectin and anticytokeratin 4. The OPC-12759 stimulates proliferation of conjunctival goblet cells in primary culture.

In vitro profile of the antidepressant candidate OPC-14523 at rat and human 5-HT1A receptors.

PubMed

Jordan, Shaun; Chen, Ruoyan; Koprivica, Vuk; Hamilton, Ronald; Whitehead, Richard E; Tottori, Katsura; Kikuchi, Tetsuro

2005-07-11

This study determined the in vitro functional profile of 1-[3-[4-(3-chlorophenyl)-1-piperazinyl]propyl]-5-methoxy-3,4-dihydro-2-quinolinone monomethanesulfonate (OPC-14523) at rat and human serotonin (5-HT) 5-HT1A receptors and binding affinity of OPC-14523 at human frontocortical 5-HT1A receptors. OPC-14523 (1 microM) increased guanosine-5'-O-(3-[35S]thio)-triphosphate ([35S]GTPgammaS) binding to 5-HT1A receptor-containing regions of rat brain tissue sections (approximately 53% of the effect of 1 microM (+)8-hydroxy-2-(di-n-propylamino)tetralin ((+)8-OH-DPAT) that were blocked by the selective 5-HT1A receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinylcyclohexanecarboxamide (WAY-100635). OPC-14523 also behaved as a partial agonist in its stimulation of [35S]GTPgammaS binding to membranes from rat hippocampus (pEC50=7.60+/-0.23, Emax=41.1% of the effect of 10 microM (+)8-OH-DPAT), human frontal cortex (pEC50=7.89+/-0.08; Emax=64% of the effect of 10 microM (+)8-OH-DPAT), and Chinese Hamster Ovary cells expressing cloned human 5-HT1A receptors (pEC50=8.0+/-0.11; Emax=85.5% of the effect of 10 microM 5-HT), and all of these effects of OPC-14523 were blocked by WAY-100635. Taken together, these data support the development of OPC-14523 as an antidepressant whose mechanism of action involves potent partial agonist activity at 5-HT1A receptors.

Pleiotrophin suppression of receptor protein tyrosine phosphatase-β/ζ maintains the self-renewal competence of fetal human oligodendrocyte progenitor cells.

PubMed

McClain, Crystal R; Sim, Fraser J; Goldman, Steven A

2012-10-24

Oligodendrocyte progenitor cells (OPCs) persist in human white matter, yet the mechanisms by which they are maintained in an undifferentiated state are unknown. Human OPCs differentially express protein tyrosine phosphatase receptor β/ζ (PTPRZ1) and its inhibitory ligand, pleiotrophin, suggesting the maintenance of an autocrine loop by which PTPRZ1 activity is tonically suppressed. PTPRZ1 constitutively promotes the tyrosine dephosphorylation of β-catenin and, thus, β-catenin participation in T cell factor (TCF)-mediated transcription. Using CD140a/PDGFRα-based fluorescence-activated cell sorting to isolate fetal OPCs from the fetal brain at gestational ages 16-22 weeks, we asked whether pleiotrophin modulated the expansion of OPCs and, if so, whether this was effected through the serial engagement of PTPRZ1 and β-catenin-dependent signals, such as TCF-mediated transcription. Lentiviral shRNAi knockdown of PTPRZ1 induced TCF-mediated transcription and substantially augmented GSK3β inhibition-induced TCF-reporter luciferase expression, suggesting dual regulation of β-catenin and the importance of PTPRZ1 as a tonic brake upon TCF-dependent transcription. Pharmacological inhibition of GSK3β triggered substrate detachment and initiated sphere formation, yet had no effect on either proliferation or net cell number. In contrast, pleiotrophin strongly potentiated the proliferation of CD140a(+)-sorted OPCs, as did PTPRZ1 knockdown, which significantly increased the total number of population doublings exhibited by OPCs before mitotic senescence. These observations suggest that pleiotrophin inhibition of PTPRZ1 contributes to the homeostatic self-renewal of OPCs and that this process is mediated by the tonic activation of β-catenin/TCF-dependent transcription.

Pleiotrophin Suppression of Receptor Protein Tyrosine Phosphatase-β/ζ Maintains the Self-Renewal Competence of Fetal Human Oligodendrocyte Progenitor Cells

PubMed Central

McClain, Crystal R.; Sim, Fraser J.

2012-01-01

Oligodendrocyte progenitor cells (OPCs) persist in human white matter, yet the mechanisms by which they are maintained in an undifferentiated state are unknown. Human OPCs differentially express protein tyrosine phosphatase receptor β/ζ (PTPRZ1) and its inhibitory ligand, pleiotrophin, suggesting the maintenance of an autocrine loop by which PTPRZ1 activity is tonically suppressed. PTPRZ1 constitutively promotes the tyrosine dephosphorylation of β-catenin and, thus, β-catenin participation in T cell factor (TCF)-mediated transcription. Using CD140a/PDGFRα-based fluorescence-activated cell sorting to isolate fetal OPCs from the fetal brain at gestational ages 16–22 weeks, we asked whether pleiotrophin modulated the expansion of OPCs and, if so, whether this was effected through the serial engagement of PTPRZ1 and β-catenin-dependent signals, such as TCF-mediated transcription. Lentiviral shRNAi knockdown of PTPRZ1 induced TCF-mediated transcription and substantially augmented GSK3β inhibition-induced TCF-reporter luciferase expression, suggesting dual regulation of β-catenin and the importance of PTPRZ1 as a tonic brake upon TCF-dependent transcription. Pharmacological inhibition of GSK3β triggered substrate detachment and initiated sphere formation, yet had no effect on either proliferation or net cell number. In contrast, pleiotrophin strongly potentiated the proliferation of CD140a+-sorted OPCs, as did PTPRZ1 knockdown, which significantly increased the total number of population doublings exhibited by OPCs before mitotic senescence. These observations suggest that pleiotrophin inhibition of PTPRZ1 contributes to the homeostatic self-renewal of OPCs and that this process is mediated by the tonic activation of β-catenin/TCF-dependent transcription. PMID:23100427

Encapsulated oligodendrocyte precursor cell fate is dependent on PDGF-AA release kinetics in a 3D microparticle-hydrogel drug delivery system.

PubMed

Pinezich, Meghan R; Russell, Lauren N; Murphy, Nicholas P; Lampe, Kyle J

2018-04-16

Biomaterial drug delivery systems (DDS) can be used to regulate growth factor release and combat the limited intrinsic regeneration capabilities of central nervous system (CNS) tissue following injury and disease. Of particular interest are systems that aid in oligodendrocyte regeneration, as oligodendrocytes generate myelin which surrounds neuronal axons and helps transmit signals throughout the CNS. Oligodendrocyte precursor cells (OPCs) are found in small numbers in the adult CNS, but are unable to effectively differentiate following CNS injury. Delivery of signaling molecules can initiate a favorable OPC response, such as proliferation or differentiation. Here, we investigate the delivery of one such molecule, platelet derived growth factor-AA (PDGF-AA), from poly(lactic-co-glycolic) acid microparticles to OPCs in a 3D polyethylene glycol-based hydrogel. The goal of this DDS was to better understand the relationship between PDGF-AA release kinetics and OPC fate. The system approximates native brain tissue stiffness, while incorporating PDGF-AA under seven different delivery scenarios. Within this DDS, supply of PDGF-AA followed by PDGF-AA withdrawal caused OPCs to upregulate gene expression of myelin basic protein (MBP) by factors of 1.6-9.2, whereas continuous supply of PDGF-AA caused OPCs to remain proliferative. At the protein expression level, we observed an upregulation in O1, a marker for mature oligodendrocytes. Together, these results show that burst release followed by withdrawal of PDGF-AA from a hydrogel DDS stimulates survival, proliferation, and differentiation of OPCs in vitro. Our results could inform the development of improved neural regeneration strategies that incorporate delivery of PDGF-AA to the injured CNS. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2018. © 2018 Wiley Periodicals, Inc.

Adenosine A₂A receptors inhibit delayed rectifier potassium currents and cell differentiation in primary purified oligodendrocyte cultures.

PubMed

Coppi, Elisabetta; Cellai, Lucrezia; Maraula, Giovanna; Pugliese, Anna Maria; Pedata, Felicita

2013-10-01

Oligodendrocyte progenitor cells (OPCs) are a population of cycling cells which persist in the adult central nervous system (CNS) where, under opportune stimuli, they differentiate into mature myelinating oligodendrocytes. Adenosine A(2A) receptors are Gs-coupled P1 purinergic receptors which are widely distributed throughout the CNS. It has been demonstrated that OPCs express A(2A) receptors, but their functional role in these cells remains elusive. Oligodendrocytes express distinct voltage-gated ion channels depending on their maturation. Here, by electrophysiological recordings coupled with immunocytochemical labeling, we studied the effects of adenosine A(2A) receptors on membrane currents and differentiation of purified primary OPCs isolated from the rat cortex. We found that the selective A(2A) agonist, CGS21680, inhibits sustained, delayed rectifier, K(+) currents (I(K)) without modifying transient (I(A)) conductances. The effect was observed in all cells tested, independently from time in culture. CGS21680 inhibition of I(K) current was concentration-dependent (10-200 nM) and blocked in the presence of the selective A(2A) antagonist SCH58261 (100 nM). It is known that I(K) currents play an important role during OPC development since their block decreases cell proliferation and differentiation. In light of these data, our further aim was to investigate whether A(2A) receptors modulate these processes. CGS21680, applied at 100 nM in the culture medium of oligodendrocyte cultures, inhibits OPC differentiation (an effect prevented by SCH58261) without affecting cell proliferation. Data demonstrate that cultured OPCs express functional A(2A) receptors whose activation negatively modulate I(K) currents. We propose that, by this mechanism, A(2A) adenosine receptors inhibit OPC differentiation. Copyright © 2013 Elsevier Ltd. All rights reserved.

Induction of Oligodendrocyte Differentiation and In Vitro Myelination by Inhibition of Rho-Associated Kinase

PubMed Central

Taylor, Christopher; Pereira, Albertina; Seng, Michelle; Tham, Chui-Se; Izrael, Michal; Webb, Michael

2014-01-01

In inflammatory demyelinating diseases such as multiple sclerosis (MS), myelin degradation results in loss of axonal function and eventual axonal degeneration. Differentiation of resident oligodendrocyte precursor cells (OPCs) leading to remyelination of denuded axons occurs regularly in early stages of MS but halts as the pathology transitions into progressive MS. Pharmacological potentiation of endogenous OPC maturation and remyelination is now recognized as a promising therapeutic approach for MS. In this study, we analyzed the effects of modulating the Rho-A/Rho-associated kinase (ROCK) signaling pathway, by the use of selective inhibitors of ROCK, on the transformation of OPCs into mature, myelinating oligodendrocytes. Here we demonstrate, with the use of cellular cultures from rodent and human origin, that ROCK inhibition in OPCs results in a significant generation of branches and cell processes in early differentiation stages, followed by accelerated production of myelin protein as an indication of advanced maturation. Furthermore, inhibition of ROCK enhanced myelin formation in cocultures of human OPCs and neurons and remyelination in rat cerebellar tissue explants previously demyelinated with lysolecithin. Our findings indicate that by direct inhibition of this signaling molecule, the OPC differentiation program is activated resulting in morphological and functional cell maturation, myelin formation, and regeneration. Altogether, we show evidence of modulation of the Rho-A/ROCK signaling pathway as a viable target for the induction of remyelination in demyelinating pathologies. PMID:25289646

Comparison of two aquaretic drugs (niravoline and OPC-31260) in cirrhotic rats with ascites and water retention.

PubMed

Bosch-Marcé, M; Poo, J L; Jiménez, W; Bordas, N; Leivas, A; Morales-Ruiz, M; Muñoz, R M; Pérez, M; Arroyo, V; Rivera, F; Rodés, J

1999-04-01

kappa-Opioid receptor agonists (niravoline) or nonpeptide antidiuretic hormone (ADH) V2 receptor antagonists (OPC-31260) possess aquaretic activity in cirrhosis; however, there is no information concerning the effects induced by the chronic administration of these drugs under this condition. To compare the renal and hormonal effects induced by the long-term oral administration of niravoline, OPC-31260, or vehicle, urine volume, urinary osmolality, sodium excretion, and urinary excretion of aldosterone (ALD) and ADH were measured in basal conditions and for 10 days after the daily oral administration of niravoline, OPC-31260, or vehicle to cirrhotic rats with ascites and water retention. Creatinine clearance, serum osmolality, ADH mRNA expression, and systemic hemodynamics were also measured at the end of the study. Niravoline increased water excretion, peripheral resistance, serum osmolality, and sodium excretion and reduced creatinine clearance, ALD and ADH excretion, and mRNA expression of ADH. OPC-31260 also increased water metabolism and sodium excretion and reduced urinary ALD, although the aquaretic effect was only evident during the first 2 days, and no effects on serum osmolality, renal filtration, and systemic hemodynamics were observed. Therefore, both agents have aquaretic efficacy, but the beneficial therapeutic effects of the long-term oral administration of niravoline are more consistent than those of OPC-31260 in cirrhotic rats with ascites and water retention.

Structure and mechanical properties of aluminosilicate geopolymer composites with Portland cement and its constituent minerals

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

Tailby, Jonathan, E-mail: jmtailby@hotmail.co; MacKenzie, Kenneth J.D.

2010-05-15

The compressive strengths and structures of composites of aluminosilicate geopolymer with the synthetic cement minerals C{sub 3}S, beta-C{sub 2}S, C{sub 3}A and commercial OPC were investigated. All the composites showed lower strengths than the geopolymer and OPC paste alone. X-ray diffraction, {sup 29}Si and {sup 27}Al MAS NMR and SEM/EDS observations indicate that hydration of the cement minerals and OPC is hindered in the presence of geopolymer, even though sufficient water was present in the mix for hydration to occur. In the absence of SEM evidence for the formation of an impervious layer around the cement mineral grains, the poormore » strength development is suggested to be due to the retarded development of C-S-H because of the preferential removal from the system of available Si because geopolymer formation is more rapid than the hydration of the cement minerals. This possibility is supported by experiments in which the rate of geopolymer formation is retarded by the substitution of potassium for sodium, by the reduction of the alkali content of the geopolymer paste or by the addition of borate. In all these cases the strength of the OPC-geopolymer composite was increased, particularly by the combination of the borate additive with the potassium geopolymer, producing an OPC-geopolymer composite stronger than hydrated OPC paste alone.« less

Effects of OPC-51803, a novel, nonpeptide vasopressin V2-receptor agonist, on micturition frequency in Brattleboro and aged rats.

PubMed

Nakamura, Shigeki; Hirano, Takahiro; Yamamura, Yoshitaka; Itoh, Shuji; Kondo, Kazumi; Mori, Toyoki; Kambe, Toshimi

2003-12-01

We assessed the effects of OPC-51803 ((5R)-2-[1-(2-chloro-4-(1-pyrrolidinyl)benzoyl)-2,3,4,5-tetrahydro-1H-1-benzazepin-5-yl]-N-isopropylacetamide), a nonpeptide vasopressin V(2)-receptor agonist, on micturition frequency in female homozygous Brattleboro rats (strain carries hereditary diabetes insipidus) and aged male Sprague-Dawley rats with polyuria. Female homozygous Brattleboro rats exhibited more diuresis and a larger micturition frequency over a 24-h period than did the heterozygous controls. In Brattleboro rats, an oral administration of OPC-51803 at 0.03 and 0.3 mg/kg significantly decreased urinary frequency and was accompanied by decreased urine volume. However, little effect was seen in the mean and maximal micturition volume. Aged male Sprague-Dawley rats (25-month-old) showed a significant increase in urine volume throughout a 0- to 24-h period compared with mature (6-month-old) rats. Orally administered OPC-51803 at 0.3 mg/kg decreased not only urine volume but also urinary frequency in aged rats. Furthermore, OPC-51803 prolonged the time prior to the first micturition. Therefore, OPC-51803 decreased micturition frequency in both rat species by reducing urine outflow. This suggests that the compound will be useful for treating micturition disorders that result in frequent micturition, such as that from polyuria, nocturnal polyuria, and some kinds of urinary incontinence.

Effects of an orally active vasopressin V1 receptor antagonist.

PubMed

Burrell, L M; Phillips, P A; Stephenson, J; Risvanis, J; Hutchins, A M; Johnston, C I

1993-05-01

1. This paper reports on the in vitro and in vivo characteristics of a non-peptide vasopressin V1 receptor antagonist 1-(1-[4-(3-acetylaminopropoxy)benzoyl]-4-piperidyl)-3,4-dihydro-2( 1H)- quinolinone (OPC-21268). 2. OPC-21268 caused a concentration-dependent displacement of the selective V1 receptor antagonist radioligand, [125I]-[d(CH2)5, sarcosine7]AVP from vasopressin V1 receptors in rat liver and kidney membranes, inhibitory concentration of 50% (IC50) 4 x 10(-8), 0.3 mol/L liver and 1.5 x 10(-8), 0.2 mol/L kidney. OPC-21268 had little effect on the selective V2 antagonist radioligand [3H]desGly-NH2(9)-d(CH2)5[D-Ileu2, Ileu4]AVP binding to V2 receptors in renal membranes (IC50 > 10(-4) mol/L). 3. After oral administration to rats, OPC-21268 was an effective V1 antagonist to both liver and kidney V1 receptors, in a dose-dependent manner. 4. These studies confirm that OPC-21268 is a potent non-peptide, orally effective V1 vasopressin receptor antagonist.

On compensation of four wave mixing effect in dispersion managed hybrid WDM-OTDM multicast overlay system with optical phase conjugation modules

NASA Astrophysics Data System (ADS)

Singh, Sukhbir; Singh, Surinder

2017-11-01

This paper investigated the effect of FWM and its suppression using optical phase conjugation modules in dispersion managed hybrid WDM-OTDM multicast overlay system. Interaction between propagating wavelength signals at higher power level causes new FWM component generation that can significant limit the system performance. OPC module consists of the pump signal and 0.6 km HNLF implemented in midway of optical link to generate destructive phase FWM components. Investigation revealed that by use of even OPC module in optical link reduces the FWM power and mitigate the interaction between wavelength signals at variable signal input power, dispersion parameter (β2) and transmission distance. System performance comparison is also made between without DM-OPC module, with DM and with DM-OPC module in scenario of FWM tolerance. The BER performance of hybrid WDM-OTDM multicast system using OPC module is improved by multiplication factor of 2 as comparable to dispersion managed and coverage distance is increased by factor of 2 as in Singh and Singh (2016).

Strength, leachability and microstructure characteristics of cement-based solidified plating sludge

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

Asavapisit, Suwimol; Naksrichum, Siripat; Harnwajanawong, Naraporn

2005-06-01

The solidification of the stabilized zinc-cyanide plating sludge was carried out using ordinary Portland cement (OPC) and pulverized fuel ash (PFA) as solidification binders. The plating sludge were used at the level of 0%, 10%, 20% and 30% dry weight, and PFA was used to replace OPC at 0%, 10%, 20% and 30% dry weight, respectively. Experimental results showed that a significant reduction in strength was observed when the plating sludge was added to both the OPC and OPC/PFA binders, but the negative effect was minimized when PFA was used as part substitute for OPC. SEM observation reveals that themore » deposition of the plating sludge on the surface of the clinkers and PFA could be the cause for hydration retardation. In addition, calcium zinc hydroxide hydrate complex and the unreacted di- and tricalcium silicates were the major phases in X-ray diffraction (XRD) patterns of the solidified plating waste hydrated for 28 days, although the retardation effect on hydration reactions but Cr concentration in toxicity characteristic leaching procedure (TCLP) leachates was lower than the U.S. EPA regulatory limit.« less

Accelerated antioxidant bioavailability of OPC-3 bioflavonoids administered as isotonic solution.

PubMed

Cesarone, Maria R; Grossi, Maria Giovanni; Di Renzo, Andrea; Errichi, Silvia; Schönlau, Frank; Wilmer, James L; Lange, Mark; Blumenfeld, Julian

2009-06-01

The degree of absorption of bioflavonoids, a diverse and complex group of plant derived phytonutrients, has been a frequent debate among scientists. Monomeric flavonoid species are known to be absorbed within 2 h. The kinetics of plasma reactive oxygen species, a reflection of bioactivity, of a commercial blend of flavonoids, OPC-3 was investigated. OPC-3 was selected to compare absorption of an isotonic flavonoid solution vs tablet form with the equivalent amount of fluid. In the case of isotonic OPC-3 the reactive oxygen species of the subject's plasma decreased significantly (p < 0.05), six times greater than OPC-3 tablets by 10 min post-consumption. After 20 min the isotonic formulation was approximately four times more bioavailable and after 40 min twice as bioavailable as the tablet, respectively. At time points 1 h and later, both isotonic and tablet formulations lowered oxidative stress, although the isotonic formulation values remained significantly better throughout the investigation period of 4 h. These findings point to a dramatically accelerated bioavailability of flavonoids delivered in an isotonic formulation. (c) 2009 John Wiley & Sons, Ltd.

Relation between speckle decorrelation and optical phase conjugation (OPC)-based turbidity suppression through dynamic scattering media: a study on in vivo mouse skin

PubMed Central

Jang, Mooseok; Ruan, Haowen; Vellekoop, Ivo M.; Judkewitz, Benjamin; Chung, Euiheon; Yang, Changhuei

2014-01-01

Light scattering in biological tissue significantly limits the accessible depth for localized optical interrogation and deep-tissue optical imaging. This challenge can be overcome by exploiting the time-reversal property of optical phase conjugation (OPC) to reverse multiple scattering events or suppress turbidity. However, in living tissue, scatterers are highly movable and the movement can disrupt time-reversal symmetry when there is a latency in the OPC playback. In this paper, we show that the motion-induced degradation of the OPC turbidity-suppression effect through a dynamic scattering medium shares the same decorrelation time constant as that determined from speckle intensity autocorrelation – a popular conventional measure of scatterer movement. We investigated this decorrelation characteristic time through a 1.5-mm-thick dorsal skin flap of a living mouse and found that it ranges from 50 ms to 2.5 s depending on the level of immobilization. This study provides information on relevant time scales for applying OPC to living tissues. PMID:25657876

PTEN negatively regulates the cell lineage progression from NG2+ glial progenitor to oligodendrocyte via mTOR-independent signaling

PubMed Central

González-Fernández, Estibaliz; Jeong, Hey-Kyeong; Fukaya, Masahiro; Kim, Hyukmin; Khawaja, Rabia R; Srivastava, Isha N; Waisman, Ari; Son, Young-Jin

2018-01-01

Oligodendrocytes (OLs), the myelin-forming CNS glia, are highly vulnerable to cellular stresses, and a severe myelin loss underlies numerous CNS disorders. Expedited OL regeneration may prevent further axonal damage and facilitate functional CNS repair. Although adult OL progenitors (OPCs) are the primary players for OL regeneration, targetable OPC-specific intracellular signaling mechanisms for facilitated OL regeneration remain elusive. Here, we report that OPC-targeted PTEN inactivation in the mouse, in contrast to OL-specific manipulations, markedly promotes OL differentiation and regeneration in the mature CNS. Unexpectedly, an additional deletion of mTOR did not reverse the enhanced OL development from PTEN-deficient OPCs. Instead, ablation of GSK3β, another downstream signaling molecule that is negatively regulated by PTEN-Akt, enhanced OL development. Our results suggest that PTEN persistently suppresses OL development in an mTOR-independent manner, and at least in part, via controlling GSK3β activity. OPC-targeted PTEN-GSK3β inactivation may benefit facilitated OL regeneration and myelin repair. PMID:29461205

Defect window analysis by using SEM-contour based shape quantifying method for sub-20nm node production

NASA Astrophysics Data System (ADS)

Hibino, Daisuke; Hsu, Mingyi; Shindo, Hiroyuki; Izawa, Masayuki; Enomoto, Yuji; Lin, J. F.; Hu, J. R.

2013-04-01

The impact on yield loss due to systematic defect which remains after Optical Proximity Correction (OPC) modeling has increased, and achieving an acceptable yield has become more difficult in the leading technology beyond 20 nm node production. Furthermore Process-Window has become narrow because of the complexity of IC design and less process margin. In the past, the systematic defects have been inspected by human-eyes. However the judgment by human-eyes is sometime unstable and not accurate. Moreover an enormous amount of time and labor will have to be expended on the one-by-one judgment for several thousands of hot-spot defects. In order to overcome these difficulties and improve the yield and manufacturability, the automated system, which can quantify the shape difference with high accuracy and speed, is needed. Inspection points could be increased for getting higher yield, if the automated system achieves our goal. Defect Window Analysis (DWA) system by using high-precision-contour extraction from SEM image on real silicon and quantifying method which can calculate the difference between defect pattern and non-defect pattern automatically, which was developed by Hitachi High-Technologies, has been applied to the defect judgment instead of the judgment by human-eyes. The DWA result which describes process behavior might be feedback to design or OPC or mask. This new methodology and evaluation results will be presented in detail in this paper.

Effects of the potential antidepressant OPC-14523 [1-[3-[4-(3-chlorophenyl)-1-piperazinyl]propyl]-5-methoxy-3,4-dihydro-2-quinolinone monomethanesulfonate] a combined sigma and 5-HT1A ligand: modulation of neuronal activity in the dorsal raphe nucleus.

PubMed

Bermack, Jordanna E; Haddjeri, Nasser; Debonnel, Guy

2004-08-01

OPC-14523 (OPC; [1-[3-[4-(3-chlorophenyl)-1-piperazinyl]propyl]-5-methoxy-3,4-dihydro-2-quinolinone monomethanesulfonate)] is a novel compound with high affinity for sigma and 5-HT(1A) receptors as well as for the 5-HT transporter. OPC has previously been shown to produce antidepressant-like effects in animal models of depression. This project set out to determine the effect of OPC on serotonergic neurotransmission and to shed light on its mechanism(s) of action. In an electrophysiological model of in vivo extracellular recordings in anesthetized rats, a 2-day treatment (1 mg/kg/day) with OPC induced a significant increase in dorsal raphe nucleus (DRN) putative 5-HT neurons' firing activity. This increase was blocked by the coadministration of NE-100 [N,N-dipropyl-2-(4-methoxy-3-(2-phenylethoxy)phenyl)-thylamine], a selective sigma(1) antagonist (10 mg/kg/day). Furthermore, after 2-day treatments with OPC, the 5-HT(1A) autoreceptor response was altered, as demonstrated by the dramatically reduced response to an increase of endogenous 5-HT induced by the acute administration of paroxetine (500 microg/kg, i.v.). However, the 5-HT(1A) agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (4 microg/kg, i.v.) maintained its ability to decrease 5-HT firing activity, an effect that was reversible by the subsequent administration of the 5-HT(1A) antagonist WAY 100635 [N-[2-(4-[2-methoxyphenyl]-1-piperazinyl)ethyl]-N-2-pyridinylcyclohexanecarboxamide] (100 microg/kg, i.v.). As 8-OH-DPAT has been shown to act preferentially through postsynaptic 5-HT(1A) receptors, our data suggests that this effect of OPC is mediated primarily by the 5-HT(1A) autoreceptor. The decreased response of the 5-HT(1A) autoreceptor to paroxetine was not blocked by the coadministration of NE-100 indicating that sigma(1) receptors are not involved in this effect. Thus, both sigma and 5-HT(1A) receptors play a role in the "antidepressant-like" effects produced by OPC, which is in keeping with previously published behavioral data. In addition, the current series of experiments suggest that OPC might have potential as an antidepressant with a rapid onset of action compared with selective serotonin reuptake inhibitor treatments, which initially suppress the firing activity of putative 5-HT neurons and require at least 2 to 3 weeks to restore the firing activity to baseline neuronal firing activity through a desensitization of the 5-HT(1A) autoreceptor.

Optimization of RET flow using test layout

NASA Astrophysics Data System (ADS)

Zhang, Yunqiang; Sethi, Satyendra; Lucas, Kevin

2008-11-01

At advanced technology nodes with extremely low k1 lithography, it is very hard to achieve image fidelity requirements and process window for some layout configurations. Quite often these layouts are within simple design rule constraints for a given technology node. It is important to have these layouts included during early RET flow development. Most of RET developments are based on shrunk layout from the previous technology node, which is possibly not good enough. A better methodology in creating test layout is required for optical proximity correction (OPC) recipe and assists feature development. In this paper we demonstrate the application of programmable test layouts in RET development. Layout pattern libraries are developed and embedded in a layout tool (ICWB). Assessment gauges are generated together with patterns for quick correction accuracy assessment. Several groups of test pattern libraries have been developed based on learning from product patterns and a layout DOE approach. The interaction between layout patterns and OPC recipe has been studied. Correction of a contact layer is quite challenge because of poor convergence and low process window. We developed test pattern library with many different contact configurations. Different OPC schemes are studied on these test layouts. The worst process window patterns are pinpointed for a given illumination condition. Assist features (AF) are frequently placed according to pre-determined rules to improve lithography process window. These rules are usually derived from lithographic models and experiments. Direct validation of AF rules is required at development phase. We use the test layout approach to determine rules in order to eliminate AF printability problem.

Matching OPC and masks on 300-mm lithography tools utilizing variable illumination settings

NASA Astrophysics Data System (ADS)

Palitzsch, Katrin; Kubis, Michael; Schroeder, Uwe P.; Schumacher, Karl; Frangen, Andreas

2004-05-01

CD control is crucial to maximize product yields on 300mm wafers. This is particularly true for DRAM frontend lithography layers, like gate level, and deep trench (capacitor) level. In the DRAM process, large areas of the chip are taken up by array structures, which are difficult to structure due to aggressive pitch requirements. Consequently, the lithography process is centered such that the array structures are printed on target. Optical proximity correction is applied to print gate level structures in the periphery circuitry on target. Only slight differences of the different Zernike terms can cause rather large variations of the proximity curves, resulting in a difference of isolated and semi-isolated lines printed on different tools. If the deviations are too large, tool specific OPC is needed. The same is true for deep trench level, where the length to width ratio of elongated contact-like structures is an important parameter to adjust the electrical properties of the chip. Again, masks with specific biases for tools with different Zernikes are needed to optimize product yield. Additionally, mask making contributes to the CD variation of the process. Theoretically, the CD deviation caused by an off-centered mask process can easily eat up the majority of the CD budget of a lithography process. In practice, masks are very often distributed intelligently among production tools, such that lens and mask effects cancel each other. However, only dose adjusting and mask allocation may still result in a high CD variation with large systematical contributions. By adjusting the illumination settings, we have successfully implemented a method to reduce CD variation on our advanced processes. Especially inner and outer sigma for annular illumination, and the numerical aperture, can be optimized to match mask and stepper properties. This process will be shown to overcome slight lens and mask differences effectively. The effects on lithography process windows have to be considered, nonetheless.

Fine Scale Baleen Whale Behavior Observed Via Tagging Over Daily Time Scales

DTIC Science & Technology

2014-09-30

During late fall 2013 and winter 2014, I built a data logger for the optical plankton counter ( OPC ) to facilitate its continued use on the NOAA Ship...Gordon Gunter. This ship has very long (> 5 km) of conducting sea cable, and we had communication issues with the OPC with the manufacturers...telemetry system over this long sea cable. To solve this problem, I adapted an existing data logger to provide power and log data from the OPC locally on

Strategies for repair of white matter: influence of osmolarity and microglia on proliferation and apoptosis of oligodendrocyte precursor cells in different basal culture media.

PubMed

Kleinsimlinghaus, Karolina; Marx, Romy; Serdar, Meray; Bendix, Ivo; Dietzel, Irmgard D

2013-01-01

The aim of the present study has been to obtain high yields of oligodendrocyte precursor cells (OPCs) in culture. This is a first step in facilitation of myelin repair. We show that, in addition to factors, known to promote proliferation, such as basic fibroblast growth factor (FGF-2) and platelet derived growth factor (PDGF) the choice of the basal medium exerts a significant influence on the yield of OPCs in cultures from newborn rats. During a culture period of up to 9 days we observed larger numbers of surviving cells in Dulbecco's Modified Eagle Medium (DMEM), and Roswell Park Memorial Institute Medium (RPMI) compared with Neurobasal Medium (NB). A larger number of A2B5-positive OPCs was found after 6 days in RPMI based media compared with NB. The percentage of bromodeoxyuridine (BrdU)-positive cells was largest in cultures maintained in DMEM and RPMI. The percentage of caspase-3 positive cells was largest in NB, suggesting that this medium inhibits OPC proliferation and favors apoptosis. A difference between NB and DMEM as well as RPMI is the reduced Na(+)-content. The addition of equiosmolar supplements of mannitol or NaCl to NB medium rescued the BrdU-incorporation rate. This suggested that the osmolarity influences the proliferation of OPCs. Plating density as well as residual microglia influence OPC survival, BrdU incorporation, and caspase-3 expression. We found, that high density cultures secrete factors that inhibit BrdU incorporation whereas the presence of additional microglia induces an increase in caspase-3 positive cells, indicative of enhanced apoptosis. An enhanced number of microglia could thus also explain the stronger inhibition of OPC differentiation observed in high density cultures in response to treatment with the cytokines TNF-α and IFN-γ. We conclude that a maximal yield of OPCs is obtained in a medium of an osmolarity higher than 280 mOsm plated at a relatively low density in the presence of as little microglia as technically achievable.

Aspirin and probenecid inhibit organic anion transporter 3-mediated renal uptake of cilostazol and probenecid induces metabolism of cilostazol in the rat.

PubMed

Wang, Chong; Wang, Changyuan; Liu, Qi; Meng, Qiang; Cang, Jian; Sun, Huijun; Peng, Jinyong; Ma, Xiaochi; Huo, Xiaokui; Liu, Kexin

2014-06-01

This study aimed to evaluate the transporter-mediated renal excretion mechanism for cilostazol and to characterize the mechanism of drug-drug interaction (DDI) between cilostazol and aspirin or probenecid. Concentrations of cilostazol and its metabolites OPC-13015 [6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)butoxy]-2(1H)-quinolinone] and OPC-13213 [3,4-dihydro-6-[4-[1-(trans-4-hydroxycyclohexyl)-1H-tetrazol-5-yl]butoxy]-2-(1H)-quinolinone] in rat biologic or cell samples were measured by liquid chromatography-tandem mass spectrometry. Coadministration with probenecid, benzylpenicillin, or aspirin decreased the cumulative urinary excretion of cilostazol and renal clearance. Concentrations of cilostazol and OPC-13213 in plasma decreased, and the concentration of OPC-13015 increased in the presence of probenecid. By contrast, rat plasma cilostazol, in combination with benzylpenicillin or aspirin, sharply increased, and concentrations of OPC-13015 and OPC-13213 did not change. In urine, OPC-13015 was below the level of detection. The cumulative urinary excretion of OPC-13213 decreased in the presence of probenecid, benzylpenicillin, or aspirin. Cilostazol was distributed in the kidney and liver, with tissue to plasma partition coefficient (Kp) values of 8.4 ml/g and 16.3 ml/g, respectively. Probenecid and aspirin reduced cilostazol distribution in the kidney. Probenecid did not affect cilostazol metabolism in the kidney but increased cilostazol metabolism in the liver, and aspirin had no effect on cilostazol metabolism. Benzylpenicillin, aspirin, and cyclo-trans-4-l-hydroxyprolyl-l-serine (JBP485) reduced cilostazol uptake in kidney slices and human organic anion transporter 3 (hOAT3)-human embryonic kidney 293 (HEK293) cells, whereas p-aminohippuric acid did not. Compared with the vector, hOAT3-HEK293 cells accumulated more cilostazol, whereas hOAT1-HEK293 cells did not. OAT3 and Oat3 play a major role in cilostazol renal excretion, whereas OAT1 and Oat1 do not. Oat3 and Cyp3a are both targets of the DDI between cilostazol and probenecid. Aspirin inhibits OAT3-mediated uptake of cilostazol and does not influence cilostazol metabolism.

Neisseria meningitidis Opc invasin binds to the sulphated tyrosines of activated vitronectin to attach to and invade human brain endothelial cells.

PubMed

Sa E Cunha, Claudia; Griffiths, Natalie J; Virji, Mumtaz

2010-05-20

The host vasculature is believed to constitute the principal route of dissemination of Neisseria meningitidis (Nm) throughout the body, resulting in septicaemia and meningitis in susceptible humans. In vitro, the Nm outer membrane protein Opc can enhance cellular entry and exit, utilising serum factors to anchor to endothelial integrins; but the mechanisms of binding to serum factors are poorly characterised. This study demonstrates that Nm Opc expressed in acapsulate as well as capsulate bacteria can increase human brain endothelial cell line (HBMEC) adhesion and entry by first binding to serum vitronectin and, to a lesser extent, fibronectin. This study also demonstrates that Opc binds preferentially to the activated form of human vitronectin, but not to native vitronectin unless the latter is treated to relax its closed conformation. The direct binding of vitronectin occurs at its Connecting Region (CR) requiring sulphated tyrosines Y(56) and Y(59). Accordingly, Opc/vitronectin interaction could be inhibited with a conformation-dependent monoclonal antibody 8E6 that targets the sulphotyrosines, and with synthetic sulphated (but not phosphorylated or unmodified) peptides spanning the vitronectin residues 43-68. Most importantly, the 26-mer sulphated peptide bearing the cell-binding domain (45)RGD(47) was sufficient for efficient meningococcal invasion of HBMECs. To our knowledge, this is the first study describing the binding of a bacterial adhesin to sulphated tyrosines of the host receptor. Our data also show that a single region of Opc is likely to interact with the sulphated regions of both vitronectin and of heparin. As such, in the absence of heparin, Opc-expressing Nm interact directly at the CR but when precoated with heparin, they bind via heparin to the heparin-binding domain of the activated vitronectin, although with a lower affinity than at the CR. Such redundancy suggests the importance of Opc/vitronectin interaction in meningococcal pathogenesis and may enable the bacterium to harness the benefits of the physiological processes in which the host effector molecule participates.

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) for detection and identification of albumin phosphylation by organophosphorus pesticides and G- and V-type nerve agents.

PubMed

John, Harald; Breyer, Felicitas; Thumfart, Jörg Oliver; Höchstetter, Hans; Thiermann, Horst

2010-11-01

Toxic organophosphorus compounds (OPC), e.g., pesticides and nerve agents (NA), are known to phosphylate distinct endogenous proteins in vivo and in vitro. OPC adducts of butyrylcholinesterase and albumin are considered to be valuable biomarkers for retrospective verification of OPC exposure. Therefore, we have detected and identified novel adducts of human serum albumin (HSA) by means of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Pure albumin and plasma were incubated with numerous pesticides and NA of the V- and G-type in different molar ratios. Samples were prepared either by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by in-gel enzymatic cleavage using endoproteinase Glu-C (Glu-C) or by combining highly albumin-selective affinity extraction with ultrafiltration followed by reduction, carbamidomethylation, and enzymatic cleavage (Glu-C) prior to MALDI-TOF MS analysis. Characteristic mass shifts for phosphylation revealed tyrosine adducts at Y(411) (Y(401)KFQNALLVRY(411)TKKVPQVSTPTLVE(425)), Y(148) and Y(150) (I(142)ARRHPY(148)FY(150)APE(153), single and double labeled), and Y(161) (L(154)LFFAKRY(161)KAAFTE(167)) produced by original NA (tabun, sarin, soman, cyclosarin, VX, Chinese VX, and Russian VX) as well as by chlorpyrifos-oxon, diisopropyl fluorophosphate (DFP), paraoxon-ethyl (POE), and profenofos. MALDI-MS/MS of the single-labeled I(142)-E(153) peptide demonstrated that Y(150) was phosphylated with preference to Y(148). Aged albumin adducts were not detected. The procedure described was reproducible and feasible for detection of adducts at the most reactive Y(411)-residue (S/N ≥ 3) when at least 1% of total albumin was labeled. This was achieved by incubating plasma with molar HSA/OPC ratios ranging from approximately 1:0.03 (all G-type NA, DFP, and POE) to 1:3 (V-type NA, profenofos). Relative signal intensity of the Y(411) adduct correlated well with the spotted relative molar amount underlining the usefulness for quantitative adduct determination. In conclusion, the current analytical design exhibits potential as a verification tool for high-dose exposure.

Reticle decision center: a novel applications platform for enhancing reticle yield and productivity at 10nm technology and beyond

NASA Astrophysics Data System (ADS)

Hwa, George; Bugata, Raj; Chiang, Kaiming; Lakkapragada, Suresh; Tolani, Vikram; Gopalakrishnan, Sandhya; Chen, Chun-Jen; Yang, Chin-Ting; Hsu, Sheng-Chang; Tuo, Laurent

2016-10-01

In the semiconductor IC manufacturing industry, challenges associated with producing defect-free photomasks have been dramatically increasing. At the 10nm technology node, since the 193nm immersion scanner numerical aperture has remained the same 1.35 as in previous nodes, more multi-patterning and aggressive SMO illumination sources are being used to effectively print smaller feature CDs and pitches. To accommodate such specialized sources, more model-based mask OPC and ILT have been used making mask designs very complicated. This in turn makes mask manufacturing very challenging especially for the defect inspection, repair, and metrology processes that need to guarantee defect-free masks. Over the past few years, considerable innovation have been made in the areas of defect inspection and disposition that has ensured continued predictability of mask quality to wafer and final chip yields. The accurate disposition of each mask defect before and after repair has been facilitated by a suite of automated applications such as ADC, LPR, RPG, AIA, etc. that work together with the inspection, repair, and metrology tools and effectively also provide the best possible utilization of the tool capability, capacity and operator resources. In this paper we introduce a new consolidated applications platform called the Reticle Decision Center (RDC) which hosts all these supporting software applications on a centralized server with direct connectivity to mask inspection, repair, metrology tools and more. The paper details how the RDC server is architected to host any application in its native operating system environment and provides for high availability with automatic failover and redundancy. The server along with its host of applications has been tightly integrated with KLA-Tencor's Teron mask inspectors. The paper concludes with showing benefits realized in mask cycle-time and yield as a result of implementing RDC into a high-volume 10nm mask-shop production line.

Statin Therapy Inhibits Remyelination in the Central Nervous System

PubMed Central

Miron, Veronique E.; Zehntner, Simone P.; Kuhlmann, Tanja; Ludwin, Samuel K.; Owens, Trevor; Kennedy, Timothy E.; Bedell, Barry J.; Antel, Jack P.

2009-01-01

Remyelination of lesions in the central nervous system contributes to neural repair following clinical relapses in multiple sclerosis. Remyelination is initiated by recruitment and differentiation of oligodendrocyte progenitor cells (OPCs) into myelinating oligodendrocytes. Simvastatin, a blood-brain barrier-permeable statin in multiple sclerosis clinical trials, has been shown to impact the in vitro processes that have been implicated in remyelination. Animals were fed a cuprizone-supplemented diet for 6 weeks to induce localized demyelination in the corpus callosum; subsequent return to normal diet for 3 weeks stimulated remyelination. Simvastatin was injected intraperitoneally during the period of coincident demyelination and OPC maturation (weeks 4 to 6), throughout the entire period of OPC responses (weeks 4 to 9), or during the remyelination-only phase (weeks 7 to 9). Simvastatin treatment (weeks 4 to 6) caused a decrease in myelin load and both Olig2strong and Nkx2.2strong OPC numbers. Simvastatin treatment (weeks 4 to 9 and 7 to 9) caused a decrease in myelin load, which was correlated with a reduction in Nkx2.2strong OPCs and an increase in Olig2strong cells, suggesting that OPCs were maintained in an immature state (Olig2strong/Nkx2.2weak). NogoA+ oligodendrocyte numbers were decreased during all simvastatin treatment regimens. Our findings suggest that simvastatin inhibits central nervous system remyelination by blocking progenitor differentiation, indicating the need to monitor effects of systemic immunotherapies that can access the central nervous system on brain tissue-repair processes. PMID:19349355

[Vasopressin (ADH)].

PubMed

Hirai, A; Uchida, D; Yoshida, S

1992-12-01

Vasopressin is thought to play an important role, not only in the metabolism of water and electrolytes, but also in the regulation of renal hemodynamics. This year, great progress has been achieved in molecular biology of vasopressin receptors. First, the cloning of a complementary DNA, encoding the rat liver V1a arginine vasopressin receptor, was reported. The liver cDNA encodes a protein with seven putative transmembrane domains, which binds arginine vasopressin and related compounds with affinities similar to the native rat V1a receptor. The messenger RNA, corresponding to the cDNA, is distributed in rat tissues, known to contain V1a receptors. Second, the cloning of a complementary DNA encoding the rat kidney V2 arginine vasopressin receptor was also successful. The kidney cDNA encodes a protein with a transmembrane topography characteristic of G protein-coupled receptors. The receptor messenger RNA is detected only in the kidney. Last year, an orally active and specific vasopressin V1 receptor antagonist, OPC-21268 was first reported. The i.v. or p.o. administration of OPC-21268 dose-dependently inhibited vasopressin-induced vasoconstriction, while that induced by angiotensin II was not affected. OPC-21268 may have clinical potentials in certain hypertensive cardiovascular disorders. In addition, an orally active and specific vasopressin V2 receptor antagonist, OPC-31260 was also reported. Oral administration of OPC-31260 inhibited antidiuretic action of arginine vasopressin. OPC-31260 is thought to be useful in the treatment of certain disorders, such as the syndrome of inappropriate secretion of ADH (SIADH).

Remyelination after Lysophosphatidyl Choline-Induced Demyelination Is Stimulated by Bone Marrow Stromal Cell-Derived Oligoprogenitor Cell Transplantation.

PubMed

Nazm Bojnordi, M; Ghasemi, H H; Akbari, E

2015-01-01

Bone marrow stromal cells (BMSCs) are a desirable cell source that may be useful for the treatment of neurodegenerative diseases given their capacity to differentiate into various types of cells. The current study aimed to investigate whether oligoprogenitor cell (OPC)-derived BMSCs have therapeutic benefits in an animal model of local demyelination. BMSCs were transdifferentiated into OPCs using a defined culture medium supplemented with a combination of inducers. The differentiation capacity of the BMSCs was evaluated at the end of the induction phase by assessing the expression levels of the glial-specific markers oligodendrocyte transcription factor 2 and O4 surface antigen. Local demyelination was induced in the corpus callosum of adult female rats via direct injection of lysophosphatidylcholine (LPC) followed by engraftment of BMSC-generated OPCs. The rats were divided into sham control, vehicle control, and cell-transplanted groups. The changes in the extent of demyelination and the robustness of the remyelination event were assessed using Luxol Fast Blue staining and immunohistochemical analysis 1 week after LPC injection and 2 weeks after cell transplantation. Consequently, transplantation of OPCs into the demyelinated corpus callosum model resulted in differentiation of the cells into mature oligodendrocytes that were immunopositive for myelin basic protein. Furthermore, OPC transplantation mitigated demyelination and augmented remyelination relative to controls. These findings suggest that BMSC-derived OPCs can be utilized in therapeutic approaches for the management of demyelination-associated diseases such as multiple sclerosis. © 2015 S. Karger AG, Basel.

Using OPC and HL7 Standards to Incorporate an Industrial Big Data Historian in a Health IT Environment.

PubMed

Cruz, Márcio Freire; Cavalcante, Carlos Arthur Mattos Teixeira; Sá Barretto, Sérgio Torres

2018-05-30

Health Level Seven (HL7) is one of the standards most used to centralize data from different vital sign monitoring systems. This solution significantly limits the data available for historical analysis, because it typically uses databases that are not effective in storing large volumes of data. In industry, a specific Big Data Historian, known as a Process Information Management System (PIMS), solves this problem. This work proposes the same solution to overcome the restriction on storing vital sign data. The PIMS needs a compatible communication standard to allow storing, and the one most commonly used is the OLE for Process Control (OPC). This paper presents a HL7-OPC Server that permits communication between vital sign monitoring systems with PIMS, thus allowing the storage of long historical series of vital signs. In addition, it carries out a review about local and cloud-based Big Medical Data researches, followed by an analysis of the PIMS in a Health IT Environment. Then it shows the architecture of HL7 and OPC Standards. Finally, it shows the HL7-OPC Server and a sequence of tests that proved its full operation and performance.

Determinants of First-Time Cancer Examinations in a Rural Community: A Mechanism for Behavior Change

PubMed Central

Guo, Yi; Emanuel, Amber S.; Shepperd, James A.; Dodd, Virginia J.; Marks, John G.; Muller, Keith E.; Riley, Joseph L.

2015-01-01

Objectives. After conducting a media campaign focusing on the importance of oral and pharyngeal cancer (OPC) examinations, we assessed mechanisms of behavior change among individuals receiving an OPC examination for the first time. Methods. We used data from 2 waves of telephone surveys of individuals residing in 36 rural census tracts in northern Florida (n = 806). The second survey occurred after our media intervention. We developed media messages and modes of message delivery with community members via focus groups and intercept interviews. We performed a mediation analysis to examine behavior change mechanisms. Results. Greater exposure to media messages corresponded with heightened concern about OPC. Heightened concern, in turn, predicted receipt of a first-time OPC examination, but only among men. Conclusions. We extended earlier studies by measuring an outcome behavior (receipt of an OPC examination) and demonstrating that the putative mechanism of action (concern about the disease) explained the link between a media intervention and engaging in the target behavior. Improving the quality of media campaigns by engaging community stakeholders in selecting messages and delivery methods is an effective strategy in building public health interventions aimed at changing behaviors. PMID:25973820

OPC-21268, an orally effective, nonpeptide vasopressin V1 receptor antagonist.

PubMed

Yamamura, Y; Ogawa, H; Chihara, T; Kondo, K; Onogawa, T; Nakamura, S; Mori, T; Tominaga, M; Yabuuchi, Y

1991-04-26

An orally effective, nonpeptide, vasopressin V1 receptor antagonist, OPC-21268, has been identified. This compound selectively antagonized binding to the V1 subtype of the vasopressin receptor in a competitive manner. In vivo, the compound acted as a specific antagonist of arginine vasopressin (AVP)-induced vasoconstriction. After oral administration in conscious rats, the compound also antagonized pressor responses to AVP. OPC-21268 can be used to study the physiological role of AVP and may be therapeutically useful in the treatment of hypertension and congestive heart failure.

Visualisation and quantification of intracellular interactions of Neisseria meningitidis and human α-actinin by confocal imaging.

PubMed

Murillo, Isabel; Virji, Mumtaz

2010-10-24

The Opc protein of Neisseria meningitidis (Nm, meningococcus) is a surface-expressed integral outer membrane protein, which can act as an adhesin and an effective invasin for human epithelial and endothelial cells. We have identified endothelial surface-located integrins as major receptors for Opc, a process which requires Opc to first bind to integrin ligands such as vitronectin and via these to the cell-expressed receptors(1). This process leads to bacterial invasion of endothelial cells(2). More recently, we observed an interaction of Opc with a 100 kDa protein found in whole cell lysates of human cells(3). We initially observed this interaction when host cell proteins separated by electrophoresis and blotted on to nitrocellulose were overlaid with Opc-expressing Nm. The interaction was direct and did not involve intermediate molecules. By mass spectrometry, we established the identity of the protein as α-actinin. As no surface expressed α-actinin was found on any of the eight cell lines examined, and as Opc interactions with endothelial cells in the presence of serum lead to bacterial entry into the target cells, we examined the possibility of the two proteins interacting intracellularly. For this, cultured human brain microvascular endothelial cells (HBMECs) were infected with Opc-expressing Nm for extended periods and the locations of internalised bacteria and α-actinin were examined by confocal microscopy. We observed time-dependent increase in colocalisation of Nm with the cytoskeletal protein, which was considerable after an eight hour period of bacterial internalisation. In addition, the use of quantitative imaging software enabled us to obtain a relative measure of the colocalisation of Nm with α-actinin and other cytoskeletal proteins. Here we present a protocol for visualisation and quantification of the colocalisation of the bacterium with intracellular proteins after bacterial entry into human endothelial cells, although the procedure is also applicable to human epithelial cells.

Aetiological heterogeneity of head and neck squamous cell carcinomas: the role of human papillomavirus infections, smoking and alcohol.

PubMed

Farsi, Nada J; Rousseau, Marie-Claude; Schlecht, Nicolas; Castonguay, Geneviève; Allison, Paul; Nguyen-Tan, Phuc Félix; Souliéres, Denis; Coutlée, Francois; Hier, Michael; Madathil, Sreenath; Franco, Eduardo L; Nicolau, Belinda

2017-12-07

Tobacco and alcohol consumption are the main risk factors for head and neck squamous cell carcinoma (HNSCC). In addition, human papillomavirus (HPV) infection plays a causal role in oropharyngeal cancer (OPC), a subset of HNSCC. We assessed the independent effects of tobacco, alcohol and HPV infection on OPC risk in the head and neck cancer (HeNCe) Life study, a hospital-based case-control study of HNSCC with frequency-matched controls by age and sex from four Montreal hospitals. Interviewers collected information on socio-demographic and behavioural factors. We tested exfoliated oral cells for HPV DNA by polymerase chain reaction (PCR). We included only OPC cases (n = 188) and controls (n = 427) without missing values for HPV, smoking or alcohol. We examined associations by estimating odds ratios (ORs) and corresponding 95% confidence intervals (CI) using unconditional logistic regression. Smoking (OR = 1.90, 95% CI: 1.04-3.45) and alcohol (OR = 2.74, 95% CI: 1.45-5.15) were associated with an increased risk of OPC independent of HPV status. Positivity for HPV 16 among heavy smokers and heavy alcohol users was associated with a 30.4-fold (95% CI: 8.94-103.26) and 18.6-fold (95% CI: 5.75-60.13) elevation in risk of OPC relative to participants who were HPV negative, respectively. Moreover, the combined effect of heavy smoking and alcohol comsumption with HPV 16 infection substantially increased OPC risk (OR = 48.76, 95% CI: 15.83-150.17) and (OR = 50.60, 95% CI: 15.96-160.40), respectively. Our results support the independent roles of smoking, alcohol and HPV infection in OPC risk and a possible combined effect. Efforts should be made to tackle these major risk factors simultaneously. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

CD-SEM metrology and OPC modeling for 2D patterning in advanced technology nodes (Conference Presentation)

NASA Astrophysics Data System (ADS)

Wallow, Thomas I.; Zhang, Chen; Fumar-Pici, Anita; Chen, Jun; Laenens, Bart; Spence, Christopher A.; Rio, David; van Adrichem, Paul; Dillen, Harm; Wang, Jing; Yang, Peng-Cheng; Gillijns, Werner; Jaenen, Patrick; van Roey, Frieda; van de Kerkhove, Jeroen; Babin, Sergey

2017-03-01

In the course of assessing OPC compact modeling capabilities and future requirements, we chose to investigate the interface between CD-SEM metrology methods and OPC modeling in some detail. Two linked observations motivated our study: 1) OPC modeling is, in principle, agnostic of metrology methods and best practice implementation. 2) Metrology teams across the industry use a wide variety of equipment, hardware settings, and image/data analysis methods to generate the large volumes of CD-SEM measurement data that are required for OPC in advanced technology nodes. Initial analyses led to the conclusion that many independent best practice metrology choices based on systematic study as well as accumulated institutional knowledge and experience can be reasonably made. Furthermore, these choices can result in substantial variations in measurement of otherwise identical model calibration and verification patterns. We will describe several experimental 2D test cases (i.e., metal, via/cut layers) that examine how systematic changes in metrology practice impact both the metrology data itself and the resulting full chip compact model behavior. Assessment of specific methodology choices will include: • CD-SEM hardware configurations and settings: these may range from SEM beam conditions (voltage, current, etc.,) to magnification, to frame integration optimizations that balance signal-to-noise vs. resist damage. • Image and measurement optimization: these may include choice of smoothing filters for noise suppression, threshold settings, etc. • Pattern measurement methodologies: these may include sampling strategies, CD- and contour- based approaches, and various strategies to optimize the measurement of complex 2D shapes. In addition, we will present conceptual frameworks and experimental methods that allow practitioners of OPC metrology to assess impacts of metrology best practice choices on model behavior. Finally, we will also assess requirements posed by node scaling on OPC model accuracy, and evaluate potential consequences for CD-SEM metrology capabilities and practices.

Drug-based modulation of endogenous stem cells promotes functional remyelination in vivo

PubMed Central

Najm, Fadi J.; Madhavan, Mayur; Zaremba, Anita; Shick, Elizabeth; Karl, Robert T.; Factor, Daniel C.; Miller, Tyler E.; Nevin, Zachary S.; Kantor, Christopher; Sargent, Alex; Quick, Kevin L.; Schlatzer, Daniela M.; Tang, Hong; Papoian, Ruben; Brimacombe, Kyle R.; Shen, Min; Boxer, Matthew B.; Jadhav, Ajit; Robinson, Andrew P.; Podojil, Joseph R.; Miller, Stephen D.; Miller, Robert H.; Tesar, Paul J.

2015-01-01

Multiple sclerosis (MS) involves an aberrant autoimmune response and progressive failure of remyelination in the central nervous system (CNS). Prevention of neural degeneration and subsequent disability requires remyelination through the generation of new oligodendrocytes, but current treatments exclusively target the immune system. Oligodendrocyte progenitor cells (OPCs) are stem cells in the CNS and the principal source of myelinating oligodendrocytes1. OPCs are abundant in demyelinated regions of MS patients, yet fail to differentiate, thereby representing a cellular target for pharmacological intervention2. To discover therapeutic compounds for enhancing myelination from endogenous OPCs, we screened a library of bioactive small molecules on mouse pluripotent epiblast stem cell (EpiSC)-derived OPCs3–5. We identified seven drugs that functioned at nanomolar doses to selectively enhance the generation of mature oligodendrocytes from OPCs in vitro. Two drugs, miconazole and clobetasol, were effective in promoting precocious myelination in organotypic cerebellar slice cultures, and in vivo in early postnatal mouse pups. Systemic delivery of each of the two drugs significantly increased the number of new oligodendrocytes and enhanced remyelination in a lysolecithin-induced mouse model of focal demyelination. Administering each of the two drugs at the peak of disease in the experimental autoimmune encephalomyelitis (EAE) mouse model of chronic progressive MS resulted in striking reversal of disease severity. Immune response assays showed that miconazole functioned directly as a remyelinating drug with no effect on the immune system, whereas clobetasol was a potent immunosuppressant as well as a remyelinating agent. Mechanistic studies showed that miconazole and clobetasol functioned in OPCs through mitogen-activated protein kinase (MAPK) and glucocorticoid receptor (GR) signaling, respectively. Furthermore, both drugs enhanced the generation of human oligodendrocytes from human OPCs in vitro. Collectively, our results provide a rationale for testing miconazole and clobetasol, or structurally-modified derivatives, to enhance remyelination in patients. PMID:25896324

Analysis of the V2 Vasopressin Receptor (V2R) Mutations Causing Partial Nephrogenic Diabetes Insipidus Highlights a Sustainable Signaling by a Non-peptide V2R Agonist.

PubMed

Makita, Noriko; Sato, Tomohiko; Yajima-Shoji, Yuki; Sato, Junichiro; Manaka, Katsunori; Eda-Hashimoto, Makiko; Ootaki, Masanori; Matsumoto, Naoki; Nangaku, Masaomi; Iiri, Taroh

2016-10-21

Disease-causing mutations in G protein-coupled receptor (GPCR) genes, including the V2 vasopressin receptor (V2R) gene, often cause misfolded receptors, leading to a defect in plasma membrane trafficking. A novel V2R mutation, T273M, identified in a boy with partial nephrogenic diabetes insipidus (NDI), shows intracellular localization and partial defects similar to the two mutants we described previously (10). Although non-peptide V2R antagonists have been shown to rescue the membrane localization of V2R mutants, their level of functional rescue is weak. Interestingly, it has been reported that a non-peptide agonist, OPC51803, activates misfolded V2R mutants intracellularly without degradation, thus potentially serving as a therapeutic agent against NDI (14). In our current experiments, however, a peptide antagonist blocked arginine vasopressin (AVP)- or OPC51803-stimulated cAMP accumulation both in COS-7 and MDCK cells, suggesting that OPC51803 mainly stimulates cell surface V2R mutants. In addition, our analyses revealed that OPC51803 works not only as a non-peptide agonist that causes activation/β-arrestin-dependent desensitization of V2R mutants expressed at the plasma membrane but also as a pharmacochaperone that promotes the endoplasmic reticulum-retained mutant maturation and trafficking to the plasma membrane. The ratio of the pharmacochaperone effect to the desensitization effect likely correlates negatively with the residual function of the tested mutants, suggesting that OPC5 has a more favorable effect on the V2R mutants with a less residual function. We speculated that the canceling of the desensitization effect of OPC51803 by the pharmacochaperone effect after long-term treatment may produce sustainable signaling, and thus pharmacochaperone agonists such as OPC51803 may serve as promising therapeutics for NDI caused by misfolded V2R mutants. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Influence of organophosphate poisoning on human dendritic cells.

PubMed

Schäfer, Marina; Koppe, Franziska; Stenger, Bernhard; Brochhausen, Christoph; Schmidt, Annette; Steinritz, Dirk; Thiermann, Horst; Kirkpatrick, Charles James; Pohl, Christine

2013-12-05

Organophosphourus compounds (OPC, including nerve agents and pesticides) exhibit acute toxicity by inhibition of acetylcholinesterase. Lung affections are frequent complications and a risk factor for death. In addition, epidemiological studies reported immunological alterations after OPC exposure. In our experiments we investigated the effects of organophosphourus pesticides dimethoate and chlorpyrifos on dendritic cells (DC) that are essential for the initial immune response, especially in the pulmonary system. DC, differentiated from the monocyte cell line THP-1 by using various cytokines (IL-4, GM-CSF, TNF-α, Ionomycin), were exposed to organophosphourus compounds at different concentrations for a 24h time period. DC were characterized by flow cytometry and immunofluorescence using typical dendritic cell markers (e.g., CD11c, CD209 and CD83). After OPC exposure we investigated cell death, the secretion profile of inflammatory mediators, changes of DC morphology, and the effect on protein kinase signalling pathways. Our results revealed a successful differentiation of THP-1 into DC. OPC exposure caused a significant concentration-dependent influence on DC: Dendrites of the DC were shortened and damaged, DC-specific cell surface markers (i.e., CD83and CD209) decreased dramatically after chlorpyrifos exposure. Interestingly, the effects caused by dimethoate were in general less pronounced. The organophosphourus compounds affected the release of inflammatory cytokines, such as IL-1ß and IL-8. The anti-inflammatory cytokine IL-10 was significantly down regulated. Protein kinases like the Akt family or ERK, which are essential for cell survival and proliferation, were inhibited by both OPC. These findings indicate that the tested organophosphourus compounds induced significant changes in cell morphology, inhibited anti-inflammatory cytokines and influenced important protein signalling pathways which are involved in regulation of apoptosis. Thus our results highlight novel aspects -apparently independent of AChE inhibition- of OPC poisoning with regard to lung toxicity. Our findings contribute to the basic understanding of pulmonary complications caused by OPC poisoning. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Analysis of the V2 Vasopressin Receptor (V2R) Mutations Causing Partial Nephrogenic Diabetes Insipidus Highlights a Sustainable Signaling by a Non-peptide V2R Agonist*

PubMed Central

Makita, Noriko; Sato, Tomohiko; Yajima-Shoji, Yuki; Sato, Junichiro; Manaka, Katsunori; Eda-Hashimoto, Makiko; Ootaki, Masanori; Matsumoto, Naoki; Nangaku, Masaomi; Iiri, Taroh

2016-01-01

Disease-causing mutations in G protein-coupled receptor (GPCR) genes, including the V2 vasopressin receptor (V2R) gene, often cause misfolded receptors, leading to a defect in plasma membrane trafficking. A novel V2R mutation, T273M, identified in a boy with partial nephrogenic diabetes insipidus (NDI), shows intracellular localization and partial defects similar to the two mutants we described previously (10). Although non-peptide V2R antagonists have been shown to rescue the membrane localization of V2R mutants, their level of functional rescue is weak. Interestingly, it has been reported that a non-peptide agonist, OPC51803, activates misfolded V2R mutants intracellularly without degradation, thus potentially serving as a therapeutic agent against NDI (14). In our current experiments, however, a peptide antagonist blocked arginine vasopressin (AVP)- or OPC51803-stimulated cAMP accumulation both in COS-7 and MDCK cells, suggesting that OPC51803 mainly stimulates cell surface V2R mutants. In addition, our analyses revealed that OPC51803 works not only as a non-peptide agonist that causes activation/β-arrestin-dependent desensitization of V2R mutants expressed at the plasma membrane but also as a pharmacochaperone that promotes the endoplasmic reticulum-retained mutant maturation and trafficking to the plasma membrane. The ratio of the pharmacochaperone effect to the desensitization effect likely correlates negatively with the residual function of the tested mutants, suggesting that OPC5 has a more favorable effect on the V2R mutants with a less residual function. We speculated that the canceling of the desensitization effect of OPC51803 by the pharmacochaperone effect after long-term treatment may produce sustainable signaling, and thus pharmacochaperone agonists such as OPC51803 may serve as promising therapeutics for NDI caused by misfolded V2R mutants. PMID:27601473

Optical proximity correction for anamorphic extreme ultraviolet lithography

NASA Astrophysics Data System (ADS)

Clifford, Chris; Lam, Michael; Raghunathan, Ananthan; Jiang, Fan; Fenger, Germain; Adam, Kostas

2017-10-01

The change from isomorphic to anamorphic optics in high numerical aperture extreme ultraviolet scanners necessitates changes to the mask data preparation flow. The required changes for each step in the mask tape out process are discussed, with a focus on optical proximity correction (OPC). When necessary, solutions to new problems are demonstrated and verified by rigorous simulation. Additions to the OPC model include accounting for anamorphic effects in the optics, mask electromagnetics, and mask manufacturing. The correction algorithm is updated to include awareness of anamorphic mask geometry for mask rule checking. OPC verification through process window conditions is enhanced to test different wafer scale mask error ranges in the horizontal and vertical directions. This work will show that existing models and methods can be updated to support anamorphic optics without major changes. Also, the larger mask size in the Y direction can result in better model accuracy, easier OPC convergence, and designs that are more tolerant to mask errors.

Electric Signals Regulate the Directional Migration of Oligodendrocyte Progenitor Cells (OPCs) via β1 Integrin.

PubMed

Zhu, Bangfu; Nicholls, Matthew; Gu, Yu; Zhang, Gaofeng; Zhao, Chao; Franklin, Robin J M; Song, Bing

2016-11-22

The guided migration of neural cells is essential for repair in the central nervous system (CNS). Oligodendrocyte progenitor cells (OPCs) will normally migrate towards an injury site to re-sheath demyelinated axons; however the mechanisms underlying this process are not well understood. Endogenous electric fields (EFs) are known to influence cell migration in vivo, and have been utilised in this study to direct the migration of OPCs isolated from neonatal Sprague-Dawley rats. The OPCs were exposed to physiological levels of electrical stimulation, and displayed a marked electrotactic response that was dependent on β1 integrin, one of the key subunits of integrin receptors. We also observed that F-actin, an important component of the cytoskeleton, was re-distributed towards the leading edge of the migrating cells, and that this asymmetric rearrangement was associated with β1 integrin function.

Pore size distribution of OPC and SRPC mortars in presence of chlorides

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

Suryavanshi, A.K.; Scantlebury, J.D.; Lyon, S.B.

1995-07-01

The pore structure of chloride-free ordinary portland cement (OPC) and sulphate resistant portland cement (SRPC) mortars are compared with the corresponding mortars with NaCl and CaCl{sub 2} added during mixing. In both OPC and SRPC mortars the addition of chlorides reduced the total accessible pore volumes compared to the corresponding chloride-free mortars. Also, in the presence of chlorides, the number of coarse pores were increased. These changes in the pore structure are believed to be due to dense calcium silicate hydrate (C-S-H) gel morphology formed in the presence of chlorides. The SRPC showed greater changes in pore structures than themore » OPC with equivalent amounts of chlorides added. This may be due to the lower chloride binding capacity of the SRPC and hence the higher availability of free chlorides to modify the gel morphology.« less

Separation of rare oligodendrocyte progenitor cells from brain using a high-throughput multilayer thermoplastic-based microfluidic device.

PubMed

Didar, Tohid Fatanat; Li, Kebin; Veres, Teodor; Tabrizian, Maryam

2013-07-01

Despite the advances made in the field of regenerative medicine, the progress in cutting-edge technologies for separating target therapeutic cells are still at early stage of development. These cells are often rare, such as stem cells or progenitor cells that their overall properties should be maintained during the separation process for their subsequent application in regenerative medicine. This work, presents separation of oligodendrocyte progenitor cells (OPCs) from rat brain primary cultures using an integrated thermoplastic elastomeric (TPE)- based multilayer microfluidic device fabricated using hot-embossing technology. OPCs are frequently used in recovery, repair and regeneration of central nervous system after injuries. Indeed, their ability to differentiate in vitro into myelinating oligodendrocytes, are extremely important for myelin repair. OPCs form 5-10% of the glial cells population. The traditional macroscale techniques for OPCs separation require pre-processing of cells and/or multiple time consuming steps with low efficiency leading very often to alteration of their properties. The proposed methodology implies to separate OPCs based on their smaller size compared to other cells from the brain tissue mixture. Using aforementioned microfluidic chip embedded with a 5 μm membrane pore size and micropumping system, a separation efficiency more than 99% was achieved. This microchip was able to operate at flow rates up to 100 μl/min, capable of separating OPCs from a confluent 75 cm(2) cell culture flask in less than 10 min, which provides us with a high-throughput and highly efficient separation expected from any cell sorting techniques. Copyright © 2013 Elsevier Ltd. All rights reserved.

Integration of Sensors, Controllers and Instruments Using a Novel OPC Architecture

PubMed Central

2017-01-01

The interconnection between sensors, controllers and instruments through a communication network plays a vital role in the performance and effectiveness of a control system. Since its inception in the 90s, the Object Linking and Embedding for Process Control (OPC) protocol has provided open connectivity for monitoring and automation systems. It has been widely used in several environments such as industrial facilities, building and energy automation, engineering education and many others. This paper presents a novel OPC-based architecture to implement automation systems devoted to R&D and educational activities. The proposal is a novel conceptual framework, structured into four functional layers where the diverse components are categorized aiming to foster the systematic design and implementation of automation systems involving OPC communication. Due to the benefits of OPC, the proposed architecture provides features like open connectivity, reliability, scalability, and flexibility. Furthermore, four successful experimental applications of such an architecture, developed at the University of Extremadura (UEX), are reported. These cases are a proof of concept of the ability of this architecture to support interoperability for different domains. Namely, the automation of energy systems like a smart microgrid and photobioreactor facilities, the implementation of a network-accessible industrial laboratory and the development of an educational hardware-in-the-loop platform are described. All cases include a Programmable Logic Controller (PLC) to automate and control the plant behavior, which exchanges operative data (measurements and signals) with a multiplicity of sensors, instruments and supervisory systems under the structure of the novel OPC architecture. Finally, the main conclusions and open research directions are highlighted. PMID:28654002

Integration of Sensors, Controllers and Instruments Using a Novel OPC Architecture.

PubMed

González, Isaías; Calderón, Antonio José; Barragán, Antonio Javier; Andújar, José Manuel

2017-06-27

The interconnection between sensors, controllers and instruments through a communication network plays a vital role in the performance and effectiveness of a control system. Since its inception in the 90s, the Object Linking and Embedding for Process Control (OPC) protocol has provided open connectivity for monitoring and automation systems. It has been widely used in several environments such as industrial facilities, building and energy automation, engineering education and many others. This paper presents a novel OPC-based architecture to implement automation systems devoted to R&D and educational activities. The proposal is a novel conceptual framework, structured into four functional layers where the diverse components are categorized aiming to foster the systematic design and implementation of automation systems involving OPC communication. Due to the benefits of OPC, the proposed architecture provides features like open connectivity, reliability, scalability, and flexibility. Furthermore, four successful experimental applications of such an architecture, developed at the University of Extremadura (UEX), are reported. These cases are a proof of concept of the ability of this architecture to support interoperability for different domains. Namely, the automation of energy systems like a smart microgrid and photobioreactor facilities, the implementation of a network-accessible industrial laboratory and the development of an educational hardware-in-the-loop platform are described. All cases include a Programmable Logic Controller (PLC) to automate and control the plant behavior, which exchanges operative data (measurements and signals) with a multiplicity of sensors, instruments and supervisory systems under the structure of the novel OPC architecture. Finally, the main conclusions and open research directions are highlighted.

Effect of different lignocellulosic wastes on Hericium americanum yield and nutritional characteristics.

PubMed

Atila, Funda; Tüzel, Yuksel; Faz Cano, Angel; Fernandez, Juan A

2017-01-01

The aim of this study was to investigate the possibility of using cottonseed hulls (CSH) and olive press cake (OPC) as new supplement materials for substrate preparation in Hericium americanum cultivation. Some chemical properties of the substrates prepared by mixtures of oak sawdust (OS) with wheat bran (WB), CSH and OPC in different ratios were determined. In addition, the effect of mixtures of OS:CSH and OS:OPC on spawn run time, yield and biological efficiency (BE), average mushroom weight and nutrition content of the fruiting body were compared with the control substrate (8OS:2WB). The yield, BE and average mushroom weight of substrates containing CSH and OPC were higher than the control substrate and increased with an increase in the rate of CSH and OPC in the mixtures. Hericium americanum showed (on a dry weight basis) 8.5-23.7% protein, 9.9-21.2 g kg -1 P, 26.6-35.8 g kg -1 K, 0.63 - 1.33 g kg -1 Mg, 0.19 - 0.23 g kg -1 Ca, 1.34-1.78 g kg -1 Na, 49.5-72.2 mg kg -1 Fe, 6.22-10.11 mg kg -1 Mn, 32.8-82.8 mg kg -1 Zn and 8.6-11.2 mg kg -1 Cu on different growing substrates. The nutritional value of mushrooms was greatly affected by the growing media. The results revealed that CSH and OPC could be used as new supplement materials for substrate preparation in H. americanum cultivation. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Hv1 proton channel facilitates production of ROS and pro-inflammatory cytokines in microglia and enhances oligodendrocyte progenitor cells damage from oxygen-glucose deprivation in vitro.

PubMed

Yu, Ying; Yu, Zhiyuan; Xie, Minjie; Wang, Wei; Luo, Xiang

2018-03-25

The contribution of microglial activation to oligodendrocyte precursor cell (OPC) damage in the brain is considered to be a principal pathophysiological feature of periventricular leukomalacia (PVL). Nicotinamide adenine dinucleotide phosphate oxidase (NOX)-dependent reactive oxygen species (ROS) produced in microglia has been shown to be significantly toxic to OPCs. The voltage-gated proton channel Hv1 is selectively expressed in microglia and is essential for NOX-dependent ROS production in the central nervous system. This study aimed to investigate the effects of microglial Hv1 deficiency on the protection of OPCs from oxygen-glucose deprivation (OGD)-induced injury in vitro. In the present study, the levels of OGD-induced ROS and pro-inflammatory cytokine production were dramatically lower in Hv1-deficient microglia (Hv1 -/- ) than in wild-type (WT) microglia. Following OGD, OPCs co-cultured with WT microglia had increased apoptosis and decreased proliferation and maturation, while those co-cultured with Hv1 -/- microglia had attenuated apoptosis and greater proliferation and differentiation. Furthermore, the attenuated damage and enhanced regeneration of OPCs were associated with decreases in extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase phosphorylation. These results indicate that the protective effects of Hv1 deficiency on OPCs are due to the suppression of ROS and pro-inflammatory cytokine production in microglia. We thus suggest that the microglial proton channel Hv1 may be a potential therapeutic target in PVL. Copyright © 2017 Elsevier Inc. All rights reserved.

Mechanical Strain Promotes Oligodendrocyte Differentiation by Global Changes of Gene Expression

PubMed Central

Jagielska, Anna; Lowe, Alexis L.; Makhija, Ekta; Wroblewska, Liliana; Guck, Jochen; Franklin, Robin J. M.; Shivashankar, G. V.; Van Vliet, Krystyn J.

2017-01-01

Differentiation of oligodendrocyte progenitor cells (OPC) to oligodendrocytes and subsequent axon myelination are critical steps in vertebrate central nervous system (CNS) development and regeneration. Growing evidence supports the significance of mechanical factors in oligodendrocyte biology. Here, we explore the effect of mechanical strains within physiological range on OPC proliferation and differentiation, and strain-associated changes in chromatin structure, epigenetics, and gene expression. Sustained tensile strain of 10–15% inhibited OPC proliferation and promoted differentiation into oligodendrocytes. This response to strain required specific interactions of OPCs with extracellular matrix ligands. Applied strain induced changes in nuclear shape, chromatin organization, and resulted in enhanced histone deacetylation, consistent with increased oligodendrocyte differentiation. This response was concurrent with increased mRNA levels of the epigenetic modifier histone deacetylase Hdac11. Inhibition of HDAC proteins eliminated the strain-mediated increase of OPC differentiation, demonstrating a role of HDACs in mechanotransduction of strain to chromatin. RNA sequencing revealed global changes in gene expression associated with strain. Specifically, expression of multiple genes associated with oligodendrocyte differentiation and axon-oligodendrocyte interactions was increased, including cell surface ligands (Ncam, ephrins), cyto- and nucleo-skeleton genes (Fyn, actinins, myosin, nesprin, Sun1), transcription factors (Sox10, Zfp191, Nkx2.2), and myelin genes (Cnp, Plp, Mag). These findings show how mechanical strain can be transmitted to the nucleus to promote oligodendrocyte differentiation, and identify the global landscape of signaling pathways involved in mechanotransduction. These data provide a source of potential new therapeutic avenues to enhance OPC differentiation in vivo. PMID:28473753

Population-based incidence trends of oropharyngeal and oral cavity cancers by sex among the poorest and underprivileged populations

PubMed Central

2014-01-01

Background Oral cancer is an important health issue, with changing incidence in many countries. Oropharyngeal cancer (OPC, in tonsil and oropharygeal areas) is increasing, while oral cavity cancer (OCC, other sites in the mouth) is decreasing. There is the need to identify high risk groups and communities for further study and intervention. The objective of this study was to determine how the incidence of OPC and OCC varied by neighbourhood socioeconomic status (SES) in British Columbia (BC), including the magnitude of any inequalities and temporal trends. Methods ICDO-3 codes were used to identify OPC and OCC cases in the BC Cancer Registry from 1981–2010. Cases were categorized by postal codes into SES quintiles (q1-q5) using VANDIX, which is a census-based, multivariate weighted index based on neighbourhood average household income, housing tenure, educational attainment, employment and family structure. Age-standardized incidence rates were determined for OPC and OCC by sex and SES quintiles and temporal trends were then examined. Results Incidence rates are increasing in both men and women for OPC, and decreasing in men and increasing in women for OCC. This change is not linear or proportionate between different SES quintiles, for there is a sharp and dramatic increase in incidence according to the deprivation status of the neighbourhood. The highest incidence rates in men for both OPC and OCC were observed in the most deprived SES quintile (q5), at 1.7 times and 2.2 times higher, respectively, than men in the least deprived quintile (q1). For OPC, the age-adjusted incidence rates significantly increased in all SES quintiles with the highest increase observed in the most deprived quintile (q5). Likewise, the highest incidence rates for both OPC and OCC in women were observed in the most deprived SES quintile (q5), at 2.1 times and 1.8 times higher, respectively, than women in the least deprived quintile (q1). Conclusion We report on SES disparities in oral cancer, emphasizing the need for community-based interventions that address access to medical care and the distribution of educational and health promotion resources among the most SES deprived communities in British Columbia. PMID:24886308

Manufacturability study of masks created by inverse lithography technology (ILT)

NASA Astrophysics Data System (ADS)

Martin, Patrick M.; Progler, C. J.; Xiao, G.; Gray, R.; Pang, L.; Liu, Y.

2005-11-01

As photolithography is pushed to fabricate deep-sub wavelength devices for 90nm, 65nm and smaller technology nodes using available exposure tools (i.e., 248nm, 193nm steppers), photomask capability is becoming extremely critical. For example, PSM masks require more complicated processing; aggressive OPC makes the writing time longer and sometimes unpredictable; and, high MEEF imposes much more stringent demands on mask quality. Therefore, in order for any new lithography technology to be adopted into production, mask manufacturability must be studied thoroughly and carefully. In this paper we will present the mask manufacturability study on mask patterns created using Inverse Lithography Technology (ILT). Unlike conventional OPC methodologies, ILT uses a unique outcome-based technology to mathematically determine the mask features that produce the desired on-wafer results. ILT solves the most critical litho challenges of the deep sub-wavelength era. Potential benefits include: higher yield; expanded litho process windows; superb pattern fidelity at 90, 65 & 45-nm nodes; and reduced time-to-silicon - all without changing the existing lithography infrastructure and design-to-silicon flow. In this study a number of cell structures were selected and used as test patterns. "Luminized patterns" were generated for binary mask and attenuated phase-shift mask. Both conventional OPC patterns and "luminized patterns" were put on a test reticle side by side, and they all have a number of variations in term of correction aggressivity level and mask complexity. Mask manufacturability, including data fracturing, writing time, mask inspection, and metrology were studied. The results demonstrate that, by optimizing the inspection recipe, masks created using ILT technology can be made and qualified using current processes with a reasonable turn-around time.

Implementation of random contact hole design with CPL mask by using IML technology

NASA Astrophysics Data System (ADS)

Hsu, Michael; Van Den Broeke, Doug; Hsu, Stephen; Chen, J. Fung; Shi, Xuelong; Corcoran, Noel; Yu, Linda

2005-11-01

The contact hole imaging is a very challenge task for the optical lithography process during IC manufacturing. Lots of RETs were proposed to improve the contrast of small opening hole. Scattering Bar (SB) OPC, together with optimized illumination, is no doubt one of the critical enablers for low k1 contact imaging. In this study, an effective model-based SB OPC based on IML technology is implemented for contact layer at 90nm, 65nm, and 45nm nodes. For our full-chip implementation flow, the first step is to determine the critical design area and then to proceed with NA and illumination optimization. Then, we selected the best NA in combination with optimum illumination via a Diffraction Optical Element (DOE). With optimized illumination, it is now possible to construct an interference map for the full-chip mask pattern. Utilizing the interference map, the model-based SB OPC is performed. Next, model OPC can be applied with the presence of SB for the entire chip. It is important to note that, for patterning at k1 near 0.35 or below, it may be necessary to include 3D mask effects with a high NA OPC model. With enhanced DOF by IML and immersion process, the low k1 production worthy contact process is feasible.

Co-ultramicronized Palmitoylethanolamide/Luteolin Promotes the Maturation of Oligodendrocyte Precursor Cells.

PubMed

Barbierato, Massimo; Facci, Laura; Marinelli, Carla; Zusso, Morena; Argentini, Carla; Skaper, Stephen D; Giusti, Pietro

2015-11-18

Oligodendrocytes have limited ability to repair the damage to themselves or to other nerve cells, as seen in demyelinating diseases like multiple sclerosis. An important strategy may be to replace the lost oligodendrocytes and/or promote the maturation of undifferentiated oligodendrocyte precursor cells (OPCs). Recent studies show that a composite of co-ultramicronized N-palmitoylethanolamine (PEA) and luteolin (co-ultramicronized PEA/luteolin, 10:1 by mass) is efficacious in improving outcome in experimental models of spinal cord and traumatic brain injuries. Here, we examined the ability of co-ultramicronized PEA/luteolin to promote progression of OPCs into a more differentiated phenotype. OPCs derived from newborn rat cortex were placed in culture and treated the following day with 10 μM co-ultramicronized PEA/luteolin. Cells were collected 1, 4 and 8 days later and analyzed for expression of myelin basic protein (MBP). qPCR and Western blot analyses revealed a time-dependent increase in expression of both mRNA for MBP and MBP content, along with an increased expression of genes involved in lipid biogenesis. Ultramicronized PEA or luteolin, either singly or in simple combination, were ineffective. Further, co-ultramicronized PEA/luteolin promoted morphological development of OPCs and total protein content without affecting proliferation. Co-ultramicronized PEA/luteolin may represent a novel pharmacological strategy to promote OPC maturation.

Formulating a low-alkalinity, high-resistance and low-heat concrete for radioactive waste repositories

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

Cau Dit Coumes, Celine; Courtois, Simone; Nectoux, Didier

2006-12-15

Investigations were carried out in order to formulate and characterize low-alkalinity and low-heat cements which would be compatible with an underground waste repository environment. Several systems comprising Ordinary Portland Cement (OPC), a fast-reacting pozzolan (silica fume (SF) or metakaolin (MK)) and, in some cases, a slow-reacting product (fly ash (FA) or blastfurnace slag (BFS)) were compared. Promising results were obtained with some binary mixtures of OPC and SF, and with some ternary blends of OPC, SF and FA or BFS: pH of water in equilibrium with the fully hydrated cements dropped below 11. Dependence of the properties of standard mortarsmore » on the high contents of FA and SF in the low-pH blends was examined. Combining SF and FA seemed attractive since SF compensated for the low reactivity of FA, while FA allowed to reduce the water demand, and dimensional variations of the mortars. Finally, low-heat ({delta}T < 20 deg. C under semi-adiabatic conditions) and high strength ({approx} 70-80 MPa) concretes were prepared from two low-pH cements: a binary blend made from 60% of OPC and 40% of SF, and a ternary blend including 37.5% OPC, 32.5% SF and 30% FA.« less

Early treatment of minocycline alleviates white matter and cognitive impairments after chronic cerebral hypoperfusion

PubMed Central

Ma, Jing; Zhang, Jing; Hou, Wei Wei; Wu, Xiao Hua; Liao, Ru Jia; Chen, Ying; Wang, Zhe; Zhang, Xiang Nan; Zhang, Li San; Zhou, Yu Dong; Chen, Zhong; Hu, Wei Wei

2015-01-01

Subcortical ischemic vascular dementia (SIVD) caused by chronic cerebral hypoperfusion develops with progressive white matter and cognitive impairments, yet no effective therapy is available. We investigated the temporal effects of minocycline on an experimental SIVD exerted by right unilateral common carotid arteries occlusion (rUCCAO). Minocycline treated at the early stage (day 0–3), but not the late stage after rUCCAO (day 4–32) alleviated the white matter and cognitive impairments, and promoted remyelination. The actions of minocycline may not involve the inhibition of microglia activation, based on the effects after the application of a microglial activation inhibitor, macrophage migration inhibitory factor, and co-treatment with lipopolysaccharides. Furthermore, minocycline treatment at the early stage promoted the proliferation of oligodendrocyte progenitor cells (OPCs) in subventricular zone, increased OPC number and alleviated apoptosis of mature oligodendrocytes in white matter. In vitro, minocycline promoted OPC proliferation and increased the percentage of OPCs in S and G2/M phases. We provided direct evidence that early treatment is critical for minocycline to alleviate white matter and cognitive impairments after chronic cerebral hypoperfusion, which may be due to its robust effects on OPC proliferation and mature oligodendrocyte loss. So, early therapeutic time window may be crucial for its application in SIVD. PMID:26174710

A radical scavenger edaravone inhibits matrix metalloproteinase-9 upregulation and blood-brain barrier breakdown in a mouse model of prolonged cerebral hypoperfusion

PubMed Central

Maki, Takakuni; Liang, Anna C.; Arai, Ken

2014-01-01

Matrix metalloproteinase-9 (MMP-9) plays key roles in the brain pathophysiology, especially in blood-brain barrier (BBB) breakdown. Therefore, inhibiting MMP-9 activity may be a promising therapy for protecting brains in cerebrovascular diseases. Here we show that in a mouse prolonged cerebral hypoperfusion model, a clinically proven radical scavenger edaravone suppressed MMP-9 and reduced BBB damage in cerebral white matter. Prolonged cerebral hypoperfusion was induced by bilateral common carotid artery stenosis in male adult C57BL/6J mice (10 weeks old). After 7 days of cerebral hypoperfusion, white matter region (e.g. corpus callosum) exhibited significant BBB leakage, assessed by IgG staining. Correspondingly, immunostaining and western blotting showed that MMP-9 was upregulated in the white matter. Edaravone treatment (3 mg/kg, i.p. at day 0 and 3) inhibited both BBB leakage and MMP-9 increase. Under the early phase of cerebral hypoperfusion conditions, oligodendrocyte precursor cells (OPCs) mainly contribute to the MMP-9 increase, but our immunostaining data showed that very little OPCs expressed MMP-9 in the edaravone-treated animals at day 7. Therefore, in vitro studies with primary rat OPCs were conducted to examine whether edaravone would directly suppressed MMP-9 expressions in OPCs. OPC cultures were exposed to sub-lethal CoCl2 for 7 days to induce prolonged chemical hypoxic stress. Prolonged chemical hypoxic stress increased MMP-9 expression in OPCs, and radical scavenging with edaravone (10 μM for 7 days) ameliorated the increase. Taken together, our proof-of-concept study demonstrates that radical scavengers may provide a potential therapeutic approach for white matter injury by suppressing BBB damage. PMID:24820542

A radical scavenger edaravone inhibits matrix metalloproteinase-9 upregulation and blood-brain barrier breakdown in a mouse model of prolonged cerebral hypoperfusion.

PubMed

Miyamoto, Nobukazu; Pham, Loc-Duyen D; Maki, Takakuni; Liang, Anna C; Arai, Ken

2014-06-24

Matrix metalloproteinase-9 (MMP-9) plays key roles in the brain pathophysiology, especially in blood-brain barrier (BBB) breakdown. Therefore, inhibiting MMP-9 activity may be a promising therapy for protecting brains in cerebrovascular diseases. Here we show that in a mouse prolonged cerebral hypoperfusion model, a clinically proven radical scavenger edaravone suppressed MMP-9 and reduced BBB damage in cerebral white matter. Prolonged cerebral hypoperfusion was induced by bilateral common carotid artery stenosis in male adult C57BL/6J mice (10 weeks old). After 7 days of cerebral hypoperfusion, white matter region (e.g. corpus callosum) exhibited significant BBB leakage, assessed by IgG staining. Correspondingly, immunostaining and western blotting showed that MMP-9 was upregulated in the white matter. Edaravone treatment (3mg/kg, i.p. at days 0 and 3) inhibited both BBB leakage and MMP-9 increase. Under the early phase of cerebral hypoperfusion conditions, oligodendrocyte precursor cells (OPCs) mainly contribute to the MMP-9 increase, but our immunostaining data showed that very little OPCs expressed MMP-9 in the edaravone-treated animals at day 7. Therefore, in vitro studies with primary rat OPCs were conducted to examine whether edaravone would directly suppressed MMP-9 expressions in OPCs. OPC cultures were exposed to sub-lethal CoCl2 for 7 days to induce prolonged chemical hypoxic stress. Prolonged chemical hypoxic stress increased MMP-9 expression in OPCs, and radical scavenging with edaravone (10μM for 7 days) ameliorated the increase. Taken together, our proof-of-concept study demonstrates that radical scavengers may provide a potential therapeutic approach for white matter injury by suppressing BBB damage. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Improving the CD linearity and proximity performance of photomasks written on the Sigma7500-II DUV laser writer through embedded OPC

NASA Astrophysics Data System (ADS)

Österberg, Anders; Ivansen, Lars; Beyerl, Angela; Newman, Tom; Bowhill, Amanda; Sahouria, Emile; Schulze, Steffen

2007-10-01

Optical proximity correction (OPC) is widely used in wafer lithography to produce a printed image that best matches the design intent while optimizing CD control. OPC software applies corrections to the mask pattern data, but in general it does not compensate for the mask writer and mask process characteristics. The Sigma7500-II deep-UV laser mask writer projects the image of a programmable spatial light modulator (SLM) using partially coherent optics similar to wafer steppers, and the optical proximity effects of the mask writer are in principle correctable with established OPC methods. To enhance mask patterning, an embedded OPC function, LinearityEqualize TM, has been developed for the Sigma7500- II that is transparent to the user and which does not degrade mask throughput. It employs a Calibre TM rule-based OPC engine from Mentor Graphics, selected for the computational speed necessary for mask run-time execution. A multinode cluster computer applies optimized table-based CD corrections to polygonized pattern data that is then fractured into an internal writer format for subsequent data processing. This embedded proximity correction flattens the linearity behavior for all linewidths and pitches, which targets to improve the CD uniformity on production photomasks. Printing results show that the CD linearity is reduced to below 5 nm for linewidths down to 200 nm, both for clear and dark and for isolated and dense features, and that sub-resolution assist features (SRAF) are reliably printed down to 120 nm. This reduction of proximity effects for main mask features and the extension of the practical resolution for SRAFs expands the application space of DUV laser mask writing.

[Protective effect of octreotide on liver warm ischemia reperfusion injury].

PubMed

Li, Jie-qun; Qi, Hai-zhi; He, Zhi-jun; Hu, Wei; Si, Zhong-zhou; Li, Yi-ning

2006-10-01

To explore the protective effect of octreotide on liver warm ischemia-reperfusion injury and its possible mechanism. Pringle's maneuver liver ischemia-reperfusion models were established. Forty eight male Sprague Daweley rats were randomly divided into a sham operation group (S group, n=16), an ischemia-reperfusion group (I/R group, n=16) and an octreotide preconditioning group (OPC group, n=16). ALT and AST in the serum were measured at 30 min after the ischemia and 120 min after the reperfusion. The histomorphological changes and ultrastructure of hepatocellular were observed by optic and transmission electronic microscope. Hepatic adenine nucleotide levels and energy changes (EC) were determined by high performance liquid chromatography (HPLC). (1) At 30 min after the ischemia and 120 min after the reperfusion, the levels of ALT and AST in the serum of OPC group was lower than those in I/R group, whereas the levels of ATP and EC in the hepatic tissue were higher than those in the I/R group (P<0.01 or P<0.05). Compared with the I/R group, the injury of hepatocellular histomorphology and ultrastructure in the OPC group was abated. (2) At 30, 60, and 120 min after the reperfusion, the levels of ATP and EC in the OPC groups were higher than those in the I/R group. During the ischemia, the levels of ATP and EC in the OPC group dropped more slowly than those in the I/R group, but ATP and EC in the OPC groups rose more quickly than those in the I/R group during the reperfusion. Octreotide precondition can improve the hepatocellular energy reserve, and protect the liver from warm ischemia-reperfusion injury. The protective of octreotide on warm ischemia-reperfusion injury may be related to its influence on endocrine secretion.

Alkylphosphocholines: influence of structural variation on biodistribution at antineoplastically active concentrations.

PubMed

Kötting, J; Berger, M R; Unger, C; Eibl, H

1992-01-01

Hexadecylphosphocholine (HPC) and octadecylphosphocholine (OPC) show very potent antitumor activity against autochthonous methylnitrosourea-induced mammary carcinomas in rats. The longer-chain and unsaturated homologue erucylphosphocholine (EPC) forms lamellar structures rather than micelles, but nonetheless exhibits antineoplastic activity. Methylnitrosourea was used in the present study to induce autochthonous mammary carcinomas in virgin Sprague-Dawley rats. At 6 and 11 days following oral therapy, the biodistribution of HPC, OPC and EPC was analyzed in the serum, tumor, liver, kidney, lung, small intestine, brain and spleen of rats by high-performance thin-layer chromatography. In contrast to the almost identical tumor response noted, the distribution of the three homologues differed markedly. The serum levels of 50 nmol/ml obtained for OPC and EPC were much lower than the value of 120 nmol/ml measured for HPC. Nevertheless, the quite different serum levels resulted in similar tumor concentrations of about 200 nmol/g for all three of the compounds. Whereas HPC preferably accumulated in the kidney (1 mumol/g), OPC was found at increased concentrations (400 nmol/g) in the spleen, kidney and lung. In spite of the high daily dose of 120 mumol/kg EPC as compared with 51 mumol/kg HPC or OPC, EPC concentrations (100-200 nmol/g) were low in most tissues. High EPC concentrations were found in the small intestine (628 nmol/g). Values of 170 nmol/g were found for HPC and OPC in the brain, whereas the EPC concentration was 120 nmol/g. Obviously, structural modifications in the alkyl chain strongly influence the distribution pattern of alkylphosphocholines in animals. Since EPC yielded the highest tissue-to-serum concentration ratio in tumor tissue (5.1) and the lowest levels in other organs, we conclude that EPC is the most promising candidate for drug development in cancer therapy.

Folate intake and the risk of oral cavity and pharyngeal cancer: a pooled analysis within the INHANCE Consortium

PubMed Central

Galeone, Carlotta; Edefonti, Valeria; Parpinel, Maria; Leoncini, Emanuele; Matsuo, Keitaro; Talamini, Renato; Olshan, Andrew F.; Zevallos, Jose P.; Winn, Deborah M.; Jayaprakash, Vijayvel; Moysich, Kirsten; Zhang, Zuo-Feng; Morgenstern, Hal; Levi, Fabio; Bosetti, Cristina; Kelsey, Karl; McClean, Michael; Schantz, Stimson; Yu, Guo-Pei; Boffetta, Paolo; Lee, Yuan-Chin Amy; Hashibe, Mia; La Vecchia, Carlo; Boccia, Stefania

2014-01-01

There are suggestions of an inverse association between folate intake and serum folate levels and the risk of oral cavity and pharyngeal cancers (OPC), but most studies are limited in sample size, with only few reporting information on the source of dietary folate. This study aims to investigate the association between folate intake and the risk of OPC within the International Head and Neck Cancer Epidemiology (INHANCE) Consortium. We analyzed pooled individual-level data from 10 case-control studies participating in the INHANCE consortium, including 5,127 cases and 13,249 controls. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were estimated for the associations between total folate intake (natural, fortification and supplementation) and natural folate only, and OPC risk. We found an inverse association between total folate intake and overall OPC risk (the adjusted OR for the highest versus the lowest quintile was 0.65, 95% CI: 0.43–0.99), with a stronger association for oral cavity (OR=0.57, 95% CI: 0.43–0.75). A similar inverse association, though somewhat weaker, was observed for folate intake from natural sources only (OR=0.64, 95% CI: 0.45–0.91). The highest OPC risk was observed in heavy alcohol drinkers with low folate intake as compared to never/light drinkers with high folate (OR=4.05, 95% CI: 3.43–4.79); the attributable proportion due to interaction was 11.1%(95% CI: 1.4–20.8%). The present project of a large pool of case-control studies supports a protective effect total folate intake on OPC risk. PMID:24974959

Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL) Signaling and Cell Death in the Immature Central Nervous System after Hypoxia-Ischemia and Inflammation*

PubMed Central

Kichev, Anton; Rousset, Catherine I.; Baburamani, Ana A.; Levison, Steven W.; Wood, Teresa L.; Gressens, Pierre; Thornton, Claire; Hagberg, Henrik

2014-01-01

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the TNF family. The interaction of TRAIL with death receptor 4 (DR4) and DR5 can trigger apoptotic cell death. The aim of this study was to investigate the role of TRAIL signaling in neonatal hypoxia-ischemia (HI). Using a neonatal mouse model of HI, mRNA, and protein expression of TRAIL, DR5 and the TRAIL decoy receptors osteoprotegerin (OPG), mDcTRAILR1, and mDcTRAILR2 were determined. In vitro, mRNA expression of these genes was measured in primary neurons and oligodendrocyte progenitor cells (OPCs) after inflammatory cytokine (TNF-α/IFN-γ) treatment and/or oxygen and glucose deprivation (OGD). The toxicity of these various paradigms was also measured. The expression of TRAIL, DR5, OPG, and mDcTRAILR2 was significantly increased after HI. In vitro, inflammatory cytokines and OGD treatment significantly induced mRNAs for TRAIL, DR5, OPG, and mDcTRAILR2 in primary neurons and of TRAIL and OPG in OPCs. TRAIL protein was expressed primarily in microglia and astroglia, whereas DR5 co-localized with neurons and OPCs in vivo. OGD enhanced TNF-α/IFN-γ toxicity in both neuronal and OPC cultures. Recombinant TRAIL exerted toxicity alone or in combination with OGD and TNF-α/IFN-γ in primary neurons but not in OPC cultures. The marked increases in the expression of TRAIL and its receptors after cytokine exposure and OGD in primary neurons and OPCs were similar to those found in our animal model of neonatal HI. The toxicity of TRAIL in primary neurons suggests that TRAIL signaling participates in neonatal brain injury after inflammation and HI. PMID:24509861

Nogo receptor blockade overcomes remyelination failure after white matter stroke and stimulates functional recovery in aged mice

PubMed Central

Sozmen, Elif G.; Rosenzweig, Shira; Llorente, Irene L.; DiTullio, David J.; Machnicki, Michal; Vinters, Harry V.; Havton, Lief A.; Giger, Roman J.; Hinman, Jason D.

2016-01-01

White matter stroke is a distinct stroke subtype, accounting for up to 25% of stroke and constituting the second leading cause of dementia. The biology of possible tissue repair after white matter stroke has not been determined. In a mouse stroke model, white matter ischemia causes focal damage and adjacent areas of axonal myelin disruption and gliosis. In these areas of only partial damage, local white matter progenitors respond to injury, as oligodendrocyte progenitors (OPCs) proliferate. However, OPCs fail to mature into oligodendrocytes (OLs) even in regions of demyelination with intact axons and instead divert into an astrocytic fate. Local axonal sprouting occurs, producing an increase in unmyelinated fibers in the corpus callosum. The OPC maturation block after white matter stroke is in part mediated via Nogo receptor 1 (NgR1) signaling. In both aged and young adult mice, stroke induces NgR1 ligands and down-regulates NgR1 inhibitors during the peak OPC maturation block. Nogo ligands are also induced adjacent to human white matter stroke in humans. A Nogo signaling blockade with an NgR1 antagonist administered after stroke reduces the OPC astrocytic transformation and improves poststroke oligodendrogenesis in mice. Notably, increased white matter repair in aged mice is translated into significant poststroke motor recovery, even when NgR1 blockade is provided during the chronic time points of injury. These data provide a perspective on the role of NgR1 ligand function in OPC fate in the context of a specific and common type of stroke and show that it is amenable to systemic intervention to promote recovery. PMID:27956620

Effects of OPC-6535 on lipopolysaccharide-induced acute liver injury in the rat: involvement of superoxide and tumor necrosis factor-alpha from hepatic macrophages.

PubMed

Hasegawa, Tadashi; Sakurai, Kazushi; Kambayashi, Yasuhiro; Saniabadi, Abby R; Nagamoto, Hisashi; Tsukada, Katsuhiko; Takahashi, Atsushi; Kuwano, Hiroyuki; Nakano, Minoru

2003-11-01

The objective of this study was to investigate the effects of OPC-6535 on Propionibacterium acnes-primed and lipopolysaccharide-induced liver injury in the rat. P. acnes was administered intravenously to the rat at 16 mg/kg 7 days before the experiments. In liver perfusion experiments, lipopolysaccharide was mixed in perfusion buffer at 2.5 microg/mL. The chemiluminescence method and histochemical reduction of nitro blue tetrazolium were used for detecting superoxide. Release of cytokines into the perfusate was examined. In in vivo experiments, lipopolysaccharide was administered intravenously to the rat at 200 microg/kg. Concentrations of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and cytokines were determined in the plasma, and myeloperoxidase activity was measured in the liver tissue. OPC-6535 was given intravenously at 1 mg/kg 30 minutes before lipopolysaccharide challenge, and was then, in perfusion experiments, added to the buffer at 10 micromol/L. In perfusion experiments, P. acnes and lipopolysaccharide caused dramatic production of superoxide, tumor necrosis factor-alpha (TNF-alpha) and growth-related oncogene/cytokine-induced neutrophil chemoattractant-1 (GRO/CINC-1). Superoxide was mainly from hepatic macrophages. Treatment with OPC-6535 suppressed superoxide and TNF-alpha but did not affect GRO/CINC-1. In in vivo experiments, P. acnes and lipopolysaccharide increased the level of TNF-alpha, GRO/CINC-1, AST and ALT in the plasma, and myeloperoxidase activity in the liver. OPC-6535 reduced TNF-alpha, AST, and ALT, but did not affect GRO/CINC-1 or myeloperoxidase. Attenuation of liver injury by OPC-6535 is believed to be due to its inhibitory effects on superoxide and TNF-alpha production by hepatic macrophages in P. acnes- and lipopolysaccharide-treated rats.

Antioxidant Protection of NADPH-Depleted Oligodendrocyte Precursor Cells Is Dependent on Supply of Reduced Glutathione.

PubMed

Kilanczyk, Ewa; Saraswat Ohri, Sujata; Whittemore, Scott R; Hetman, Michal

2016-08-01

The pentose phosphate pathway is the main source of NADPH, which by reducing oxidized glutathione, contributes to antioxidant defenses. Although oxidative stress plays a major role in white matter injury, significance of NADPH for oligodendrocyte survival has not been yet investigated. It is reported here that the NADPH antimetabolite 6-amino-NADP (6AN) was cytotoxic to cultured adult rat spinal cord oligodendrocyte precursor cells (OPCs) as well as OPC-derived oligodendrocytes. The 6AN-induced necrosis was preceded by increased production of superoxide, NADPH depletion, and lower supply of reduced glutathione. Moreover, survival of NADPH-depleted OPCs was improved by the antioxidant drug trolox. Such cells were also protected by physiological concentrations of the neurosteroid dehydroepiandrosterone (10(-8) M). The protection by dehydroepiandrosterone was associated with restoration of reduced glutathione, but not NADPH, and was sensitive to inhibition of glutathione synthesis. A similar protective mechanism was engaged by the cAMP activator forskolin or the G protein-coupled estrogen receptor (GPER/GPR30) ligand G1. Finally, treatment with the glutathione precursor N-acetyl cysteine reduced cytotoxicity of 6AN. Taken together, NADPH is critical for survival of OPCs by supporting their antioxidant defenses. Consequently, injury-associated inhibition of the pentose phosphate pathway may be detrimental for the myelination or remyelination potential of the white matter. Conversely, steroid hormones and cAMP activators may promote survival of NADPH-deprived OPCs by increasing a NADPH-independent supply of reduced glutathione. Therefore, maintenance of glutathione homeostasis appears as a critical effector mechanism for OPC protection against NADPH depletion and preservation of the regenerative potential of the injured white matter. © The Author(s) 2016.

In vitro investigation of efficacy of new reactivators on OPC inhibited rat brain acetylcholinesterase.

PubMed

Atanasov, Vasil N; Petrova, Iskra; Dishovsky, Christophor

2013-03-25

Organophosphorus compounds (OPC) were developed as warfare nerve agents. They are also widely used as pesticides. The drug therapy of intoxication with OPC includes mainly combination of cholinesterase (ChE) reactivators and cholinolytics. There is no single ChE reactivator having an ability to reactivate sufficiently the inhibited enzyme due to the high variability of chemical structure of the inhibitors. The difficulties in reactivation of ChE activity and slight antidote effect regarding intoxication with some OPC are some of the reasons for continuous efforts to obtain new reactivators of ChE. The aim of the present study was to evaluate the efficacy of some ChE reactivators against OPC intoxication (tabun, paraoxon and dichlorvos) in in vitro experiments and to compare their activity to that known for some currently used oximes (obidoxime, HI-6, 2-PAM). Experiments were carried out using rat brain acetylcholinesterase (AChE). Reactivators showed different activity in the reactivation of rat brain AChE after dichlorvos, paraoxon and tabun inhibition. AChE was easier reactivated after paraoxon treatment. The best effect showed BT-07-4M, obidoxime, TMB-4 and BT-08 from the group of symmetric oximes, and Toxidin, BT-05 and BT-03 from asymmetric compounds. The reactivation of brain AChE inhibited with tabun demonstrated better activity of new compound BT-07-4M, TMB-4 and obidoxime from symmetric oximes, and BT-05 and BT-03 possessing asymmetric structure. All compounds showed low activity toward inhibition of AChE caused by dichlorvos. Comparison of two main structure types (symmetric/asymmetric) showed that the symmetric compounds reactivated better AChE, inhibited with this OPC, than asymmetric ones. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Nogo receptor blockade overcomes remyelination failure after white matter stroke and stimulates functional recovery in aged mice.

PubMed

Sozmen, Elif G; Rosenzweig, Shira; Llorente, Irene L; DiTullio, David J; Machnicki, Michal; Vinters, Harry V; Havton, Lief A; Giger, Roman J; Hinman, Jason D; Carmichael, S Thomas

2016-12-27

White matter stroke is a distinct stroke subtype, accounting for up to 25% of stroke and constituting the second leading cause of dementia. The biology of possible tissue repair after white matter stroke has not been determined. In a mouse stroke model, white matter ischemia causes focal damage and adjacent areas of axonal myelin disruption and gliosis. In these areas of only partial damage, local white matter progenitors respond to injury, as oligodendrocyte progenitors (OPCs) proliferate. However, OPCs fail to mature into oligodendrocytes (OLs) even in regions of demyelination with intact axons and instead divert into an astrocytic fate. Local axonal sprouting occurs, producing an increase in unmyelinated fibers in the corpus callosum. The OPC maturation block after white matter stroke is in part mediated via Nogo receptor 1 (NgR1) signaling. In both aged and young adult mice, stroke induces NgR1 ligands and down-regulates NgR1 inhibitors during the peak OPC maturation block. Nogo ligands are also induced adjacent to human white matter stroke in humans. A Nogo signaling blockade with an NgR1 antagonist administered after stroke reduces the OPC astrocytic transformation and improves poststroke oligodendrogenesis in mice. Notably, increased white matter repair in aged mice is translated into significant poststroke motor recovery, even when NgR1 blockade is provided during the chronic time points of injury. These data provide a perspective on the role of NgR1 ligand function in OPC fate in the context of a specific and common type of stroke and show that it is amenable to systemic intervention to promote recovery.

HPV-Associated Head and Neck Cancer: Unique Features of Epidemiology and Clinical Management

PubMed Central

Maxwell, Jessica H.; Grandis, Jennifer R.; Ferris, Robert L.

2017-01-01

Human papillomavirus (HPV) is a recently identified causative agent for a subset of head and neck cancers, primarily in the oropharynx, and is largely responsible for the rising worldwide incidence of oropharyngeal cancer (OPC). Patients with HPV-positive OPC have distinct risk factor profiles and generally have a better prognosis than patients with traditional, HPV-negative, head and neck cancer. Concurrent chemotherapy and radiation is a widely accepted primary treatment modality for many patients with HPV-positive OPC. However, recent advances in surgical modalities, including transoral laser and robotic surgery, have led to the reemergence of primary surgical treatment for HPV-positive patients. Clinical trials are under way to determine optimal treatment strategies for the growing subset of patients with HPV-positive OPC. Similarly, identifying those patients with HPV-positive cancer who are at risk for recurrence and poor survival is critical in order to tailor individual treatment regimens and avoid potential undertreatment. PMID:26332002

Optical proximity correction for anamorphic extreme ultraviolet lithography

NASA Astrophysics Data System (ADS)

Clifford, Chris; Lam, Michael; Raghunathan, Ananthan; Jiang, Fan; Fenger, Germain; Adam, Kostas

2017-10-01

The change from isomorphic to anamorphic optics in high numerical aperture (NA) extreme ultraviolet (EUV) scanners necessitates changes to the mask data preparation flow. The required changes for each step in the mask tape out process are discussed, with a focus on optical proximity correction (OPC). When necessary, solutions to new problems are demonstrated, and verified by rigorous simulation. Additions to the OPC model include accounting for anamorphic effects in the optics, mask electromagnetics, and mask manufacturing. The correction algorithm is updated to include awareness of anamorphic mask geometry for mask rule checking (MRC). OPC verification through process window conditions is enhanced to test different wafer scale mask error ranges in the horizontal and vertical directions. This work will show that existing models and methods can be updated to support anamorphic optics without major changes. Also, the larger mask size in the Y direction can result in better model accuracy, easier OPC convergence, and designs which are more tolerant to mask errors.

Optical phase conjugation (OPC)-assisted isotropic focusing.

PubMed

Jang, Mooseok; Sentenac, Anne; Yang, Changhuei

2013-04-08

Isotropic optical focusing - the focusing of light with axial confinement that matches its lateral confinement, is important for a broad range of applications. Conventionally, such focusing is achieved by overlapping the focused beams from a pair of opposite-facing microscope objective lenses. However the exacting requirements for the alignment of the objective lenses and the method's relative intolerance to sample turbidity have significantly limited its utility. In this paper, we present an optical phase conjugation (OPC)-assisted isotropic focusing method that can address both challenges. We exploit the time-reversal nature of OPC playback to naturally guarantee the overlap of the two focused beams even when the objective lenses are significantly misaligned (up to 140 microns transversely and 80 microns axially demonstrated). The scattering correction capability of OPC also enabled us to accomplish isotropic focusing through thick scattering samples (demonstrated with samples of ~7 scattering mean free paths). This method can potentially improve 4Pi microscopy and 3D microstructure patterning.

Oilwell Power Controller (OPC)

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

Not Available

1993-08-01

The Oil Well Power Controller (OPC) prototype units is nearing completion. This device is an oilwell beam pump controller and data logger. Applications for this device have been for an electrical power saving device, pump off control, parafffin detection, demand power load control, chemical treatment data, dynamometer and pump efficiency data. Preliminary results appear vary promising. A total of ten OPC rod pump controllers were assembled and installed on oilwells in several areas of Central and Western United States. Data was analyzed on these wells and forwarded to the participating oil companies. Cost savings on each individual oil well participatingmore » in the OPC testing vary considerably, savings on some situations have been outstanding. In situations where the pump efficiency was determined to be low, the cost savings have been considerable. Cost savings due to preventive maintenance are also present, but are difficult to pin point an exact dollar amount at the present time. A break out of actual cost data obtained on some of the oilwells controlled and monitored with the oilwell power controller.« less

Hydration of Portland cement with additions of calcium sulfoaluminates

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

Le Saout, Gwenn, E-mail: gwenn.le-saout@mines-ales.fr; Lothenbach, Barbara; Hori, Akihiro

2013-01-15

The effect of mineral additions based on calcium aluminates on the hydration mechanism of ordinary Portland cement (OPC) was investigated using isothermal calorimetry, thermal analysis, X-ray diffraction, scanning electron microscopy, solid state nuclear magnetic resonance and pore solution analysis. Results show that the addition of a calcium sulfoaluminate cement (CSA) to the OPC does not affect the hydration mechanism of alite but controls the aluminate dissolution. In the second blend investigated, a rapid setting cement, the amorphous calcium aluminate reacts very fast to ettringite. The release of aluminum ions strongly retards the hydration of alite but the C-S-H has amore » similar composition as in OPC with no additional Al to Si substitution. As in CSA-OPC, the aluminate hydration is controlled by the availability of sulfates. The coupling of thermodynamic modeling with the kinetic equations predicts the amount of hydrates and pore solution compositions as a function of time and validates the model in these systems.« less

OPC modeling by genetic algorithm

NASA Astrophysics Data System (ADS)

Huang, W. C.; Lai, C. M.; Luo, B.; Tsai, C. K.; Tsay, C. S.; Lai, C. W.; Kuo, C. C.; Liu, R. G.; Lin, H. T.; Lin, B. J.

2005-05-01

Optical proximity correction (OPC) is usually used to pre-distort mask layouts to make the printed patterns as close to the desired shapes as possible. For model-based OPC, a lithographic model to predict critical dimensions after lithographic processing is needed. The model is usually obtained via a regression of parameters based on experimental data containing optical proximity effects. When the parameters involve a mix of the continuous (optical and resist models) and the discrete (kernel numbers) sets, the traditional numerical optimization method may have difficulty handling model fitting. In this study, an artificial-intelligent optimization method was used to regress the parameters of the lithographic models for OPC. The implemented phenomenological models were constant-threshold models that combine diffused aerial image models with loading effects. Optical kernels decomposed from Hopkin"s equation were used to calculate aerial images on the wafer. Similarly, the numbers of optical kernels were treated as regression parameters. This way, good regression results were obtained with different sets of optical proximity effect data.

NEWFIRM Software--System Integration Using OPC

NASA Astrophysics Data System (ADS)

Daly, P. N.

2004-07-01

The NOAO Extremely Wide-Field Infra-Red Mosaic (NEWFIRM) camera is being built to satisfy the survey science requirements on the KPNO Mayall and CTIO Blanco 4m telescopes in an era of 8m+ aperture telescopes. Rather than re-invent the wheel, the software system to control the instrument has taken existing software packages and re-used what is appropriate. The result is an end-to-end observation control system using technology components from DRAMA, ORAC, observing tools, GWC, existing in-house motor controllers and new developments like the MONSOON pixel server.

A smart way to identify and extract repeated patterns of a layout

NASA Astrophysics Data System (ADS)

Wei, Fang; Gu, Tingting; Chu, Zhihao; Zhang, Chenming; Chen, Han; Zhu, Jun; Hu, Xinyi; Du, Chunshan; Wan, Qijian; Liu, Zhengfang

2018-03-01

As integrated circuits (IC) technology moves forward, manufacturing process is facing more and more challenges. Optical proximity correction (OPC) has been playing an important role in the whole manufacturing process. In the deep sub-micron technology, OPC engineers not only need to guarantee the layout designs to be manufacturable but also take a more precise control of the critical patterns to ensure a high performance circuit. One of the tasks that would like to be performed is the consistency checking as the identical patterns under identical context should have identical OPC results in theory, like SRAM regions. Consistency checking is essentially a technique of repeated patterns identification, extraction and derived patterns (i.e. OPC results) comparison. The layout passing to the OPC team may not have enough design hierarchical information either because the original designs may have undergone several layout processing steps or some other unknown reasons. This paper presents a generic way to identify and extract repeated layout structures in SRAM regions purely based on layout pattern analysis through Calibre Pattern Matching and Calibre equation-based DRC (eqDRC). Without Pattern Matching and eqDRC, it will take lots of effort to manually get it done by trial and error, it is almost impossible to automate the pattern analysis process. Combining Pattern Matching and eqDRC opens a new way to implement this flow. The repeated patterns must have some fundamental features for measurement of pitches in the horizontal and vertical direction separately by Calibre eqDRC and meanwhile can be a helper to generate some anchor points which will be the starting points for Pattern Matching to capture patterns. The informative statistical report from the pattern search tells the match counts individually for each patterns captured. Experiment shows that this is a smart way of identifying and extracting repeated structures effectively. The OPC results are the derived layers on these repeated structures, by running pattern search using design layers as pattern layers and OPC results as marker layers, it is an easy job to compare the consistency.

Open-label randomized clinical trial of atropine bolus injection versus incremental boluses plus infusion for organophosphate poisoning in Bangladesh.

PubMed

Abedin, Mohammed Joynal; Sayeed, Abdullah Abu; Basher, Ariful; Maude, Richard J; Hoque, Gofranul; Faiz, M A

2012-06-01

Severe organophosphate compound (OPC) poisoning is an important clinical problem in many countries of the world. Unfortunately, little clinical research has been performed and little evidence exists with which to determine the best therapy. A study was therefore undertaken to determine the optimal dosing regimen for atropine in the treatment of OPC poisoning. An open-label randomized clinical trial was conducted in Chittagong Medical College Hospital, Chittagong, Bangladesh, on 156 hospitalized individuals with OPC poisoning from June to September 2006. The aim was to compare the efficacy and safety of conventional bolus doses with individualized incremental doses of atropine for atropinization followed by continuous atropine infusion for management of OPC poisoning. Inclusion criteria were patients with a clear history of OPC poisoning with clear clinical signs of toxicity, i.e. features of cholinergic crisis. The patients were observed for at least 96 h. Immediate outcome and complications were recorded. Out of 156 patients, 81 patients received conventional bolus dose atropine (group A) and 75 patients received rapidly incremental doses of atropine followed by infusion (group B). The mortality in group 'A' was 22.5% (18/80) and in group 'B' 8% (6/75) (p < 0.05). The mean duration of atropinization in group 'A' was 151.74 min compared to 23.90 min for group 'B' (p < 0.001). More patients in group A experienced atropine toxicity than in group 'B' (28.4% versus 12.0%, p < 0.05); intermediate syndrome was more common in group 'A' than in group 'B' (13.6% versus 4%, p < 0.05), and respiratory support was required more often for patients in group 'A' than in group 'B' (24.7% versus 8%, p < 0.05). Rapid incremental dose atropinization followed by atropine infusion reduces mortality and morbidity from OPC poisoning and shortens the length of hospital stay and recovery. Incremental atropine and infusion should become the treatment of choice for OPC poisoning. Given the paucity of existing evidence, further clinical studies should be performed to determine the optimal dosing regimen of atropine that most rapidly and safely achieves atropinization in these patients.

[In vitro and in vivo studies on the cardioprotective action of oligomeric procyanidins in a Crataegus extract of leaves and blooms].

PubMed

Chatterjee, S S; Koch, E; Jaggy, H; Krzeminski, T

1997-07-01

Cardioprotective effects of a standardized extract from leaves with flowers of Crataegus (WS-1442; content of oligomeric procyandins [OPC]: 18.75%) have recently been demonstrated in an ischemia-reperfusion model in rats. Further studies were now conducted to clarify the mechanism of action and to identify active constituents involved in these effects of WS-1442. Exhausting partitioning between ethyl acetate/water and successive ultrafiltration of the aqueous layer led to the quantitative recovery of three fractions, which were tested for their in vitro radical scavenging (RS) and human neutrophil elastase (HNE) inhibitory activity. The lipophilic ethylacetate-soluble fraction A, enriched in flavone derivatives and constituting 14.9% of WS-1442, was as active as WS-1442 in inhibiting HNE. However, its RS activity was only about half that of the primary extract. Although 67.9% of WS-1442 was recovered in a water-soluble low molecular weight fraction B, this fraction displayed only weak RS and HNE inhibiting activity. In contrast, the RS and HNE inhibiting potencies of an essentially flavone-free and OPC-rich fraction C (21.3% of WS-1442) were significantly higher (inhibition of lipid peroxidation: IC50 0.3 microgram/ml; inhibition of HNE: IC50 0.84 microgram/ml) as those of WS-1442. The RS and HNE inhibitory activities of the extract and those of its fractions correlated well with their OPC-content but not with their concentration of flavonols. These results demonstrate that OPCs of Crataegus extracts possess stronger radical scavenging activities than flavone derivatives or other constituents. In addition, the oligomeric components are potent inhibitors of HNE. Oral administration of 20 mg/kg/d of the OPC-rich fraction C to rats afforded similar protection against ischemia-reperfusion induced pathologies as treatment with WS-1442 at a dose of 100 mg/kg/d. These observations indicate that radical scavenging and elastase inhibitory activities could indeed be involved in the observed cardioprotective effects of WS-1442, and demonstrate that OPCs are major orally active constituents of WS-1442. Thus, Crataegus extracts used therapeutically for cardiovascular diseases should be analyzed and standardized for their OPC-content.

OPC for curved designs in application to photonics on silicon

NASA Astrophysics Data System (ADS)

Orlando, Bastien; Farys, Vincent; Schneider, Loïc.; Cremer, Sébastien; Postnikov, Sergei V.; Millequant, Matthieu; Dirrenberger, Mathieu; Tiphine, Charles; Bayle, Sébastian; Tranquillin, Céline; Schiavone, Patrick

2016-03-01

Today's design for photonics devices on silicon relies on non-Manhattan features such as curves and a wide variety of angles with minimum feature size below 100nm. Industrial manufacturing of such devices requires optimized process window with 193nm lithography. Therefore, Resolution Enhancement Techniques (RET) that are commonly used for CMOS manufacturing are required. However, most RET algorithms are based on Manhattan fragmentation (0°, 45° and 90°) which can generate large CD dispersion on masks for photonic designs. Industrial implementation of RET solutions to photonic designs is challenging as most currently available OPC tools are CMOS-oriented. Discrepancy from design to final results induced by RET techniques can lead to lower photonic device performance. We propose a novel sizing algorithm allowing adjustment of design edge fragments while preserving the topology of the original structures. The results of the algorithm implementation in the rule based sizing, SRAF placement and model based correction will be discussed in this paper. Corrections based on this novel algorithm were applied and characterized on real photonics devices. The obtained results demonstrate the validity of the proposed correction method integrated in Inscale software of Aselta Nanographics.

Atmospheric Chemistry of Hydrocarbon Fuels. Volume 2. Outdoor Chamber Data Tabulations. Part 1

DTIC Science & Technology

1981-11-01

6800 SN100015D 4600 B-NOX-1 BENDIX NOX ANALYZER MDB8101BX SN300038-2 4350 CLIMET CLIMET OPC MD4208 SN76-148 4130 EPPLEY ARB LAB; EPPLEY 11692 UV...SN300038-2 4350 CLIMET CLIMET OPC MD1208 SN76-148 4130 EPPLEY ARB LAB; EPPLEY 11692 UV RADIOMETER 4000 ECD-3 AF-LAB; 122 5% CARBOWAX-600; ECD AFF- 7...121; POROPAK N ; FID S2200 DMS-I RM-121; DIMETHYLSULFOLANE; FID 4600 B-NOX-I BENDIX NOX ANALYZER MD81O1BX SN300038-2 4350 CLIMET CLIMET OPC MD:208 SN76

[The mechanism of the transport of organophosphorus compounds across the histo-hematic barriers].

PubMed

Miroshkina, V N; Kosmachev, A B; Salova, L S

1999-01-01

It was demonstrated in experiments on mice [correction of rats] that the transport of organophosphorus compounds (OPC) through membranes of the histohematic barriers (HHB) of the organism occurs by means of diffusion. The rate of this process depends on the interaction of OPC with the specific sites of binding with the tissues, among which the enzyme carboxylesterase plays an important part. It is suggested that both the rate and direction of OPC diffusion are determined by the relationship between the values of affinity of the ligands for the sites of their specific binding found on both sides of the HHB.

A-Kinase Anchor Protein 12 Is Required for Oligodendrocyte Differentiation in Adult White Matter.

PubMed

Maki, Takakuni; Choi, Yoon Kyung; Miyamoto, Nobukazu; Shindo, Akihiro; Liang, Anna C; Ahn, Bum Ju; Mandeville, Emiri T; Kaji, Seiji; Itoh, Kanako; Seo, Ji Hae; Gelman, Irwin H; Lok, Josephine; Takahashi, Ryosuke; Kim, Kyu-Won; Lo, Eng H; Arai, Ken

2018-05-01

Oligodendrocyte precursor cells (OPCs) give rise to oligodendrocytes in cerebral white matter. However, the underlying mechanisms that regulate this process remain to be fully defined, especially in adult brains. Recently, it has been suggested that signaling via A-kinase anchor protein 12 (AKAP12), a scaffolding protein that associates with intracellular molecules such as protein kinase A, may be involved in Schwann cell homeostasis and peripheral myelination. Here, we asked whether AKAP12 also regulates the mechanisms of myelination in the CNS. AKAP12 knockout mice were compared against wild-type (WT) mice in a series of neurochemical and behavioral assays. Compared with WTs, 2-months old AKAP12 knockout mice exhibited loss of myelin in white matter of the corpus callosum, along with perturbations in working memory as measured by a standard Y-maze test. Unexpectedly, very few OPCs expressed AKAP12 in the corpus callosum region. Instead, pericytes appeared to be one of the major AKAP12-expressing cells. In a cell culture model system, conditioned culture media from normal pericytes promoted in-vitro OPC maturation. However, conditioned media from AKAP12-deficient pericytes did not support the OPC function. These findings suggest that AKAP12 signaling in pericytes may be required for OPC-to-oligodendrocyte renewal to maintain the white matter homeostasis in adult brain. Stem Cells 2018;36:751-760. © AlphaMed Press 2018.

Myelin-mediated inhibition of oligodendrocyte precursor differentiation can be overcome by pharmacological modulation of Fyn-RhoA and protein kinase C signalling

PubMed Central

Baer, Alexandra S.; Syed, Yasir A.; Kang, Sung Ung; Mitteregger, Dieter; Vig, Raluca; ffrench-Constant, Charles; Franklin, Robin J. M.; Altmann, Friedrich; Lubec, Gert

2009-01-01

Failure of oligodendrocyte precursor cell (OPC) differentiation contributes significantly to failed myelin sheath regeneration (remyelination) in chronic demyelinating diseases. Although the reasons for this failure are not completely understood, several lines of evidence point to factors present following demyelination that specifically inhibit differentiation of cells capable of generating remyelinating oligodendrocytes. We have previously demonstrated that myelin debris generated by demyelination inhibits remyelination by inhibiting OPC differentiation and that the inhibitory effects are associated with myelin proteins. In the present study, we narrow down the spectrum of potential protein candidates by proteomic analysis of inhibitory protein fractions prepared by CM and HighQ column chromatography followed by BN/SDS/SDS–PAGE gel separation using Nano-HPLC-ESI-Q-TOF mass spectrometry. We show that the inhibitory effects on OPC differentiation mediated by myelin are regulated by Fyn-RhoA-ROCK signalling as well as by modulation of protein kinase C (PKC) signalling. We demonstrate that pharmacological or siRNA-mediated inhibition of RhoA-ROCK-II and/or PKC signalling can induce OPC differentiation in the presence of myelin. Our results, which provide a mechanistic link between myelin, a mediator of OPC differentiation inhibition associated with demyelinating pathologies and specific signalling pathways amenable to pharmacological manipulation, are therefore of significant potential value for future strategies aimed at enhancing CNS remyelination. PMID:19208690

Protective effect of oligomeric proanthocyanidins against alcohol-induced liver steatosis and injury in mice.

PubMed

Wang, Zhiguo; Su, Bo; Fan, Sumei; Fei, Haixia; Zhao, Wei

2015-03-20

The long-term consumption of alcohol has been associated with multiple pathologies at all levels, such as alcoholism, chronic pancreatitis, malnutrition, alcoholic liver disease (ALD) and cancer. In the current study, we investigated the protective effect of oligomeric proanthocyanidins (OPC) against alcohol-induced liver steatosis and injury and the possible mechanisms using ethanol-induced chronic liver damage mouse models. The results showed that OPC significantly improved alcohol-induced dyslipidemia and alleviated liver steatosis by reducing levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total triglyceride (TG), total cholesterol (TC), low-density cholesterol (LDL-c) and liver malondialdehyde (MDA), and increasing levels of serum high-density lipoprotein (HDL-c), liver superoxide dismutase (SOD). Further investigation indicated that OPC markedly decreased the expressions of lipid synthesis genes and inflammation genes such as sterol regulatory element-binding protein-1c (Srebp-1c), protein-2 (Srebp2), interleukin IL-1β, IL-6 and TNF-α. Furthermore, AML-12 cells line was used to investigate the possible mechanisms which indicated that OPC might alleviate liver steatosis and damage through AMP-activated protein kinase (AMPK) activation involving oxidative stress. In conclusion, our study demonstrated excellent protective effect of OPC against alcohol-induced liver steatosis and injury, which could a potential drug for the treatment of alcohol-induced liver injury in the future. Copyright © 2015 Elsevier Inc. All rights reserved.

Cannabidiol protects oligodendrocyte progenitor cells from inflammation-induced apoptosis by attenuating endoplasmic reticulum stress

PubMed Central

Mecha, M; Torrao, A S; Mestre, L; Carrillo-Salinas, F J; Mechoulam, R; Guaza, C

2012-01-01

Cannabidiol (CBD) is the most abundant cannabinoid in Cannabis sativa that has no psychoactive properties. CBD has been approved to treat inflammation, pain and spasticity associated with multiple sclerosis (MS), of which demyelination and oligodendrocyte loss are hallmarks. Thus, we investigated the protective effects of CBD against the damage to oligodendrocyte progenitor cells (OPCs) mediated by the immune system. Doses of 1 μM CBD protect OPCs from oxidative stress by decreasing the production of reactive oxygen species. CBD also protects OPCs from apoptosis induced by LPS/IFNγ through the decrease of caspase 3 induction via mechanisms that do not involve CB1, CB2, TRPV1 or PPARγ receptors. Tunicamycin-induced OPC death was attenuated by CBD, suggesting a role of endoplasmic reticulum (ER) stress in the mode of action of CBD. This protection against ER stress-induced apoptosis was associated with reduced phosphorylation of eiF2α, one of the initiators of the ER stress pathway. Indeed, CBD diminished the phosphorylation of PKR and eiF2α induced by LPS/IFNγ. The pro-survival effects of CBD in OPCs were accompanied by decreases in the expression of ER apoptotic effectors (CHOP, Bax and caspase 12), and increased expression of the anti-apoptotic Bcl-2. These findings suggest that attenuation of the ER stress pathway is involved in the ‘oligoprotective' effects of CBD during inflammation. PMID:22739983

Survival and human papillomavirus in oropharynx cancer in TAX 324: a subset analysis from an international phase III trial.

PubMed

Posner, M R; Lorch, J H; Goloubeva, O; Tan, M; Schumaker, L M; Sarlis, N J; Haddad, R I; Cullen, K J

2011-05-01

The association between human papillomavirus (HPV) and overall survival (OS) in oropharynx cancer (OPC) was retrospectively examined in TAX 324, a phase III trial of sequential therapy for locally advanced head and neck cancer. Accrual for TAX 324 was completed in 2003 and data updated through 2008. Pretherapy tumor biopsies were studied by PCR for human papillomavirus type 16 and linked to OS, progression-free survival (PFS) and demographics. Of 264 patients with OPC, 111 (42%) had evaluable biopsies; 56 (50%) were HPV+ and 55 (50%) were HPV-. HPV+ patients were significantly younger (54 versus 58 years, P = 0.02), had T1/T2 primary cancers (49% versus 20%, P = 0.001), and had a performance status of zero (77% versus 49%, P = 0.003). OS and PFS were better for HPV+ patients (OS, hazard ratio = 0.20, P < 0.0001). Local-regional failure was less in HPV+ patients (13% versus 42%, P = 0.0006); at 5 years, 82% of HPV+ patients were alive compared with 35% of HPV- patients (P < 0.0001). HPV+ OPC has a different biology compared with HPV- OPC; 5-year OS, PFS, and local-regional control are unprecedented. These results support the possibility of selectively reducing therapy and long-term morbidity in HPV+ OPC while preserving survival and approaching HPV- disease with more aggressive treatment.

Co-ultramicronized Palmitoylethanolamide/Luteolin Promotes the Maturation of Oligodendrocyte Precursor Cells

PubMed Central

Barbierato, Massimo; Facci, Laura; Marinelli, Carla; Zusso, Morena; Argentini, Carla; Skaper, Stephen D.; Giusti, Pietro

2015-01-01

Oligodendrocytes have limited ability to repair the damage to themselves or to other nerve cells, as seen in demyelinating diseases like multiple sclerosis. An important strategy may be to replace the lost oligodendrocytes and/or promote the maturation of undifferentiated oligodendrocyte precursor cells (OPCs). Recent studies show that a composite of co-ultramicronized N-palmitoylethanolamine (PEA) and luteolin (co-ultramicronized PEA/luteolin, 10:1 by mass) is efficacious in improving outcome in experimental models of spinal cord and traumatic brain injuries. Here, we examined the ability of co-ultramicronized PEA/luteolin to promote progression of OPCs into a more differentiated phenotype. OPCs derived from newborn rat cortex were placed in culture and treated the following day with 10 μM co-ultramicronized PEA/luteolin. Cells were collected 1, 4 and 8 days later and analyzed for expression of myelin basic protein (MBP). qPCR and Western blot analyses revealed a time-dependent increase in expression of both mRNA for MBP and MBP content, along with an increased expression of genes involved in lipid biogenesis. Ultramicronized PEA or luteolin, either singly or in simple combination, were ineffective. Further, co-ultramicronized PEA/luteolin promoted morphological development of OPCs and total protein content without affecting proliferation. Co-ultramicronized PEA/luteolin may represent a novel pharmacological strategy to promote OPC maturation. PMID:26578323

Bioinformatic analysis of meningococcal Msf and Opc to inform vaccine antigen design

PubMed Central

Andreae, Clio A.; Sessions, Richard B.; Virji, Mumtaz

2018-01-01

Neisseria meningitidis is an antigenically and genetically variable Gram-negative bacterium and a causative agent of meningococcal meningitis and septicaemia. Meningococci encode many outer membrane proteins, including Opa, Opc, Msf, fHbp and NadA, identified as being involved in colonisation of the host and evasion of the immune response. Although vaccines are available for the prevention of some types of meningococcal disease, none currently offer universal protection. We have used sequences within the Neisseria PubMLST database to determine the variability of msf and opc in 6,500 isolates. In-silico analysis revealed that although opc is highly conserved, it is not present in all isolates, with most isolates in clonal complex ST-11 lacking a functional opc. In comparison, msf is found in all meningococcal isolates, and displays diversity in the N-terminal domain. We identified 20 distinct Msf sequence variants (Msf SV), associated with differences in number of residues within the putative Vn binding motifs. Moreover, we showed distinct correlations with certain Msf SVs and isolates associated with either hyperinvasive lineages or those clonal complexes associated with a carriage state. We have demonstrated differences in Vn binding between three Msf SVs and generated a cross reactive Msf polyclonal antibody. Our study has highlighted the importance of using large datasets to inform vaccine development and provide further information on the antigenic diversity exhibited by N. meningitidis. PMID:29547646

Pixel-based OPC optimization based on conjugate gradients.

PubMed

Ma, Xu; Arce, Gonzalo R

2011-01-31

Optical proximity correction (OPC) methods are resolution enhancement techniques (RET) used extensively in the semiconductor industry to improve the resolution and pattern fidelity of optical lithography. In pixel-based OPC (PBOPC), the mask is divided into small pixels, each of which is modified during the optimization process. Two critical issues in PBOPC are the required computational complexity of the optimization process, and the manufacturability of the optimized mask. Most current OPC optimization methods apply the steepest descent (SD) algorithm to improve image fidelity augmented by regularization penalties to reduce the complexity of the mask. Although simple to implement, the SD algorithm converges slowly. The existing regularization penalties, however, fall short in meeting the mask rule check (MRC) requirements often used in semiconductor manufacturing. This paper focuses on developing OPC optimization algorithms based on the conjugate gradient (CG) method which exhibits much faster convergence than the SD algorithm. The imaging formation process is represented by the Fourier series expansion model which approximates the partially coherent system as a sum of coherent systems. In order to obtain more desirable manufacturability properties of the mask pattern, a MRC penalty is proposed to enlarge the linear size of the sub-resolution assistant features (SRAFs), as well as the distances between the SRAFs and the main body of the mask. Finally, a projection method is developed to further reduce the complexity of the optimized mask pattern.

Bioinformatic analysis of meningococcal Msf and Opc to inform vaccine antigen design.

PubMed

Andreae, Clio A; Sessions, Richard B; Virji, Mumtaz; Hill, Darryl J

2018-01-01

Neisseria meningitidis is an antigenically and genetically variable Gram-negative bacterium and a causative agent of meningococcal meningitis and septicaemia. Meningococci encode many outer membrane proteins, including Opa, Opc, Msf, fHbp and NadA, identified as being involved in colonisation of the host and evasion of the immune response. Although vaccines are available for the prevention of some types of meningococcal disease, none currently offer universal protection. We have used sequences within the Neisseria PubMLST database to determine the variability of msf and opc in 6,500 isolates. In-silico analysis revealed that although opc is highly conserved, it is not present in all isolates, with most isolates in clonal complex ST-11 lacking a functional opc. In comparison, msf is found in all meningococcal isolates, and displays diversity in the N-terminal domain. We identified 20 distinct Msf sequence variants (Msf SV), associated with differences in number of residues within the putative Vn binding motifs. Moreover, we showed distinct correlations with certain Msf SVs and isolates associated with either hyperinvasive lineages or those clonal complexes associated with a carriage state. We have demonstrated differences in Vn binding between three Msf SVs and generated a cross reactive Msf polyclonal antibody. Our study has highlighted the importance of using large datasets to inform vaccine development and provide further information on the antigenic diversity exhibited by N. meningitidis.

Corrosion Behavior of Carbon Steel in Concrete Material Composed of Tin Slag Waste in Aqueous Chloride Solution

NASA Astrophysics Data System (ADS)

Rustandi, Andi; Cahyadi, Agung; Taruli Siallagan, Sonia; Wafa' Nawawi, Fuad; Pratesa, Yudha

2018-01-01

Tin slag is a byproduct of tin ore smelting process which is rarely utilized. The main purpose of this work is to investigate the use of tin slag for concrete cement material application compared to the industrial Ordinary Portland Cement (OPC). Tin slag composition was characterized by XRD and XRF analysis. The characterization results showed the similar chemical composition of tin slag and OPC. It also revealed the semi crystalline structure of tin slag sample. Several electrochemical tests were performed to evaluate corrosion behavior of tin slag, OPC and various mixed composition of both materials and the addition of CaO. The corrosion behavior of OPC and tin slag were evaluated by using Cyclic Polarization, Electrochemical Impedance Spectroscopy (EIS) and Electrochemical Frequency Modulation (EFM) methods. Aqueous sodium chloride (NaCl) solution with 3.5% w.t concentration which similar to seawater was used as the electrolyte in this work. The steel specimen used as the reinforce bar (rebar) material of the concrete was carbon steel AISI 1045. The rebar was embedded in the concrete cement which composed of OPC and the various composition of tin slag including slag without addition of CaO and slag mixed with addition of 50 % CaO. The electrochemical tests results revealed that tin slag affected its corrosion behavior which becoming more active and increasing the corrosion rate as well as decreasing the electrochemical impedance.

Effect of moderate liver impairment on the pharmacokinetics of opicapone.

PubMed

Rocha, José Francisco; Santos, Ana; Falcão, Amílcar; Lopes, Nelson; Nunes, Teresa; Pinto, Roberto; Soares-da-Silva, Patrício

2014-03-01

Opicapone (OPC) is a novel catechol-O-methyltransferase (COMT) inhibitor to be used as adjunctive therapy in levodopa-treated patients with Parkinson's disease. The purpose of this study was to evaluate the effect of moderate liver impairment on the pharmacokinetics (PK) and pharmacodynamics (PD; effect on COMT activity) of OPC. An open-label, parallel-group study in patients (n = 8) with moderate liver impairment (Child-Pugh category B, score of 7 to 9) and matched healthy subjects (n = 8, control) with normal liver function. All subjects received a single 50-mg oral dose of OPC, with plasma and urine concentrations of opicapone and its metabolites measured up to 72 h post-dose, including soluble COMT (S-COMT) activity. A one-way analysis of variance (ANOVA) was used to compare the main PK and PD parameters between groups. Point estimates (PE) of geometric mean ratios (GMR) and corresponding 90 % confidence intervals (90%CI) for the ratio hepatic/control subjects of each parameter were calculated and compared with the reference interval (80-125 %). Exposure to opicapone (AUC and Cmax) increased significantly in patients with moderate hepatic impairment (PE [90%CI]: AUC0-∞, 184 % [135-250 %]; Cmax, 189 % [144-249 %]). Although apparent total clearance (CL/F) of opicapone was decreased by ∼35 %, similar elimination half-life and unbound/bound fractions of opicapone were observed between the two groups. Both rate and extent of exposure to BIA 9-1103 were higher in the hepatically impaired group, but not statistically significant compared with the control group. Similar to the parent (opicapone), the observed increase in exposure to BIA 9-1106 was statistically significant in the hepatically impaired group over the control group. BIA 9-1106 was the only metabolite detected in urine and its urine PK parameters were in accordance with plasma data. Maximum S-COMT inhibition (Emax) occurred earlier for the hepatically impaired group with values of 100 % and 91.2 % for the hepatically impaired and control groups respectively. Both Emax and AUEC for the hepatically impaired group reached statistical significance over the control group. OPC was well tolerated in both hepatically impaired and control groups. The bioavailability of an orally administered single dose of 50 mg OPC was significantly higher in patients with moderate chronic hepatic impairment, perhaps by a reduced first-pass effect. As the tolerability profile of OPC was favourable under the conditions of this study and its exposure is completely purged from systemic circulation before the subsequent dose administration, no OPC dose adjustment is needed in patients with mild to moderate chronic hepatic impairment. However, as OPC is under clinical development for use as adjunctive therapy in levodopa-treated patients with Parkinson's disease, an adjustment of levodopa and/or OPC regimens in patients should be carefully considered based on a potentially enhanced levodopa dopaminergic response and the associated tolerability.

The Overt Pronoun Constraint across Three Dialects of Spanish

ERIC Educational Resources Information Center

Gelormini-Lezama, Carlos; Huepe, David; Herrera, Eduar; Melloni, Margherita; Manes, Facundo; García, Adolfo M.; Ibáñez, Agustín

2016-01-01

The overt pronoun constraint (OPC) states that, in null subject languages, overt pronoun subjects of embedded clauses cannot be bound by "wh-" or quantifier antecedents. Through the administration of two written questionnaires, we examined the OPC in 246 monolingual native speakers of three dialects of Spanish, spoken in Barranquilla…

Coast Guard Cutter Procurement: Background and Issues for Congress

DTIC Science & Technology

2013-07-24

strategy for the OPC; Coast Guard Cutter Procurement: Background and Issues for Congress Congressional Research Service • the potential for using...Acquisition Strategy ........................................................... 24 2012 Testimony...Guard’s funding requests and acquisition strategies for the NSC, OPC, and FRC programs. Congress’s decisions on these three programs could

Training and Development through Adult Learning Theory.

ERIC Educational Resources Information Center

Swagar, Colleen

This report analyzes the employee training program at the Outdoor Program Centre (OPC) of the University of Calgary and offers recommendations that may be of benefit to other outdoor recreation centers. The OPC offers products and services such as facility access, equipment rentals, instructional and recreational programs, and repair services for…

Enabling Occupational Performance of Children through Coaching Parents: Three Case Reports

ERIC Educational Resources Information Center

Graham, Fiona; Rodger, Sylvia; Ziviani, Jenny

2010-01-01

This study explores the use of occupational performance coaching (OPC) with three parent-child dyads using descriptive case study methodology. OPC is a parent-directed intervention in which parents are coached to improve their own or their children's performance in home and community contexts. In this study, parent and child performance was…

Evaluation of a New Thrust in the Delivery of Mental Health Services: Outpatient Commitment.

ERIC Educational Resources Information Center

Hiday, Virginia Aldige'; Scheid-Cook, Teresa L.

The North Carolina State Legislature made outpatient commitment (OPC) criteria less restrictive than involuntary hospitalization criteria, provided an enforcement mechanism, gave facilities and staff immunity from liability, and allocated funds for OPC patients. Data collected in a state-wide study of civil commitment respondents in North Carolina…

Subependymal Zone-Derived Oligodendroblasts Respond to Focal Demyelination but Fail to Generate Myelin in Young and Aged Mice.

PubMed

Kazanis, Ilias; Evans, Kimberley A; Andreopoulou, Evangelia; Dimitriou, Christina; Koutsakis, Christos; Karadottir, Ragnhildur Thora; Franklin, Robin J M

2017-03-14

Two populations of oligodendrogenic progenitors co-exist within the corpus callosum (CC) of the adult mouse. Local, parenchymal oligodendrocyte progenitor cells (pOPCs) and progenitors generated in the subependymal zone (SEZ) cytogenic niche. pOPCs are committed perinatally and retain their numbers through self-renewing divisions, while SEZ-derived cells are relatively "young," being constantly born from neural stem cells. We compared the behavior of these populations, labeling SEZ-derived cells using hGFAP:Cre Ert2 mice, within the homeostatic and regenerating CC of the young-adult and aging brain. We found that SEZ-derived oligodendroglial progenitors have limited self-renewing potential and are therefore not bona fide OPCs but rather "oligodendroblasts" more similar to the neuroblasts of the neurogenic output of the SEZ. In the aged CC their mitotic activity is much reduced, although they still act as a "fast-response element" to focal demyelination. In contrast to pOPCs, they fail to generate mature myelinating oligodendrocytes at all ages studied. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Metabolism of a new positive inotropic agent, 3,4-dihydro-6-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl]-2(1H)- quinolinone (OPC-8212) in the rat, mouse, dog, monkey and human.

PubMed

Miyamoto, G; Sasabe, H; Tominaga, N; Uegaki, N; Tominaga, M; Shimizu, T

1988-10-01

1. After OPC-8212 was orally given to rats, mice, dogs, monkeys and humans, its metabolites were identified by n.m.r. and mass spectrometry, and their concentrations in the plasma, urine and faeces of these species were measured by high-performance liquid chromatography (h.p.l.c.). 2. Hydrolysis of the amide group, oxidation and cleavage of the piperazine ring, O-demethylation of the methoxy group, and conjugation were proposed as metabolic pathways of OPC-8212. 3. In rats, mice and monkeys given OPC-8212 orally, metabolites M-1 to M-6 were detected in the plasma, urine and faeces, while M-1, -4, -5 and M-6 were detected in dogs, and M-1, M-3, M-4, M-5 and M-6 were detected in humans. 4. Conjugates of metabolites M-6 and M-7, with glucuronic acid and sulphuric acid, were observed in the urine of rats and humans.

The Cultural and Social Context of Oral and Pharyngeal Cancer Risk and Control among Hispanics in New York

PubMed Central

Cruz, Gustavo D.; Shulman, Lawrence C.; Kumar, Jayanth V.; Salazar, Christian R.

2007-01-01

New York City (NYC) has one of the highest incidence and mortality rates of oral and pharyngeal cancer (OPC) for Hispanics of any major U.S. city. This qualitative assessment explores OPC awareness, attitudes, and screening practices among at-risk Hispanics, health care providers, and community leaders in a Hispanic neighborhood of NYC. Four focus groups (N=39) were conducted with at-risk Hispanics. Structured interviews were conducted with ten health care providers (four physicians, four dentists, two dental hygienists) and three key community leaders. Results showed major gaps in OPC awareness across all key stakeholders. Focus group participants expressed difficulty in accessing appropriate health care. Health care providers were not familiar with OPC prevention and early detection practices. Community leaders lacked the knowledge and resources necessary for advocating prevention and early detection for their constituencies. All participants reported cultural, social, and structural barriers to prevention. There is a need for developing a comprehensive, culturally competent health communication program that targets all key stakeholders in the at-risk Hispanic community of NYC. PMID:17982210

A calorimetric and microstructural study of solidified toxic wastes. Part 2: A model for poisoning of OPC hydration

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

Hills, C.D.; Sollars, C.J.; Perry, R.

1994-01-01

During cement-based processing of certain hazardous wastes the hydration reactions thought to be responsible for solidification can be poisoned and appear to be retarded indefinitely. A number of wastes known to be capable of poisoning hydration were added to ordinary Portland cement (OPC) and classified on the basis of interference effects observed. This paper reports the results from a characterization of these wastes and the subsequent addition to OPC of waste components identified as significant in single and combined additions. The effects of these additions were examined by conduction calorimetry and microstructural techniques. A comparison of results showed that itmore » was possible to reproduce the poisoning effects observed previously with real wastes by an addition of combined metal hydroxides only. These results suggest that poisoning results from the synergistic effects of compounds contained in the waste. A model, representing the early hydration of OPC, has been modified and is presented and its application in explaining poisoning of hydration is discussed.« less

Direct numerical simulation of turbulent channel flow with spanwise alternatively distributed strips control

NASA Astrophysics Data System (ADS)

Ni, Weidan; Lu, Lipeng; Fang, Jian; Moulinec, Charles; Yao, Yufeng

2018-05-01

The effect of spanwise alternatively distributed strips (SADS) control on turbulent flow in a plane channel has been studied by direct numerical simulations to investigate the characteristics of large-scale streamwise vortices (LSSVs) induced by small-scale active wall actuation, and their potential in suppressing flow separation. SADS control is realized by alternatively arranging out-of-phase control (OPC) and in-phase control (IPC) wall actuations on the lower channel wall surface, in the spanwise direction. It is found that the coherent structures are suppressed or enhanced alternatively by OPC or IPC, respectively, leading to the formation of a vertical shear layer, which is responsible for the LSSVs’ presence. Large-scale low-speed region can also be observed above the OPC strips, which resemble large-scale low-speed streaks. LSSVs are found to be in a statistically-converged steady state and their cores are located between two neighboring OPC and IPC strips. Their motions contribute significantly to the momentum transport in the wall-normal and spanwise directions, demonstrating their potential ability to suppress flow separation.

Modification of the education system for organ procurement coordinators in Japan after the revision of the Japanese Organ Transplantation Act.

PubMed

Konaka, S; Kato, O; Ashikari, J; Fukushima, N

2012-05-01

From October 1997 to July 2010, only 86 brain-dead (BD) organ donations were obtained and no organs were retrieved from children under 15 years of age because of the strict Japan Organ Transplantation Act. The Act was revised on July 17, 2010, allowing organs to be donated after BD with family consent. To manage the increased donations after the revision, the Japan Organ Transplant Network (JOT) employed 10 organ procurement coordinators (OPCs) and modified its education systems. We retrospectively reviewed the modified education programs to evaluate whether they were effective and whether the processes of organ donation were promptly performed after the revision of the Act. The modifications of education program were: changing OPC to guideline manuals to correspond to the revised Transplant Act; OPCs were taught the new organ procurement system; and a special education program was provided for the 10 newcomers for 2 months. After 12 months of the revision, 58 BD organ donations were accomplished, whereas they had averaged 6.6 in a year before the revision. Two pediatric BD organ donations were accomplished without problem. One priority organ donation to a relative was performed uneventfully. After applying the modified education program, skilled JOT OPCs and leader JOT OPCs increased. To manage increased organ donations after the revision of the Act, the educational system was modified and 58 brain dead organ donations were performed safely. Copyright © 2012 Elsevier Inc. All rights reserved.

Human papilloma virus infection in head and neck cancer.

PubMed

Tribius, Silke; Hoffmann, Markus

2013-03-01

The causal link between cervical cancer and human papilloma virus (HPV) is well known. It is now becoming clear that some types of squamous-cell carcinoma of the head and neck, particularly oropharyngeal carcinoma (OPC), are also linked to HPV infection. The development of vaccines against certain HPV genotypes has changed the management strategy for HPV-associated diseases of the uterine cervix. An analogous approach is now being considered for the prevention of HPV-associated diseases of the head and neck. We review pertinent articles retrieved by a selective search of the literature for phase II and III trials providing evidence about a possible effect of HPV status on the survival rates of patients with OPC. Seven trials fulfilled our search criteria: four phase III trials with retrospective HPV analysis and three phase II trials with retrospective and prospective HPV analysis. Patients with HPV-positive OPC survive significantly longer than those with HPV-negative OPC. Tobacco smoking has been identified as a negative prognostic factor in patients with either HPV-negative or HPV-positive disease. The established treatment strategy for OPC in patients with and without the traditional risk factors (tobacco and alcohol consumption) is now being reconsidered in the light of what we have learned about the role of HPV infection. Ongoing and projected clinical trials with risk-factor stratification may soon lead to changes in treatment. Further study is needed to answer the question whether HPV infection in the head and neck region is carcinogenic.

Influence of Titanium Dioxide Nanoparticles on the Sulfate Attack upon Ordinary Portland Cement and Slag-Blended Mortars

PubMed Central

Atta-ur-Rehman; Qudoos, Abdul; Kim, Hong Gi

2018-01-01

In this study, the effects of titanium dioxide (TiO2) nanoparticles on the sulfate attack resistance of ordinary Portland cement (OPC) and slag-blended mortars were investigated. OPC and slag-blended mortars (OPC:Slag = 50:50) were made with water to binder ratio of 0.4 and a binder to sand ratio of 1:3. TiO2 was added as an admixture as 0%, 3%, 6%, 9% and 12% of the binder weight. Mortar specimens were exposed to an accelerated sulfate attack environment. Expansion, changes in mass and surface microhardness were measured. Scanning Electron Microscopy (SEM), Energy Dispersive Spectroscopy (EDS), X-ray Diffraction (XRD), Thermogravimetry Analysis (TGA) and Differential Scanning Calorimetry (DSC) tests were conducted. The formation of ettringite and gypsum crystals after the sulfate attack were detected. Both these products had caused crystallization pressure in the microstructure of mortars and deteriorated the mortars. Our results show that the addition of nano-TiO2 accelerated expansion, variation in mass, loss of surface microhardness and widened cracks in OPC and slag-blended mortars. Nano-TiO2 containing slag-blended mortars were more resistant to sulfate attack than nano-TiO2 containing OPC mortars. Because nano-TiO2 reduced the size of coarse pores, so it increased crystallization pressure due to the formation of ettringite and gypsum thus led to more damage under sulfate attack. PMID:29495616

Metal1 patterning study for random-logic applications with 193i, using calibrated OPC for litho and etch

NASA Astrophysics Data System (ADS)

Mailfert, Julien; Van de Kerkhove, Jeroen; De Bisschop, Peter; De Meyer, Kristin

2014-03-01

A Metal1-layer (M1) patterning study is conducted on 20nm node (N20) for random-logic applications. We quantified the printability performance on our test vehicle for N20, corresponding to Poly/M1 pitches of 90/64nm, and with a selected minimum M1 gap size of 70nm. The Metal1 layer is patterned with 193nm immersion lithography (193i) using Negative Tone Developer (NTD) resist, and a double-patterning Litho-Etch-Litho-Etch (LELE) process. Our study is based on Logic test blocks that we OPCed with a combination of calibrated models for litho and for etch. We report the Overlapping Process Window (OPW), based on a selection of test structures measured after-etch. We find that most of the OPW limiting structures are EOL (End-of-Line) configurations. Further analysis of these individual OPW limiters will reveal that they belong to different types, such as Resist 3D (R3D) and Mask 3D (M3D) sensitive structures, limiters related to OPC (Optical Proximity Corrections) options such as assist placement, or the choice of CD metrics and tolerances for calculation of the process windows itself. To guide this investigation, we will consider a `reference OPC' case to be compared with other solutions. In addition, rigorous simulations and OPC verifications will complete the after-etch measurements to help us to validate our experimental findings.

Development of the Use of Alternative Cements for the Treatment of Intermediate Level Waste

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

Hayes, M.; Godfrey, I.H.

2007-07-01

This paper describes initial development studies undertaken to investigate the potential use of alternative, non ordinary Portland cement (OPC) based encapsulation matrices to treat historic legacy wastes within the UK's Intermediate Level Waste (ILW) inventory. Currently these wastes are encapsulated in composite OPC cement systems based on high replacement with blast furnace slag of pulverised fuel ash. However, the high alkalinity of these cements can lead to high corrosion rates with reactive metals found in some wastes releasing hydrogen and forming expansive corrosion products. This paper therefore details preliminary results from studies on two commercial products, calcium sulfo-aluminate (CSA) andmore » magnesium phosphate (MP) cement which react with a different hydration chemistry, and which may allow wastes containing these metals to be encapsulated with lower reactivity. The results indicate that grouts can be formulated from both cements over a range of water contents and reactant ratios that have significantly improved fluidity in comparison to typical OPC cements. All designed mixes set in 24 hours with zero bleed and the pH values in the plastic state were in the range 10-11 for CSA and 5-7 for MP cements. In addition, a marked reduction in aluminium corrosion rate has been observed in both types of cements compared to a composite OPC system. These results therefore provide encouragement that both cement types can provide a possible alternative to OPC in the immobilisation of reactive wastes, however further investigation is needed. (authors)« less

Culture conditions tailored to the cell of origin are critical for maintaining native properties and tumorigenicity of glioma cells

PubMed Central

Ledur, Pítia F.; He, Hua; Harris, Alexandra R.; Minussi, Darlan C.; Zhou, Hai-Yan; Shaffrey, Mark E.; Asthagiri, Ashok; Lopes, Maria Beatriz S.; Schiff, David; Lu, Yi-Cheng; Mandell, James W.; Lenz, Guido; Zong, Hui

2016-01-01

Background Cell culture plays a pivotal role in cancer research. However, culture-induced changes in biological properties of tumor cells profoundly affect research reproducibility and translational potential. Establishing culture conditions tailored to the cancer cell of origin could resolve this problem. For glioma research, it has been previously shown that replacing serum with defined growth factors for neural stem cells (NSCs) greatly improved the retention of gene expression profile and tumorigenicity. However, among all molecular subtypes of glioma, our laboratory and others have previously shown that the oligodendrocyte precursor cell (OPC) rather than the NSC serves as the cell of origin for the proneural subtype, raising questions regarding the suitability of NSC-tailored media for culturing proneural glioma cells. Methods OPC-originated mouse glioma cells were cultured in conditions for normal OPCs or NSCs, respectively, for multiple passages. Gene expression profiles, morphologies, tumorigenicity, and drug responsiveness of cultured cells were examined in comparison with freshly isolated tumor cells. Results OPC media-cultured glioma cells maintained tumorigenicity, gene expression profiles, and morphologies similar to freshly isolated tumor cells. In contrast, NSC-media cultured glioma cells gradually lost their OPC features and most tumor-initiating ability and acquired heightened sensitivity to temozolomide. Conclusions To improve experimental reproducibility and translational potential of glioma research, it is important to identify the cell of origin, and subsequently apply this knowledge to establish culture conditions that allow the retention of native properties of tumor cells. PMID:27106408

Cdk5 phosphorylation of WAVE2 regulates oligodendrocyte precursor cell migration through nonreceptor tyrosine kinase Fyn.

PubMed

Miyamoto, Yuki; Yamauchi, Junji; Tanoue, Akito

2008-08-13

Myelin formation of the CNS is a complex and dynamic process. Before the onset of myelination, oligodendrocytes (OLs), the myelin-forming glia of the CNS, proliferate and migrate along axons. Little is known about the molecular mechanisms underlying the early myelination processes. Here, we show that platelet-derived growth factor (PDGF), the crucial physiological ligand in early OL development, controls the migration of oligodendrocyte precursor cells (OPCs) through cyclin-dependent kinase 5 (Cdk5). PDGF stimulates Cdk5 activity in a time-dependent manner, whereas suppression of Cdk5 by the specific inhibitor roscovitine or by the retrovirus encoding short-hairpin RNA for Cdk5 impairs PDGF-dependent OPC migration. The activation of Cdk5 by PDGF is mediated by the phosphorylation of the nonreceptor tyrosine kinase, Fyn, whose inhibition reduces PDGF-dependent OPC migration. Furthermore, Cdk5 regulates PDGF-dependent OPC migration through the direct phosphorylation of WASP (Wiskott-Aldrich syndrome protein)-family verprolin-homologous protein 2 (WAVE2). Cdk5 phosphorylates WAVE2 at Ser-137 in vitro. Infection of the WAVE2 construct harboring the Ser-137-to-Ala reduces PDGF-dependent migration. Together, PDGF regulates OPC migration through an as-yet-unidentified signaling cascade coupling Fyn kinase to Cdk5 phosphorylation of WAVE2. These results provide new insights into both the role of Cdk5 in glial cells and the molecular mechanisms controlling the early developmental stage of OLs.

Survival and human papillomavirus in oropharynx cancer in TAX 324: a subset analysis from an international phase III trial

PubMed Central

Posner, M. R.; Lorch, J. H.; Goloubeva, O.; Tan, M.; Schumaker, L. M.; Sarlis, N. J.; Haddad, R. I.; Cullen, K. J.

2011-01-01

Background: The association between human papillomavirus (HPV) and overall survival (OS) in oropharynx cancer (OPC) was retrospectively examined in TAX 324, a phase III trial of sequential therapy for locally advanced head and neck cancer. Methods: Accrual for TAX 324 was completed in 2003 and data updated through 2008. Pretherapy tumor biopsies were studied by PCR for human papillomavirus type 16 and linked to OS, progression-free survival (PFS) and demographics. Results: Of 264 patients with OPC, 111 (42%) had evaluable biopsies; 56 (50%) were HPV+ and 55 (50%) were HPV−. HPV+ patients were significantly younger (54 versus 58 years, P = 0.02), had T1/T2 primary cancers (49% versus 20%, P = 0.001), and had a performance status of zero (77% versus 49%, P = 0.003). OS and PFS were better for HPV+ patients (OS, hazard ratio = 0.20, P < 0.0001). Local–regional failure was less in HPV+ patients (13% versus 42%, P = 0.0006); at 5 years, 82% of HPV+ patients were alive compared with 35% of HPV− patients (P < 0.0001). Conclusions: HPV+ OPC has a different biology compared with HPV− OPC; 5-year OS, PFS, and local–regional control are unprecedented. These results support the possibility of selectively reducing therapy and long-term morbidity in HPV+ OPC while preserving survival and approaching HPV− disease with more aggressive treatment. PMID:21317223

HPV-relatedness definitions for classifying HPV-related oropharyngeal cancer patient do impact on TNM classification and patients' survival.

PubMed

Taberna, Miren; Mena, Marisa; Tous, Sara; Pavón, Miquel Angel; Oliva, Marc; León, Xavier; Garcia, Jacinto; Guix, Marta; Hijano, Rafael; Bonfill, Teresa; Aguilà, Antón; Alemany, Laia; Mesía, Ricard

2018-01-01

Given the different nature and better outcomes of oropharyngeal carcinoma (OPC) associated with human papillomavirus (HPV) infection, a novel clinical stage classification for HPV-related OPC has been accepted for the 8th edition AJCC TNM (ICON-S model). However, it is still unclear the HPV-relatedness definition with best diagnostic accuracy and prognostic value. The aim of this study was to compare different staging system models proposed for HPV-related OPC patients: 7th edition AJCC TNM, RPA stage with non-anatomic factors (Princess Margaret), RPA with N categories for nasopharyngeal cancer (MD-Anderson) and AHR-new (ICON-S), according to different HPV-relatedness definitions: HPV-DNA detection plus an additional positive marker (p16INK4a or HPV-mRNA), p16INK4a positivity alone or the combination of HPV-DNA/p16INK4a positivity as diagnostic tests. A total of 788 consecutive OPC cases diagnosed from 1991 to 2013 were considered eligible for the analysis. Of these samples, 66 (8.4%) were positive for HPV-DNA and (p16INK4a or HPV-mRNA), 83 (10.5%) were p16INK4a positive and 58 (7.4%) were double positive for HPV-DNA/p16INK4a. ICON-S model was the staging system, which performed better in our series when using at least two biomarkers to define HPV-causality. When the same analysis was performed considering only p16INK4a-positivity, RPA stage with non-anatomic factors (Princess Margaret) has the best classification based on AIC criteria. HPV-relatedness definition for classifying HPV-related OPC patient do impact on TNM classification and patients' survival. Further studies assessing HPV-relatedness definitions are warranted to better classify HPV-related OPC patients in the era of de-escalation clinical trials.

Human Papillomavirus and Overall Survival After Progression of Oropharyngeal Squamous Cell Carcinoma

PubMed Central

Fakhry, Carole; Zhang, Qiang; Nguyen-Tan, Phuc Felix; Rosenthal, David; El-Naggar, Adel; Garden, Adam S.; Soulieres, Denis; Trotti, Andy; Avizonis, Vilija; Ridge, John Andrew; Harris, Jonathan; Le, Quynh-Thu; Gillison, Maura

2014-01-01

Purpose Risk of cancer progression is reduced for patients with human papillomavirus (HPV) –positive oropharynx cancer (OPC) relative to HPV-negative OPC, but it is unknown whether risk of death after progression is similarly reduced. Patients and Methods Patients with stage III-IV OPC enrolled onto Radiation Therapy Oncology Group trials 0129 or RTOG 0522 who had known tumor p16 status plus local, regional, and/or distant progression after receiving platinum-based chemoradiotherapy were eligible for a retrospective analysis of the association between tumor p16 status and overall survival (OS) after disease progression. Rates were estimated by Kaplan-Meier method and compared by log-rank; hazard ratios (HRs) were estimated by Cox models. Tests and models were stratified by treatment protocol. Results A total of 181 patients with p16-positive (n = 105) or p16-negative (n = 76) OPC were included in the analysis. Patterns of failure and median time to progression (8.2 v 7.3 months; P = .67) were similar for patients with p16-positive and p16-negative tumors. After a median follow-up period of 4.0 years after disease progression, patients with p16-positive OPC had significantly improved survival rates compared with p16-negative patients (2-year OS, 54.6% v 27.6%; median, 2.6 v 0.8 years; P < .001). p16-positive tumor status (HR, 0.48; 95% CI, 0.31 to 0.74) and receipt of salvage surgery (HR, 0.48; 95% CI; 0.27 to 0.84) reduced risk of death after disease progression whereas distant versus locoregional progression (HR, 1.99; 95% CI, 1.28 to 3.09) increased risk, after adjustment for tumor stage and cigarette pack-years at enrollment. Conclusion Tumor HPV status is a strong and independent predictor of OS after disease progression and should be a stratification factor for clinical trials for patients with recurrent or metastatic OPC. PMID:24958820

Dosimetric advantages of intensity-modulated proton therapy for oropharyngeal cancer compared with intensity-modulated radiation: A case-matched control analysis

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

Holliday, Emma B.; Kocak-Uzel, Esengul; Department of Radiation Therapy, Beykent University, Istanbul

A potential advantage of intensity-modulated proton therapy (IMPT) over intensity-modulated (photon) radiation therapy (IMRT) in the treatment of oropharyngeal carcinoma (OPC) is lower radiation dose to several critical structures involved in the development of nausea and vomiting, mucositis, and dysphagia. The purpose of this study was to quantify doses to critical structures for patients with OPC treated with IMPT and compare those with doses on IMRT plans generated for the same patients and with a matched cohort of patients actually treated with IMRT. In this study, 25 patients newly diagnosed with OPC were treated with IMPT between 2011 and 2012.more » Comparison IMRT plans were generated for these patients and for additional IMRT-treated controls extracted from a database of patients with OPC treated between 2000 and 2009. Cases were matched based on the following criteria, in order: unilateral vs bilateral therapy, tonsil vs base of tongue primary, T-category, N-category, concurrent chemotherapy, induction chemotherapy, smoking status, sex, and age. Results showed that the mean doses to the anterior and posterior oral cavity, hard palate, larynx, mandible, and esophagus were significantly lower with IMPT than with IMRT comparison plans generated for the same cohort, as were doses to several central nervous system structures involved in the nausea and vomiting response. Similar differences were found when comparing dose to organs at risks (OARs) between the IMPT cohort and the case-matched IMRT cohort. In conclusion, these findings suggest that patients with OPC treated with IMPT may experience fewer and less severe side effects during therapy. This may be the result of decreased beam path toxicities with IMPT due to lower doses to several dysphagia, odynophagia, and nausea and vomiting–associated OARs. Further study is needed to evaluate differences in long-term disease control and chronic toxicity between patients with OPC treated with IMPT in comparison to those treated with IMRT.« less

Perineurial Glial Plasticity and the Role of TGF-β in the Development of the Blood-Nerve Barrier.

PubMed

Morris, Angela D; Lewis, Gwendolyn M; Kucenas, Sarah

2017-05-03

Precisely orchestrated interactions between spinal motor axons and their ensheathing glia are vital for forming and maintaining functional spinal motor nerves. Following perturbations to peripheral myelinating glial cells, centrally derived oligodendrocyte progenitor cells (OPCs) ectopically exit the spinal cord and myelinate peripheral nerves in myelin with CNS characteristics. However, whether remaining peripheral ensheathing glia, such as perineurial glia, properly encase the motor nerve despite this change in glial cell and myelin composition, remains unknown. Using zebrafish mutants in which OPCs migrate out of the spinal cord and myelinate peripheral motor axons, we assayed perineurial glial development, maturation, and response to injury. Surprisingly, in the presence of OPCs, perineurial glia exited the CNS normally. However, aspects of their development, response to injury, and function were altered compared with wildtype larvae. In an effort to better understand the plasticity of perineurial glia in response to myelin perturbations, we identified transforming growth factor-β1 as a partial mediator of perineurial glial development. Together, these results demonstrate the incredible plasticity of perineurial glia in the presence of myelin perturbations. SIGNIFICANCE STATEMENT Peripheral neuropathies can result from damage or dysregulation of the insulating myelin sheath surrounding spinal motor axons, causing pain, inefficient nerve conduction, and the ectopic migration of oligodendrocyte progenitor cells (OPCs), the resident myelinating glial cell of the CNS, into the periphery. How perineurial glia, the ensheathing cells that form the protective blood-nerve barrier, are impacted by this myelin composition change is unknown. Here, we report that certain aspects of perineurial glial development and injury responses are mostly unaffected in the presence of ectopic OPCs. However, perineurial glial function is disrupted along nerves containing centrally derived myelin, demonstrating that, although perineurial glial cells display plasticity despite myelin perturbations, the blood-nerve barrier is compromised in the presence of ectopic OPCs. Copyright © 2017 the authors 0270-6474/17/374790-18$15.00/0.

HPV-relatedness definitions for classifying HPV-related oropharyngeal cancer patient do impact on TNM classification and patients’ survival

PubMed Central

Mena, Marisa; Tous, Sara; Pavón, Miquel Angel; Oliva, Marc; León, Xavier; Garcia, Jacinto; Guix, Marta; Hijano, Rafael; Bonfill, Teresa; Aguilà, Antón; Alemany, Laia; Mesía, Ricard

2018-01-01

Background Given the different nature and better outcomes of oropharyngeal carcinoma (OPC) associated with human papillomavirus (HPV) infection, a novel clinical stage classification for HPV-related OPC has been accepted for the 8th edition AJCC TNM (ICON-S model). However, it is still unclear the HPV-relatedness definition with best diagnostic accuracy and prognostic value. Material and methods The aim of this study was to compare different staging system models proposed for HPV-related OPC patients: 7th edition AJCC TNM, RPA stage with non-anatomic factors (Princess Margaret), RPA with N categories for nasopharyngeal cancer (MD-Anderson) and AHR-new (ICON-S), according to different HPV-relatedness definitions: HPV-DNA detection plus an additional positive marker (p16INK4a or HPV-mRNA), p16INK4a positivity alone or the combination of HPV-DNA/p16INK4a positivity as diagnostic tests. Results A total of 788 consecutive OPC cases diagnosed from 1991 to 2013 were considered eligible for the analysis. Of these samples, 66 (8.4%) were positive for HPV-DNA and (p16INK4a or HPV-mRNA), 83 (10.5%) were p16INK4a positive and 58 (7.4%) were double positive for HPV-DNA/p16INK4a. ICON-S model was the staging system, which performed better in our series when using at least two biomarkers to define HPV-causality. When the same analysis was performed considering only p16INK4a-positivity, RPA stage with non-anatomic factors (Princess Margaret) has the best classification based on AIC criteria. Conclusion HPV-relatedness definition for classifying HPV-related OPC patient do impact on TNM classification and patients’ survival. Further studies assessing HPV-relatedness definitions are warranted to better classify HPV-related OPC patients in the era of de-escalation clinical trials. PMID:29664911

OPC-67683, a Nitro-Dihydro-Imidazooxazole Derivative with Promising Action against Tuberculosis In Vitro and In Mice

PubMed Central

Matsumoto, Makoto; Hashizume, Hiroyuki; Tomishige, Tatsuo; Kawasaki, Masanori; Tsubouchi, Hidetsugu; Sasaki, Hirofumi; Shimokawa, Yoshihiko; Komatsu, Makoto

2006-01-01

Background Tuberculosis (TB) is still a leading cause of death worldwide. Almost a third of the world's population is infected with TB bacilli, and each year approximately 8 million people develop active TB and 2 million die as a result. Today's TB treatment, which dates back to the 1970s, is long and burdensome, requiring at least 6 mo of multidrug chemotherapy. The situation is further compounded by the emergence of multidrug-resistant TB (MDR-TB) and by the infection's lethal synergy with HIV/AIDS. Global health and philanthropic organizations are now pleading for new drug interventions that can address these unmet needs in TB treatment. Methods and Findings Here we report OPC-67683, a nitro-dihydro-imidazooxazole derivative that was screened to help combat the unmet needs in TB treatment. The compound is a mycolic acid biosynthesis inhibitor found to be free of mutagenicity and to possess highly potent activity against TB, including MDR-TB, as shown by its exceptionally low minimum inhibitory concentration (MIC) range of 0.006–0.024 μg/ml in vitro and highly effective therapeutic activity at low doses in vivo. Additionally, the results of the post-antibiotic effect of OPC-67683 on intracellular Mycobacterium tuberculosis showed the agent to be highly and dose-dependently active also against intracellular M. tuberculosis H37Rv after a 4-h pulsed exposure, and this activity at a concentration of 0.1 μg/ml was similar to that of the first-line drug rifampicin (RFP) at a concentration of 3 μg/ml. The combination of OPC-67683 with RFP and pyrazinamide (PZA) exhibited a remarkably quicker eradication (by at least 2 mo) of viable TB bacilli in the lung in comparison with the standard regimen consisting of RFP, isoniazid (INH), ethambutol (EB), and PZA. Furthermore, OPC-67683 was not affected by nor did it affect the activity of liver microsome enzymes, suggesting the possibility for OPC-67683 to be used in combination with drugs, including anti-retrovirals, that induce or are metabolized by cytochrome P450 enzymes. Conclusions We concluded that based on these properties OPC-67683 has the potential to be used as a TB drug to help combat the unmet needs in TB treatment. PMID:17132069

Oligodendrocyte precursor cell transplantation promotes functional recovery following contusive spinal cord injury in rats and is associated with altered microRNA expression

PubMed Central

Yang, Jin; Xiong, Liu-Lin; Wang, You-Cui; He, Xiang; Jiang, Ling; Fu, Song-Jun; Han, Xue-Fei; Liu, Jia; Wang, Ting-Hua

2018-01-01

It has been reported that oligodendrocyte precursor cells (OPCs) may be used to treat contusive spinal cord injury (SCC), and may alter microRNA (miRNA/miR) expression following SCC in rats. However, the association between miRNA expression and the treatment of rats with SCC with OPC transplantation remain unclear. The present study transplanted OPCs into the spinal cord of rats with SCC and subsequently used the Basso, Beattie and Bresnahan (BBB) score to assess the functional recovery and pain scores. An miRNA assay was performed to detect differentially expressed miRNAs in the spinal cord of SCC rats transplanted with OPCs, compared with SCC rats transplanted with medium. Quantitative polymerase chain reaction was used to verify significantly altered miRNA expression levels. The results demonstrated that OPC transplantation was able to improve motor recovery and relieve mechanical allodynia in rats with SCC. In addition, through a miRNA assay, 45 differentially expressed miRNAs (40 upregulated miRNAs and 5 downregulated miRNAs) were detected in the spinal cord of rats in the OPC group compared with in the Medium group. Differentially expressed miRNAs were identified according to the following criteria: Fold change >2 and P<0.05. Furthermore, quantitative polymerase chain reaction was used to verify the most highly upregulated (miR-375-3p and miR-1-3p) and downregulated (miR-363-3p, miR-449a-5p and miR-3074) spinal cord miRNAs that were identified in the miRNA assay. In addition, a bioinformatics analysis of these miRNAs indicated that miR-375 and miR-1 may act primarily to inhibit cell proliferation and apoptosis via transcriptional and translational regulation, whereas miR-363, miR-449a and miR-3074 may act primarily to inhibit cell proliferation and neuronal differentiation through transcriptional regulation. These results suggested that OPC transplantation may promote functional recovery of rats with SCC, which may be associated with the expression of various miRNAs in the spinal cord, including miR-375-3p, miR-1-3p, miR-363-3p, miR-449a-5p and miR-3074. PMID:29115639

OPC-67683, a nitro-dihydro-imidazooxazole derivative with promising action against tuberculosis in vitro and in mice.

PubMed

Matsumoto, Makoto; Hashizume, Hiroyuki; Tomishige, Tatsuo; Kawasaki, Masanori; Tsubouchi, Hidetsugu; Sasaki, Hirofumi; Shimokawa, Yoshihiko; Komatsu, Makoto

2006-11-01

Tuberculosis (TB) is still a leading cause of death worldwide. Almost a third of the world's population is infected with TB bacilli, and each year approximately 8 million people develop active TB and 2 million die as a result. Today's TB treatment, which dates back to the 1970s, is long and burdensome, requiring at least 6 mo of multidrug chemotherapy. The situation is further compounded by the emergence of multidrug-resistant TB (MDR-TB) and by the infection's lethal synergy with HIV/AIDS. Global health and philanthropic organizations are now pleading for new drug interventions that can address these unmet needs in TB treatment. Here we report OPC-67683, a nitro-dihydro-imidazooxazole derivative that was screened to help combat the unmet needs in TB treatment. The compound is a mycolic acid biosynthesis inhibitor found to be free of mutagenicity and to possess highly potent activity against TB, including MDR-TB, as shown by its exceptionally low minimum inhibitory concentration (MIC) range of 0.006-0.024 microg/ml in vitro and highly effective therapeutic activity at low doses in vivo. Additionally, the results of the post-antibiotic effect of OPC-67683 on intracellular Mycobacterium tuberculosis showed the agent to be highly and dose-dependently active also against intracellular M. tuberculosis H37Rv after a 4-h pulsed exposure, and this activity at a concentration of 0.1 microg/ml was similar to that of the first-line drug rifampicin (RFP) at a concentration of 3 microg/ml. The combination of OPC-67683 with RFP and pyrazinamide (PZA) exhibited a remarkably quicker eradication (by at least 2 mo) of viable TB bacilli in the lung in comparison with the standard regimen consisting of RFP, isoniazid (INH), ethambutol (EB), and PZA. Furthermore, OPC-67683 was not affected by nor did it affect the activity of liver microsome enzymes, suggesting the possibility for OPC-67683 to be used in combination with drugs, including anti-retrovirals, that induce or are metabolized by cytochrome P450 enzymes. We concluded that based on these properties OPC-67683 has the potential to be used as a TB drug to help combat the unmet needs in TB treatment.

RSDL decontamination of human skin contaminated with the nerve agent VX.

PubMed

Thors, L; Lindberg, S; Johansson, S; Koch, B; Koch, M; Hägglund, L; Bucht, A

2017-03-05

Dermal exposure to low volatile organophosphorus compounds (OPC) may lead to penetration through the skin and uptake in the blood circulation. Skin decontamination of toxic OPCs, such as pesticides and chemical warfare nerve agents, might therefore be crucial for mitigating the systemic toxicity following dermal exposure. Reactive skin decontamination lotion (RSDL) has been shown to reduce toxic effects in animals dermally exposed to the nerve agent VX. In the present study, an in vitro flow-through diffusion cell was utilized to evaluate the efficacy of RSDL for decontamination of VX exposed to human epidermis. In particular, the impact of timing in the initiation of decontamination and agent dilution in water was studied. The impact of the lipophilic properties of VX in the RSDL decontamination was additionally addressed by comparing chemical degradation in RSDL and decontamination efficacy between the VX and the hydrophilic OPC triethyl phosphonoacetate (TEPA). The epidermal membrane was exposed to 20, 75 or 90% OPC diluted in deionized water and the decontamination was initiated 5, 10, 30, 60 or 120min post-exposure. Early decontamination of VX with RSDL, initiated 5-10min after skin exposure, was very effective. Delayed decontamination initiated 30-60min post-exposure was less effective but still the amount of penetrated agent was significantly reduced, while further delayed start of decontamination to 120min resulted in very low efficacy. Comparing RSDL decontamination of VX with that of TEPA showed that the decontamination efficacy at high agent concentrations was higher for VX. The degradation mechanism of VX and TEPA during decontamination was dissected by 31 P NMR spectroscopy of the OPCs following reactions with RSDL and its three nucleophile components. The degradation rate was clearly associated with the high pH of the specific solution investigated; i.e. increased pH resulted in a more rapid degradation. In addition, the solubility of the OPC in RSDL also influenced the degradation rate since the degradation of VX was significantly faster when the NMR analysis was performed in the organic solvent acetonitrile compared to water. In conclusion, we have applied the in vitro flow-through diffusion cell for evaluation of skin decontamination procedures of human epidermis exposed to OPCs. It was demonstrated that early decontamination is crucial for efficient mitigation of epidermal penetration of VX and that almost complete removal of the nerve agent from the skin surface is possible. Our data also indicate that the pH of RSDL together with the solubility of OPC in RSDL are of primary importance for the decontamination efficacy. Copyright © 2017 Elsevier B.V. All rights reserved.

Compact 2D OPC modeling of a metal oxide EUV resist for a 7nm node BEOL layer

NASA Astrophysics Data System (ADS)

Lyons, Adam; Rio, David; Lee, Sook; Wallow, Thomas; Delorme, Maxence; Fumar-Pici, Anita; Kocsis, Michael; de Schepper, Peter; Greer, Michael; Stowers, Jason K.; Gillijns, Werner; De Simone, Danilo; Bekaert, Joost

2017-03-01

Inpria has developed a directly patternable metal oxide hard-mask as a high-resolution photoresist for EUV lithography1. In this contribution, we describe a Tachyon 2D OPC full-chip model for an Inpria resist as applied to an N7 BEOL block mask application.

Linking Laboratory Experiences to the Real World: The Extraction of Octylphenoxyacetic Acid from Water

ERIC Educational Resources Information Center

Loyo-Rosales, Jorge E.; Torrents, Alba; Rosales-Rivera, Georgina C.; Rice, Clifford C.

2006-01-01

Several chemical concepts to the extraction of a water pollutant OPC (octylphenoxyacetic acid) is presented. As an introduction to the laboratory experiment, a discussion on endocrine disrupters is conducted to familiarize the student with the background of the experiment and to explain the need for the extraction and quantitation of the OPC which…

JLIFE: THE JEFFERSON LAB INTERACTIVE FRONT END FOR THE OPTICAL PROPAGATION CODE

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

Watson, Anne M.; Shinn, Michelle D.

2013-08-01

We present details on a graphical interface for the open source software program Optical Propagation Code, or OPC. This interface, written in Java, allows a user with no knowledge of OPC to create an optical system, with lenses, mirrors, apertures, etc. and the appropriate drifts between them. The Java code creates the appropriate Perl script that serves as the input for OPC. The mode profile is then output at each optical element. The display can be either an intensity profile along the x axis, or as an isometric 3D plot which can be tilted and rotated. These profiles can bemore » saved. Examples of the input and output will be presented.« less

Research and development on the construction of 2D light-driven droplet manipulation platform based on light modulation of TiOPc impedance

NASA Astrophysics Data System (ADS)

Chen, Yi-Chen; Chen, Ho-Tsung; Lee, Chih-Kung

2014-03-01

The newly developed configuration included adopting the photosensitive electrode material TiOPc (titanyl phthalocyanine) to create electrowetting on dielectric (EWOD) mechanism. With this new development, the electric potential on the surface of TiOPc could be on-line real-time changed and defined spatially by illuminating spatially distributed light beam patterns. We tried to control the polarized droplets in our EWOD devices by using different light intensities. The experimental results clearly demonstrated that the relationship of light intensity and electrowetting phenomena can provide us with a feasible platform to construct optofluidic chip with potential autonomous manipulation of samples for point-of-care home medical detection applications.

Synthesis of actual knowledge on machine-tool monitoring methods and equipment

NASA Astrophysics Data System (ADS)

Tanguy, J. C.

1988-06-01

Problems connected with the automatic supervision of production were studied. Many different automatic control devices are now able to identify defects in the tools, but the solutions proposed to detect optimal limits in the utilization of a tool are not satisfactory.

The control system of the 12-m medium-size telescope prototype: a test-ground for the CTA array control

NASA Astrophysics Data System (ADS)

Oya, I.; Anguner, E. A.; Behera, B.; Birsin, E.; Fuessling, M.; Lindemann, R.; Melkumyan, D.; Schlenstedt, S.; Schmidt, T.; Schwanke, U.; Sternberger, R.; Wegner, P.; Wiesand, S.

2014-07-01

The Cherenkov Telescope Array (CTA) will be the next generation ground-based very-high energy -ray observatory. CTA will consist of two arrays: one in the Northern hemisphere composed of about 20 telescopes, and the other one in the Southern hemisphere composed of about 100 telescopes, both arrays containing telescopes of different sizes and types and in addition numerous auxiliary devices. In order to provide a test-ground for the CTA array control, the steering software of the 12-m medium size telescope (MST) prototype deployed in Berlin has been implemented using the tools and design concepts under consideration to be used for the control of the CTA array. The prototype control system is implemented based on the Atacama Large Millimeter/submillimeter Array (ALMA) Common Software (ACS) control middleware, with components implemented in Java, C++ and Python. The interfacing to the hardware is standardized via the Object Linking and Embedding for Process Control Unified Architecture (OPC UA). In order to access the OPC UA servers from the ACS framework in a common way, a library has been developed that allows to tie the OPC UA server nodes, methods and events to the equivalents in ACS components. The front-end of the archive system is able to identify the deployed components and to perform the sampling of the monitoring points of each component following time and value change triggers according to the selected configurations. The back-end of the archive system of the prototype is composed by two different databases: MySQL and MongoDB. MySQL has been selected as storage of the system configurations, while MongoDB is used to have an efficient storage of device monitoring data, CCD images, logging and alarm information. In this contribution, the details and conclusions on the implementation of the control software of the MST prototype are presented.

The application of phase grating to CLM technology for the sub-65nm node optical lithography

NASA Astrophysics Data System (ADS)

Yoon, Gi-Sung; Kim, Sung-Hyuck; Park, Ji-Soong; Choi, Sun-Young; Jeon, Chan-Uk; Shin, In-Kyun; Choi, Sung-Woon; Han, Woo-Sung

2005-06-01

As a promising technology for sub-65nm node optical lithography, CLM(Chrome-Less Mask) technology among RETs(Resolution Enhancement Techniques) for low k1 has been researched worldwide in recent years. CLM has several advantages, such as relatively simple manufacturing process and competitive performance compared to phase-edge PSM's. For the low-k1 lithography, we have researched CLM technique as a good solution especially for sub-65nm node. As a step for developing the sub-65nm node optical lithography, we have applied CLM technology in 80nm-node lithography with mesa and trench method. From the analysis of the CLM technology in the 80nm lithography, we found that there is the optimal shutter size for best performance in the technique, the increment of wafer ADI CD varied with pattern's pitch, and a limitation in patterning various shapes and size by OPC dead-zone - OPC dead-zone in CLM technique is the specific region of shutter size that dose not make the wafer CD increased more than a specific size. And also small patterns are easily broken, while fabricating the CLM mask in mesa method. Generally, trench method has better optical performance than mesa. These issues have so far restricted the application of CLM technology to a small field. We approached these issues with 3-D topographic simulation tool and found that the issues could be overcome by applying phase grating in trench-type CLM. With the simulation data, we made some test masks which had many kinds of patterns with many different conditions and analyzed their performance through AIMS fab 193 and exposure on wafer. Finally, we have developed the CLM technology which is free of OPC dead-zone and pattern broken in fabrication process. Therefore, we can apply the CLM technique into sub-65nm node optical lithography including logic devices.

To do it or to let an automatic tool do it? The priority of control over effort.

PubMed

Osiurak, François; Wagner, Clara; Djerbi, Sara; Navarro, Jordan

2013-01-01

The aim of the present study is to provide experimental data relevant to the issue of what leads humans to use automatic tools. Two answers can be offered. The first is that humans strive to minimize physical and/or cognitive effort (principle of least effort). The second is that humans tend to keep their perceived control over the environment (principle of more control). These two factors certainly play a role, but the question raised here is to what do people give priority in situations wherein both manual and automatic actions take the same time - minimizing effort or keeping perceived control? To answer that question, we built four experiments in which participants were confronted with a recurring choice between performing a task manually (physical effort) or in a semi-automatic way (cognitive effort) versus using an automatic tool that completes the task for them (no effort). In this latter condition, participants were required to follow the progression of the automatic tool step by step. Our results showed that participants favored the manual or semi-automatic condition over the automatic condition. However, when they were offered the opportunity to perform recreational tasks in parallel, the shift toward manual condition disappeared. The findings give support to the idea that people give priority to keeping control over minimizing effort.

Erythropoietin promotes oligodendrogenesis and myelin repair following lysolecithin-induced injury in spinal cord slice culture

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

Cho, Yun Kyung; Kim, Gunha; Park, Serah

2012-01-13

Highlights: Black-Right-Pointing-Pointer Lysolecithin-induced demyelination elevated EpoR expression in OPCs. Black-Right-Pointing-Pointer In association with elevated EpoR, EPO increased OPCs proliferation. Black-Right-Pointing-Pointer EPO enhanced the oligodendrogenesis via activation of JAK2 pathway. Black-Right-Pointing-Pointer EPO promoted myelin repair following lysolecithin-induced demyelination. -- Abstract: Here, we sought to delineate the effect of EPO on the remyelination processes using an in vitro model of demyelination. We report that lysolecithin-induced demyelination elevated EPO receptor (EpoR) expression in oligodendrocyte progenitor cells (OPCs), facilitating the beneficial effect of EPO on the formation of oligodendrocytes (oligodendrogenesis). In the absence of EPO, the resultant remyelination was insufficient, possibly due to amore » limiting number of oligodendrocytes rather than their progenitors, which proliferate in response to lysolecithin-induced injury. By EPO treatment, lysolecithin-induced proliferation of OPCs was accelerated and the number of myelinating oligodendrocytes and myelin recovery was increased. EPO also enhanced the differentiation of neural progenitor cells expressing EpoR at high level toward the oligodendrocyte-lineage cells through activation of cyclin E and Janus kinase 2 pathways. Induction of myelin-forming oligodendrocytes by high dose of EPO implies that EPO might be the key factor influencing the final differentiation of OPCs. Taken together, our data suggest that EPO treatment could be an effective way to enhance remyelination by promoting oligodendrogenesis in association with elevated EpoR expression in spinal cord slice culture after lysolecithin-induced demyelination.« less

A patient-centered approach to counseling patients with head and neck cancer undergoing human papillomavirus testing: a clinician's guide.

PubMed

Chu, Amy; Genden, Eric; Posner, Marshall; Sikora, Andrew

2013-01-01

The International Agency for Research on Cancer and the National Cancer Institute have acknowledged human papillomavirus (HPV)-16 as an independent risk factor for oropharyngeal cancer (OPC). HPV-positive oropharyngeal cancer (HPVOPC) is a sexually transmitted entity that is on the rise; within the next 10 years, the annual number of HPV-associated OPC cases is projected to exceed the annual number of cervical cancer cases in the United States. Recognition of HPV status in OPC has broad implications beyond the traditional oncological concerns of timely diagnosis, accurate staging, and appropriate treatment of cancer patients. The National Comprehensive Cancer Network recommends testing the tumor site for HPV-status during OPC management; it is likely this will become a standard component of care for patients with high-probability tumors of the oropharynx. As the practice of HPV testing becomes more common, it behooves providers to be able to adequately address the concerns of patients with HPVOPC. Although there are currently few relevant studies focusing on this population, existing literature on HPV-infected women and patients with cervical cancer strongly supports the concept that patients with HPVOPC need education to optimally address concerns such as self-blame, guilt, intimacy, and interpersonal relationships. When HPV testing is done, it should be accompanied by evidence-driven and patient-centered counseling to best minimize negative psychosocial outcomes and ensure optimum health promotion. Based on the current state of the literature, this article is intended to be a reference for physicians to effectively manage psychosocial outcomes when diagnosing patients with HPV-associated OPC.

Adverse impact of intermittent portal clamping on long-term postoperative outcomes in hepatocellular carcinoma.

PubMed

Hao, S; Chen, S; Yang, X; Wan, C

2017-01-01

Introduction To evaluate the impact of intermittent portal clamping (IPC) on long-term postoperative outcomes in patients with hepatocellular carcinoma (HCC). Methods Clinical records of 355 patients underwent curative liver resection for HCC in January 2007 to December 2010 were retrospectively reviewed. According to how portal clamping was performed, patients were grouped as: IPC, n=113; other portal clamping (OPC), n=190; and no portal clamping (NPC), n=52. Results Median recurrence-free survival (RFS) was statistically significantly shorter in the IPC (39.4 months) than OPC (47.3 months, p=0.010) and NPC groups (51.4 months, p=0.008). Median overall survival (OS) was also significantly shorter with IPC (46.3 months), versus 52.9 months with OPC (p=0.022) and 56.2 months with NPC (p=0.015). Kaplan-Meier survival analysis revealed that 5-year cumulative RFS was much lower in the IPC (42.5%) than OPC (50.9%, p=0.014) and NPC groups (49.6%, p=0.013). Five-year cumulative OS was also much lower in the IPC (44.9%) than OPC (58.0%, p=0.020) and NPC groups (57.7%, p=0.025). On univariate analysis, tumour grade, size and number, TNM stage, blood transfusion, vascular invasion and IPC were significantly inversely correlated with RFS and OS. On multivariate analysis, tumour size and number, blood transfusion, vascular invasion and IPC remained significant. Conclusions Our study suggests that IPC is an independent risk factor for poor long-term postoperative outcomes in patients with HCC.

Oral-resident natural Th17 cells and γδ T cells control opportunistic Candida albicans infections.

PubMed

Conti, Heather R; Peterson, Alanna C; Brane, Lucas; Huppler, Anna R; Hernández-Santos, Nydiaris; Whibley, Natasha; Garg, Abhishek V; Simpson-Abelson, Michelle R; Gibson, Gregory A; Mamo, Anna J; Osborne, Lisa C; Bishu, Shrinivas; Ghilardi, Nico; Siebenlist, Ulrich; Watkins, Simon C; Artis, David; McGeachy, Mandy J; Gaffen, Sarah L

2014-09-22

Oropharyngeal candidiasis (OPC) is an opportunistic fungal infection caused by Candida albicans. OPC is frequent in HIV/AIDS, implicating adaptive immunity. Mice are naive to Candida, yet IL-17 is induced within 24 h of infection, and susceptibility is strongly dependent on IL-17R signaling. We sought to identify the source of IL-17 during the early innate response to candidiasis. We show that innate responses to Candida require an intact TCR, as SCID, IL-7Rα(-/-), and Rag1(-/-) mice were susceptible to OPC, and blockade of TCR signaling by cyclosporine induced susceptibility. Using fate-tracking IL-17 reporter mice, we found that IL-17 is produced within 1-2 d by tongue-resident populations of γδ T cells and CD3(+)CD4(+)CD44(hi)TCRβ(+)CCR6(+) natural Th17 (nTh17) cells, but not by TCR-deficient innate lymphoid cells (ILCs) or NK cells. These cells function redundantly, as TCR-β(-/-) and TCR-δ(-/-) mice were both resistant to OPC. Whereas γδ T cells were previously shown to produce IL-17 during dermal candidiasis and are known to mediate host defense at mucosal surfaces, nTh17 cells are poorly understood. The oral nTh17 population expanded rapidly after OPC, exhibited high TCR-β clonal diversity, and was absent in Rag1(-/-), IL-7Rα(-/-), and germ-free mice. These findings indicate that nTh17 and γδ T cells, but not ILCs, are key mucosal sentinels that control oral pathogens. © 2014 Conti et al.

Alterations in plasma lipid profile patterns in head and neck cancer and oral precancerous conditions.

PubMed

Patel, P S; Shah, M H; Jha, F P; Raval, G N; Rawal, R M; Patel, M M; Patel, J B; Patel, D D

2004-01-01

The changes in lipid profile have long been associated with cancer because lipids play a key role in maintenance of cell integrity. The present study evaluated alterations in plasma lipid profile in untreated head and neck cancer patients as well as patients with oral precancerous conditions (OPC) and its association with habit of tobacco consumption. This hospital-based case control study included 184 head and neck cancer patients, 153 patients with OPC and 52 controls. Plasma lipids including: (i) Total cholesterol, (ii) LDL cholesterol (LDLC), (iii) HDL cholesterol (HDLC) (iv) VLDL cholesterol (VLDLC) and (v) triglycerides were analysed by spectrophotometric kits. Student's t-test was performed to compare mean values of the parameters. A significant decrease in plasma total cholesterol and HDLC was observed in cancer patients (P=0.008 and P=0.000 respectively) as well as in patients with OPC (P=0.014 and P=0.000, respectively) as compared to the controls. The plasma VLDL and triglycerides levels were significantly lower in cancer patients as compared to the patients with OPC (P=0.04) and controls (P=0.059). The tobacco habituates showed lower plasma lipid levels than the non-habituates. Our data strengthen the evidence of an inverse relationship between plasma lipid levels and head and neck malignancies as well as OPC. The lower levels of plasma cholesterol and other lipid constituents in patients might be due to their increased utilization by neoplastic cells for new membrane biogenesis. The findings strongly warrant an in-depth study of alterations in plasma lipid profile in head neck cancer patients.

Reactive astrocyte COX2-PGE2 production inhibits oligodendrocyte maturation in neonatal white matter injury.

PubMed

Shiow, Lawrence R; Favrais, Geraldine; Schirmer, Lucas; Schang, Anne-Laure; Cipriani, Sara; Andres, Christian; Wright, Jaclyn N; Nobuta, Hiroko; Fleiss, Bobbi; Gressens, Pierre; Rowitch, David H

2017-12-01

Inflammation is a major risk factor for neonatal white matter injury (NWMI), which is associated with later development of cerebral palsy. Although recent studies have demonstrated maturation arrest of oligodendrocyte progenitor cells (OPCs) in NWMI, the identity of inflammatory mediators with direct effects on OPCs has been unclear. Here, we investigated downstream effects of pro-inflammatory IL-1β to induce cyclooxygenase-2 (COX2) and prostaglandin E2 (PGE2) production in white matter. First, we assessed COX2 expression in human fetal brain and term neonatal brain affected by hypoxic-ischemic encephalopathy (HIE). In the developing human brain, COX2 was expressed in radial glia, microglia, and endothelial cells. In human term neonatal HIE cases with subcortical WMI, COX2 was strongly induced in reactive astrocytes with "A2" reactivity. Next, we show that OPCs express the EP1 receptor for PGE2, and PGE2 acts directly on OPCs to block maturation in vitro. Pharmacologic blockade with EP1-specific inhibitors (ONO-8711, SC-51089), or genetic deficiency of EP1 attenuated effects of PGE2. In an IL-1β-induced model of NWMI, astrocytes also exhibit "A2" reactivity and induce COX2. Furthermore, in vivo inhibition of COX2 with Nimesulide rescues hypomyelination and behavioral impairment. These findings suggest that neonatal white matter astrocytes can develop "A2" reactivity that contributes to OPC maturation arrest in NWMI through induction of COX2-PGE2 signaling, a pathway that can be targeted for neonatal neuroprotection. © 2017 Wiley Periodicals, Inc.

Gaseous mercury from curing concretes that contain fly ash: laboratory measurements

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

Danold W. Golightly; Ping Sun; Chin-Min Cheng

2005-08-01

Total gaseous mercury in headspace air was measured for enclosed concretes dry curing at 40 C for intervals of 2, 28, and 56 days. Release of mercury was confirmed for ordinary Portland cement concrete (OPC) and three concretes in which class F fly ash from coal-combustion substituted for a fraction of the cement: (a) 33% fly ash (FA33), (b) 55% fly ash (FA55), and (c) 33% fly ash plus 0.5% mercury-loaded powdered activated carbon (HgPAC). Mean rates of mercury release (0.10-0.43 ng/day per kg of concrete) over the standard first 28 days of curing followed the order OPC {lt} FA33more » {approximately} FA55 {lt} HgPAC. The mercury flux from exposed surfaces of these concretes ranged from 1.9 {+-} 0.5 to 8.1 {+-} 2.0 ng/m{sup 2}/h, values similar to the average flux for multiple natural substrates in Nevada, 4.2 {+-} 1.4 ng/m{sup 2}/h, recently published by others. Air sampling extending for 28 days beyond the initial 28-day maturation for OPC, FA55, and HgPAC suggested that the average Hg release rate by OPC is constant over 56 days and that mercury release rates for FA55 and HgPAC may ultimately diminish to levels exhibited by OPC concrete. The release of mercury from all samples was less than 0.1% of total mercury content over the initial curing period, implying that nearly all of the mercury was retained in the concrete. 20 refs., 3 figs., 3 tabs.« less

Mitigation of nonlinear fiber distortion using optical phase conjugation for mode-division multiplexed transmission

NASA Astrophysics Data System (ADS)

Zhang, Kai; Gao, Guanjun; Zhang, Jie; Fei, Aimei; Cvijetic, Milorad

2018-07-01

We have investigated and proposed the use of optical phase conjugation (OPC) technique to mitigate the impact of fiber nonlinearities in mode-division multiplexed transmission systems. Numerical simulations are performed for three wavelengths, each loaded with 200 Gb/s dual-polarization 16-level quadrature amplitude modulation (DP-16QAM) format, in weakly guided two-mode fiber. It is known that differential mode group delay (DMGD) in mode-division multiplexed (MDM) transmission systems could be beneficial for system performance of MDM system with MIMO compensation in place. On the other side, for MDM system with OPC in place, the presence of DMGD may limit the overall benefits since signal power evolution per spatial modes should be symmetrical at the system midpoint in order to realize an effective compensation of the nonlinear effects. Our simulation results show that in the reference case (in the absence of DMGD), the employment of OPC module would lead to an average Q-factor improvement of approximately 10 dB. At the same time, in the presence of DMGD, an average Q-factor improvement would be ∼2.8 dB for WDM case. In addition, due to asymmetrical signal power map, the penalties induced by a periodic amplification process cannot be ideally compensated by the midpoint insertion of OPC. However, by accounting the impacts of both DMGD and asymmetrical signal power map, the insertion of the OPC system will still lead to an average Q-factor improvement of ∼1 dB for WDM channel arrangement.

Densities and Diel Vertical Migration of Mysis relicta in Lake Superior: A Comparison of Optical Plankton Encounter and Net-based Approaches

EPA Science Inventory

In this study, we used data from an OPC, and LOPC, and vertical net tows to estimate densities and describe the day/night vertical distribution of Mysis at a series of stations distributed throughout Lake Superior, and to evaluate the efficacy of using (L)OPC for examining DVM of...

Liver X receptor β is essential for the differentiation of radial glial cells to oligodendrocytes in the dorsal cortex.

PubMed

Xu, P; Xu, H; Tang, X; Xu, L; Wang, Y; Guo, L; Yang, Z; Xing, Y; Wu, Y; Warner, M; Gustafsson, J-A; Fan, X

2014-08-01

Several psychiatric disorders are associated with aberrant white matter development, suggesting oligodendrocyte and myelin dysfunction in these diseases. There are indications that radial glial cells (RGCs) are involved in initiating myelination, and may contribute to the production of oligodendrocyte progenitor cells (OPCs) in the dorsal cortex. Liver X receptors (LXRs) are involved in maintaining normal myelin in the central nervous system (CNS), however, their function in oligodendrogenesis and myelination is not well understood. Here, we demonstrate that loss of LXRβ function leads to abnormality in locomotor activity and exploratory behavior, signs of anxiety and hypomyelination in the corpus callosum and optic nerve, providing in vivo evidence that LXRβ deletion delays both oligodendrocyte differentiation and maturation. Remarkably, along the germinal ventricular zone-subventricular zone and corpus callosum there is reduced OPC production from RGCs in LXRβ(-/-) mice. Conversely, in cultured RGC an LXR agonist led to increased differentiation into OPCs. Collectively, these results suggest that LXRβ, by driving RGCs to become OPCs in the dorsal cortex, is critical for white matter development and CNS myelination, and point to the involvement of LXRβ in psychiatric disorders.

Human papillomavirus in cervical cancer and oropharyngeal cancer: One cause, two diseases.

PubMed

Berman, Tara A; Schiller, John T

2017-06-15

Human papillomavirus (HPV) causes greater than 5% of cancers worldwide, including all cervical cancers and an alarmingly increasing proportion of oropharyngeal cancers (OPCs). Despite markedly reduced cervical cancer incidence in industrialized nations with organized screening programs, cervical cancer remains the second most common cause of death from cancer in women worldwide, as developing countries lack resources for universal, high-quality screening. In the United States, HPV-related OPC is only 1 of 5 cancers with a rising incidence since 1975 and now has taken over the cervix as the most common site of HPV-related cancer. Similar trends follow throughout North America and Europe. The need for early detection and prevention is paramount. Despite the common etiologic role of HPV in the development of cervical cancer and HPV-associated OPC, great disparity exists between incidence, screening modalities (or lack thereof), treatment, and prevention in these 2 very distinct cohorts. These differences in cervical cancer and HPV-associated OPC and their impact are discussed here. Cancer 2017;123:2219-2229. © 2017 American Cancer Society. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

IL-17 Receptor Signaling in Oral Epithelial Cells Is Critical for Protection against Oropharyngeal Candidiasis.

PubMed

Conti, Heather R; Bruno, Vincent M; Childs, Erin E; Daugherty, Sean; Hunter, Joseph P; Mengesha, Bemnet G; Saevig, Danielle L; Hendricks, Matthew R; Coleman, Bianca M; Brane, Lucas; Solis, Norma; Cruz, J Agustin; Verma, Akash H; Garg, Abhishek V; Hise, Amy G; Richardson, Jonathan P; Naglik, Julian R; Filler, Scott G; Kolls, Jay K; Sinha, Satrajit; Gaffen, Sarah L

2016-11-09

Signaling through the IL-17 receptor (IL-17R) is required to prevent oropharyngeal candidiasis (OPC) in mice and humans. However, the IL-17-responsive cell type(s) that mediate protection are unknown. Using radiation chimeras, we were able to rule out a requirement for IL-17RA in the hematopoietic compartment. We saw remarkable concordance of IL-17-controlled gene expression in C. albicans-infected human oral epithelial cells (OECs) and in tongue tissue from mice with OPC. To interrogate the role of the IL-17R in OECs, we generated mice with conditional deletion of IL-17RA in superficial oral and esophageal epithelial cells (Il17ra ΔK13 ). Following oral Candida infection, Il17ra ΔK13 mice exhibited fungal loads and weight loss indistinguishable from Il17ra -/- mice. Susceptibility in Il17ra ΔK13 mice correlated with expression of the antimicrobial peptide β-defensin 3 (BD3, Defb3). Consistently, Defb3 -/- mice were susceptible to OPC. Thus, OECs dominantly control IL-17R-dependent responses to OPC through regulation of BD3 expression. Copyright © 2016 Elsevier Inc. All rights reserved.

Optical and electrical properties of TiOPc doped Alq3 thin films

NASA Astrophysics Data System (ADS)

Ramar, M.; Suman, C. K.; Tyagi, Priyanka; Srivastava, R.

2015-06-01

The Titanyl phthalocyanine (TiOPc) was doped in Tris (8-hydroxyquinolinato) aluminum (Alq3) with different concentration. The thin film of optimized doping concentration was studied extensively for optical and electrical properties. The optical properties, studied using ellipsometry, absorption and photoluminescence. The absorption peak of Alq3 and TiOPc was observed at 387 nm and 707 nm and the photo-luminescence intensity (PL) peak of doped thin film was observed at 517 nm. The DC and AC electrical properties of the thin film were studied by current density-voltage (J-V) characteristics and impedance over a frequency range of 100 Hz - 1 MHz. The electron mobility calculated from trap-free space-charge limited region (SCLC) is 0.17×10-5 cm2/Vs. The Cole-Cole plots shows that the TiOPc doped Alq3 thin film can be represented by a single parallel resistance RP and capacitance CP network with a series resistance RS (10 Ω). The value of RP and CP at zero bias was 1587 Ω and 2.568 nF respectively. The resistance RP decreases with applied bias whereas the capacitance CP remains almost constant.

Interaction between BaCO{sub 3} and OPC/BFS composite cements at 20 {sup o}C and 60 {sup o}C

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

Utton, C.A., E-mail: c.utton@sheffield.ac.u; Gallucci, E.; Hill, J.

2011-03-15

A BaCO{sub 3} slurry, containing radioactive {sup 14}C, is produced during the reprocessing of spent nuclear fuel. This slurry is encapsulated in a Portland-blastfurnace slag composite cement. The effect of BaCO{sub 3} on the hydration of OPC and Portland-blastfurnace slag cements has been studied in this work. Samples containing a simulant BaCO{sub 3} slurry were cured for up to 720 days at 20 and 60 {sup o}C and analysed by XRD, SEM(EDX) and ICC. BaCO{sub 3} reacted with OPC to precipitate BaSO{sub 4} from a reaction between soluble sulfate and BaCO{sub 3}. Calcium monocarboaluminate subsequently formed from the carbonate released.more » The monocarboaluminate precipitated as crystals in voids formed during hydration. At 60 {sup o}C in OPC, it was not identified by XRD, suggesting the phase is unstable in this system around this temperature. In the Portland-blastfurnace slag cements containing BaCO{sub 3}, less monocarboaluminate and BaSO{sub 4} were formed, but the hydration of BFS was promoted and monocarboaluminate was stable up to 60 {sup o}C.« less

Rules based process window OPC

NASA Astrophysics Data System (ADS)

O'Brien, Sean; Soper, Robert; Best, Shane; Mason, Mark

2008-03-01

As a preliminary step towards Model-Based Process Window OPC we have analyzed the impact of correcting post-OPC layouts using rules based methods. Image processing on the Brion Tachyon was used to identify sites where the OPC model/recipe failed to generate an acceptable solution. A set of rules for 65nm active and poly were generated by classifying these failure sites. The rules were based upon segment runlengths, figure spaces, and adjacent figure widths. 2.1 million sites for active were corrected in a small chip (comparing the pre and post rules based operations), and 59 million were found at poly. Tachyon analysis of the final reticle layout found weak margin sites distinct from those sites repaired by rules-based corrections. For the active layer more than 75% of the sites corrected by rules would have printed without a defect indicating that most rulesbased cleanups degrade the lithographic pattern. Some sites were missed by the rules based cleanups due to either bugs in the DRC software or gaps in the rules table. In the end dramatic changes to the reticle prevented catastrophic lithography errors, but this method is far too blunt. A more subtle model-based procedure is needed changing only those sites which have unsatisfactory lithographic margin.

Evaluation of SAGE II and Balloon-Borne Stratospheric Aerosol Measurements: Evaluation of Aerosol Measurements from SAGE II, HALOE, and Balloonborne Optical Particle Counters

NASA Technical Reports Server (NTRS)

Hervig, Mark; Deshler, Terry; Moddrea, G. (Technical Monitor)

2002-01-01

Stratospheric aerosol measurements from the University of Wyoming balloonborne optical particle counters (OPCs), the Stratospheric Aerosol and Gas Experiment (SAGE) II, and the Halogen Occultation Experiment (HALOE) were compared in the period 1982-2000, when measurements were available. The OPCs measure aerosol size distributions, and HALOE multiwavelength (2.45-5.26 micrometers) extinction measurements can be used to retrieve aerosol size distributions. Aerosol extinctions at the SAGE II wavelengths (0.386-1.02 micrometers) were computed from these size distributions and compared to SAGE II measurements. In addition, surface areas derived from all three experiments were compared. While the overall impression from these results is encouraging, the agreement can change with latitude, altitude, time, and parameter. In the broadest sense, these comparisons fall into two categories: high aerosol loading (volcanic periods) and low aerosol loading (background periods and altitudes above 25 km). When the aerosol amount was low, SAGE II and HALOE extinctions were higher than the OPC estimates, while the SAGE II surface areas were lower than HALOE and the OPCS. Under high loading conditions all three instruments mutually agree to within 50%.

Performance of portland limestone cements: Cements designed to be more sustainable that include up to 15% limestone addition

NASA Astrophysics Data System (ADS)

Barrett, Timothy J.

In 2009, ASTM and AASHTO permitted the use of up to 5% interground limestone in ordinary portland cement (OPC) as a part of a change to ASTM C150/AASHTO M85. When this work was initiated a new proposal was being discussed that would enable up to 15% interground limestone cement to be considered in ASTM C595/AASHTO M234. This work served to provide rapid feedback to the state department of transportation and concrete industry for use in discussions regarding these specifications. Since the time this work was initiated, ASTM C595/AASHTO M234 was passed (2012c) and PLCs are now able to be specified, however they are still not widely used. The proposal for increasing the volume of limestone that would be permitted to be interground in cement is designed to enable more sustainable construction, which may significantly reduce the CO2 that is embodied in the built infrastructure while also extending the life of cement quarries. Research regarding the performance of cements with interground limestone has been conducted by the cement industry since these cements became widely used in Europe over three decades ago, however this work focuses on North American Portland Limestone Cements (PLCs) which are specifically designed to achieve similar performance as the OPCs they replace.This thesis presents a two-phase study in which the potential for application of cements containing limestone was assessed. The first phase of this study utilized a fundamental approach to determine whether cement with up to 15% of interground or blended limestone can be used as a direct substitute to ordinary portland cement. The second phase of the study assessed the concern of early age shrinkage and cracking potential when using PLCs, as these cements are typically ground finer than their OPC counterparts. For the first phase of the study, three commercially produced PLCs were obtained and compared to three commercially produced OPCs made from the same clinker. An additional cement was tested where the limestone was blended (i.e., not interground) as needed, enabling variation of the size of the limestone particles. In addition, one of the commercially produced OPCs and PLCs were used with fly ash. A series of standardized tests were run to assess the physical effects of intergrinding limestone in portland cement, the effect of limestone presence and method of inclusion on the hydration reaction, and the associated mechanical and transport properties of concretes made with these limestone cements. The second phase of the study used a commercially produced OPC, a PLC, and a PLC-slag all made from the same parent clinker to quantify the early age shrinkage and cracking potential. The study presents a series of tests that quantify the fundamental origins of shrinkage in cementitious materials to elucidate the differences between PLC and OPC. The bulk shrinkage of these systems is then quantified under free and restrained conditions to provide an assessment of the susceptibility for cracking in portland limestone cements. The results of the first phase of this thesis showed that in general the PLC and OPC systems have similar hydration, set, and mechanical performance. Transport properties in this study show behavior that is +/- 30% of the conventional OPC system depending on the system. Literature has shown similar freeze-thaw resistance when these materials are used in properly air entrained mixtures, and the results for PLC systems with fly ash show added performance. Based on these results it appears that PLC that meets ASTM C595/AASHTO M234 should be able to be used interchangeably with OPC, while it should also be noted that the investigation of the influence of salts and sulfates on PLCs is still ongoing and should be monitored. The results of the second phase of this thesis showed that while the PLCs are finer, this comes primarily by reducing the very large particles (clinker particles greater than 30 microns) using advanced separator technology and increasing the number of very fine limestone particles. This results in the cements tested having similar autogenous shrinkage development in the PLC systems compared to the OPC, with slightly less shrinkage in the PLC-slag system. The stress that develops when this shrinkage is restrained is very similar in comparing the OPC, PLC and PLC-slag systems and the PLC mixture tends to crack at a similar or slightly earlier times.

Phase 2 testing results of immobilization of WTP effluent management facility vaporator bottoms simulant

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

Reigel, M.; Cozzi, A.; McCabe, D.

2017-09-08

The Hanford Waste Treatment and Immobilization Plant (WTP) Low Activity Waste (LAW) vitrification facility will generate an aqueous condensate recycle stream (LAW Melter Off-Gas Condensate) from the primary off-gas system. This work examined three waste form formulations based on previous testing with related simulants: 8 wt% ordinary portland cement (OPC), 47 wt% blast furnace slag (BFS), 45 wt% fly ash (FA) known as Cast Stone formulation; 20 wt% Aquaset® II-GH and 80 wt% BFS; 20 wt% OPC and 80 wt% BFS. These tests successfully produced one waste form that set within five days (Cast Stone formulation); however the other twomore » formulations, Aquaset® II-GH/BFS and OPC/BFS, took approximately eight and fourteen days to set, respectively.« less

Pluripotent stem cell-derived radial glia-like cells as stable intermediate for efficient generation of human oligodendrocytes.

PubMed

Gorris, Raphaela; Fischer, Julia; Erwes, Kim Lina; Kesavan, Jaideep; Peterson, Daniel A; Alexander, Michael; Nöthen, Markus M; Peitz, Michael; Quandel, Tamara; Karus, Michael; Brüstle, Oliver

2015-12-01

Neural precursor cells (NPCs) derived from human pluripotent stem cells (hPSCs) represent an attractive tool for the in vitro generation of various neural cell types. However, the developmentally early NPCs emerging during hPSC differentiation typically show a strong propensity for neuronal differentiation, with more limited potential for generating astrocytes and, in particular, for generating oligodendrocytes. This phenomenon corresponds well to the consecutive and protracted generation of neurons and GLIA during normal human development. To obtain a more gliogenic NPC type, we combined growth factor-mediated expansion with pre-exposure to the differentiation-inducing agent retinoic acid and subsequent immunoisolation of CD133-positive cells. This protocol yields an adherent and self-renewing population of hindbrain/spinal cord radial glia (RG)-like neural precursor cells (RGL-NPCs) expressing typical neural stem cell markers such as nestin, ASCL1, SOX2, and PAX6 as well as RG markers BLBP, GLAST, vimentin, and GFAP. While RGL-NPCs maintain the ability for tripotential differentiation into neurons, astrocytes, and oligodendrocytes, they exhibit greatly enhanced propensity for oligodendrocyte generation. Under defined differentiation conditions promoting the expression of the major oligodendrocyte fate-determinants OLIG1/2, NKX6.2, NKX2.2, and SOX10, RGL-NPCs efficiently convert into NG2-positive oligodendroglial progenitor cells (OPCs) and are subsequently capable of in vivo myelination. Representing a stable intermediate between PSCs and OPCs, RGL-NPCs expedite the generation of PSC-derived oligodendrocytes with O4-, 4860-, and myelin basic protein (MBP)-positive cells that already appear within 7 weeks following growth factor withdrawal-induced differentiation. Thus, RGL-NPCs may serve as robust tool for time-efficient generation of human oligodendrocytes from embryonic and induced pluripotent stem cells. © 2015 Wiley Periodicals, Inc.

Raman spectroscopy for characterizing and determining the pozzolanic reactivity of fly ashes

NASA Astrophysics Data System (ADS)

Garg, Nishant

The efficacy and potential of Raman spectroscopy in characterization of a commercial Ordinary Portland Cement (OPC) and three fly ashes (FA's), and their evolving hydration products were studied in this Master's thesis work. While there have been several studies focusing on the application of Raman spectroscopy to synthetic, pure samples, work on commercial cementitious systems is scarce. This work covers this gap by evaluating mixtures containing cements and fly ashes. The study first involved determination followed by establishment of instrumental configuration and testing parameters optimum for studying cementitious materials both in the dry and wet form. It was found that by tweaking several parameters, collection methodologies and analysis techniques, improved, representative and reproducible data could be obtained. Mapping a representative area to determine the spatial distribution and concentration of sulfates and hydroxides on sample surfaces was found to be the most effective way to study these complex and heterogeneous systems. The Raman dry analysis of OPC and three different FA's of varying calcium contents and reactivity was able to identify the major mineralogical phases in these binders and the results were in correlation with the X-ray diffraction data. The observed calcium and sulfate phases and their relative concentration also agreed well with the supplementary compositional data obtained from X-ray fluorescence and Atomic absorption spectrometry. The wet analysis of pastes prepared with 100% OPC and 50%OPC+50%FA(1,2,3) followed the hydration process of the systems for 56 days (0, 0.2, 2, 4, 8, 12, 16, 20, 24, 48, 72 hours, 7, 14, 21, 28, and 56 days). Consistency of trends in the hydration mechanism of such pastes was only obtained when studies were focused on narrow wavenumber ranges: 950--1050 cm-1 for evolution of sulfates and 3600--3700cm-1 for evolution of hydroxides. Gradual disappearance of Gypsum with a parallel formation of Ettringite was clearly visible in most mixes, while transition of AFt to AFm was not very obvious and needs further research. Evolution of hydroxides showed the gradual spatial growth of portlandite in the studied areas of the samples. The growth rate and concentration of portlandite in different fly ash-cement-water mixes was correlated to the reactivity of the given fly ashes. While a clear connection wasnot established, several observations were made based on the interpretation of the obtained data. This lack of agreement between expected and observed results may be attributed to the heterogeneity of the studied materials, potential problems in sample preparations as well as limitations of the technique. Overall, Raman was effectively applied to the study of commercial, cementitious systems---this work being one of the early attempts if not the first attempt to study multi-phase fly ash blended cement pastes. While Raman may not be able to completely characterize and analyze such systems as a standalone tool, it definitely has a great potential in serving as a supplementary tool for deeper understanding of cement chemistry and hydration mechanisms.

Effect of p16 Status on the Quality-of-Life Experience During Chemoradiation for Locally Advanced Oropharyngeal Cancer: A Substudy of Randomized Trial Trans-Tasman Radiation Oncology Group (TROG) 02.02 (HeadSTART).

PubMed

Ringash, Jolie; Fisher, Richard; Peters, Lester; Trotti, Andy; O'Sullivan, Brian; Corry, June; Kenny, Lizbeth; Nuyts, Sandra; Wratten, Chris; Rischin, Danny

2017-03-15

Human papillomavirus-associated oropharyngeal cancer (OPC) has a favorable prognosis. Current research de-escalates treatment, aiming to improve quality of life (QOL). Understanding the QOL experience with current standard treatment (chemoradiation therapy) provides context for emerging data. We report the impact of p16 status on QOL for patients with stage III or IV OPC undergoing chemoradiation therapy in an international phase 3 trial (TROG 02.02 [HeadSTART]). A subgroup analysis by p16 status was conducted in patients with OPC treated in a phase 3 randomized trial. The study subset with OPC and known p16 status was mainly from Australasia, Western Europe, and North America. Of 861 participants, 200 had OPC, known p16 status, and baseline QOL data; 82 were p16 negative and 118 were p16 positive. Radiation therapy (70 Gy over a period of 7 weeks) was given concurrently with 3 cycles of either cisplatin (100 mg/m 2 ) or cisplatin (75 mg/m 2 ) plus tirapazamine. QOL was measured with the Functional Assessment of Cancer Therapy-Head and Neck (FACT-H&N) questionnaire at baseline and 2, 6, 12, 23, and 38 months. Because no significant difference in QOL score was observed between arms, results by p16 status are reported with arms combined. The p16-positive patients were younger, had a better Eastern Cooperative Oncology Group performance status, and were less often current smokers. Our primary hypothesis that the change in FACT-H&N score from baseline to 6 months would be more favorable in the p16-positive cohort was not met (p16 positive, -6.3; p16 negative, -1.8; P=.14). The mean baseline FACT-H&N score was statistically and clinically significantly better in p16-positive patients (111 vs 102, P<.001); at 2 months, scores declined in both groups but more dramatically for p16-positive patients. By 12 months, p16-positive patients again had superior scores. A higher baseline FACT-H&N score and p16-positive status were independent predictors of overall survival. Patients with p16-positive OPC exhibited better baseline QOL but showed a more dramatic QOL drop with concurrent chemoradiation. Given the favorable prognosis of p16-positive OPC, efforts to reduce the QOL burden of treatment are warranted. Copyright © 2016 Elsevier Inc. All rights reserved.

UIVerify: A Web-Based Tool for Verification and Automatic Generation of User Interfaces

NASA Technical Reports Server (NTRS)

Shiffman, Smadar; Degani, Asaf; Heymann, Michael

2004-01-01

In this poster, we describe a web-based tool for verification and automatic generation of user interfaces. The verification component of the tool accepts as input a model of a machine and a model of its interface, and checks that the interface is adequate (correct). The generation component of the tool accepts a model of a given machine and the user's task, and then generates a correct and succinct interface. This write-up will demonstrate the usefulness of the tool by verifying the correctness of a user interface to a flight-control system. The poster will include two more examples of using the tool: verification of the interface to an espresso machine, and automatic generation of a succinct interface to a large hypothetical machine.

The effects of the mechanical–chemical stabilization process for municipal solid waste incinerator fly ash on the chemical reactions in cement paste

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

Chen, Cheng-Gang; Sun, Chang-Jung, E-mail: sun.3409@hotmail.com; Gau, Sue-Huai

2013-04-15

Highlights: ► Milling extracted MSWI fly ash. ► Increasing specific surface area, destruction of the crystalline texture, and increasing the amount of amorphous materials. ► Increasing heavy metal stability. ► Inducing pozzolanic reactions and increasing the early and later strength of the cement paste. - Abstract: A water extraction process can remove the soluble salts present in municipal solid waste incinerator (MSWI) fly ash, which will help to increase the stability of the synthetic materials produced from the MSWI fly ash. A milling process can be used to stabilize the heavy metals found in the extracted MSWI fly ash (EA)more » leading to the formation of a non-hazardous material. This milled extracted MSWI fly ash (MEA) was added to an ordinary Portland cement (OPC) paste to induce pozzolanic reactions. The experimental parameters included the milling time (96 h), water to binder ratios (0.38, 0.45, and 0.55), and curing time (1, 3, 7 and 28 days). The analysis procedures included inductively coupled plasma atomic emission spectroscopy (ICP/AES), BET, mercury intrusion porosimetry (MIP), X-ray diffraction (XRD), and nuclear magnetic resonance (NMR) imaging. The results of the analyses indicate that the milling process helped to stabilize the heavy metals in the MEA, with an increase in the specific surface area of about 50 times over that of OPC. The addition of the MEA to the OPC paste decreased the amount of Ca(OH){sub 2} and led to the generation of calcium–silicate–hydrates (C–S–H) which in turned increased the amount of gel pores and middle sized pores in the cement. Furthermore, a comparison shows an increase in the early and later strength over that of OPC paste without the addition of the milled extracted ash. In other words, the milling process could stabilize the heavy metals in the MEA and had an activating effect on the MEA, allowing it to partly substitute OPC in OPC paste.« less

Evaluation of SAGE II and Balloon-Borne Stratospheric Aerosol Measurements

NASA Technical Reports Server (NTRS)

2002-01-01

Under funding from this proposal we evaluated measurements of stratospheric sulfate aerosols from three platforms. Two were satellite platforms providing solar extinction measurements, the Stratospheric Aerosol and Gas Experiment (SAGE) II using wavelengths from 0.386 - 1.02 microns, and the Halogen Occultation Experiment (HALOE) using wavelengths from 2.45 to 5.26 microns. The third set of measurements was from in situ sampling by balloonborne optical particle counters (OPCs). The goal was to determine the consistency among these data sets. This was accomplished through analysis of the existing measurement records, and through additional balloonborne OPC flights coinciding with new SAGE II observations over Laramie, Wyoming. All analyses used the SAGE II v 6.0 data. This project supported two balloon flights per year over Laramie dedicated to SAGE II coincidence. Because logistical factors, such as poor surface weather or unfavorable payload impact location, can make it difficult to routinely obtain close coincidences with SAGE II, we attempt to conduct nearly every Laramie flight (roughly one per month) in conjunction with a SAGE II overpass. The Laramie flight frequency has varied over the years depending on field commitments and funding sources. Current support for the Laramie measurements is from the National Science Foundation in addition to support from this NASA grant. We have also completed a variety of comparisons using aerosol measurements from SAGE II, OPCs, and HALOE. The instruments were compared for their various estimates of aerosol extinction at the SAGE II wavelengths and for aerosol surface area. Additional results, such as illustrated here, can be found in a recently accepted manuscript describing comparisons between SAGE II, HALOE, and OPCs for the period 1982 - 2000. While overall, the impression from these results is encouraging, the agreement of the measurements changes with latitude, altitude, time, and parameter. In the broadest sense, these comparisons fall into two categories: high aerosol loading (volcanic periods) and low aerosol loading (background periods and altitudes above 25 km). When the aerosol amount is low SAGE II and HALOE extinctions are higher than the OPC estimates, while the SAGE II surface areas are lower than HALOE and the OPCS. Under high loading conditions, all three instruments mutually agree to within 50%.

Atypical Clinical Behavior of p16-Confirmed HPV-Related Oropharyngeal Squamous Cell Carcinoma Treated With Radical Radiotherapy

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

Huang Shaohui; Perez-Ordonez, Bayardo; Liu Feifei

Purpose: To report atypical clinical behavior observed in human papillomavirus (HPV)-related oropharyngeal carcinoma (OPC) treated with radiotherapy. Methods and Materials: A retrospective cohort study was conducted for all newly diagnosed OPC cases treated with radiotherapy on July 1, 2003 to April 30, 2009. HPV positivity was determined by p16 immunostaining in tumors. The incidence of additional malignancies and the pattern of distant metastases (DMs) were compared between the HPV-positive (HPV+) and HPV-negative (HPV-) cohorts. Results: HPV status was evaluated in 318 of 613 consecutive OPC cases (52%), showing 236 HPV+ and 82 HPV- patients. Compared with HPV-, HPV+ cases weremore » less likely to have additional malignancies (prior: 11% vs. 20%, p = 0.038; synchronous: 1% vs. 9%, p = 0.001; metachronous: 6% vs. 16%, p = 0.003). Whereas the majority (10 of 12) of HPV- additional head-and-neck (HN) mucosal malignancies were in the oral cavity, there was none (0 of 7) in the HPV+ cohort (p < 0.001). HPV+ synchronous HN second primaries (SPs) were in the supraglottis, post-cricoid, and nasopharynx; metachronous HN SPs were in the glottis, supraglottis, and ethmoid plus glottis/post-cricoid region. All SPs that could be tested were HPV+. There was no difference in DM rate (10% vs. 15%, p = 0.272), but HPV+ DMs were more likely to involve multiple organs (46% vs. 0%, p = 0.005) and unusual sites. Conclusions: This study reports atypical clinical behavior seen in HPV+ OPC, including multicentric lesions in HN mucosa and DM to multiple organs and unusual sites. The frequency of these events is low, but they may have clinical implications. The routine assessment of HPV status for all OPC is warranted.« less

The Protein Tyrosine Phosphatase Shp2 Is Required for the Generation of Oligodendrocyte Progenitor Cells and Myelination in the Mouse Telencephalon

PubMed Central

Ehrman, Lisa A.; Nardini, Diana; Ehrman, Sarah; Rizvi, Tilat A.; Gulick, James; Krenz, Maike; Dasgupta, Biplab; Robbins, Jeffrey; Ratner, Nancy; Nakafuku, Masato

2014-01-01

The protein tyrosine phosphatase Shp2 (PTPN11) is crucial for normal brain development and has been implicated in dorsal telencephalic neuronal and astroglia cell fate decisions. However, its roles in the ventral telencephalon and during oligodendrogenesis in the telencephalon remain largely unknown. Shp2 gain-of-function (GOF) mutations are observed in Noonan syndrome, a type of RASopathy associated with multiple phenotypes, including cardiovascular, craniofacial, and neurocognitive abnormalities. To gain insight into requirements for Shp2 (LOF) and the impact of abnormal Shp2 GOF mutations, we used a Shp2 conditional mutant allele (LOF) and a cre inducible Shp2-Q79R GOF transgenic mouse in combination with Olig2cre/+ mice to target embryonic ventral telencephalic progenitors and the oligodendrocyte lineage. In the absence of Shp2 (LOF), neuronal cell types originating from progenitors in the ventral telencephalon were generated, but oligodendrocyte progenitor cell (OPC) generation was severely impaired. Late embryonic and postnatal Shp2 cKOs showed defects in the generation of OPCs throughout the telencephalon and subsequent reductions in white matter myelination. Conversely, transgenic expression of the Shp2 GOF Noonan syndrome mutation resulted in elevated OPC numbers in the embryo and postnatal brain. Interestingly, expression of this mutation negatively influenced myelination as mice displayed abnormal myelination and fewer myelinated axons in the white matter despite elevated OPC numbers. Increased proliferating OPCs and elevated MAPK activity were also observed during oligodendrogenesis after expression of Shp2 GOF mutation. These results support the notion that appropriate Shp2 activity levels control the number as well as the differentiation of oligodendrocytes during development. PMID:24599474

The protein tyrosine phosphatase Shp2 is required for the generation of oligodendrocyte progenitor cells and myelination in the mouse telencephalon.

PubMed

Ehrman, Lisa A; Nardini, Diana; Ehrman, Sarah; Rizvi, Tilat A; Gulick, James; Krenz, Maike; Dasgupta, Biplab; Robbins, Jeffrey; Ratner, Nancy; Nakafuku, Masato; Waclaw, Ronald R

2014-03-05

The protein tyrosine phosphatase Shp2 (PTPN11) is crucial for normal brain development and has been implicated in dorsal telencephalic neuronal and astroglia cell fate decisions. However, its roles in the ventral telencephalon and during oligodendrogenesis in the telencephalon remain largely unknown. Shp2 gain-of-function (GOF) mutations are observed in Noonan syndrome, a type of RASopathy associated with multiple phenotypes, including cardiovascular, craniofacial, and neurocognitive abnormalities. To gain insight into requirements for Shp2 (LOF) and the impact of abnormal Shp2 GOF mutations, we used a Shp2 conditional mutant allele (LOF) and a cre inducible Shp2-Q79R GOF transgenic mouse in combination with Olig2(cre/+) mice to target embryonic ventral telencephalic progenitors and the oligodendrocyte lineage. In the absence of Shp2 (LOF), neuronal cell types originating from progenitors in the ventral telencephalon were generated, but oligodendrocyte progenitor cell (OPC) generation was severely impaired. Late embryonic and postnatal Shp2 cKOs showed defects in the generation of OPCs throughout the telencephalon and subsequent reductions in white matter myelination. Conversely, transgenic expression of the Shp2 GOF Noonan syndrome mutation resulted in elevated OPC numbers in the embryo and postnatal brain. Interestingly, expression of this mutation negatively influenced myelination as mice displayed abnormal myelination and fewer myelinated axons in the white matter despite elevated OPC numbers. Increased proliferating OPCs and elevated MAPK activity were also observed during oligodendrogenesis after expression of Shp2 GOF mutation. These results support the notion that appropriate Shp2 activity levels control the number as well as the differentiation of oligodendrocytes during development.

An organotypic slice culture model of chronic white matter injury with maturation arrest of oligodendrocyte progenitors.

PubMed

Dean, Justin M; Riddle, Art; Maire, Jennifer; Hansen, Kelly D; Preston, Marnie; Barnes, Anthony P; Sherman, Larry S; Back, Stephen A

2011-07-05

CNS myelination disturbances commonly occur in chronic white matter lesions in neurodevelopmental and adult neurological disorders. Recent studies support that myelination failure can involve a disrupted cellular repair mechanism where oligodendrocyte (OL) progenitor cells (OPCs) proliferate in lesions with diffuse astrogliosis, but fail to fully differentiate to mature myelinating OLs. There are no in vitro models that reproduce these features of myelination failure. Forebrain coronal slices from postnatal day (P) 0.5/1 rat pups were cultured for 1, 5, or 9 days in vitro (DIV). Slices rapidly exhibited diffuse astrogliosis and accumulation of the extracellular matrix glycosaminoglycan hyaluronan (HA), an inhibitor of OPC differentiation and re-myelination. At 1 DIV ~1.5% of Olig2+ OLs displayed caspase-3 activation, which increased to ~11.5% by 9 DIV. At 1 DIV the density of PDGFRα+ and PDGFRα+/Ki67+ OPCs were significantly elevated compared to 0 DIV (P < 0.01). Despite this proliferative response, at 9 DIV ~60% of white matter OLs were late progenitors (preOLs), compared to ~7% in the postnatal day 10 rat (P < 0.0001), consistent with preOL maturation arrest. Addition of HA to slices significantly decreased the density of MBP+ OLs at 9 DIV compared to controls (217 ± 16 vs. 328 ± 17 cells/mm2, respectively; P = 0.0003), supporting an inhibitory role of HA in OL lineage progression in chronic lesions. Diffuse white matter astrogliosis and early OPC proliferation with impaired OL maturation were reproduced in this model of myelination failure. This system may be used to define mechanisms of OPC maturation arrest and myelination failure related to astrogliosis and HA accumulation.

The Adaptor CARD9 Is Required for Adaptive but Not Innate Immunity to Oral Mucosal Candida albicans Infections

PubMed Central

Bishu, Shrinivas; Hernández-Santos, Nydiaris; Simpson-Abelson, Michelle R.; Huppler, Anna R.; Conti, Heather R.; Ghilardi, Nico; Mamo, Anna J.

2014-01-01

Oropharyngeal candidiasis (OPC [thrush]) is an opportunistic infection caused by the commensal fungus Candida albicans. OPC is common in individuals with HIV/AIDS, infants, patients on chemotherapy, and individuals with congenital immune defects. Immunity to OPC is strongly dependent on the interleukin-23 (IL-23)/IL-17R axis, as mice and humans with defects in IL-17R signaling (IL17F, ACT1, IL-17RA) or in genes that direct Th17 differentiation (STAT3, STAT1, CARD9) are prone to mucocutaneous candidiasis. Conventional Th17 cells are induced in response to C. albicans infection via signals from C-type lectin receptors, which signal through the adaptor CARD9, leading to production of Th17-inducing cytokines such as IL-6, IL-1β, and IL-23. Recent data indicate that IL-17 can also be made by numerous innate cell subsets. These innate “type 17” cells resemble conventional Th17 cells, but they can be activated without need for prior antigen exposure. Because C. albicans is not a commensal organism in rodents and mice are thus naive to this fungus, we had the opportunity to assess the role of CARD9 in innate versus adaptive responses using an OPC infection model. As expected, CARD9−/− mice failed to mount an adaptive Th17 response following oral Candida infection. Surprisingly, however, CARD9−/− mice had preserved innate IL-17-dependent responses to Candida and were almost fully resistant to OPC. Thus, CARD9 is important primarily for adaptive immunity to C. albicans, whereas alternate recognition systems appear to be needed for effective innate responses. PMID:24379290

Oral-resident natural Th17 cells and γδ T cells control opportunistic Candida albicans infections

PubMed Central

Conti, Heather R.; Peterson, Alanna C.; Brane, Lucas; Huppler, Anna R.; Hernández-Santos, Nydiaris; Whibley, Natasha; Garg, Abhishek V.; Simpson-Abelson, Michelle R.; Gibson, Gregory A.; Mamo, Anna J.; Osborne, Lisa C.; Bishu, Shrinivas; Ghilardi, Nico; Siebenlist, Ulrich; Watkins, Simon C.; Artis, David; McGeachy, Mandy J.

2014-01-01

Oropharyngeal candidiasis (OPC) is an opportunistic fungal infection caused by Candida albicans. OPC is frequent in HIV/AIDS, implicating adaptive immunity. Mice are naive to Candida, yet IL-17 is induced within 24 h of infection, and susceptibility is strongly dependent on IL-17R signaling. We sought to identify the source of IL-17 during the early innate response to candidiasis. We show that innate responses to Candida require an intact TCR, as SCID, IL-7Rα−/−, and Rag1−/− mice were susceptible to OPC, and blockade of TCR signaling by cyclosporine induced susceptibility. Using fate-tracking IL-17 reporter mice, we found that IL-17 is produced within 1–2 d by tongue-resident populations of γδ T cells and CD3+CD4+CD44hiTCRβ+CCR6+ natural Th17 (nTh17) cells, but not by TCR-deficient innate lymphoid cells (ILCs) or NK cells. These cells function redundantly, as TCR-β−/− and TCR-δ−/− mice were both resistant to OPC. Whereas γδ T cells were previously shown to produce IL-17 during dermal candidiasis and are known to mediate host defense at mucosal surfaces, nTh17 cells are poorly understood. The oral nTh17 population expanded rapidly after OPC, exhibited high TCR-β clonal diversity, and was absent in Rag1−/−, IL-7Rα−/−, and germ-free mice. These findings indicate that nTh17 and γδ T cells, but not ILCs, are key mucosal sentinels that control oral pathogens. PMID:25200028

Culture conditions tailored to the cell of origin are critical for maintaining native properties and tumorigenicity of glioma cells.

PubMed

Ledur, Pítia F; Liu, Chong; He, Hua; Harris, Alexandra R; Minussi, Darlan C; Zhou, Hai-Yan; Shaffrey, Mark E; Asthagiri, Ashok; Lopes, Maria Beatriz S; Schiff, David; Lu, Yi-Cheng; Mandell, James W; Lenz, Guido; Zong, Hui

2016-10-01

Cell culture plays a pivotal role in cancer research. However, culture-induced changes in biological properties of tumor cells profoundly affect research reproducibility and translational potential. Establishing culture conditions tailored to the cancer cell of origin could resolve this problem. For glioma research, it has been previously shown that replacing serum with defined growth factors for neural stem cells (NSCs) greatly improved the retention of gene expression profile and tumorigenicity. However, among all molecular subtypes of glioma, our laboratory and others have previously shown that the oligodendrocyte precursor cell (OPC) rather than the NSC serves as the cell of origin for the proneural subtype, raising questions regarding the suitability of NSC-tailored media for culturing proneural glioma cells. OPC-originated mouse glioma cells were cultured in conditions for normal OPCs or NSCs, respectively, for multiple passages. Gene expression profiles, morphologies, tumorigenicity, and drug responsiveness of cultured cells were examined in comparison with freshly isolated tumor cells. OPC media-cultured glioma cells maintained tumorigenicity, gene expression profiles, and morphologies similar to freshly isolated tumor cells. In contrast, NSC-media cultured glioma cells gradually lost their OPC features and most tumor-initiating ability and acquired heightened sensitivity to temozolomide. To improve experimental reproducibility and translational potential of glioma research, it is important to identify the cell of origin, and subsequently apply this knowledge to establish culture conditions that allow the retention of native properties of tumor cells. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Analysis of the cochlear amplifier fluid pump hypothesis.

PubMed

Zagadou, Brissi Franck; Mountain, David C

2012-04-01

We use analysis of a realistic three-dimensional finite-element model of the tunnel of Corti (ToC) in the middle turn of the gerbil cochlea tuned to the characteristic frequency (CF) of 4 kHz to show that the anatomical structure of the organ of Corti (OC) is consistent with the hypothesis that the cochlear amplifier functions as a fluid pump. The experimental evidence for the fluid pump is that outer hair cell (OHC) contraction and expansion induce oscillatory flow in the ToC. We show that this oscillatory flow can produce a fluid wave traveling in the ToC and that the outer pillar cells (OPC) do not present a significant barrier to fluid flow into the ToC. The wavelength of the resulting fluid wave launched into the tunnel at the CF is 1.5 mm, which is somewhat longer than the wavelength estimated for the classical traveling wave. This fluid wave propagates at least one wavelength before being significantly attenuated. We also investigated the effect of OPC spacing on fluid flow into the ToC and found that, for physiologically relevant spacing between the OPCs, the impedance estimate is similar to that of the underlying basilar membrane. We conclude that the row of OPCs does not significantly impede fluid exchange between ToC and the space between the row of OPC and the first row of OHC-Dieter's cells complex, and hence does not lead to excessive power loss. The BM displacement resulting from the fluid pumped into the ToC is significant for motion amplification. Our results support the hypothesis that there is an additional source of longitudinal coupling, provided by the ToC, as required in many non-classical models of the cochlear amplifier.

Investigating Biochemical and Developmental Dependencies of Lignification with a Click-Compatible Monolignol Analog in Arabidopsis thaliana Stems

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

Pandey, Jyotsna L.; Kiemle, Sarah N.; Richard, Tom L.

Lignin is a key structural component of plant cell walls that provides rigidity, strength, and resistance against microbial attacks. This hydrophobic polymer also serves a crucial role in water transport. Despite its abundance and essential functions, several aspects of lignin biosynthesis and deposition remain cryptic. Lignin precursors are known to be synthesized in the cytoplasm by complex biosynthetic pathways, after which they are transported to the apoplastic space, where they are polymerized via free radical coupling reactions into polymeric lignin. However, the lignin deposition process and the factors controlling it are unclear. In this study, the biochemical and developmental dependenciesmore » of lignification were investigated using a click-compatible monolignol analog, 3-O-propargylcaffeyl alcohol (3-OPC), which can incorporate into both in vitro polymerized lignin and Arabidopsis thaliana tissues. Fluorescence labeling of 3-OPC using click chemistry followed by confocal fluorescence microscopy enabled the detection and imaging of 3-OPC incorporation patterns. These patterns were consistent with endogenous lignification observed in different developmental stages of Arabidopsis stems. However, the concentration of supplied monolignols influenced where lignification occurred at the subcellular level, with low concentrations being deposited in cell corners and middle lamellae and high concentrations also being deposited in secondary walls. Experimental inhibition of multiple lignification factors confirmed that 3-OPC incorporation proceeds via a free radical coupling mechanism involving peroxidases/laccases and reactive oxygen species (ROS). Finally, the presence of peroxide-producing enzymes determined which cell walls lignified: adding exogenous peroxide and peroxidase caused cells that do not naturally lignify in Arabidopsis stems to lignify. In conclusion, 3-OPC accurately mimics natural lignification patterns in different developmental stages of Arabidopsis stems and allows for the dissection of key biochemical and enzymatic factors controlling lignification.« less

Apoptosis and proliferation of oligodendrocyte progenitor cells in the irradiated rodent spinal cord

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

Atkinson, Shelley L.; Li Yuqing; Wong, C. Shun

2005-06-01

Purpose: Oligodendrocytes undergo early apoptosis after irradiation. The aim of this study was to determine the relationship between oligodendroglial apoptosis and proliferation of oligodendrocyte progenitor cells (OPC) in the irradiated central nervous system. Methods and Materials: Adult rats and p53 transgenic mice were given single doses of 2 Gy, 8 Gy, or 22 Gy to the cervical spinal cord. Apoptosis was assessed using TUNEL (Tdt-mediated dUTP terminal nick-end labeling) staining or by examining nuclear morphology. Oligodendrocyte progenitor cells were identified with an NG2 antibody or by in situ hybridization for platelet-derived growth factor receptor {alpha}. Proliferation of OPC was assessedmore » by in vivo bromodeoxyuridine (BrdU) labeling and subsequent immunohistochemistry. Because radiation-induced apoptosis of oligodendroglial cells is p53 dependent, p53 transgenic mice were used to study the relationship between apoptosis and cell proliferation. Results: Oligodendrocyte progenitor cells underwent apoptosis within 24 h of irradiation in the rat. That did not result in a change in OPC density at 24 h. Oligodendrocyte progenitor cell density was significantly reduced by 2-4 weeks, but showed recovery by 6 weeks after irradiation. An increase in BrdU-labeled cells was observed at 2 weeks after 8 Gy or 22 Gy, and proliferating cells in the rat spinal cord were immunoreactive for NG2. The mouse spinal cord showed a similar early cell proliferation after irradiation. No difference was observed in the proliferation response in the spinal cord of p53 -/- mice compared with wild type animals. Conclusions: Oligodendroglial cells undergo early apoptosis and OPC undergo early proliferation after ionizing radiation. However, apoptosis is not likely to be the trigger for early proliferation of OPC in the irradiated central nervous system.« less

Investigating Biochemical and Developmental Dependencies of Lignification with a Click-Compatible Monolignol Analog in Arabidopsis thaliana Stems

PubMed Central

Pandey, Jyotsna L.; Kiemle, Sarah N.; Richard, Tom L.; Zhu, Yimin; Cosgrove, Daniel J.; Anderson, Charles T.

2016-01-01

Lignin is a key structural component of plant cell walls that provides rigidity, strength, and resistance against microbial attacks. This hydrophobic polymer also serves a crucial role in water transport. Despite its abundance and essential functions, several aspects of lignin biosynthesis and deposition remain cryptic. Lignin precursors are known to be synthesized in the cytoplasm by complex biosynthetic pathways, after which they are transported to the apoplastic space, where they are polymerized via free radical coupling reactions into polymeric lignin. However, the lignin deposition process and the factors controlling it are unclear. In this study, the biochemical and developmental dependencies of lignification were investigated using a click-compatible monolignol analog, 3-O-propargylcaffeyl alcohol (3-OPC), which can incorporate into both in vitro polymerized lignin and Arabidopsis thaliana tissues. Fluorescence labeling of 3-OPC using click chemistry followed by confocal fluorescence microscopy enabled the detection and imaging of 3-OPC incorporation patterns. These patterns were consistent with endogenous lignification observed in different developmental stages of Arabidopsis stems. However, the concentration of supplied monolignols influenced where lignification occurred at the subcellular level, with low concentrations being deposited in cell corners and middle lamellae and high concentrations also being deposited in secondary walls. Experimental inhibition of multiple lignification factors confirmed that 3-OPC incorporation proceeds via a free radical coupling mechanism involving peroxidases/laccases and reactive oxygen species (ROS). Finally, the presence of peroxide-producing enzymes determined which cell walls lignified: adding exogenous peroxide and peroxidase caused cells that do not naturally lignify in Arabidopsis stems to lignify. In summary, 3-OPC accurately mimics natural lignification patterns in different developmental stages of Arabidopsis stems and allows for the dissection of key biochemical and enzymatic factors controlling lignification. PMID:27630649

Investigating Biochemical and Developmental Dependencies of Lignification with a Click-Compatible Monolignol Analog in Arabidopsis thaliana Stems

DOE PAGES

Pandey, Jyotsna L.; Kiemle, Sarah N.; Richard, Tom L.; ...

2016-08-31

Lignin is a key structural component of plant cell walls that provides rigidity, strength, and resistance against microbial attacks. This hydrophobic polymer also serves a crucial role in water transport. Despite its abundance and essential functions, several aspects of lignin biosynthesis and deposition remain cryptic. Lignin precursors are known to be synthesized in the cytoplasm by complex biosynthetic pathways, after which they are transported to the apoplastic space, where they are polymerized via free radical coupling reactions into polymeric lignin. However, the lignin deposition process and the factors controlling it are unclear. In this study, the biochemical and developmental dependenciesmore » of lignification were investigated using a click-compatible monolignol analog, 3-O-propargylcaffeyl alcohol (3-OPC), which can incorporate into both in vitro polymerized lignin and Arabidopsis thaliana tissues. Fluorescence labeling of 3-OPC using click chemistry followed by confocal fluorescence microscopy enabled the detection and imaging of 3-OPC incorporation patterns. These patterns were consistent with endogenous lignification observed in different developmental stages of Arabidopsis stems. However, the concentration of supplied monolignols influenced where lignification occurred at the subcellular level, with low concentrations being deposited in cell corners and middle lamellae and high concentrations also being deposited in secondary walls. Experimental inhibition of multiple lignification factors confirmed that 3-OPC incorporation proceeds via a free radical coupling mechanism involving peroxidases/laccases and reactive oxygen species (ROS). Finally, the presence of peroxide-producing enzymes determined which cell walls lignified: adding exogenous peroxide and peroxidase caused cells that do not naturally lignify in Arabidopsis stems to lignify. In conclusion, 3-OPC accurately mimics natural lignification patterns in different developmental stages of Arabidopsis stems and allows for the dissection of key biochemical and enzymatic factors controlling lignification.« less

Limestone and Silica Powder Replacements for Cement: Early-Age Performance.

PubMed

Bentz, Dale P; Ferraris, Chiara F; Jones, Scott Z; Lootens, Didier; Zunino, Franco

2017-04-01

Developing functional concrete mixtures with less ordinary portland cement (OPC) has been one of the key objectives of the 21 st century sustainability movement. While the supplies of many alternatives to OPC (such as fly ash or slag) may be limited, those of limestone and silica powders produced by crushing rocks seem virtually endless. The present study examines the chemical and physical influences of these powders on the rheology, hydration, and setting of cement-based materials via experiments and three-dimensional microstructural modeling. It is shown that both limestone and silica particle surfaces are active templates (sites) for the nucleation and growth of cement hydration products, while the limestone itself is also somewhat soluble, leading to the formation of carboaluminate hydration products. Because the filler particles are incorporated as active members of the percolated backbone that constitutes initial setting of a cement-based system, replacements of up to 50 % of the OPC by either of these powders on a volumetric basis have minimal impact on the initial setting time, and even a paste with only 5 % OPC and 95 % limestone powder by volume achieves initial set within 24 h. While their influence on setting is similar, the limestone and silica powders produce pastes with quite different rheological properties, when substituted at the same volume level. When proceeding from setting to later age strength development, one must also consider the dilution of the system due to cement removal, along with the solubility/reactivity of the filler. However, for applications where controlled (prompt) setting is more critical than developing high strengths, such as mortar tile adhesives, grouts, and renderings, significant levels of these powder replacements for cement can serve as sustainable, functional alternatives to the oft-employed 100 % OPC products.

Synthesis and structural characterization of group 4 metal carboxylates for nanowire production.

PubMed

Boyle, Timothy J; Yonemoto, Daniel T; Doan, Thu Q; Alam, Todd M

2014-12-01

The synthesis and characterization of a series of group 4 carboxylate derivatives ([M(ORc)4] where M = Ti, Zr, Hf) was undertaken for potential utility as precursors to ceramic nanowires. The attempted syntheses of the [M(ORc)4] precursors were undertaken from the reaction of [M(OBu(t))4] with a select set of carboxylic acids (H-ORc where ORc = OPc (O2CCH(CH3)2), OBc (O2CC(CH3)3), ONc (O2CCH2C(CH3)3)). The products were identified by single-crystal X-ray diffraction studies as [Ti(η(2)-OBc)3(OBu(t))] (1), [Zr2(μ3-O)(μ-OPc)4(μ,η(2)-OPc)(η(2)-OPc)]2 (2), [H]2[Zr(η(2)-OBc)2(OBc)2(OBc)2] (3), [Zr(μ-ONc)2(η(2)-ONc)2]2 (4), or [Hf(μ-ORc)2(η(2)-ORc)2]2 [ORc = OPc (5), OBc (6, shown), ONc (7)]. The majority of compounds (4-7) were isolated as dinuclear species with a dodecahedral-like (CN-8) bonding mode around the metals due to chelation and bridging of the ORc ligand. The two monomers (1 and 3) were found to adopt a capped trigonal prismatic and CN-8 geometry, respectively, due to chelating ORc and terminal ORc or OBu(t) ligands. The metals of the oxo-species 2 were isolated in octahedral and CN-8 arrangements. These compounds were then processed by electrospinning methods (applied voltage 10 kV, flow rate 30-60 μL/min, electric field 0.5 kV/cm), and wire-like morphologies were isolated using compounds 4, 6 (shown), and 7.

Squamous cell carcinoma of the larynx arising in multifocal pharyngolaryngeal oncocytic papillary cystadenoma: a case report and review of the literature.

PubMed

Stenner, Markus; Müller, Klaus-Michael; Koopmann, Mario; Rudack, Claudia

2014-09-01

We report on a rare case of a laryngeal carcinoma arising in a multifocal pharyngolaryngeal oncocytic papillary cystadenoma (OPC). The disease of a 63-year-old man is well documented by computed and positron emission tomography, histology, and electron microscopy. We could show that an OPC can even develop in the pharynx. The coexistence of both tumors makes this a challenging diagnosis for pathologists. Treated by surgery and radiotherapy, both lesions dissolved. Based on the literature available, we discuss the theory that the laryngeal carcinoma might be the result of a true metaplasia facilitated by chronic irritation and recommend a regular follow-up for OPC too. As in benign oncocytic lesions, we could show that the detection of numerous mitochondria is a diagnostic indicator for malignant variants as well.

Squamous Cell Carcinoma of the Larynx Arising in Multifocal Pharyngolaryngeal Oncocytic Papillary Cystadenoma

PubMed Central

Stenner, Markus; Müller, Klaus-Michael; Koopmann, Mario; Rudack, Claudia

2014-01-01

Abstract We report on a rare case of a laryngeal carcinoma arising in a multifocal pharyngolaryngeal oncocytic papillary cystadenoma (OPC). The disease of a 63-year-old man is well documented by computed and positron emission tomography, histology, and electron microscopy. We could show that an OPC can even develop in the pharynx. The coexistence of both tumors makes this a challenging diagnosis for pathologists. Treated by surgery and radiotherapy, both lesions dissolved. Based on the literature available, we discuss the theory that the laryngeal carcinoma might be the result of a true metaplasia facilitated by chronic irritation and recommend a regular follow-up for OPC too. As in benign oncocytic lesions, we could show that the detection of numerous mitochondria is a diagnostic indicator for malignant variants as well. PMID:25211046

Oropharyngeal cancer and human papilloma virus: evolving diagnostic and management paradigms.

PubMed

Buckley, Lisa; Gupta, Ruta; Ashford, Bruce; Jabbour, Joe; Clark, Jonathan R

2016-06-01

The significant increase in human papilloma virus (HPV)-associated oropharyngeal carcinoma (OPC) over recent years has lead to a surge in research and an improved understanding of the disease. Most patients with HPV-associated OPC present with cystic nodal metastases with a small primary tumour, and respond well to all treatment modalities including primary surgery and primary chemoradiotherapy. Current research is evaluating treatment de-escalation to reduce long-term treatment-associated morbidities. Transoral robotic surgery (TORS) is particularly relevant as the transoral approach allows small primary tumours to be removed with lower morbidity than traditional surgical approaches. The current American Joint Committee on Cancer staging system for oropharyngeal cancer does not appropriately stratify HPV-associated OPC; hence, alternative risk stratification and staging classifications are being proposed. © 2015 Royal Australasian College of Surgeons.

Asymmetry-defective oligodendrocyte progenitors are glioma precursors

PubMed Central

Sugiarto, Sista; Persson, Anders I.; Munoz, Elena Gonzalez; Waldhuber, Markus; Lamagna, Chrystelle; Andor, Noemi; Hanecker, Patrizia; Ayers-Ringler, Jennifer; Phillips, Joanna; Siu, Jason; Lim, Daniel; Vandenberg, Scott; Stallcup, William; Berger, Mitchel S.; Bergers, Gabriele; Weiss, William A.; Petritsch, Claudia

2012-01-01

Summary Postnatal oligodendrocyte progenitor cells (OPC) self-renew, generate mature oligodendrocytes, and are a cellular origin of oligodendrogliomas. We show that the proteoglycan NG2 segregates asymmetrically during mitosis to generate OPC cells of distinct fate. NG2 is required for asymmetric segregation of EGFR to the NG2+ progeny, which consequently activates EGFR and undergoes EGF-dependent proliferation and self-renewal. In contrast, the NG2− progeny differentiates. In a mouse model, decreased NG2 asymmetry coincides with premalignant, abnormal self-renewal rather than differentiation and with tumor-initiating potential. Asymmetric division of human NG2+ cells is prevalent in non-neoplastic tissue but is decreased in oligodendrogliomas. Regulators of asymmetric cell division are misexpressed in low-grade oligodendrogliomas. Our results identify loss of asymmetric division associated with the neoplastic transformation of OPC. PMID:21907924

In Vivo PET Imaging of Myelin Damage and Repair in the Spinal Cord

DTIC Science & Technology

2012-10-01

oligodendrocyte precursor cells ( OPCs ) that are subsequently activated and distributed to the damaged axons. However, the remyelination process is often...We hypothesize that myelin repair can be achieved by therapeutic agents that stimulate the endogenous promotion of remyelination by host OPCs ...specific uptake signal; 5) Rapid clearance of radiotracer from other organs (e.g, lung, heart, liver , etc) to ensure optimal dosimetry; 6) Minimal probe

Results of JAUS OPC Experiment 3.0

DTIC Science & Technology

2006-05-01

AFRL-ML-TY-TP-2006-4555 POSTPRINT RESULTS OF JAUS OPC EXPERIMENT 3.0 M.N. Clark Harris Corporation-GCSD Melbourne FL 32902-0037...permission to manufacture, use, or sell any patented invention that may relate to them. This technical report was reviewed and cleared for public...Service (NTIS). Reference PAO Case Number AFRL/MLQ-06-069. This report is releasable to the National Technical Information Service (NTIS) where

Tactical Implications for Peacemaking in Ethnic Conflict

DTIC Science & Technology

1993-02-04

means to achieve unity of effort; but unity of effort is achievable without unity of command. Second, units exhibited great versatility. Third , the Army...reviews the post-Persian Gulf War operations, emphasizing OPC. The third section analyzes some tactical lessons learned from OPC. This section uses the...commitments have not decreased. Third , the nation and the Army cannot afford a standing force dedicated to every type of contingency. Finally

Candida glabrata Binding to Candida albicans Hyphae Enables Its Development in Oropharyngeal Candidiasis.

PubMed

Tati, Swetha; Davidow, Peter; McCall, Andrew; Hwang-Wong, Elizabeth; Rojas, Isolde G; Cormack, Brendan; Edgerton, Mira

2016-03-01

Pathogenic mechanisms of Candida glabrata in oral candidiasis, especially because of its inability to form hyphae, are understudied. Since both Candida albicans and C. glabrata are frequently co-isolated in oropharyngeal candidiasis (OPC), we examined their co-adhesion in vitro and observed adhesion of C. glabrata only to C. albicans hyphae microscopically. Mice were infected sublingually with C. albicans or C. glabrata individually, or with both species concurrently, to study their ability to cause OPC. Infection with C. glabrata alone resulted in negligible infection of tongues; however, colonization by C. glabrata was increased by co-infection or a pre-established infection with C. albicans. Furthermore, C. glabrata required C. albicans for colonization of tongues, since decreasing C. albicans burden with fluconazole also reduced C. glabrata. C. albicans hyphal wall adhesins Als1 and Als3 were important for in vitro adhesion of C. glabrata and to establish OPC. C. glabrata cell wall protein coding genes EPA8, EPA19, AWP2, AWP7, and CAGL0F00181 were implicated in mediating adhesion to C. albicans hyphae and remarkably, their expression was induced by incubation with germinated C. albicans. Thus, we found a near essential requirement for the presence of C. albicans for both initial colonization and establishment of OPC infection by C. glabrata.

Candida glabrata Binding to Candida albicans Hyphae Enables Its Development in Oropharyngeal Candidiasis

PubMed Central

Tati, Swetha; Davidow, Peter; McCall, Andrew; Hwang-Wong, Elizabeth; Rojas, Isolde G.; Cormack, Brendan; Edgerton, Mira

2016-01-01

Pathogenic mechanisms of Candida glabrata in oral candidiasis, especially because of its inability to form hyphae, are understudied. Since both Candida albicans and C. glabrata are frequently co-isolated in oropharyngeal candidiasis (OPC), we examined their co-adhesion in vitro and observed adhesion of C. glabrata only to C. albicans hyphae microscopically. Mice were infected sublingually with C. albicans or C. glabrata individually, or with both species concurrently, to study their ability to cause OPC. Infection with C. glabrata alone resulted in negligible infection of tongues; however, colonization by C. glabrata was increased by co-infection or a pre-established infection with C. albicans. Furthermore, C. glabrata required C. albicans for colonization of tongues, since decreasing C. albicans burden with fluconazole also reduced C. glabrata. C. albicans hyphal wall adhesins Als1 and Als3 were important for in vitro adhesion of C. glabrata and to establish OPC. C. glabrata cell wall protein coding genes EPA8, EPA19, AWP2, AWP7, and CAGL0F00181 were implicated in mediating adhesion to C. albicans hyphae and remarkably, their expression was induced by incubation with germinated C. albicans. Thus, we found a near essential requirement for the presence of C. albicans for both initial colonization and establishment of OPC infection by C. glabrata. PMID:27029023

Bone cell-materials interaction on Si microchannels with bioinert coatings.

PubMed

Condie, Russell; Bose, Susmita; Bandyopadhyay, Amit

2007-07-01

Bone implant life is dependent upon integration of biomaterial surfaces with local osteoblasts. This investigation studied the effects of various microchannel parameters and surface chemistry on immortalized osteoblast precursor cell (OPC1) adhesion. Cell-materials interactions were observed within channels of varying length, width, tortuosity, convergence, divergence and chemistry. Si wafers were used to create four distinct 1cm(2) designs of varying channel dimensions. After anisotropic chemical etching to a depth of 120microm, wafers were sputter coated with gold and titanium; and on another surface SiO(2) was grown to vary the surface chemistry of these microchannels. OPC1 cells were seeded in the central cavity of each chip before incubation in tissue culture plates. On days 5, 11 and 16, samples were taken out, fixed and processed for microscopic analysis. Samples were visually characterized, qualitatively scored and analyzed. Channel walls did not contain OPC1 migration, but showed locally interrupted adhesion. Scores for channels of floor widths as narrow as 350microm were significantly reduced. No statistically significant preference was detected for gold, titanium or SiO(2) surfaces. Bands of OPC1 cells appeared to align with nearby channels, suggesting that cell morphology may be controlled by topography of the design to improve osseointegration.

Palm Oil Fuel Ash (POFA) and Eggshell Powder (ESP) as Partial Replacement for Cement in Concrete

NASA Astrophysics Data System (ADS)

Ezdiani Mohamad, Mazizah; Mahmood, Ali A.; Min, Alicia Yik Yee; Nur Nadhira A., R.

2018-03-01

This study is an attempt to partially replace Ordinary Portland cement (OPC) in concrete with palm oil fuel ash (POFA) and eggshell powder (ESP). The mix proportions of POFA and ESP were varied at 10% of cement replacement and compared with OPC concrete as control specimen. The fineness of POFA is characterized by passing through 300 μm sieve and ESP by passing through 75 μm sieve. Compressive strength testing was conducted on concrete specimens to determine the optimum mix proportion of POFA and ESP. Generally the compressive strength of OPC concrete is higher compared to POFA-ESP concrete. Based on the results of POFA-ESP concrete overall, it shows that the optimum mix proportion of concrete is 6%POFA:4% ESP achieved compressive strength of 38.60 N/mm2 at 28 days. The compressive strength of OPC concrete for the same period was 42.37 N/mm2. Higher water demand in concrete is needed due to low fineness of POFA that contributing to low compressive strength of POFA-ESP concrete. However, the compressive strength and workability of the POFA-ESP concrete were within the ranges typically encountered in regular concrete mixtures indicating the viability of this replacement procedure for structural and non-structural applications.

Improving the accuracy of operation coding in surgical discharge summaries

PubMed Central

Martinou, Eirini; Shouls, Genevieve; Betambeau, Nadine

2014-01-01

Procedural coding in surgical discharge summaries is extremely important; as well as communicating to healthcare staff which procedures have been performed, it also provides information that is used by the hospital's coding department. The OPCS code (Office of Population, Censuses and Surveys Classification of Surgical Operations and Procedures) is used to generate the tariff that allows the hospital to be reimbursed for the procedure. We felt that the OPCS coding on discharge summaries was often incorrect within our breast and endocrine surgery department. A baseline measurement over two months demonstrated that 32% of operations had been incorrectly coded, resulting in an incorrect tariff being applied and an estimated loss to the Trust of £17,000. We developed a simple but specific OPCS coding table in collaboration with the clinical coding team and breast surgeons that summarised all operations performed within our department. This table was disseminated across the team, specifically to the junior doctors who most frequently complete the discharge summaries. Re-audit showed 100% of operations were accurately coded, demonstrating the effectiveness of the coding table. We suggest that specifically designed coding tables be introduced across each surgical department to ensure accurate OPCS codes are used to produce better quality surgical discharge summaries and to ensure correct reimbursement to the Trust. PMID:26734286

Modeling of a data exchange process in the Automatic Process Control System on the base of the universal SCADA-system

NASA Astrophysics Data System (ADS)

Topolskiy, D.; Topolskiy, N.; Solomin, E.; Topolskaya, I.

2016-04-01

In the present paper the authors discuss some ways of solving energy saving problems in mechanical engineering. In authors' opinion one of the ways of solving this problem is integrated modernization of power engineering objects of mechanical engineering companies, which should be intended for the energy supply control efficiency increase and electric energy commercial accounting improvement. The author have proposed the usage of digital current and voltage transformers for these purposes. To check the compliance of this equipment with the IEC 61850 International Standard, we have built a mathematic model of the data exchange process between measuring transformers and a universal SCADA-system. The results of modeling show that the discussed equipment corresponds to the mentioned Standard requirements and the usage of the universal SCADA-system for these purposes is preferable and economically reasonable. In modeling the authors have used the following software: MasterScada, Master OPC_DI_61850, OPNET.

U.S. High Seas Marine Text Forecasts by Area

Science.gov Websites

Flooding Tsunamis 406 EPIRB's U.S. High Seas Marine Text Forecasts by Area OPC N.Atlantic High Seas Forecast NHC N.Atlantic High Seas Forecast OPC N.Pacific High Seas Forecast HFO N.Pacific High Seas Forecast NHC N.Pacific High Seas Forecast HFO S.Pacific High Seas Forecast U.S. High Seas Marine Text

Parallel states of pathological Wnt signaling in neonatal brain injury and colon cancer

PubMed Central

Fancy, Stephen P.J.; Harrington, Emily P.; Baranzini, Sergio E.; Silbereis, John C.; Shiow, Lawrence R.; Yuen, Tracy J.; Huang, Eric J.; Lomvardas, Stavros; Rowitch, David H.

2014-01-01

In colon cancer, mutation of the Wnt repressor Adenomatous polyposis coli (APC) leads to a state of aberrant and unrestricted “high-activity” signaling. However, relevance of high Wnt tone in non-genetic human disease is unknown. Here we demonstrate that distinct Wnt activity functional states determine oligodendrocyte precursor (OPC) differentiation and myelination. Murine OPCs with genetic Wnt dysregulation (high tone) express multiple genes in common with colon cancer including Lef1, SP5, Ets2, Rnf43 and Dusp4. Surprisingly, we find that OPCs in lesions of hypoxic human neonatal white matter injury upregulate markers of high Wnt activity and lack expression of APC. Finally, we show lack of Wnt repressor tone promotes permanent white matter injury after mild hypoxic insult. These findings suggest a state of pathological high-activity Wnt signaling in human disease tissues that lack pre-disposing genetic mutation. PMID:24609463

Titanyl phthalocyanine ambipolar thin film transistors making use of carbon nanotube electrodes

NASA Astrophysics Data System (ADS)

Coppedè, Nicola; Valitova, Irina; Mahvash, Farzaneh; Tarabella, Giuseppe; Ranzieri, Paolo; Iannotta, Salvatore; Santato, Clara; Martel, Richard; Cicoira, Fabio

2014-12-01

The capability of efficiently injecting charge carriers into organic films and finely tuning their morphology and structure is crucial to improve the performance of organic thin film transistors (OTFTs). In this work, we investigate OTFTs employing carbon nanotubes (CNTs) as the source-drain electrodes and, as the organic semiconductor, thin films of titanyl phthalocyanine (TiOPc) grown by supersonic molecular beam deposition (SuMBD). While CNT electrodes have shown an unprecedented ability to improve charge injection in OTFTs, SuMBD is an effective technique to tune film morphology and structure. Varying the substrate temperature during deposition, we were able to grow both amorphous (low substrate temperature) and polycrystalline (high substrate temperature) films of TiOPc. Regardless of the film morphology and structure, CNT electrodes led to superior charge injection and transport performance with respect to benchmark Au electrodes. Vacuum annealing of polycrystalline TiOPc films with CNT electrodes yielded ambipolar OTFTs.

Optical proximity correction (OPC) in near-field lithography with pixel-based field sectioning time modulation

NASA Astrophysics Data System (ADS)

Oh, Seonghyeon; Han, Dandan; Shim, Hyeon Bo; Hahn, Jae W.

2018-01-01

Subwavelength features have been successfully demonstrated in near-field lithography. In this study, the point spread function (PSF) of a near-field beam spot from a plasmonic ridge nanoaperture is discussed with regard to the complex decaying characteristic of a non-propagating wave and the asymmetry of the field distribution for pattern design. We relaxed the shape complexity of the field distribution with pixel-based optical proximity correction (OPC) for simplifying the pattern image distortion. To enhance the pattern fidelity for a variety of arbitrary patterns, field-sectioning structures are formulated via convolutions with a time-modulation function and a transient PSF along the near-field dominant direction. The sharpness of corners and edges, and line shortening can be improved by modifying the original target pattern shape using the proposed approach by considering both the pattern geometry and directionality of the field decay for OPC in near-field lithography.

Optical proximity correction (OPC) in near-field lithography with pixel-based field sectioning time modulation.

PubMed

Oh, Seonghyeon; Han, Dandan; Shim, Hyeon Bo; Hahn, Jae W

2018-01-26

Subwavelength features have been successfully demonstrated in near-field lithography. In this study, the point spread function (PSF) of a near-field beam spot from a plasmonic ridge nanoaperture is discussed with regard to the complex decaying characteristic of a non-propagating wave and the asymmetry of the field distribution for pattern design. We relaxed the shape complexity of the field distribution with pixel-based optical proximity correction (OPC) for simplifying the pattern image distortion. To enhance the pattern fidelity for a variety of arbitrary patterns, field-sectioning structures are formulated via convolutions with a time-modulation function and a transient PSF along the near-field dominant direction. The sharpness of corners and edges, and line shortening can be improved by modifying the original target pattern shape using the proposed approach by considering both the pattern geometry and directionality of the field decay for OPC in near-field lithography.

Standard Reference Line Combined with One-Point Calibration-Free Laser-Induced Breakdown Spectroscopy (CF-LIBS) to Quantitatively Analyze Stainless and Heat Resistant Steel.

PubMed

Fu, Hongbo; Wang, Huadong; Jia, Junwei; Ni, Zhibo; Dong, Fengzhong

2018-01-01

Due to the influence of major elements' self-absorption, scarce observable spectral lines of trace elements, and relative efficiency correction of experimental system, accurate quantitative analysis with calibration-free laser-induced breakdown spectroscopy (CF-LIBS) is in fact not easy. In order to overcome these difficulties, standard reference line (SRL) combined with one-point calibration (OPC) is used to analyze six elements in three stainless-steel and five heat-resistant steel samples. The Stark broadening and Saha - Boltzmann plot of Fe are used to calculate the electron density and the plasma temperature, respectively. In the present work, we tested the original SRL method, the SRL with the OPC method, and intercept with the OPC method. The final calculation results show that the latter two methods can effectively improve the overall accuracy of quantitative analysis and the detection limits of trace elements.

EUV local CDU healing performance and modeling capability towards 5nm node

NASA Astrophysics Data System (ADS)

Jee, Tae Kwon; Timoshkov, Vadim; Choi, Peter; Rio, David; Tsai, Yu-Cheng; Yaegashi, Hidetami; Koike, Kyohei; Fonseca, Carlos; Schoofs, Stijn

2017-10-01

Both local variability and optical proximity correction (OPC) errors are big contributors to the edge placement error (EPE) budget which is closely related to the device yield. The post-litho contact hole healing will be demonstrated to meet after-etch local variability specifications using a low dose, 30mJ/cm2 dose-to-size, positive tone developed (PTD) resist with relevant throughput in high volume manufacturing (HVM). The total local variability of the node 5nm (N5) contact holes will be characterized in terms of local CD uniformity (LCDU), local placement error (LPE), and contact edge roughness (CER) using a statistical methodology. The CD healing process has complex etch proximity effects, so the OPC prediction accuracy is challenging to meet EPE requirements for the N5. Thus, the prediction accuracy of an after-etch model will be investigated and discussed using ASML Tachyon OPC model.

Early age strength increase of fly ash blended cement by a ternary hardening accelerating admixture

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

Hoang, Kien; Justnes, Harald; SINTEF Building and Infrastructure

The applicability of a combination of sodium thiocyanate (NaSCN), diethanolamine (DEA) and glycerol (Gly) with small dosages as a ternary hardening accelerating admixture for fly ash blended cement (OPC-FA) was studied. The ternary admixture induced higher early and later age mortar strength at both low (5 °C) and normal (20 °C) temperature. Despite used in lower dosage the ternary admixture led to higher strength of the investigated OPC-FA system than other chemicals (e.g. sodium sulfate). Results obtained from isothermal calorimetry, thermogravimetric analysis (TGA) and X-ray diffraction (XRD) showed that the ternary admixture accelerated the cement hydration and increased the amountmore » of AFm (notably calcium hemicarboaluminate hydrate) in the hydration products. A synergistic effect between the three components of the accelerator on the hydration of OPC-FA system was observed.« less

Comparison of efficiency of terminal differentiation of oligodendrocytes from induced pluripotent stem cells versus embryonic stem cells in vitro.

PubMed

Tokumoto, Yasuhito; Ogawa, Shinichiro; Nagamune, Teruyuki; Miyake, Jun

2010-06-01

Oligodendrocytes are the myelinating cells of the central nervous system (CNS), and defects in these cells can result in the loss of CNS functions. Although oligodendrocyte progenitor cells transplantation therapy is an effective cure for such symptoms, there is no readily available source of these cells. Recent studies have described the generation of induced pluripotent stem cells (iPS cells) from somatic cells, leading to anticipation of this technique as a novel therapeutic tool in regenerative medicine. In this study, we evaluated the ability of iPS cells derived from mouse embryonic fibroblasts to differentiate into oligodendrocytes and compared this with the differential ability of mouse embryonic stem cells (ES cells). Experiments using an in vitro oligodendrocyte differentiation protocol that was optimized to ES cells demonstrated that 2.3% of iPS cells differentiated into O4(+) oligodendrocytes compared with 24.0% of ES cells. However, the rate of induction of A2B5(+) oligodendrocyte precursor cell (OPC) was similar for both iPS-derived cells and ES-derived cells (14.1% and 12.6%, respectively). These findings suggest that some intracellular factors in iPS cells inhibit the terminal differentiation of oligodendrocytes from the OPC stage. (c) 2009 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

A semi-automatic annotation tool for cooking video

NASA Astrophysics Data System (ADS)

Bianco, Simone; Ciocca, Gianluigi; Napoletano, Paolo; Schettini, Raimondo; Margherita, Roberto; Marini, Gianluca; Gianforme, Giorgio; Pantaleo, Giuseppe

2013-03-01

In order to create a cooking assistant application to guide the users in the preparation of the dishes relevant to their profile diets and food preferences, it is necessary to accurately annotate the video recipes, identifying and tracking the foods of the cook. These videos present particular annotation challenges such as frequent occlusions, food appearance changes, etc. Manually annotate the videos is a time-consuming, tedious and error-prone task. Fully automatic tools that integrate computer vision algorithms to extract and identify the elements of interest are not error free, and false positive and false negative detections need to be corrected in a post-processing stage. We present an interactive, semi-automatic tool for the annotation of cooking videos that integrates computer vision techniques under the supervision of the user. The annotation accuracy is increased with respect to completely automatic tools and the human effort is reduced with respect to completely manual ones. The performance and usability of the proposed tool are evaluated on the basis of the time and effort required to annotate the same video sequences.

Evaluation of a simple method for the automatic assignment of MeSH descriptors to health resources in a French online catalogue.

PubMed

Névéol, Aurélie; Pereira, Suzanne; Kerdelhué, Gaetan; Dahamna, Badisse; Joubert, Michel; Darmoni, Stéfan J

2007-01-01

The growing number of resources to be indexed in the catalogue of online health resources in French (CISMeF) calls for curating strategies involving automatic indexing tools while maintaining the catalogue's high indexing quality standards. To develop a simple automatic tool that retrieves MeSH descriptors from documents titles. In parallel to research on advanced indexing methods, a bag-of-words tool was developed for timely inclusion in CISMeF's maintenance system. An evaluation was carried out on a corpus of 99 documents. The indexing sets retrieved by the automatic tool were compared to manual indexing based on the title and on the full text of resources. 58% of the major main headings were retrieved by the bag-of-words algorithm and the precision on main heading retrieval was 69%. Bag-of-words indexing has effectively been used on selected resources to be included in CISMeF since August 2006. Meanwhile, on going work aims at improving the current version of the tool.

MatchGUI: A Graphical MATLAB-Based Tool for Automatic Image Co-Registration

NASA Technical Reports Server (NTRS)

Ansar, Adnan I.

2011-01-01

MatchGUI software, based on MATLAB, automatically matches two images and displays the match result by superimposing one image on the other. A slider bar allows focus to shift between the two images. There are tools for zoom, auto-crop to overlap region, and basic image markup. Given a pair of ortho-rectified images (focused primarily on Mars orbital imagery for now), this software automatically co-registers the imagery so that corresponding image pixels are aligned. MatchGUI requires minimal user input, and performs a registration over scale and inplane rotation fully automatically

Automated hotspot analysis with aerial image CD metrology for advanced logic devices

NASA Astrophysics Data System (ADS)

Buttgereit, Ute; Trautzsch, Thomas; Kim, Min-ho; Seo, Jung-Uk; Yoon, Young-Keun; Han, Hak-Seung; Chung, Dong Hoon; Jeon, Chan-Uk; Meyers, Gary

2014-09-01

Continuously shrinking designs by further extension of 193nm technology lead to a much higher probability of hotspots especially for the manufacturing of advanced logic devices. The CD of these potential hotspots needs to be precisely controlled and measured on the mask. On top of that, the feature complexity increases due to high OPC load in the logic mask design which is an additional challenge for CD metrology. Therefore the hotspot measurements have been performed on WLCD from ZEISS, which provides the benefit of reduced complexity by measuring the CD in the aerial image and qualifying the printing relevant CD. This is especially of advantage for complex 2D feature measurements. Additionally, the data preparation for CD measurement becomes more critical due to the larger amount of CD measurements and the increasing feature diversity. For the data preparation this means to identify these hotspots and mark them automatically with the correct marker required to make the feature specific CD measurement successful. Currently available methods can address generic pattern but cannot deal with the pattern diversity of the hotspots. The paper will explore a method how to overcome those limitations and to enhance the time-to-result in the marking process dramatically. For the marking process the Synopsys WLCD Output Module was utilized, which is an interface between the CATS mask data prep software and the WLCD metrology tool. It translates the CATS marking directly into an executable WLCD measurement job including CD analysis. The paper will describe the utilized method and flow for the hotspot measurement. Additionally, the achieved results on hotspot measurements utilizing this method will be presented.

Quality of Life and Performance Status From a Substudy Conducted Within a Prospective Phase 3 Randomized Trial of Concurrent Accelerated Radiation Plus Cisplatin With or Without Cetuximab for Locally Advanced Head and Neck Carcinoma: NRG Oncology Radiation Therapy Oncology Group 0522.

PubMed

Truong, Minh Tam; Zhang, Qiang; Rosenthal, David I; List, Marcie; Axelrod, Rita; Sherman, Eric; Weber, Randal; Nguyen-Tân, Phuc Felix; El-Naggar, Adel; Konski, André; Galvin, James; Schwartz, David; Trotti, Andy; Silverman, Craig; Singh, Anurag; Godette, Karen; Bonner, James A; Jones, Christopher U; Garden, Adam S; Shenouda, George; Matthiesen, Chance; Le, Quynh-Thu; Bruner, Deborah

2017-03-15

To analyze the quality of life (QOL) and performance status (PS) (secondary outcome) in patients with stage III to IV head and neck cancer (HNC) enrolled on a prospective randomized phase 3 trial comparing radiation-cisplatin without cetuximab (CIS) or with cetuximab (CET/CIS). The QOL hypothesis proposed a between-arm difference in Functional Assessment of Cancer Therapy-Head and Neck (FACT-HN) total score of ≥10% of the instrument range from baseline to 1 year. Patients who gave consent to the QOL/PS study completed the FACT-HN, Performance Status Scale for HNC (PSS-HN), and EuroQol (EQ-5D) at baseline through to 5 years. The pretreatment QOL/PS scores were correlated with outcome and p16 status in patients with oropharyngeal cancer (OPC). Of 818 analyzable patients, the 1-year change from baseline score for FACT-HN total was -0.41 (CIS arm) and -5.11 (CET/CIS arm) (P=.016), representing a 3.2% between-arm change of the FACT-HN total score. The mean EQ-5D index and PSS-HN scores were not significantly different between arms. The p16-positive OPC patients had significantly higher baseline and 1-year scores for PSS-HN, FACT-HN total, physical and functional subscales, and 2-years for the EQ-5D index compared with p16-negative OPC patients. Higher pretreatment PSS-HN diet, PSS-HN eating, FACT-HN, and EQ-5D index scores were associated with better overall survival (OS) and progression-free (PFS) survival on multivariate analysis. Higher baseline FACT-HN total, functional, physical subscale, and EQ-5D index scores were associated with improved OS and PFS in p16-positive OPC patients but not in p16-negative and non-OPC patients. There was no clinically meaningful difference in QOL/PS between arms. The p16-positive OPC patients had significantly higher QOL/PS than did p16-negative patients. Pretreatment QOL/PS is a significant independent predictor of outcome in locally advanced HNC. Copyright © 2016 Elsevier Inc. All rights reserved.

Subgroup Analysis According to Human Papillomavirus Status and Tumor Site of a Randomized Phase II Trial Comparing Cetuximab and Cisplatin Combined With Radiation Therapy for Locally Advanced Head and Neck Cancer.

PubMed

Buglione, Michela; Maddalo, Marta; Corvò, Renzo; Pirtoli, Luigi; Paiar, Fabiola; Lastrucci, Luciana; Stefanacci, Marco; Belgioia, Liliana; Crociani, Monica; Vecchio, Stefania; Bonomo, Pierluigi; Bertocci, Silvia; Borghetti, Paolo; Pasinetti, Nadia; Triggiani, Luca; Costa, Loredana; Tonoli, Sandro; Grisanti, Salvatore; Magrini, Stefano Maria

2017-03-01

We report a subgroup analysis primarily focused on human papillomavirus (HPV)-related oropharyngeal cancer (OPC) from the Cetuximab Plus Radiotherapy Versus Cisplatin Plus Radiotherapy in Locally Advanced Head and Neck Cancer (CTXMAB+RT; ClinicalTrials.gov identifier NCT01216020) trial comparing radiation therapy with concomitant cisplatin (CDDP) versus concomitant cetuximab (CTX) as first-line treatment of locally advanced head and neck cancer. The data from all the patients in the CTXMAB+RT trial were reviewed and separately analyzed in 3 groups: p16-positive OPC, p16-negative OPC, and all other cancer sites. The endpoints of interest were locoregional control (LC), metastasis-free survival, cancer-specific survival (CSS), and overall survival (OS). Severe and fatal infectious complications were also reanalyzed to more thoroughly investigate the association between CTX treatment and potentially life-threatening reactions. A total of 33 patients had OPC. The HPV status was available for 30 of the 33 patients. Thus, 3 patients treated with CDDP but with unknown HPV status were excluded from the survival analysis. The small number of patients in each group did not allow for significance to be reached for any of the outcomes analyzed. A trend favored the CDDP arm in the p16-positive group for the 2-year LC and OS/CSS rates (100% vs 72.9% and 100% vs 77.8% for CDDP vs CTX). In this group of patients, the hazard ratio for the treatment arm (CTX vs CDDP) was 4.7 (95% confidence interval [CI] 0.5-40.3) for LC, 3.4 (95% CI 0.4-30.5) for OS, and 2.4 for CSS (95% CI 0.2-23.2). A survival benefit favoring the CDDP arm was not evident in the p16-negative OPC group or for patients with cancer located in other sites. Serious or fatal infectious complications occurred only in the CTX arm. In patients with p16-positive OPC in the CTXMAB+RT trial, CTX had lower efficacy than CDDP, with possible implications for treatment selection in this clinical setting. Copyright © 2016 Elsevier Inc. All rights reserved.

Motor imaginary-based brain-machine interface design using programmable logic controllers for the disabled.

PubMed

Jeyabalan, Vickneswaran; Samraj, Andrews; Loo, Chu Kiong

2010-10-01

Aiming at the implementation of brain-machine interfaces (BMI) for the aid of disabled people, this paper presents a system design for real-time communication between the BMI and programmable logic controllers (PLCs) to control an electrical actuator that could be used in devices to help the disabled. Motor imaginary signals extracted from the brain’s motor cortex using an electroencephalogram (EEG) were used as a control signal. The EEG signals were pre-processed by means of adaptive recursive band-pass filtrations (ARBF) and classified using simplified fuzzy adaptive resonance theory mapping (ARTMAP) in which the classified signals are then translated into control signals used for machine control via the PLC. A real-time test system was designed using MATLAB for signal processing, KEP-Ware V4 OLE for process control (OPC), a wireless local area network router, an Omron Sysmac CPM1 PLC and a 5 V/0.3A motor. This paper explains the signal processing techniques, the PLC's hardware configuration, OPC configuration and real-time data exchange between MATLAB and PLC using the MATLAB OPC toolbox. The test results indicate that the function of exchanging real-time data can be attained between the BMI and PLC through OPC server and proves that it is an effective and feasible method to be applied to devices such as wheelchairs or electronic equipment.

In vitro metabolism and interaction of cilostazol with human hepatic cytochrome P450 isoforms.

PubMed

Abbas, R; Chow, C P; Browder, N J; Thacker, D; Bramer, S L; Fu, C J; Forbes, W; Odomi, M; Flockhart, D A

2000-03-01

1. Cilostazol (OPC-13013) undergoes extensive hepatic metabolism. The hydroxylation of the quinone moiety of cilostazol to OPC-13326 was the predominant route in all the liver preparations studies. The hydroxylation of the hexane moiety to OPC-13217 was the second most predominant route in vitro. 2. Ketoconazole (1 microM) was the most potent inhibitor of both quinone and hexane hydroxylation. Both the CYP2D6 inhibitor quinidine (0.1 microM) and the CYP2C19 inhibitor omeprazole (10 microM) failed to consistently inhibit metabolism of cilostazol via either of these two predominant routes. 3. Data obtained from a bank of pre-characterized human liver microsomes demonstrated a stronger correlation (r2=0.68, P < 0.01) between metabolism of cilostazol to OPC-13326 and metabolism of felodipine, a CYP3A probe, that with probes for any other isoform. Cimetidine demonstrated concentration-dependent competitive inhibition of the metabolism of cilostazol by both routes. 4. Kinetic data demonstrated a Km value of 101 microM for cilostazol, suggesting a relatively low affinity of cilostazol for CYP3A. While recombinant CYP1A2, CYP2D6 and CYP2C19 were also able to catalyze formation of specific cilostazol metabolites, they did not appear to contribute significantly to cilostazol metabolism in whole human liver microsomes.

Optical and electrical properties of TiOPc doped Alq{sub 3} thin films

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

Ramar, M.; Suman, C. K., E-mail: sumanck@nplindia.org; Tyagi, Priyanka

2015-06-24

The Titanyl phthalocyanine (TiOPc) was doped in Tris (8-hydroxyquinolinato) aluminum (Alq3) with different concentration. The thin film of optimized doping concentration was studied extensively for optical and electrical properties. The optical properties, studied using ellipsometry, absorption and photoluminescence. The absorption peak of Alq{sub 3} and TiOPc was observed at 387 nm and 707 nm and the photo-luminescence intensity (PL) peak of doped thin film was observed at 517 nm. The DC and AC electrical properties of the thin film were studied by current density-voltage (J-V) characteristics and impedance over a frequency range of 100 Hz - 1 MHz. The electron mobility calculated from trap-free space-chargemore » limited region (SCLC) is 0.17×10{sup −5} cm{sup 2}/Vs. The Cole-Cole plots shows that the TiOPc doped Alq{sub 3} thin film can be represented by a single parallel resistance R{sub P} and capacitance C{sub P} network with a series resistance R{sub S} (10 Ω). The value of R{sub P} and C{sub P} at zero bias was 1587 Ω and 2.568 nF respectively. The resistance R{sub P} decreases with applied bias whereas the capacitance C{sub P} remains almost constant.« less

New mechanism of oral immunity to mucosal candidiasis in hyper-IgE syndrome

PubMed Central

Conti, HR; Baker, O; Freeman, AF; Jang, WS; Holland, SM; Li, RA; Edgerton, M; Gaffen, SL

2011-01-01

Oropharyngeal candidiasis (OPC, thrush) is an opportunistic infection caused by the commensal fungus Candida albicans. An understanding of immunity to Candida has recently begun to unfold with the identification of fungal pattern-recognition receptors such as C-type lectin receptors, which trigger protective T-helper (Th)17 responses in the mucosa. Hyper-IgE syndrome (HIES/Job’s syndrome) is a rare congenital immunodeficiency characterized by dominant-negative mutations in signal transducer and activator of transcription 3, which is downstream of the Th17-inductive cytokines interleukin (IL)-6 and IL-23, and hence patients with HIES exhibit dramatic Th17 deficits. HIES patients develop oral and mucocutaneous candidiasis, supporting a protective role for Th17 cells in immunity to OPC. However, the Th17-dependent mechanisms of antifungal immunity in OPC are still poorly defined. An often unappreciated aspect of oral immunity is saliva, which is rich in antimicrobial proteins (AMPs) and exerts direct antifungal activity. In this study, we show that HIES patients show significant impairment in salivary AMPs, including β-defensin 2 and Histatins. This tightly correlates with reduced candidacidal activity of saliva and concomitantly elevated colonization with Candida. Moreover, IL-17 induces histatins in cultured salivary gland cells. This is the first demonstration that HIES is associated with defective salivary activity, and provides a mechanism for the severe susceptibility of these patients to OPC. PMID:21346738

Interleukin-17-induced protein lipocalin 2 is dispensable for immunity to oral candidiasis.

PubMed

Ferreira, Maria Carolina; Whibley, Natasha; Mamo, Anna J; Siebenlist, Ulrich; Chan, Yvonne R; Gaffen, Sarah L

2014-03-01

Oropharyngeal candidiasis (OPC; thrush) is an opportunistic fungal infection caused by the commensal microbe Candida albicans. Immunity to OPC is strongly dependent on CD4+ T cells, particularly those of the Th17 subset. Interleukin-17 (IL-17) deficiency in mice or humans leads to chronic mucocutaneous candidiasis, but the specific downstream mechanisms of IL-17-mediated host defense remain unclear. Lipocalin 2 (Lcn2; 24p3; neutrophil gelatinase-associated lipocalin [NGAL]) is an antimicrobial host defense factor produced in response to inflammatory cytokines, particularly IL-17. Lcn2 plays a key role in preventing iron acquisition by bacteria that use catecholate-type siderophores, and lipocalin 2(-/-) mice are highly susceptible to infection by Escherichia coli and Klebsiella pneumoniae. The role of Lcn2 in mediating immunity to fungi is poorly defined. Accordingly, in this study, we evaluated the role of Lcn2 in immunity to oral infection with C. albicans. Lcn2 is strongly upregulated following oral infection with C. albicans, and its expression is almost entirely abrogated in mice with defective IL-17 signaling (IL-17RA(-/-) or Act1(-/-) mice). However, Lcn2(-/-) mice were completely resistant to OPC, comparably to wild-type (WT) mice. Moreover, Lcn2 deficiency mediated protection from OPC induced by steroid immunosuppression. Therefore, despite its potent regulation during C. albicans infection, Lcn2 is not required for immunity to mucosal candidiasis.

New mechanism of oral immunity to mucosal candidiasis in hyper-IgE syndrome.

PubMed

Conti, H R; Baker, O; Freeman, A F; Jang, W S; Holland, S M; Li, R A; Edgerton, M; Gaffen, S L

2011-07-01

Oropharyngeal candidiasis (OPC, thrush) is an opportunistic infection caused by the commensal fungus Candida albicans. An understanding of immunity to Candida has recently begun to unfold with the identification of fungal pattern-recognition receptors such as C-type lectin receptors, which trigger protective T-helper (Th)17 responses in the mucosa. Hyper-IgE syndrome (HIES/Job's syndrome) is a rare congenital immunodeficiency characterized by dominant-negative mutations in signal transducer and activator of transcription 3, which is downstream of the Th17-inductive cytokines interleukin (IL)-6 and IL-23, and hence patients with HIES exhibit dramatic Th17 deficits. HIES patients develop oral and mucocutaneous candidiasis, supporting a protective role for Th17 cells in immunity to OPC. However, the Th17-dependent mechanisms of antifungal immunity in OPC are still poorly defined. An often unappreciated aspect of oral immunity is saliva, which is rich in antimicrobial proteins (AMPs) and exerts direct antifungal activity. In this study, we show that HIES patients show significant impairment in salivary AMPs, including β-defensin 2 and Histatins. This tightly correlates with reduced candidacidal activity of saliva and concomitantly elevated colonization with Candida. Moreover, IL-17 induces histatins in cultured salivary gland cells. This is the first demonstration that HIES is associated with defective salivary activity, and provides a mechanism for the severe susceptibility of these patients to OPC.

Accuracy limit of rigid 3-point water models

NASA Astrophysics Data System (ADS)

Izadi, Saeed; Onufriev, Alexey V.

2016-08-01

Classical 3-point rigid water models are most widely used due to their computational efficiency. Recently, we introduced a new approach to constructing classical rigid water models [S. Izadi et al., J. Phys. Chem. Lett. 5, 3863 (2014)], which permits a virtually exhaustive search for globally optimal model parameters in the sub-space that is most relevant to the electrostatic properties of the water molecule in liquid phase. Here we apply the approach to develop a 3-point Optimal Point Charge (OPC3) water model. OPC3 is significantly more accurate than the commonly used water models of same class (TIP3P and SPCE) in reproducing a comprehensive set of liquid bulk properties, over a wide range of temperatures. Beyond bulk properties, we show that OPC3 predicts the intrinsic charge hydration asymmetry (CHA) of water — a characteristic dependence of hydration free energy on the sign of the solute charge — in very close agreement with experiment. Two other recent 3-point rigid water models, TIP3PFB and H2ODC, each developed by its own, completely different optimization method, approach the global accuracy optimum represented by OPC3 in both the parameter space and accuracy of bulk properties. Thus, we argue that an accuracy limit of practical 3-point rigid non-polarizable models has effectively been reached; remaining accuracy issues are discussed.

Investigation of the layout and optical proximity correction effects to control the trench etching process on 4H-SiC

NASA Astrophysics Data System (ADS)

Kyoung, Sinsu; Jung, Eun-Sik; Sung, Man Young

2017-07-01

Although trench gate and super-junction technology have micro-trench problems when applied to the SiC process due to the material characteristics. In this paper, area effects are analyzed from the test element group with various patterns and optical proximity correction (OPC) methods are proposed and analyzed to reduce micro-trenches in the SiC trench etching process. First, the loading effects were analyzed from pattern samples with various trench widths (Wt). From experiments, the area must limited under a proper size for a uniform etching profile and reduced micro-trenches because a wider area accelerates the etch rate. Second, the area effects were more severely unbalanced at corner patterns because the corner pattern necessarily has an in-corner and out-corner that have different etching areas to each other. We can balance areas using OPC patterns to overcome this. Experiments with OPC represented improved micro-trench profile from when comparing differences of trench depth (Δdt) at out corner and in corner. As a result, the area effects can be used to improve the trench profile with optimized etching process conditions. Therefore, the trench gate and super-junction pillar of the SiC power MOSFET can have an improved uniform profile without micro-trenches using proper design and OPC.[Figure not available: see fulltext.

Influence of lead on stabilization/solidification by ordinary Portland cement and magnesium phosphate cement.

PubMed

Wang, Yan-Shuai; Dai, Jian-Guo; Wang, Lei; Tsang, Daniel C W; Poon, Chi Sun

2018-01-01

Inorganic binder-based stabilization/solidification (S/S) of Pb-contaminated soil is a commonly used remediation approach. This paper investigates the influences of soluble Pb species on the hydration process of two types of inorganic binders: ordinary Portland cement (OPC) and magnesium potassium phosphate cement (MKPC). The environmental leachability, compressive strength, and setting time of the cement products are assessed as the primary performance indicators. The mechanisms of Pb involved in the hydration process are analyzed through X-ray diffraction (XRD), hydration heat evolution, and thermogravimetric analyses. Results show that the presence of Pb imposes adverse impact on the compressive strength (decreased by 30.4%) and the final setting time (prolonged by 334.7%) of OPC, but it exerts much less influence on those of MKPC. The reduced strength and delayed setting are attributed to the retarded hydration reaction rate of OPC during the induction period. These results suggest that the OPC-based S/S of soluble Pb mainly depends on physical encapsulation by calcium-silicate-hydrate (CSH) gels. In contrast, in case of MKPC-based S/S process, chemical stabilization with residual phosphate (pyromorphite and lead phosphate precipitation) and physical fixation of cementitious struvite-K are the major mechanisms. Therefore, MKPC is a more efficient and chemically stable inorganic binder for the Pb S/S process. Copyright © 2017 Elsevier Ltd. All rights reserved.

Properties of Chemically Combusted Calcium Carbide Residue and Its Influence on Cement Properties.

PubMed

Sun, Hongfang; Li, Zishanshan; Bai, Jing; Memon, Shazim Ali; Dong, Biqin; Fang, Yuan; Xu, Weiting; Xing, Feng

2015-02-13

Calcium carbide residue (CCR) is a waste by-product from acetylene gas production. The main component of CCR is Ca(OH)₂, which can react with siliceous materials through pozzolanic reactions, resulting in a product similar to those obtained from the cement hydration process. Thus, it is possible to use CCR as a substitute for Portland cement in concrete. In this research, we synthesized CCR and silica fume through a chemical combustion technique to produce a new reactive cementitious powder (RCP). The properties of paste and mortar in fresh and hardened states (setting time, shrinkage, and compressive strength) with 5% cement replacement by RCP were evaluated. The hydration of RCP and OPC (Ordinary Portland Cement) pastes was also examined through SEM (scanning electron microscope). Test results showed that in comparison to control OPC mix, the hydration products for the RCP mix took longer to formulate. The initial and final setting times were prolonged, while the drying shrinkage was significantly reduced. The compressive strength at the age of 45 days for RCP mortar mix was found to be higher than that of OPC mortar and OPC mortar with silica fume mix by 10% and 8%, respectively. Therefore, the synthesized RCP was proved to be a sustainable active cementitious powder for the strength enhanced of building materials, which will result in the diversion of significant quantities of this by-product from landfills.

Automatic Tension Adjuster For Flexible-Shaft Grinder

NASA Technical Reports Server (NTRS)

Burley, Richard K.; Hoult, William S.

1990-01-01

Flexible shaft of grinding tool automatically maintained in tension by air pressure. Probelike tool bent to reach hard-to-reach areas for grinding and polishing. Unless shaft held in tension, however, it rubs against its sheath, overheating and wearing out quickly. By taking up slack in flexible cable, tension adjuster reduces friction and enables tool to operate more efficiently, in addition to lengthening operating life.

An automatic alignment tool to improve repeatability of left ventricular function and dyssynchrony parameters in serial gated myocardial perfusion SPECT studies

PubMed Central

Zhou, Yanli; Faber, Tracy L.; Patel, Zenic; Folks, Russell D.; Cheung, Alice A.; Garcia, Ernest V.; Soman, Prem; Li, Dianfu; Cao, Kejiang; Chen, Ji

2013-01-01

Objective Left ventricular (LV) function and dyssynchrony parameters measured from serial gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) using blinded processing had a poorer repeatability than when manual side-by-side processing was used. The objective of this study was to validate whether an automatic alignment tool can reduce the variability of LV function and dyssynchrony parameters in serial gated SPECT MPI. Methods Thirty patients who had undergone serial gated SPECT MPI were prospectively enrolled in this study. Thirty minutes after the first acquisition, each patient was repositioned and a gated SPECT MPI image was reacquired. The two data sets were first processed blinded from each other by the same technologist in different weeks. These processed data were then realigned by the automatic tool, and manual side-by-side processing was carried out. All processing methods used standard iterative reconstruction and Butterworth filtering. The Emory Cardiac Toolbox was used to measure the LV function and dyssynchrony parameters. Results The automatic tool failed in one patient, who had a large, severe scar in the inferobasal wall. In the remaining 29 patients, the repeatability of the LV function and dyssynchrony parameters after automatic alignment was significantly improved from blinded processing and was comparable to manual side-by-side processing. Conclusion The automatic alignment tool can be an alternative method to manual side-by-side processing to improve the repeatability of LV function and dyssynchrony measurements by serial gated SPECT MPI. PMID:23211996

DSC: software tool for simulation-based design of control strategies applied to wastewater treatment plants.

PubMed

Ruano, M V; Ribes, J; Seco, A; Ferrer, J

2011-01-01

This paper presents a computer tool called DSC (Simulation based Controllers Design) that enables an easy design of control systems and strategies applied to wastewater treatment plants. Although the control systems are developed and evaluated by simulation, this tool aims to facilitate the direct implementation of the designed control system to the PC of the full-scale WWTP (wastewater treatment plants). The designed control system can be programmed in a dedicated control application and can be connected to either the simulation software or the SCADA of the plant. To this end, the developed DSC incorporates an OPC server (OLE for process control) which facilitates an open-standard communication protocol for different industrial process applications. The potential capabilities of the DSC tool are illustrated through the example of a full-scale application. An aeration control system applied to a nutrient removing WWTP was designed, tuned and evaluated with the DSC tool before its implementation in the full scale plant. The control parameters obtained by simulation were suitable for the full scale plant with only few modifications to improve the control performance. With the DSC tool, the control systems performance can be easily evaluated by simulation. Once developed and tuned by simulation, the control systems can be directly applied to the full-scale WWTP.

Integrated model-based retargeting and optical proximity correction

NASA Astrophysics Data System (ADS)

Agarwal, Kanak B.; Banerjee, Shayak

2011-04-01

Conventional resolution enhancement techniques (RET) are becoming increasingly inadequate at addressing the challenges of subwavelength lithography. In particular, features show high sensitivity to process variation in low-k1 lithography. Process variation aware RETs such as process-window OPC are becoming increasingly important to guarantee high lithographic yield, but such techniques suffer from high runtime impact. An alternative to PWOPC is to perform retargeting, which is a rule-assisted modification of target layout shapes to improve their process window. However, rule-based retargeting is not a scalable technique since rules cannot cover the entire search space of two-dimensional shape configurations, especially with technology scaling. In this paper, we propose to integrate the processes of retargeting and optical proximity correction (OPC). We utilize the normalized image log slope (NILS) metric, which is available at no extra computational cost during OPC. We use NILS to guide dynamic target modification between iterations of OPC. We utilize the NILS tagging capabilities of Calibre TCL scripting to identify fragments with low NILS. We then perform NILS binning to assign different magnitude of retargeting to different NILS bins. NILS is determined both for width, to identify regions of pinching, and space, to locate regions of potential bridging. We develop an integrated flow for 1x metal lines (M1) which exhibits lesser lithographic hotspots compared to a flow with just OPC and no retargeting. We also observe cases where hotspots that existed in the rule-based retargeting flow are fixed using our methodology. We finally also demonstrate that such a retargeting methodology does not significantly alter design properties by electrically simulating a latch layout before and after retargeting. We observe less than 1% impact on latch Clk-Q and D-Q delays post-retargeting, which makes this methodology an attractive one for use in improving shape process windows without perturbing designed values.

Esophageal candidiasis in pediatric acquired immunodeficiency syndrome: clinical manifestations and risk factors.

PubMed

Chiou, C C; Groll, A H; Gonzalez, C E; Callender, D; Venzon, D; Pizzo, P A; Wood, L; Walsh, T J

2000-08-01

Little is known about the epidemiology and clinical features of esophageal candidiasis (EC) in pediatric AIDS. We therefore investigated the clinical presentation and risk factors of EC in a large prospectively monitored population of HIV-infected children at the National Cancer Institute. We reviewed the records of all HIV-infected children (N = 448) followed between 1987 and 1995 for a history of esophageal candidiasis to characterize the epidemiology, clinical features, therapeutic interventions and outcome of esophageal candidiasis. To understand further the risk factors for EC in pediatric AIDS, we then performed a matched case-control analysis of 25 patients for whom control cases were available. There were 51 episodes of EC documented in 36 patients with 23 male and 13 female patients (0.2 to 17 years; median CD4, count 11/microl), representing a frequency of EC of 8.0%. Concurrent oropharyngeal candidiasis (OPC) was the most common clinical presentation of EC (94%); other signs and symptoms included odynophagia (80%), retrosternal pain (57%), fever (29%), nausea/vomiting (24%), drooling (12%), dehydration (12%), hoarseness (6%) and upper gastrointestinal bleeding (6%). The causative organism documented in 36 episodes (18 from OPC, 17 from endoscopic biopsy and 1 from autopsy) was Candida albicans in all cases. Patients received treatment for EC with amphotericin B (63%), fluconazole (29%), ketoconazole (4%) or itraconazole (1%). A clinical response was documented in all 45 evaluable episodes. In 6 other cases, EC was a final event without contributing to the cause of death. By a conditional logistic regression model for matched data, the best predictor of EC was the presence of prior OPC (P<0.0001), followed by CD4 count and CD4 percentage (P = 0.0002) and use of antibacterial antibiotics (P = 0.0013). The risks associated with low CD4 count were independent of that of prior OPC. EC in pediatric AIDS is a debilitating infection, which develops in the setting of prior OPC, low CD4 counts and previous antibiotics.

Evaluation of Fieldbus and OPC for Advanced Life Support

NASA Technical Reports Server (NTRS)

Boulanger, Richard P.; Cardinale, Paul; Bradley, Matthew; Luna, Bernadette (Technical Monitor)

2000-01-01

FOUNDATION(Tm) Fieldbus and OP(TM) (OLE(TM)for Process Control) technologies were integrated into an existing control system for a crop growth chamber at NASA Ames Research Center. FOUNDATION(TM) Fieldbus is a digital, bi-directional, multi-drop, serial communications network which functions essentially as a LAN for sensors. FOUNDATION(TM) Fieldbus is heterarchical, with publishers and subscribers of data performing complex control functions at low levels without centralized control and its associated overhead. OPC(TM) is a set of interfaces which replace proprietary drivers with a transparent means of exchanging data between the fieldbus and applications. The objectives were: (1) to integrate FOUNDATION(TM) Fieldbus into existing ALS hardware and determine its overall effectiveness and reliability and, (2) to quantify any savings produced by using fieldbus and OPC technologies. We encountered several problems with the FOUNDATION(TM) Fieldbus hardware chosen. Our hardware exposed 100 data for each channel of the fieldbus. The fieldbus configurator software used to program the fieldbus was simply not adequate. The fieldbus was also not inherently reliable. It lost its settings twice during our tests for unknown reasons. OPC also had issues. It did not function at all as supplied, requiring substitution of some of its components with those from other vendors. It would stop working after a fixed period of time. Certain database calls eventually lock the machine. Overall, we would not recommend FOUNDATION(TM) Fieldbus: it was too difficult to implement with little overall added value. It also seems unlikely that FOUNDATION(TM) Fieldbus will gain sufficient penetration into the laboratory instrument market to ever be cost effective for the ALS community. OPC had good reliability and performance once a stable installation was achieved. It allowed a rapid change to an alternative software strategy when our first strategy failed. It is a cost effective solution to distributed control systems development.

What you see is not what you catch: a comparison of concurrently collected net, Optical Plankton Counter, and Shadowed Image Particle Profiling Evaluation Recorder data from the northeast Gulf of Mexico

NASA Astrophysics Data System (ADS)

Remsen, Andrew; Hopkins, Thomas L.; Samson, Scott

2004-01-01

Zooplankton and suspended particles were sampled in the upper 100 m of the Gulf of Mexico with the High Resolution Sampler. This towed-platform can concurrently sample zooplankton with plankton nets, an Optical Plankton Counter (OPC) and the Shadowed Image Particle Profiling and Evaluation Recorder (SIPPER), a zooplankton imaging system. This allowed for direct comparison of mesozooplankton abundance, biomass, taxonomic composition and size distributions between simultaneously collected net samples, OPC data, and digital imagery. While the net data were numerically and taxonomically similar to that of previous studies in the region, analysis of the SIPPER imagery revealed that nets significantly underestimated larvacean, doliolid, protoctist and cnidarian/ctenophore abundance by 300%, 379%, 522% and 1200%, respectively. The inefficiency of the nets in sampling the fragile and gelatinous zooplankton groups led to a dry-weight biomass estimate less than half that of the SIPPER total and suggests that this component of the zooplankton assemblage is more important than previously determined for this region. Additionally, using the SIPPER data we determined that more than 29% of all mesozooplankton-sized particles occurred within 4 mm of another particle and therefore would not be separately counted by the OPC. This suggests that coincident counting is a major problem for the OPC even at the low zooplankton abundances encountered in low latitude oligotrophic systems like the Gulf. Furthermore, we found that the colonial cyanobacterium Trichodesmium was the most abundant recognizable organism in the SIPPER dataset, while it was difficult to quantify with the nets. For these reasons, the traditional method of using net samples to ground truth OPC data would not be adequate in describing the particle assemblage described here. Consequently we suggest that in situ imaging sensors be included in any comprehensive study of mesozooplankton.

Automatic Certification of Kalman Filters for Reliable Code Generation

NASA Technical Reports Server (NTRS)

Denney, Ewen; Fischer, Bernd; Schumann, Johann; Richardson, Julian

2005-01-01

AUTOFILTER is a tool for automatically deriving Kalman filter code from high-level declarative specifications of state estimation problems. It can generate code with a range of algorithmic characteristics and for several target platforms. The tool has been designed with reliability of the generated code in mind and is able to automatically certify that the code it generates is free from various error classes. Since documentation is an important part of software assurance, AUTOFILTER can also automatically generate various human-readable documents, containing both design and safety related information. We discuss how these features address software assurance standards such as DO-178B.

Automatic alternative phase-shift mask CAD layout tool for gate shrinkage of embedded DRAM in logic below 0.18 μm

NASA Astrophysics Data System (ADS)

Ohnuma, Hidetoshi; Kawahira, Hiroichi

1998-09-01

An automatic alternative phase shift mask (PSM) pattern layout tool has been newly developed. This tool is dedicated for embedded DRAM in logic device to shrink gate line width with improving line width controllability in lithography process with a design rule below 0.18 micrometers by the KrF excimer laser exposure. The tool can crete Levenson type PSM used being coupled with a binary mask adopting a double exposure method for positive photo resist. By using graphs, this tool automatically creates alternative PSM patterns. Moreover, it does not give any phase conflicts. By adopting it to actual embedded DRAM in logic cells, we have provided 0.16 micrometers gate resist patterns at both random logic and DRAM areas. The patterns were fabricated using two masks with the double exposure method. Gate line width has been well controlled under a practical exposure-focus window.

Paediatric Automatic Phonological Analysis Tools (APAT).

PubMed

Saraiva, Daniela; Lousada, Marisa; Hall, Andreia; Jesus, Luis M T

2017-12-01

To develop the pediatric Automatic Phonological Analysis Tools (APAT) and to estimate inter and intrajudge reliability, content validity, and concurrent validity. The APAT were constructed using Excel spreadsheets with formulas. The tools were presented to an expert panel for content validation. The corpus used in the Portuguese standardized test Teste Fonético-Fonológico - ALPE produced by 24 children with phonological delay or phonological disorder was recorded, transcribed, and then inserted into the APAT. Reliability and validity of APAT were analyzed. The APAT present strong inter- and intrajudge reliability (>97%). The content validity was also analyzed (ICC = 0.71), and concurrent validity revealed strong correlations between computerized and manual (traditional) methods. The development of these tools contributes to fill existing gaps in clinical practice and research, since previously there were no valid and reliable tools/instruments for automatic phonological analysis, which allowed the analysis of different corpora.

Automatically Assessing Lexical Sophistication: Indices, Tools, Findings, and Application

ERIC Educational Resources Information Center

Kyle, Kristopher; Crossley, Scott A.

2015-01-01

This study explores the construct of lexical sophistication and its applications for measuring second language lexical and speaking proficiency. In doing so, the study introduces the Tool for the Automatic Analysis of LExical Sophistication (TAALES), which calculates text scores for 135 classic and newly developed lexical indices related to word…

Ensuring production-worthy OPC recipes using large test structure arrays

NASA Astrophysics Data System (ADS)

Cork, Christopher; Zimmermann, Rainer; Mei, Xin; Shahin, Alexander

2007-03-01

The continual shrinking of design rules as the industry follows Moore's Law and the associated need for low k1 processes, have resulted in more layout configurations becoming difficult to print within the required tolerances. OPC recipes have needed to become more complex as tolerances decreased and acceptable corrections harder to find with simple algorithms. With this complexity comes the possibility of coding errors and ensuring the solutions are truly general. OPC Verification tools can check the quality of a correction based on pre-determined specifications for CD variation, line-end pullback and Edge Placement Error and then highlight layout configuration where violations are found. The problem facing a Mask Tape-Out group is that they usually have little control over the Design Styles coming in. Different approaches to eliminating problematic layouts have included highly restrictive Design Rules [1], whereby certain pitches or orientations are disallowed. Now these design rules are either becoming too complex or they overly restrict the designer from benefiting from the reduced pitch of the new node. The tight link between Design and Mask Tape-Out found in Integrated Device Manufacturers [2] (IDMs) i.e. companies that control both design and manufacturing can do much to dictate manufacturing friendly layout styles, and push ownership of problem resolution back to design groups. In fact this has been perceived as such an issue that a new class of products for designers that perform Lithographic Compliance Check on design layout is an emerging technology [3]. In contrast to IDMs, Semiconductor Foundries are presented with a much larger variety of design styles and a set of Fabless customers who generally are less knowledgeable in terms of understanding the impact of their layout on manufacturability and how to correct issues. The robustness requirements of a foundry's OPC correction recipe, therefore needs to be greater than that for an IDM's tape-out group. An OPC correction recipe which gives acceptable verification results, based solely on one customer GDS is clearly not sufficient to guarantee that all future tape-outs from multiple customers will be similarly clean. Ad hoc changes made in reaction to problems seen at verification are risky, while they may solve one particular layout issue on one product there is no guarantee that the problem may simply shift to another configuration on a yet to be manufactured part. The need to re-qualify a recipe over multiple products at each recipe change can easily results in excessive computational requirements. A single layer at an advanced node typically needs overnight runs on a large processor farm. Much of this layout, however, is extremely repetitive, made from a few standard cells placed tens of thousands of times. An alternative and more efficient approach, suggested by this paper as a screening methodology, is to encapsulate the problematic structures into a programmable test structure array. The dimensions of these test structures are parameterized in software such that they can be generated with these dimensions varied over the space of the design rules and conceivable design styles. By verifying the new recipe over these test structures one could more quickly gain confidence that this recipe would be robust over multiple tape-outs. This paper gives some examples of the implementation of this methodology.

Staff Movements

NASA Astrophysics Data System (ADS)

Huber, M. C. E.

1986-09-01

Los astronomos de ESO dedican una considerable parte de su tiempo a la preparacion de solicitudes para tiempo de observacion en La Silla. Sin embargo, debido a la gran demanda par los telescopios, se debe hacer una seleccion, aveces drastica, de los programas de observacion presentados. EI Comite de Programas de Observacion (OPC) tiene como tarea evaluar el merito cientifico de las solicitudes presentadas. Basada en las recomendaciones dei OPC, ESO prepara una Lista de Tiempos de Observacion en la cual distribuye el tiempo disponible en los telescopios a los programas mejor evaluados.

Adding Automatic Evaluation to Interactive Virtual Labs

ERIC Educational Resources Information Center

Farias, Gonzalo; Muñoz de la Peña, David; Gómez-Estern, Fabio; De la Torre, Luis; Sánchez, Carlos; Dormido, Sebastián

2016-01-01

Automatic evaluation is a challenging field that has been addressed by the academic community in order to reduce the assessment workload. In this work we present a new element for the authoring tool Easy Java Simulations (EJS). This element, which is named automatic evaluation element (AEE), provides automatic evaluation to virtual and remote…

Chromatin remodeling and histone modification in the conversion of oligodendrocyte precursors to neural stem cells

PubMed Central

Kondo, Toru; Raff, Martin

2004-01-01

We showed previously that purified rat oligodendrocyte precursor cells (OPCs) can be induced by extracellular signals to convert to multipotent neural stem-like cells (NSLCs), which can then generate both neurons and glial cells. Because the conversion of precursor cells to stem-like cells is of both intellectual and practical interest, it is important to understand its molecular basis. We show here that the conversion of OPCs to NSLCs depends on the reactivation of the sox2 gene, which in turn depends on the recruitment of the tumor suppressor protein Brca1 and the chromatin-remodeling protein Brahma (Brm) to an enhancer in the sox2 promoter. Moreover, we show that the conversion is associated with the modification of Lys 4 and Lys 9 of histone H3 at the same enhancer. Our findings suggest that the conversion of OPCs to NSLCs depends on progressive chromatin remodeling, mediated in part by Brca1 and Brm. PMID:15574597

Osteoblast Production by Reserved Progenitor Cells in Zebrafish Bone Regeneration and Maintenance.

PubMed

Ando, Kazunori; Shibata, Eri; Hans, Stefan; Brand, Michael; Kawakami, Atsushi

2017-12-04

Mammals cannot re-form heavily damaged bones as in large fracture gaps, whereas zebrafish efficiently regenerate bones even after amputation of appendages. However, the source of osteoblasts that mediate appendage regeneration is controversial. Several studies in zebrafish have shown that osteoblasts are generated by dedifferentiation of existing osteoblasts at injured sites, but other observations suggest that de novo production of osteoblasts also occurs. In this study, we found from cell-lineage tracing and ablation experiments that a group of cells reserved in niches serves as osteoblast progenitor cells (OPCs) and has a significant role in fin ray regeneration. Besides regeneration, OPCs also supply osteoblasts for normal bone maintenance. We further showed that OPCs are derived from embryonic somites, as is the case with embryonic osteoblasts, and are replenished from mesenchymal precursors in adult zebrafish. Our findings reveal that reserved progenitors are a significant and complementary source of osteoblasts for zebrafish bone regeneration. Copyright © 2017 Elsevier Inc. All rights reserved.

Enabling full-field physics-based optical proximity correction via dynamic model generation

NASA Astrophysics Data System (ADS)

Lam, Michael; Clifford, Chris; Raghunathan, Ananthan; Fenger, Germain; Adam, Kostas

2017-07-01

As extreme ultraviolet lithography becomes closer to reality for high volume production, its peculiar modeling challenges related to both inter and intrafield effects have necessitated building an optical proximity correction (OPC) infrastructure that operates with field position dependency. Previous state-of-the-art approaches to modeling field dependency used piecewise constant models where static input models are assigned to specific x/y-positions within the field. OPC and simulation could assign the proper static model based on simulation-level placement. However, in the realm of 7 and 5 nm feature sizes, small discontinuities in OPC from piecewise constant model changes can cause unacceptable levels of edge placement errors. The introduction of dynamic model generation (DMG) can be shown to effectively avoid these dislocations by providing unique mask and optical models per simulation region, allowing a near continuum of models through the field. DMG allows unique models for electromagnetic field, apodization, aberrations, etc. to vary through the entire field and provides a capability to precisely and accurately model systematic field signatures.

Head and neck cancers associated with exposure to the September 11, 2001 World Trade Center terrorist attacks.

PubMed

Leeman, Jonathan E; McBride, Sean M; Spielsinger, Daniel; Sherman, Eric J; Wong, Richard; Riaz, Nadeem; Lee, Nancy Y; Tsai, Chiaojung Jillian

2018-06-15

Exposure at the World Trade Center (WTC) terrorist collapse site on September 11, 2001 has been associated with increased cancer risk, though observational studies have identified very few cases of head and neck cancer (HNC) in exposed individuals. Eighty seven patients were identified who presented to our institution with HNC diagnosed from 2002 to 2017 who reported WTC exposure. The annual number and proportion of WTC-exposed HNC patients has been steadily increasing since 2002, with most cancers developing >10 years following the event. Furthermore, WTC-exposed patients with human papillomavirus (HPV)-positive OPC experienced significantly inferior outcomes compared with non-WTC exposed patients with HPV+ OPC (disease free survival 80.1% vs. 65.6% at 4 years, p = 0.04). This single institution study cannot establish evidence of exposure-mediated causation but higher recurrence rates in the WTC-exposed HPV+ OPC population suggest a treatment refractory tumor biology and possible exposure synergism with HPV-mediated oncogenesis. © 2018 UICC.

Automatic Assessment of 3D Modeling Exams

ERIC Educational Resources Information Center

Sanna, A.; Lamberti, F.; Paravati, G.; Demartini, C.

2012-01-01

Computer-based assessment of exams provides teachers and students with two main benefits: fairness and effectiveness in the evaluation process. This paper proposes a fully automatic evaluation tool for the Graphic and Virtual Design (GVD) curriculum at the First School of Architecture of the Politecnico di Torino, Italy. In particular, the tool is…

Building Automatic Grading Tools for Basic of Programming Lab in an Academic Institution

NASA Astrophysics Data System (ADS)

Harimurti, Rina; Iwan Nurhidayat, Andi; Asmunin

2018-04-01

The skills of computer programming is a core competency that must be mastered by students majoring in computer sciences. The best way to improve this skill is through the practice of writing many programs to solve various problems from simple to complex. It takes hard work and a long time to check and evaluate the results of student labs one by one, especially if the number of students a lot. Based on these constrain, web proposes Automatic Grading Tools (AGT), the application that can evaluate and deeply check the source code in C, C++. The application architecture consists of students, web-based applications, compilers, and operating systems. Automatic Grading Tools (AGT) is implemented MVC Architecture and using open source software, such as laravel framework version 5.4, PostgreSQL 9.6, Bootstrap 3.3.7, and jquery library. Automatic Grading Tools has also been tested for real problems by submitting source code in C/C++ language and then compiling. The test results show that the AGT application has been running well.

Electrical safety device

DOEpatents

White, David B.

1991-01-01

An electrical safety device for use in power tools that is designed to automatically discontinue operation of the power tool upon physical contact of the tool with a concealed conductive material. A step down transformer is used to supply the operating power for a disconnect relay and a reset relay. When physical contact is made between the power tool and the conductive material, an electrical circuit through the disconnect relay is completed and the operation of the power tool is automatically interrupted. Once the contact between the tool and conductive material is broken, the power tool can be quickly and easily reactivated by a reset push button activating the reset relay. A remote reset is provided for convenience and efficiency of operation.

Role of nitric oxide and antioxidant enzymes in the pathogenesis of oral cancer.

PubMed

Patel, Jayendrakumar B; Shah, Franky D; Shukla, Shilin N; Shah, Pankaj M; Patel, Prabhudas S

2009-01-01

Oral cancer is the leading malignancy in India. Nitric oxide and antioxidant enzymes play an important role in etiology of oral cancer. Therefore, the present study evaluates nitric oxide and antioxidant enzyme levels in healthy individual without tobacco habits (NHT, N=30) and healthy individuals with tobacco habits (WHT, n=90), patients with oral precancers (OPC, n=15) and oral cancer patients (n=126). Blood samples were collected from the subjects. NO2 + NO3 (nitrite+nitrate), superoxide dismutase (SOD) and catalase levels were estimated using highly specific spectrophotometeric methods. Statistical analysis was done by SPSS statistical software version 10. Mean plasma NO2 + NO3 levels were elevated in patients with OPC and oral cancer patients as compared to the controls. Mean activities of erythrocyte SOD and catalase were higher in WHT than NHT. Erythrocyte SOD and catalase levels were higher in WHT and patients with OPC as compared to NHT. The erythrocyte SOD and catalase activities were lower in oral cancer patients than patients with OPC. The erythrocyte SOD activity was higher in advanced oral cancer than the early disease. Erythrocyte catalase activity was lower in poorly differentiated tumors than well and moderately differentiated tumors. Pearson's correlation analysis revealed that alterations in plasma NO2 + NO3 levels were negatively associated with changes in erythrocyte SOD activities. The data revealed that the alterations in antioxidant activities were associated with production of nitric oxide in oral cancer, which may have significant role in oral carcinogenesis.

Interleukin-17-Induced Protein Lipocalin 2 Is Dispensable for Immunity to Oral Candidiasis

PubMed Central

Ferreira, Maria Carolina; Whibley, Natasha; Mamo, Anna J.; Siebenlist, Ulrich; Chan, Yvonne R.

2014-01-01

Oropharyngeal candidiasis (OPC; thrush) is an opportunistic fungal infection caused by the commensal microbe Candida albicans. Immunity to OPC is strongly dependent on CD4+ T cells, particularly those of the Th17 subset. Interleukin-17 (IL-17) deficiency in mice or humans leads to chronic mucocutaneous candidiasis, but the specific downstream mechanisms of IL-17-mediated host defense remain unclear. Lipocalin 2 (Lcn2; 24p3; neutrophil gelatinase-associated lipocalin [NGAL]) is an antimicrobial host defense factor produced in response to inflammatory cytokines, particularly IL-17. Lcn2 plays a key role in preventing iron acquisition by bacteria that use catecholate-type siderophores, and lipocalin 2−/− mice are highly susceptible to infection by Escherichia coli and Klebsiella pneumoniae. The role of Lcn2 in mediating immunity to fungi is poorly defined. Accordingly, in this study, we evaluated the role of Lcn2 in immunity to oral infection with C. albicans. Lcn2 is strongly upregulated following oral infection with C. albicans, and its expression is almost entirely abrogated in mice with defective IL-17 signaling (IL-17RA−/− or Act1−/− mice). However, Lcn2−/− mice were completely resistant to OPC, comparably to wild-type (WT) mice. Moreover, Lcn2 deficiency mediated protection from OPC induced by steroid immunosuppression. Therefore, despite its potent regulation during C. albicans infection, Lcn2 is not required for immunity to mucosal candidiasis. PMID:24343647

Oropharyngeal candidiasis in head and neck cancer patients in Iran: Species identification, antifungal susceptibility and pathogenic characterization.

PubMed

Jahanshiri, Z; Manifar, S; Moosa, H; Asghari-Paskiabi, F; Mahmoodzadeh, H; Shams-Ghahfarokhi, M; Razzaghi-Abyaneh, M

2018-06-01

Oropharyngeal candidiasis (OPC) is the most frequent opportunistic fungal infection in head and neck cancer patients. This study was done to identify the Candida species, which cause OPC, and to evaluate their antifungal susceptibility pattern and pathogenic characteristics in Iranian head and neck cancer patients treated by radiotherapy. The oral clinical samples were determined by culturing on CHROMagar, carbohydrate assimilation and ITS sequencing methods. Biofilm formation, phospholipase and proteinase activity and antifungal susceptibility were examined too. Among 54 patients with confirmed OPC, 39 (72.22%) patients were male and 15 (27.77%) were female. The most frequently Candida species from a total of 60 isolates was C. albicans (53.3%), followed by C. tropicalis (21.66%), C. glabrata (15%), C. kefyr (5%) and C. dubliniensis (1.66%). All the isolates were high-producers of biofilm. All of Candida isolates were proteinase positive and 47 isolates (81.04%) represented phospholipase activity. The maximum and minimum rates of antifungal resistance belonged to ketoconazole (93.75% of C. albicans and 89.28% of Candida non-albicans) and fluconazole (62.50% and 42.85% of C. albicans and Candida non-albicans), respectively. The most effective antifungal against all candida isolates was fluconazole. Our data can estimate abundance of OPC in male and female head and neck cancer patients and is helpful to use effective strategies for antifungal treatment, prophylaxis, and preventive therapies in these patients. Copyright © 2018. Published by Elsevier Masson SAS.

Model-based virtual VSB mask writer verification for efficient mask error checking and optimization prior to MDP

NASA Astrophysics Data System (ADS)

Pack, Robert C.; Standiford, Keith; Lukanc, Todd; Ning, Guo Xiang; Verma, Piyush; Batarseh, Fadi; Chua, Gek Soon; Fujimura, Akira; Pang, Linyong

2014-10-01

A methodology is described wherein a calibrated model-based `Virtual' Variable Shaped Beam (VSB) mask writer process simulator is used to accurately verify complex Optical Proximity Correction (OPC) and Inverse Lithography Technology (ILT) mask designs prior to Mask Data Preparation (MDP) and mask fabrication. This type of verification addresses physical effects which occur in mask writing that may impact lithographic printing fidelity and variability. The work described here is motivated by requirements for extreme accuracy and control of variations for today's most demanding IC products. These extreme demands necessitate careful and detailed analysis of all potential sources of uncompensated error or variation and extreme control of these at each stage of the integrated OPC/ MDP/ Mask/ silicon lithography flow. The important potential sources of variation we focus on here originate on the basis of VSB mask writer physics and other errors inherent in the mask writing process. The deposited electron beam dose distribution may be examined in a manner similar to optical lithography aerial image analysis and image edge log-slope analysis. This approach enables one to catch, grade, and mitigate problems early and thus reduce the likelihood for costly long-loop iterations between OPC, MDP, and wafer fabrication flows. It moreover describes how to detect regions of a layout or mask where hotspots may occur or where the robustness to intrinsic variations may be improved by modification to the OPC, choice of mask technology, or by judicious design of VSB shots and dose assignment.

Modulation of the Innate Immune Response by Human Neural Precursors Prevails over Oligodendrocyte Progenitor Remyelination to Rescue a Severe Model of Pelizaeus-Merzbacher Disease.

PubMed

Marteyn, Antoine; Sarrazin, Nadège; Yan, Jun; Bachelin, Corinne; Deboux, Cyrille; Santin, Mathieu D; Gressens, Pierre; Zujovic, Violetta; Baron-Van Evercooren, Anne

2016-04-01

Pelizaeus-Merzbacher disease (PMD) results from an X-linked misexpression of proteolipid protein 1 (PLP1). This leukodystrophy causes severe hypomyelination with progressive inflammation, leading to neurological dysfunctions and shortened life expectancy. While no cure exists for PMD, experimental cell-based therapy in the dysmyelinated shiverer model suggested that human oligodendrocyte progenitor cells (hOPCs) or human neural precursor cells (hNPCs) are promising candidates to treat myelinopathies. However, the fate and restorative advantages of human NPCs/OPCs in a relevant model of PMD has not yet been addressed. Using a model of Plp1 overexpression, resulting in demyelination with progressive inflammation, we compared side-by-side the therapeutic benefits of intracerebrally grafted hNPCs and hOPCs. Our findings reveal equal integration of the donor cells within presumptive white matter tracks. While the onset of exogenous remyelination was earlier in hOPCs-grafted mice than in hNPC-grafted mice, extended lifespan occurred only in hNPCs-grafted animals. This improved survival was correlated with reduced neuroinflammation (microglial and astrocytosis loads) and microglia polarization toward M2-like phenotype followed by remyelination. Thus modulation of neuroinflammation combined with myelin restoration is crucial to prevent PMD pathology progression and ensure successful rescue of PMD mice. These findings should help to design novel therapeutic strategies combining immunomodulation and stem/progenitor cell-based therapy for disorders associating hypomyelination with inflammation as observed in PMD. © 2015 AlphaMed Press.

Calcium sulfoaluminate cement blended with OPC: A potential binder to encapsulate low-level radioactive slurries of complex chemistry

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

Cau Dit Coumes, Celine; Courtois, Simone; Peysson, Sandrine

Investigations were carried out in order to solidify in cement a low-level radioactive waste of complex chemistry obtained by mixing two process streams, a slurry produced by ultra-filtration and an evaporator concentrate with a salinity of 600 gxL{sup -1}. Direct cementation with Portland cement (OPC) was not possible due to a very long setting time of cement resulting from borates and phosphates contained in the waste. According to a classical approach, this difficulty could be solved by pre-treating the waste to reduce adverse cement-waste interactions. A two-stage process was defined, including precipitation of phosphates and sulfates at 60 deg. Cmore » by adding calcium and barium hydroxide to the waste stream, and encapsulation with a blend of OPC and calcium aluminate cement (CAC) to convert borates into calcium quadriboroaluminate. The material obtained with a 30% waste loading complied with specifications. However, the pre-treatment step made the process complex and costly. A new alternative was then developed: the direct encapsulation of the waste with a blend of OPC and calcium sulfoaluminate cement (CSA) at room temperature. Setting inhibition was suppressed, which probably resulted from the fact that, when hydrating, CSA cement formed significant amounts of ettringite and calcium monosulfoaluminate hydrate which incorporated borates into their structure. As a consequence, the waste loading could be increased to 56% while keeping acceptable properties at the laboratory scale.« less

Safe corrosion inhibitor for treating cooling water on heat power engineering plants

NASA Astrophysics Data System (ADS)

Nikolaeva, L. A.; Khasanova, D. I.; Mukhutdinova, E. R.; Safin, D. Kh.; Sharifullin, I. G.

2017-08-01

Heat power engineering (HPE) consumes significant volumes of water. There are, therefore, problems associated with corrosion, biological fouling, salt deposits, and sludge formation on functional surfaces of heat power equipment. One of the effective ways to solve these problems is the use of inhibitory protection. The development of new Russian import-substituting environmentally friendly inhibitors is very relevant. This work describes experimental results on the OPC-800 inhibitor (TU 2415-092-00206 457-2013), which was produced at Karpov Chemical Plant and designed to remove mineral deposits, scale, and biological fouling from the surfaces of water-rotation node systems on HPE objects. This reagent is successfully used as an effective corrosion inhibitor in the water recycling systems of Tatarstan petrochemical enterprises. To save fresh make-up water, the circulating system is operated in a no-blow mode, which is characterized by high evaporation and salt content coefficients. It was experimentally found that corrosion rate upon treatment of recycled water with the OPC-800 inhibitor is 0.08-0.10 mm/year. HPE mainly uses inhibitors based on oxyethylidene diphosphonic (OEDPA) and nitrilotrimethylphosphonic (NTMPA) acids. The comparative characteristic of inhibition efficiency for OPC-800 and OEDF-Zn-U2 is given. The results obtained indicate that OPC-800 can be used as an inhibitor for treatment of cooling water in HPE plants. In this case, it is necessary to take into account the features of water rotation of a thermal power plant.

Automatic feed system for ultrasonic machining

DOEpatents

Calkins, Noel C.

1994-01-01

Method and apparatus for ultrasonic machining in which feeding of a tool assembly holding a machining tool toward a workpiece is accomplished automatically. In ultrasonic machining, a tool located just above a workpiece and vibrating in a vertical direction imparts vertical movement to particles of abrasive material which then remove material from the workpiece. The tool does not contact the workpiece. Apparatus for moving the tool assembly vertically is provided such that it operates with a relatively small amount of friction. Adjustable counterbalance means is provided which allows the tool to be immobilized in its vertical travel. A downward force, termed overbalance force, is applied to the tool assembly. The overbalance force causes the tool to move toward the workpiece as material is removed from the workpiece.

Physical resist models and their calibration: their readiness for accurate EUV lithography simulation

NASA Astrophysics Data System (ADS)

Klostermann, U. K.; Mülders, T.; Schmöller, T.; Lorusso, G. F.; Hendrickx, E.

2010-04-01

In this paper, we discuss the performance of EUV resist models in terms of predictive accuracy, and we assess the readiness of the corresponding model calibration methodology. The study is done on an extensive OPC data set collected at IMEC for the ShinEtsu resist SEVR-59 on the ASML EUV Alpha Demo Tool (ADT), with the data set including more than thousand CD values. We address practical aspects such as the speed of calibration and selection of calibration patterns. The model is calibrated on 12 process window data series varying in pattern width (32, 36, 40 nm), orientation (H, V) and pitch (dense, isolated). The minimum measured feature size at nominal process condition is a 32 nm CD at a dense pitch of 64 nm. Mask metrology is applied to verify and eventually correct nominal width of the drawn CD. Cross-sectional SEM information is included in the calibration to tune the simulated resist loss and sidewall angle. The achieved calibration RMS is ~ 1.0 nm. We show what elements are important to obtain a well calibrated model. We discuss the impact of 3D mask effects on the Bossung tilt. We demonstrate that a correct representation of the flare level during the calibration is important to achieve a high predictability at various flare conditions. Although the model calibration is performed on a limited subset of the measurement data (one dimensional structures only), its accuracy is validated based on a large number of OPC patterns (at nominal dose and focus conditions) not included in the calibration; validation RMS results as small as 1 nm can be reached. Furthermore, we study the model's extendibility to two-dimensional end of line (EOL) structures. Finally, we correlate the experimentally observed fingerprint of the CD uniformity to a model, where EUV tool specific signatures are taken into account.

Oral and oropharyngeal cancer and the role of sexual behaviour: a systematic review.

PubMed

Chancellor, James A; Ioannides, Sally J; Elwood, James M

2016-09-19

This systematic review identified and evaluated the evidence for the role of sexual behaviours in the development of oropharyngeal cancers (OPCs) and oral cavity cancers (OCCs). Following the PRISMA guidelines, we identified observational and interventional studies reporting associations between several different sexual behaviours and OPC or OCC. Study quality was assessed independently by two reviewers using a validated scoring system. From 513 papers identified, 21, reporting on 20 studies, fulfilled the inclusion criteria. Two cohort studies were rated as moderate quality. The 18 case-control studies were rated as weak; nine comparing people with OPC or OCC to people without cancer, eight comparing HPV-positive to HPV-negative cancer patients and one comparing OPCs to other head and neck cancers. One study was a pooled analysis of seven of the included studies with some additional information. Twelve sexual behaviours were assessed and 69 associations reported. The studies differed in the comparisons made, the sexual behaviours assessed, and how these were reported and categorized, so no quantitative meta-analyses were appropriate. Most studies combined OPC and OCC. Several significantly increased risks were seen with a high number of lifetime sexual partners (nine studies) and with the practice of oral sex (five studies), although two studies found a significant negative association with OCC and ever performing oral sex. Two cohort studies of men and women in homosexual relationships found increases in oral cancer risk, and a cohort study of men married to women who had a history of cervical cancer also showed an increased risk of oral cancers. Results for other sexual behaviours were limited and inconsistent, and these included the following: younger age at first sexual intercourse, number of lifetime oral sex partners, the practice of oral-anal sex, the number of oral-anal sex partners, and ever performing anal sex. Only one study assessed casual sex, never or rare use of a condom and having a sexual partner with a history of genital warts, finding significant associations in the two former behaviours. The current evidence for sexual behaviours being risk factors for oral and oropharyngeal cancer is limited and inconsistent. Evidence suggests that the number of sexual partners and performing oral sex are associated with a greater risk. Furthermore men whose partners have had cervical cancer may have an increased risk. More studies looking at OPC specifically will be useful to determine whether these behaviours are subsite-selective. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Automatic programming of simulation models

NASA Technical Reports Server (NTRS)

Schroer, Bernard J.; Tseng, Fan T.; Zhang, Shou X.; Dwan, Wen S.

1988-01-01

The objective of automatic programming is to improve the overall environment for describing the program. This improved environment is realized by a reduction in the amount of detail that the programmer needs to know and is exposed to. Furthermore, this improved environment is achieved by a specification language that is more natural to the user's problem domain and to the user's way of thinking and looking at the problem. The goal of this research is to apply the concepts of automatic programming (AP) to modeling discrete event simulation system. Specific emphasis is on the design and development of simulation tools to assist the modeler define or construct a model of the system and to then automatically write the corresponding simulation code in the target simulation language, GPSS/PC. A related goal is to evaluate the feasibility of various languages for constructing automatic programming simulation tools.

Improvement in defect classification efficiency by grouping disposition for reticle inspection

NASA Astrophysics Data System (ADS)

Lai, Rick; Hsu, Luke T. H.; Chang, Peter; Ho, C. H.; Tsai, Frankie; Long, Garrett; Yu, Paul; Miller, John; Hsu, Vincent; Chen, Ellison

2005-11-01

As the lithography design rule of IC manufacturing continues to migrate toward more advanced technology nodes, the mask error enhancement factor (MEEF) increases and necessitates the use of aggressive OPC features. These aggressive OPC features pose challenges to reticle inspection due to high false detection, which is time-consuming for defect classification and impacts the throughput of mask manufacturing. Moreover, higher MEEF leads to stricter mask defect capture criteria so that new generation reticle inspection tool is equipped with better detection capability. Hence, mask process induced defects, which were once undetectable, are now detected and results in the increase of total defect count. Therefore, how to review and characterize reticle defects efficiently is becoming more significant. A new defect review system called ReviewSmart has been developed based on the concept of defect grouping disposition. The review system intelligently bins repeating or similar defects into defect groups and thus allows operators to review massive defects more efficiently. Compared to the conventional defect review method, ReviewSmart not only reduces defect classification time and human judgment error, but also eliminates desensitization that is formerly inevitable. In this study, we attempt to explore the most efficient use of ReviewSmart by evaluating various defect binning conditions. The optimal binning conditions are obtained and have been verified for fidelity qualification through inspection reports (IRs) of production masks. The experiment results help to achieve the best defect classification efficiency when using ReviewSmart in the mask manufacturing and development.

Tetracycline-regulated expression of OLIG2 gene in human dental pulp stem cells lead to mouse sciatic nerve regeneration upon transplantation.

PubMed

Askari, N; Yaghoobi, M M; Shamsara, M; Esmaeili-Mahani, S

2015-10-01

Numerous studies have indicated dental pulp stem cells (DPSCs) potency to differentiate into several types of cell lineages. Oligodendrocyte lineage transcription factor 2 (OLIG2) plays an important role in the oligodendrogenic pathway. In this study, a tetracycline (Tet)-inducible system expressing OLIG2 gene was transfected into human DPSCs to direct their differentiation toward oligodendrocyte progenitor cells (OPCs). Following induction, the expression of stage-specific markers was studied by Reverse Transcription quantitative Polymerase Chain Reaction (RT-qPCR), immunocytochemistry and western blotting. In the following, the cells were transplanted into the mouse model of local sciatic demyelination damage by lysolecithin. Recovery of lysolecithin-induced lesions in sciatic nerve was studied by treadmill exercise, von Frey filament test and hind paw withdrawal in response to a thermal stimulus. Improvement of behavioral symptoms was efficiently observed from the second week to the sixth week post-transplantation. Our findings showed that exogenous expression of the OLIG2 gene by a Tet-regulated system could be used as an efficient way to induce the differentiation of DPSCs into functional oligodendrocytes. Meanwhile, the DPSC-derived OPCs have relevant therapeutic potential in the animal model of sciatic nerve injury and therefore might represent a valuable tool for stem cell-based therapy in inflammatory and degenerative diseases of the peripheral and central nervous systems (CNSs). Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

A novel image toggle tool for comparison of serial mammograms: automatic density normalization and alignment-development of the tool and initial experience.

PubMed

Honda, Satoshi; Tsunoda, Hiroko; Fukuda, Wataru; Saida, Yukihisa

2014-12-01

The purpose is to develop a new image toggle tool with automatic density normalization (ADN) and automatic alignment (AA) for comparing serial digital mammograms (DMGs). We developed an ADN and AA process to compare the images of serial DMGs. In image density normalization, a linear interpolation was applied by taking two points of high- and low-brightness areas. The alignment was calculated by determining the point of the greatest correlation while shifting the alignment between the current and prior images. These processes were performed on a PC with a 3.20-GHz Xeon processor and 8 GB of main memory. We selected 12 suspected breast cancer patients who had undergone screening DMGs in the past. Automatic processing was retrospectively performed on these images. Two radiologists subjectively evaluated them. The process of the developed algorithm took approximately 1 s per image. In our preliminary experience, two images could not be aligned approximately. When they were aligned, image toggling allowed detection of differences between examinations easily. We developed a new tool to facilitate comparative reading of DMGs on a mammography viewing system. Using this tool for toggling comparisons might improve the interpretation efficiency of serial DMGs.

The automatic back-check mechanism of mask tooling database and automatic transmission of mask tooling data

NASA Astrophysics Data System (ADS)

Xu, Zhe; Peng, M. G.; Tu, Lin Hsin; Lee, Cedric; Lin, J. K.; Jan, Jian Feng; Yin, Alb; Wang, Pei

2006-10-01

Nowadays, most foundries have paid more and more attention in order to reduce the CD width. Although the lithography technologies have developed drastically, mask data accuracy is still a big challenge than before. Besides, mask (reticle) price also goes up drastically such that data accuracy needs more special treatments.We've developed a system called eFDMS to guarantee the mask data accuracy. EFDMS is developed to do the automatic back-check of mask tooling database and the data transmission of mask tooling. We integrate our own EFDMS systems to engage with the standard mask tooling system K2 so that the upriver and the downriver processes of the mask tooling main body K2 can perform smoothly and correctly with anticipation. The competition in IC marketplace is changing from high-tech process to lower-price gradually. How to control the reduction of the products' cost more plays a significant role in foundries. Before the violent competition's drawing nearer, we should prepare the cost task ahead of time.

Automatic Tool for Local Assembly Structures

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

Whole community shotgun sequencing of total DNA (i.e. metagenomics) and total RNA (i.e. metatranscriptomics) has provided a wealth of information in the microbial community structure, predicted functions, metabolic networks, and is even able to reconstruct complete genomes directly. Here we present ATLAS (Automatic Tool for Local Assembly Structures) a comprehensive pipeline for assembly, annotation, genomic binning of metagenomic and metatranscriptomic data with an integrated framework for Multi-Omics. This will provide an open source tool for the Multi-Omic community at large.

Long-Term Quality of Life After Swallowing and Salivary-Sparing Chemo–Intensity Modulated Radiation Therapy in Survivors of Human Papillomavirus–Related Oropharyngeal Cancer

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

Vainshtein, Jeffrey M.; Moon, Dominic H.; Feng, Felix Y.

Purpose: To evaluate long-term health-related quality of life (HRQOL) in 2 prospective studies of chemo–intensity modulated radiation therapy (chemo-IMRT) for oropharyngeal cancer (OPC). Methods and Materials: Of 93 patients with stage III/IV OPC treated on prospective studies of swallowing and salivary organ-sparing chemo-IMRT, 69 were eligible for long-term HRQOL assessment. Three validated patient-reported instruments, the Head and Neck QOL (HNQOL) questionnaire, the University of Washington quality of life (UWQOL) questionnaire, and the Xerostomia Questionnaire (XQ), previously administered from baseline through 2 years in the parent studies, were readministered at long-term follow-up, along with the Short-Form 36. Long-term changes in HRQOL frommore » before treatment and 2 years were evaluated. Results: Forty patients (58%) with a median follow-up of 6.5 years participated, 39 of whom (97.5%) had confirmed human papillomavirus–positive OPC. Long term, no clinically significant worsening was detected in mean HRQOL scores compared with 2 years, with stable or improved HRQOL from before treatment in nearly all domains. “Moderate” or greater severity problems were uncommon, reported by 5% of patients for eating, 5% for swallowing, and 2.5% and 5% by HNQOL and UWQOL summary scores, respectively. Freedom from percutaneous endoscopic gastrostomy tube dependence and stricture dilation beyond 2 years was 97.5% and 95%, respectively. Eleven percent and 14% of patients reported “moderate” or “severe” long-term worsening in HNQOL Pain and Overall Bother domains, respectively, which were associated with mean dose to the cervical esophagus, larynx, and pharyngeal constrictors. Conclusions: At more than 6 years' median follow-up, OPC patients treated with swallowing and salivary organ-sparing chemo-IMRT reported stable or improved HRQOL in nearly all domains compared with both before treatment and 2-year follow-up. New late toxicity after 2 years was uncommon. Further emphasis on sparing the swallowing organs may yield additional HRQOL gains for long-term OPC survivors.« less

Wnt Signaling Specifies Anteroposterior Progenitor Zone Identity in the Drosophila Visual Center.

PubMed

Suzuki, Takumi; Trush, Olena; Yasugi, Tetsuo; Takayama, Rie; Sato, Makoto

2016-06-15

During brain development, various types of neuronal populations are produced from different progenitor pools to produce neuronal diversity that is sufficient to establish functional neuronal circuits. However, the molecular mechanisms that specify the identity of each progenitor pool remain obscure. Here, we show that Wnt signaling is essential for the specification of the identity of posterior progenitor pools in the Drosophila visual center. In the medulla, the largest component of the visual center, different types of neurons are produced from two progenitor pools: the outer proliferation center (OPC) and glial precursor cells (GPCs; also known as tips of the OPC). We found that OPC-type neurons are produced from the GPCs at the expense of GPC-type neurons when Wnt signaling is suppressed in the GPCs. In contrast, GPC-type neurons are ectopically induced when Wnt signaling is ectopically activated in the OPC. These results suggest that Wnt signaling is necessary and sufficient for the specification of the progenitor pool identity. We also found that Homothorax (Hth), which is temporally expressed in the OPC, is ectopically induced in the GPCs by suppression of Wnt signaling and that ectopic induction of Hth phenocopies the suppression of Wnt signaling in the GPCs. Thus, Wnt signaling is involved in regionalization of the fly visual center through the specification of the progenitor pool located posterior to the medulla by suppressing Hth expression. Brain consists of considerably diverse neurons of different origins. In mammalian brain, excitatory and inhibitory neurons derive from the dorsal and ventral telencephalon, respectively. Multiple progenitor pools also contribute to the neuronal diversity in fly brain. However, it has been unclear how differences between these progenitor pools are established. Here, we show that Wnt signaling, an evolutionarily conserved signaling, is involved in the process that establishes the differences between these progenitor pools. Because β-catenin signaling, which is under the control of Wnt ligands, specifies progenitor pool identity in the developing mammalian thalamus, Wnt signaling-mediated specification of progenitor pool identity may be conserved in insect and mammalian brains. Copyright © 2016 the authors 0270-6474/16/366503-11$15.00/0.

OPC-13013, a cyclic nucleotide phosphodiesterase type III, inhibitor, inhibits cell proliferation and transdifferentiation of cultured rat hepatic stellate cells.

PubMed

Shimizu, E; Kobayashi, Y; Oki, Y; Kawasaki, T; Yoshimi, T; Nakamura, H

1999-01-01

Activated hepatic stellate cells (HSC; lipocytes; Ito cells) proliferate and are responsible for extracellular matrix synthesis during hepatic fibrogenesis. During activation, HSC undergo transdifferentiation into myofibroblasts expressing alpha-smooth muscle actin (alpha-SMA). Adenosine 3', 5'-cyclic monophosphate (cyclic AMP) is an ubiquitous intracellular signaling molecule, and is upregulated by the activation of adenylate cyclase and downregulated via hydrolysis by cyclic nucleotide phosphodiesterases (PDEs). Recently, increased intracellular cyclic AMP has been shown to inhibit HSC activation. The aim of the current study was to determine the effects of inhibition of PDEs on cell proliferation and transdifferentiation in cultured rat HSC. Cell proliferation was determined by [3H]thymidine incorporation, and Western blot analysis was performed for detection of alpha-SMA, a phenotypic marker of transdifferentiation into myofibroblast. When the cells were exposed to 3-isobutyl-1-methylxanthine (IBMX; 50-1000 microM), a nonselective PDE inhibitor, serum-stimulated [3H]thymidine incorporation was suppressed in a dose-dependent manner with a maximum inhibition of 66% at a concentration of 500 microM OPC-13013 (1-60 microM), a selective PDE III isoenzyme inhibitor, induced a dose-dependent inhibitory effect on serum-stimulated DNA synthesis that reached a maximum inhibition of 95% at a concentration of 60 microM, while neither 8-methoxymethyl-3-isobutyl-1-methylxanthine (8-MMX), a PDE I isoenzyme inhibitor, nor Ro-20-1724, a PDE IV isoenzyme inhibitor, had an inhibitory effect. Western blot analysis revealed that IBMX or OPC-13013 decreased alpha-SMA expression, while other selective PDE isoenzyme inhibitors did not have a suppressive effect. IBMX, OPC-13013 or Ro-20-1724, but not 8-MMX augmented forskolin-induced increase in intracellular cyclic AMP levels although cyclic AMP levels were not affected by treatment with any of these PDE inhibitors alone. These data indicate that inhibition of PDEs, especially PDE III isoenzyme, can produce an inhibitory effect on HSC activation. The PDE III isoenzyme may contribute to the regulation of HSC activation during fibrogenesis. In addition, OPC-13013 may have the potential to inhibit initiation and progression of hepatic fibrosis by interfering with HSC activation.

CXCL12 Gene Therapy Ameliorates Ischemia-Induced White Matter Injury in Mouse Brain.

PubMed

Li, Yaning; Tang, Guanghui; Liu, Yanqun; He, Xiaosong; Huang, Jun; Lin, Xiaojie; Zhang, Zhijun; Yang, Guo-Yuan; Wang, Yongting

2015-10-01

Remyelination is an important repair process after ischemic stroke-induced white matter injury. It often fails because of the insufficient recruitment of oligodendrocyte progenitor cells (OPCs) to the demyelinated site or the inefficient differentiation of OPCs to oligodendrocytes. We investigated whether CXCL12 gene therapy promoted remyelination after middle cerebral artery occlusion in adult mice. The results showed that CXCL12 gene therapy at 1 week after ischemia could protect myelin sheath integrity in the perifocal region, increase the number of platelet-derived growth factor receptor-α (PDGFRα)-positive and PDGFRα/bromodeoxyuridine-double positive OPCs in the subventricular zone, and further enhance their migration to the ischemic lesion area. Coadministration of AMD3100, the antagonist for CXCL12 receptor CXCR4, eliminated the beneficial effect of CXCL12 on myelin sheath integrity and negatively influenced OPC proliferation and migration. At 5 weeks after ischemia, CXCR4 was found on the PDGFRα- and/or neuron/glia type 2 (NG2)-positive OPCs but not on the myelin basic protein-positive mature myelin sheaths, and CXCR7 was only expressed on the mature myelin sheath in the ischemic mouse brain. Our data indicated that CXCL12 gene therapy effectively protected white matter and promoted its repair after ischemic injury. The treatment at 1 week after ischemia is effective, suggesting that this strategy has a longer therapeutic time window than the treatments currently available. This study has demonstrated for the first time that CXCL12 gene therapy significantly ameliorates brain ischemia-induced white matter injury and promotes oligodendrocyte progenitor cell proliferation in the subventricular zone and migration to the perifocal area in the ischemic mouse brain. Additional data showed that CXCR4 receptor plays an important role during the proliferation and migration of oligodendrocyte progenitor cells, and CXCR7 might play a role during maturation. In contrast to many experimental studies that provide treatment before ischemic insult, CXCL12 gene therapy was performed 1 week after brain ischemia, which significantly prolonged the therapeutic time window of brain ischemia. ©AlphaMed Press.

Simultaneous quantitation of delamanid (OPC-67683) and its eight metabolites in human plasma using UHPLC-MS/MS.

PubMed

Meng, Min; Smith, Benjamin; Johnston, Brad; Carter, Spencer; Brisson, Jerry; Roth, Sharin E

2015-10-01

Delamanid (OPC-67683) is a novel nitro-dihydroimidazo-oxazole derivative that is being developed by Otsuka Pharmaceutical Co., Ltd., Japan (referred to as Otsuka hereafter) for the treatment of tuberculosis (TB). An ultra-high performance liquid chromatographic-tandem mass spectrometry (UHPLC-MS/MS) method has been developed and validated for the determination of OPC-67683 and its eight metabolites, DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721 and DM-6722 in human plasma to support regulated clinical development. During method development several technical challenges such as poor chromatography, separation of structural isomers, conversion of the analytes, instability in matrix and long cycle time were encountered and overcome. A protein precipitation extraction (PPE) was used to extract plasma samples (50μL) and the resulting extracts were analyzed using reversed phase UHPLC-MS/MS with a electrospray (ESI) and selected reaction monitoring (SRM). The method was fully validated over the calibration curve range of 1.00-500ng/mL for all nine analytes with linear regression and 1/x(2) weighting according to regulatory guidance for bioanalysis. Based on three inter-day precision and accuracy runs, the between-run % relative standard deviation (RSD) for all nine analytes varied from 0.0 to 11.9% and the accuracy ranged from 92.7% to 102.5% of nominal at all quality controls (QC) concentrations, including the lower limit of quantitation (LLOQ) QC at 1.00ng/mL. The extraction recovery of OPC-67683 and its eight metabolites were above 95%. Various short term and long term solution and matrix stability were established including the stability of OPC-67683 and its eight metabolites in human plasma for 708 days at -70°C. Although this method has been used to support regulated clinic studies during the last decade and over ten thousand samples have been analyzed, this is the first time that the method development process and validation data have been published. Copyright © 2015 Elsevier B.V. All rights reserved.

Teaching with technology: automatically receiving information from the internet and web.

PubMed

Wink, Diane M

2010-01-01

In this bimonthly series, the author examines how nurse educators can use the Internet and Web-based computer technologies such as search, communication, and collaborative writing tools, social networking and social bookmarking sites, virtual worlds, and Web-based teaching and learning programs. This article presents information and tools related to automatically receiving information from the Internet and Web.

Hypothermia-induced increase of oligodendrocyte precursor cells: Possible involvement of plasmalemmal voltage-dependent anion channel 1.

PubMed

Imada, Shinya; Yamamoto, Masahiro; Tanaka, Kayoko; Seiwa, Chika; Watanabe, Kenji; Kamei, Yoshimasa; Kozuma, Shiro; Taketani, Yuji; Asou, Hiroaki

2010-12-01

Hypothermia is believed to suppress cell proliferation by inducing apoptosis/necrosis and phase-specific/nonspecific cell cycle arrest, which are, directly or indirectly, related to a reduced energy supply. Intriguingly, hypothermia is known to improve neurological recovery of animals and humans exposed to focal brain hypoxic-ischemic injury. The underlying mechanism of the neuroprotective effect of hypothermia is unclear, although the prevention of neural cell apoptosis is thought to play a role. Herein we demonstrate that in vitro cell culture of oligodendrocyte precursor cells (OPCs) under conditions of mild hypothermia (31.5°C) results in an increase in cell number relative to cells cultured under normothermic conditions (37°C). Cell cycle analysis, immunoblotting of cyclins, TUNEL assay, and immunocytochemistry of OPC differentiation markers suggest that hypothermia shifts the balance between proliferation and apoptosis/differentiation toward proliferation. A combination of transcriptome analysis, pharmacological intervention, and immunoaffinity-based assays suggests a possible involvement of the Gα13-Rho GTPase Cdc42-ERK1/2 signaling cascade and voltage-dependent anion channel 1 (VDAC1), which associate or dissociate with Gα13 protein at 37°C and 31.5°C, respectively. Immunoelectron microscopy revealed the presence of VDAC1 in the plasma membrane of OPCs. Furthermore, the exogenous addition of impermeable VDAC1 inhibitors enhanced proliferation of OPCs at 37°C. These results may contribute to the elucidation of the mechanism of hypothermic neuroprotection as well as the possible novel role of plasmalemmal VDAC1. Copyright © 2010 Wiley-Liss, Inc.

Vasotocin- and mesotocin-induced increases in short-circuit current across tree frog skin.

PubMed

Takada, Makoto; Fujimaki-Aoba, Kayo; Hokari, Shigeru

2011-02-01

In adult amphibian skin, Na(+) crosses from outside to inside. This Na(+) transport can be measured as the amiloride-blockable short-circuit current (SCC) across the skin. We investigated the effects of arginine vasotocin (AVT) and mesotocin (MT), and those of antagonists of the vasopressin and oxytocin receptors, on the SCC across Hyla japonica skin. (1) Both AVT (100 pmol/L or more) and MT (1 nmol/L or more) increased the SCC. (2) The AVT- and MT-induced increases in SCC recovered with time (downregulation). (3) These AVT/MT-induced effects were blocked by application of OPC-31260 (vasopressin V(2)-receptor antagonist). (4) The OPC-31260 concentration needed to block the AVT-induced response was lower upon post-application (after application of agonist) than upon pre-application (before application of agonist), suggesting the number of receptors may have decreased after AVT application. (5) Upon repeated application of AVT (100 pmol/L), the induced SCC increase did not differ significantly between the 1st and 2nd applications. (6) The time to reach the half-maximum value of the AVT-induced or MT-induced increase in SCC was not significantly different between washout and post-application of OPC-31260, suggesting that post-application of OPC-31260 cleared AVT and MT from their receptors. The effects of AVT, MT, and their antagonists in H. japonica, which is adapted to a terrestrial habitat, are compared with our previously published data on Rana catesbeiana (=Lithobates catesbeianus), which is adapted to a semiaquatic habitat.

Organic Anion-Transporting Polypeptide and Efflux Transporter-Mediated Hepatic Uptake and Biliary Excretion of Cilostazol and Its Metabolites in Rats and Humans.

PubMed

Wang, Chong; Huo, Xiaokui; Wang, Changyuan; Meng, Qiang; Liu, Zhihao; Sun, Pengyuan; Cang, Jian; Sun, Huijun; Liu, Kexin

2017-09-01

Cilostazol undergoes extensive liver metabolism. However, the transporter-mediated hepatic disposition of cilostazol remains unknown. The present study was performed to investigate the hepatic uptake and biliary excretion of cilostazol and its metabolites (OPC-13015 and OPC-13213) using rat liver and human transporter-transfected cells in vitro. Cilostazol uptake by rat liver slices and isolated rat hepatocytes exhibited time-, concentration-, and temperature dependency and was decreased by Oatp inhibitors, which suggested that Oatp was involved in the hepatic uptake of cilostazol. Cilostazol uptake in rat hepatocytes, OATP1B1-, and OATP1B3-HEK293 cells indicated a saturable process with K m values of 2.7 μM, 17.7 μM, and 2.7 μM, respectively. Epigallocatechin gallate, cyclosporin A, rifampicin, and telmisartan inhibited cilostazol uptake in OATP1B1/1B3-HEK293 cells with K i values close to their clinical plasma concentration, which suggested possible drug-drug interactions in humans via OATP1B1/1B3. Moreover, the cumulative biliary excretion of cilostazol and OPC-13015 was significantly decreased by quinidine, bilirubin, and novobiocin in perfused rat liver, but OPC-13213 biliary excretion was only inhibited by novobiocin, which suggested that the efflux transporters Mrp2, Bcrp, and P-gp were involved in the biliary excretion of cilostazol and its metabolites. Our findings indicated that multiple transporters were involved in the hepatic disposition of cilostazol and its metabolites. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

A simple, xeno-free method for oligodendrocyte generation from human neural stem cells derived from umbilical cord: engagement of gelatinases in cell commitment and differentiation.

PubMed

Sypecka, Joanna; Ziemka-Nalecz, Małgorzata; Dragun-Szymczak, Patrycja; Zalewska, Teresa

2017-05-01

Oligodendrocyte progenitors (OPCs) are ranked among the most likely candidates for cell-based strategies aimed at treating neurodegenerative diseases accompanied by dys/demyelination of the central nervous system (CNS). In this regard, different sources of stem cells are being tested to elaborate xeno-free protocols for efficient generation of OPCs for clinical applications. In the present study, neural stem cells of human umbilical cord blood (HUCB-NSCs) have been used to derive OPCs and subsequently to differentiate them into mature, GalC-expressing oligodendrocytes. Applied components of the extracellular matrix (ECM) and the analogues of physiological substances known to increase glial commitment of neural stem cells have been shown to significantly increase the yield of the resulting OPC fraction. The efficiency of ECM components in promoting oligodendrocyte commitment and differentiation prompted us to investigate the potential role of gelatinases in those processes. Subsequently, endogenous and ECM metalloproteinases (MMPs) activity has been compared with that detected in primary cultures of rat oligodendrocytes in vitro, as well as in rat brains in vivo. The data indicate that gelatinases are engaged in gliogenesis both in vitro and in vivo, although differently, which presumably results from distinct extracellular conditions. In conclusion, the study presents an efficient xeno-free method of deriving oligodendrocyte from HUCB-NSCs and analyses the engagement of MMP-2/MMP-9 in the processes of cell commitment and maturation. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Human Traumatic Brain Injury Results in Oligodendrocyte Death and Increases the Number of Oligodendrocyte Progenitor Cells.

PubMed

Flygt, Johanna; Gumucio, Astrid; Ingelsson, Martin; Skoglund, Karin; Holm, Jonatan; Alafuzoff, Irina; Marklund, Niklas

2016-06-01

Oligodendrocyte (OL) death may contribute to white matter pathology, a common cause of network dysfunction and persistent cognitive problems in patients with traumatic brain injury (TBI). Oligodendrocyte progenitor cells (OPCs) persist throughout the adult CNS and may replace dead OLs. OL death and OPCs were analyzed by immunohistochemistry of human brain tissue samples, surgically removed due to life-threatening contusions and/or focal brain swelling at 60.6 ± 75 hours (range 4-192 hours) postinjury in 10 severe TBI patients (age 51.7 ± 18.5 years). Control brain tissue was obtained postmortem from 5 age-matched patients without CNS disorders. TUNEL and CC1 co-labeling was used to analyze apoptotic OLs, which were increased in injured brain tissue (p < 0.05), without correlation with time from injury until surgery. The OPC markers Olig2, A2B5, NG2, and PDGFR-α were used. In contrast to the number of single-labeled Olig2, A2B5, NG2, and PDGFR-α-positive cells, numbers of Olig2 and A2B5 co-labeled cells were increased in TBI samples (p < 0.05); this was inversely correlated with time from injury to surgery (r = -0.8, p < 0.05). These results indicate that severe focal human TBI results in OL death and increases in OPCs postinjury, which may influence white matter function following TBI. © 2016 American Association of Neuropathologists, Inc. All rights reserved.

Adsorption of superplasticizer admixtures on alkali-activated slag pastes

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

Palacios, M.; Houst, Y.F.; Bowen, P.

2009-08-15

Alkali-activated slag (AAS) binders are obtained by a manufacturing process less energy-intensive than ordinary Portland cement (OPC) and involves lower greenhouse gasses emission. These alkaline cements allow the production of high mechanical strength and durable concretes. In the present work, the adsorption of different superplasticizer admixtures (naphthalene-based, melamine-based and a vinyl copolymer) on the slag particles in AAS pastes using alkaline solutions with different pH values have been studied in detail. The effect of the superplasticizers on the yield stress and plastic viscosity of the AAS and OPC pastes have been also evaluated. The results obtained allowed us to concludemore » that the adsorption of the superplasticizers on AAS pastes is independent of the pH of the alkaline solutions used and lower than on OPC pastes. However, the effect of the admixtures on the rheological parameters depends directly on the type and dosage of the superplasticizer as well as of the binder used and, in the case of the AAS, on the pH of the alkaline activator solution. In 11.7-pH NaOH-AAS pastes the dosages of the superplasticizers required to attain similar reduction in the yield stress are ten-fold lower than for Portland cement. In this case the superplasticizers studied show a fluidizing effect considerably higher in 11.7-pH NaOH-AAS pastes than in OPC pastes. In 13.6-pH NaOH-AAS pastes, the only admixture observed to affect the rheological parameters is the naphthalene-based admixture due to its higher chemical stability in such extremely alkaline media.« less

Assessing the effects of automatically delivered stimulation on the use of simple exercise tools by students with multiple disabilities.

PubMed

Lancioni, Giulio E; Singh, Nirbhay N; O'Reilly, Mark F; Oliva, Doretta; Campodonico, Francesca; Groeneweg, Jop

2003-01-01

We assessed the effects of automatically delivered stimulation on the activity level and mood (indices of happiness) of three students with multiple disabilities during their use of a stepper and a stationary bicycle. The stimulation involved a pool of favorite stimulus events that were delivered automatically, through an electronic control system, while the students were active in using the aforementioned exercise tools. Data showed that stimulation had an overall positive impact, but this was not evident on both measures (i.e., level of activity and indices of happiness) or with both exercise tools across students. These findings are discussed in relation to the outcome of an earlier study in the area by the same authors and in terms of practical implications for daily contexts.

Efficient cascade multiple heterojunction organic solar cells with inverted structure

NASA Astrophysics Data System (ADS)

Guo, Tingting; Li, Mingtao; Qiao, Zhenfang; Yu, Leiming; Zhao, Jianhong; Feng, Nianjun; Shi, Peiguang; Wang, Xiaoyan; Pu, Xiaoyun; Wang, Hai

2018-05-01

In this work, we demonstrate an efficient cascade multiple heterojunction organic solar cell with inverted structure. By using two donor materials, poly(3-hexylthiosphene) (P3HT) and titanyl phthalocyanine (TiOPc), as well as two acceptor materials, [6,6]-phenyl C61 butyric acid methyl ester (PCBM) and C60, the cascade multiple heterojunctions of P3HT:PCBM/TiOPc:C60/C60 have been constructed. Applying the optimized inverted configuration of FTO/Zinc Tin Oxide (ZTO)/C60 (30 nm)/TiOPc:C60 (1:1.5, 25 nm)/P3HT:PCBM (1:0.8, 100 nm)/MoO3 (4 nm)/Ag, the considerably enhanced open circuit voltage (VOC) and short circuit current (JSC) can be harvested together, and the power conversion efficiency (PCE) is three times higher than that of the control cell with conventional structure. The significant improvements of the inverted cell are mostly due to the broadened spectral absorption and high efficient multi-interface exciton dissociation in the cascade multiple heterojunctions, indicating that the optimized cascade heterojunctions match the inverted structure well.

APOBEC3A associates with human papillomavirus genome integration in oropharyngeal cancers.

PubMed

Kondo, S; Wakae, K; Wakisaka, N; Nakanishi, Y; Ishikawa, K; Komori, T; Moriyama-Kita, M; Endo, K; Murono, S; Wang, Z; Kitamura, K; Nishiyama, T; Yamaguchi, K; Shigenobu, S; Muramatsu, M; Yoshizaki, T

2017-03-23

The prevalence of human papillomavirus (HPV)-related oropharyngeal cancers has been increasing in developed countries. We recently demonstrated that members of the apolipoprotein B mRNA-editing catalytic polypeptide 3 (APOBEC3, A3) family, which are antiviral factors, can induce hypermutation of HPV DNA in vitro. In the present study, we found numerous C-to-T and G-to-A hypermutations in the HPV16 genome in oropharyngeal cancer (OPC) biopsy samples using differential DNA denaturation PCR and next-generation sequencing. A3s were more abundantly expressed in HPV16-positive OPCs than in HPV-negative, as assessed using immunohistochemistry and reverse transcription quantitative PCR. In addition, interferons upregulated A3s in an HPV16-positive OPC cell line. Furthermore, quantitative PCR analysis of HPV DNA suggests that APOBEC3A (A3A) expression is strongly correlated with the integration of HPV DNA. These results suggest that HPV16 infection may upregulate A3A expression, thereby increasing the chance of viral DNA integration. The role of A3A in HPV-induced carcinogenesis is discussed.

Study of the Microstructure Evolution of Low-pH Cements Based on Ordinary Portland Cement (OPC) by Mid- and Near-Infrared Spectroscopy, and Their Influence on Corrosion of Steel Reinforcement.

PubMed

García Calvo, José Luis; Sánchez Moreno, Mercedes; Alonso Alonso, María Cruz; Hidalgo López, Ana; García Olmo, Juan

2013-06-18

Low-pH cements are designed to be used in underground repositories for high level waste. When they are based on Ordinary Portland Cements (OPC), high mineral admixture contents must be used which significantly modify their microstructure properties and performance. This paper evaluates the microstructure evolution of low-pH cement pastes based on OPC plus silica fume and/or fly ashes, using Mid-Infrared and Near-Infrared spectroscopy to detect cement pastes mainly composed of high polymerized C-A-S-H gels with low C/S ratios. In addition, the lower pore solution pH of these special cementitious materials have been monitored with embedded metallic sensors. Besides, as the use of reinforced concrete can be required in underground repositories, the influence of low-pH cementitious materials on steel reinforcement corrosion was analysed. Due to their lower pore solution pH and their different pore solution chemical composition a clear influence on steel reinforcement corrosion was detected.

EpiTools, A software suite for presurgical brain mapping in epilepsy: Intracerebral EEG.

PubMed

Medina Villalon, S; Paz, R; Roehri, N; Lagarde, S; Pizzo, F; Colombet, B; Bartolomei, F; Carron, R; Bénar, C-G

2018-06-01

In pharmacoresistant epilepsy, exploration with depth electrodes can be needed to precisely define the epileptogenic zone. Accurate location of these electrodes is thus essential for the interpretation of Stereotaxic EEG (SEEG) signals. As SEEG analysis increasingly relies on signal processing, it is crucial to make a link between these results and patient's anatomy. Our aims were thus to develop a suite of software tools, called "EpiTools", able to i) precisely and automatically localize the position of each SEEG contact and ii) display the results of signal analysis in each patient's anatomy. The first tool, GARDEL (GUI for Automatic Registration and Depth Electrode Localization), is able to automatically localize SEEG contacts and to label each contact according to a pre-specified nomenclature (for instance that of FreeSurfer or MarsAtlas). The second tool, 3Dviewer, enables to visualize in the 3D anatomy of the patient the origin of signal processing results such as rate of biomarkers, connectivity graphs or Epileptogenicity Index. GARDEL was validated in 30 patients by clinicians and proved to be highly reliable to determine within the patient's individual anatomy the actual location of contacts. GARDEL is a fully automatic electrode localization tool needing limited user interaction (only for electrode naming or contact correction). The 3Dviewer is able to read signal processing results and to display them in link with patient's anatomy. EpiTools can help speeding up the interpretation of SEEG data and improving its precision. Copyright © 2018 Elsevier B.V. All rights reserved.

Designed tools for analysis of lithography patterns and nanostructures

NASA Astrophysics Data System (ADS)

Dervillé, Alexandre; Baderot, Julien; Bernard, Guilhem; Foucher, Johann; Grönqvist, Hanna; Labrosse, Aurélien; Martinez, Sergio; Zimmermann, Yann

2017-03-01

We introduce a set of designed tools for the analysis of lithography patterns and nano structures. The classical metrological analysis of these objects has the drawbacks of being time consuming, requiring manual tuning and lacking robustness and user friendliness. With the goal of improving the current situation, we propose new image processing tools at different levels: semi automatic, automatic and machine-learning enhanced tools. The complete set of tools has been integrated into a software platform designed to transform the lab into a virtual fab. The underlying idea is to master nano processes at the research and development level by accelerating the access to knowledge and hence speed up the implementation in product lines.

Higher-order automatic differentiation of mathematical functions

NASA Astrophysics Data System (ADS)

Charpentier, Isabelle; Dal Cappello, Claude

2015-04-01

Functions of mathematical physics such as the Bessel functions, the Chebyshev polynomials, the Gauss hypergeometric function and so forth, have practical applications in many scientific domains. On the one hand, differentiation formulas provided in reference books apply to real or complex variables. These do not account for the chain rule. On the other hand, based on the chain rule, the automatic differentiation has become a natural tool in numerical modeling. Nevertheless automatic differentiation tools do not deal with the numerous mathematical functions. This paper describes formulas and provides codes for the higher-order automatic differentiation of mathematical functions. The first method is based on Faà di Bruno's formula that generalizes the chain rule. The second one makes use of the second order differential equation they satisfy. Both methods are exemplified with the aforementioned functions.

Configuration-specific electronic structure of strongly interacting interfaces: TiOPc on Cu(110)

NASA Astrophysics Data System (ADS)

Maughan, Bret; Zahl, Percy; Sutter, Peter; Monti, Oliver L. A.

2017-12-01

We use low-temperature scanning tunneling microscopy in combination with angle-resolved ultraviolet and two-photon photoemission spectroscopy to investigate the interfacial electronic structure of titanyl phthalocyanine (TiOPc) on Cu(110). We show that the presence of two unique molecular adsorption configurations is crucial for a molecular-level analysis of the hybridized interfacial electronic structure. Specifically, thermally induced self-assembly exposes marked adsorbate-configuration-specific contributions to the interfacial electronic structure. The results of this work demonstrate an avenue towards understanding and controlling interfacial electronic structure in chemisorbed films even for the case of complex film structure.

Automatic Differentiation as a tool in engineering design

NASA Technical Reports Server (NTRS)

Barthelemy, Jean-Francois M.; Hall, Laura E.

1992-01-01

Automatic Differentiation (AD) is a tool that systematically implements the chain rule of differentiation to obtain the derivatives of functions calculated by computer programs. In this paper, it is assessed as a tool for engineering design. The paper discusses the forward and reverse modes of AD, their computing requirements, and approaches to implementing AD. It continues with application to two different tools to two medium-size structural analysis problems to generate sensitivity information typically necessary in an optimization or design situation. The paper concludes with the observation that AD is to be preferred to finite differencing in most cases, as long as sufficient computer storage is available.

Impact of translation on named-entity recognition in radiology texts

PubMed Central

Pedro, Vasco

2017-01-01

Abstract Radiology reports describe the results of radiography procedures and have the potential of being a useful source of information which can bring benefits to health care systems around the world. One way to automatically extract information from the reports is by using Text Mining tools. The problem is that these tools are mostly developed for English and reports are usually written in the native language of the radiologist, which is not necessarily English. This creates an obstacle to the sharing of Radiology information between different communities. This work explores the solution of translating the reports to English before applying the Text Mining tools, probing the question of what translation approach should be used. We created MRRAD (Multilingual Radiology Research Articles Dataset), a parallel corpus of Portuguese research articles related to Radiology and a number of alternative translations (human, automatic and semi-automatic) to English. This is a novel corpus which can be used to move forward the research on this topic. Using MRRAD we studied which kind of automatic or semi-automatic translation approach is more effective on the Named-entity recognition task of finding RadLex terms in the English version of the articles. Considering the terms extracted from human translations as our gold standard, we calculated how similar to this standard were the terms extracted using other translations. We found that a completely automatic translation approach using Google leads to F-scores (between 0.861 and 0.868, depending on the extraction approach) similar to the ones obtained through a more expensive semi-automatic translation approach using Unbabel (between 0.862 and 0.870). To better understand the results we also performed a qualitative analysis of the type of errors found in the automatic and semi-automatic translations. Database URL: https://github.com/lasigeBioTM/MRRAD PMID:29220455

Does smoking alter the mutation profile of human papillomavirus-driven head and neck cancers?

PubMed

Mirghani, Haitham; Lacroix, Ludovic; Rossoni, Caroline; Sun, Roger; Aupérin, Anne; Casiraghi, Odile; Villepelet, Aude; Lacave, Roger; Faucher, Gladwys; Marty, Virginie; Ferté, Charles; Soria, Jean Charles; Even, Caroline

2018-05-01

Human papillomavirus (HPV)-driven oropharyngeal cancer (OPC) patients are characterised by a better prognosis than their HPV-negative counterparts. However, this significant survival advantage is not homogeneous and among HPV-positive patients those with a smoking history have a significantly increased risk of oncologic failure. The reason why tobacco consumption impacts negatively the prognosis is still elusive. Tobacco might induce additional genetic alterations leading to a more aggressive phenotype. The purpose of this study was to characterise the mutational profile of HPV-positive OPCs by smoking status. We hypothesise a higher frequency of mutations affecting smokers. Targeted next-generation sequencing of 39 genes that are recurrently mutated in head and neck cancers (HNCs) caused by tobacco/alcohol consumption was performed in 62 HPV-driven OPC cases including smokers and non-smokers. The study population included 37 (60%) non-smokers and 25 (40%) smokers. Twenty (32%) patients had no mutation, 14 (23%) had 1 mutation and 28 (45%) had 2 or more mutations. The most commonly mutated genes regardless of tobacco consumption were PIK3CA (19%), MLL2 (19%), TP53 (8%), FAT 1 (15%), FBXW7 (16%), NOTCH1 (10%) and FGFR3 (10%). Mutation rate was not significantly different in smokers compared with non-smokers even when analyses focused on heavy smokers (>20 pack-years vs. <20 pack-years). Similarly, there was no significant difference in mutations patterns according to tobacco consumption. In HPV-positive patients, smoking does not increase the mutation rate of genes that are recurrently mutated in traditional HNC. Additional studies are warranted to further describe the molecular landscape of HPV-driven OPC according to tobacco consumption. Copyright © 2018 Elsevier Ltd. All rights reserved.

Safety and tolerability of the free-radical scavenger OPC-14117 in Huntington's disease. The Huntington Study Group.

PubMed

1998-05-01

Oxidative damage due to free-radical generation in the setting of underlying defects of neuronal energy metabolism has been implicated as a pathogenetic mechanism for Huntington's disease (HD). The authors conducted a randomized, double-blind, placebo-controlled, multicenter trial of the tolerability of OPC-14117, a lipophilic free-radical scavenger that concentrates in the brain. Ambulatory patients with HD received OPC-14117 60 mg/d, 120 mg/d, 240 mg/d, or placebo and were assessed by the Unified Huntington's Disease Rating Scale (UHDRS) for 20 weeks, including 12 or 16 weeks of assigned treatment and 8 or 4 weeks of blinded withdrawal of the study drug. Tolerability was measured by the proportion of patients completing the initial 12-week course of treatment on their originally assigned regimen. Sixty-four patients were enrolled in the study, 56 of whom completed the 12 weeks of treatment. Treatment was discontinued in four patients (1 placebo, 1 60 mg/d, 2 240 mg/d) due to asymptomatic but persistent serum elevations of liver transaminase. Two patients (1 60 mg/d and 1 120 mg/d) withdrew because of increased involuntary movements, one patient (60 mg/d) withdrew due to persistent dry eyes, and one patient (120 mg/d) withdrew because of persistent vomiting. There were no significant differences between treatment arms in the primary measures of tolerability, the frequency and types of clinical adverse events, or the clinical/functional features of HD. OPC-14117 was safe and generally well tolerated; however, elevations of liver transaminase suggested that continued surveillance monitoring is warranted in conducting more long-term studies of this antioxidant therapy.

Therapeutic efficacy of the non-peptide AVP antagonist OPC-31260 in cirrhotic rats.

PubMed

Tsuboi, Y; Ishikawa, S; Fujisawa, G; Okada, K; Saito, T

1994-07-01

The present study was undertaken to determine whether a non-peptide arginine vasopressin (AVP) antagonist [5-dimethylamino-1-(4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetra hydro-1H- benzazepine] (OPC-31260) improves the impaired water excretion in rats with experimental liver cirrhosis. Male Wistar rats weighing 200 to 250 g were injected in an equal volume (4 ml/kg) of carbon tetrachloride and olive oil at an interval of seven days for three months, causing liver cirrhosis with ascites. Control rats were injected with only olive oil. Body weight (body wt) and hematocrit (Hct) were lower in the cirrhotic rats than the control rats (body wt 360.7 vs. 238.5 g, P < 0.01; Hct 46.3 vs. 39.2%, P < 0.01). A water loading test (30 ml/kg) was carried out and 20-minute urine collections were made for three hours. The percent of water load excreted was 62.5% in the cirrhotic rats, a value significantly less than that of 102.1% in the control rats. However, its percent increased to 215.1% after the oral administration of 5 mg/kg OPC-31260 (P < 0.01). Minimal urinary osmolality (UOsm) was 185.5 mOsm/kg H2O in the cirrhotic rats receiving the vehicle, a value greater than the control rats of 125.5 mOsm/kg H2O (P < 0.01). The oral administration of 5 mg/kg OPC-31260 reduced minimal UOsm to 85.2 mOsm/kg H2O in the cirrhotic rats (P < 0.01). Urinary excretion of sodium was lower in the cirrhotic rats than the control rats (87.1 vs. 312.4 microEq/3 hr, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of hepatic impairment on the pharmacokinetics of a single dose of cilostazol.

PubMed

Bramer, S L; Forbes, W P

1999-01-01

The pharmacokinetic profiles of cilostazol and its metabolites following a single oral dose of cilostazol 100 mg were compared between individuals with impaired and normal liver function. The study was conducted as a single-centre, open-label, single dose pharmacokinetic and tolerability trial. 12 patients with impaired and compensated liver function were compared with 12 volunteers with normal liver function. Participants in each group were matched for gender, age and weight. Of the 12 patients with hepatic impairment examined in this study, 10 had mild impairment (Child-Pugh class A) and 2 had moderate impairment (Child-Pugh class B). Blood and urine were collected up to 144 hours after drug administration. Pharmacokinetics were determined by noncompartmental methods. Protein binding did not differ between the groups (95.2% healthy volunteers, 94.6% hepatically impaired patients). Mean +/- SD unbound oral clearance of cilostazol decreased by 8.6% because of hepatic impairment (3380 +/- 1400 ml/min in healthy volunteers, 3260 +/- 2030 ml/min in hepatically impaired patients). Total urinary excretion of metabolites was significantly higher in healthy volunteers (26 vs 17% of dose). Overall, the pharmacokinetics of cilostazol and its metabolites, OPC-13213 and OPC-13015, were not substantially different in those with mild and moderate hepatic disease compared with values in healthy volunteers. Except for terminal-phase disposition half-life and apparent terminal-phase volume of distribution for cilostazol, the ratios of geometric means of pharmacokinetic parameters for plasma cilostazol, OPC-13213 and OPC-13015 in those with hepatic impairment versus healthy volunteers were close to 100%. Based on the results of the pharmacokinetic analysis, dose adjustment in patients with mild hepatic impairment is not necessary. However, caution should be exercised when cilostazol is administered to patients with moderate or severe hepatic impairment.

Cost effective solution using inverse lithography OPC for DRAM random contact layer

NASA Astrophysics Data System (ADS)

Jun, Jinhyuck; Hwang, Jaehee; Choi, Jaeseung; Oh, Seyoung; Park, Chanha; Yang, Hyunjo; Dam, Thuc; Do, Munhoe; Lee, Dong Chan; Xiao, Guangming; Choi, Jung-Hoe; Lucas, Kevin

2017-04-01

Many different advanced devices and design layers currently employ double patterning technology (DPT) as a means to overcome lithographic and OPC limitations at low k1 values. Certainly device layers with k1 value below 0.25 require DPT or other pitch splitting methodologies. DPT has also been used to improve patterning of certain device layers with k1 values slightly above 0.25, due to the difficulty of achieving sufficient pattern fidelity with only a single exposure. Unfortunately, this broad adoption of DPT also came with a significant increase in patterning process cost. In this paper, we discuss the development of a single patterning technology process using an integrated Inverse Lithography Technology (ILT) flow for mask synthesis. A single pattering technology flow will reduce the manufacturing cost for a k1 > 0.25 full chip random contact layer in a memory device by replacing the more expensive DPT process with ILT flow, while also maintaining good lithographic production quality and manufacturable OPC/RET production metrics. This new integrated flow consists of applying ILT to the difficult core region and traditional rule-based assist features (RBAFs) with OPC to the peripheral region of a DRAM contact layer. Comparisons of wafer results between the ILT process and the non-ILT process showed the lithographic benefits of ILT and its ability to enable a robust single patterning process for this low-k1 device layer. Advanced modeling with a negative tone develop (NTD) process achieved the accuracy levels needed for ILT to control feature shapes through dose and focus. Details of these afore mentioned results will be described in the paper.

Method for auto-alignment of digital optical phase conjugation systems based on digital propagation

PubMed Central

Jang, Mooseok; Ruan, Haowen; Zhou, Haojiang; Judkewitz, Benjamin; Yang, Changhuei

2014-01-01

Optical phase conjugation (OPC) has enabled many optical applications such as aberration correction and image transmission through fiber. In recent years, implementation of digital optical phase conjugation (DOPC) has opened up the possibility of its use in biomedical optics (e.g. deep-tissue optical focusing) due to its ability to provide greater-than-unity OPC reflectivity (the power ratio of the phase conjugated beam and input beam to the OPC system) and its flexibility to accommodate additional wavefront manipulations. However, the requirement for precise (pixel-to-pixel matching) alignment of the wavefront sensor and the spatial light modulator (SLM) limits the practical usability of DOPC systems. Here, we report a method for auto-alignment of a DOPC system by which the misalignment between the sensor and the SLM is auto-corrected through digital light propagation. With this method, we were able to accomplish OPC playback with a DOPC system with gross sensor-SLM misalignment by an axial displacement of up to~1.5 cm, rotation and tip/tilt of ~5∘, and in-plane displacement of ~5 mm (dependent on the physical size of the sensor and the SLM). Our auto-alignment method robustly achieved a DOPC playback peak-to-background ratio (PBR) corresponding to more than ~30 % of the theoretical maximum. As an additional advantage, the auto-alignment procedure can be easily performed at will and, as such, allows us to correct for small mechanical drifts within the DOPC systems, thus overcoming a previously major DOPC system vulnerability. We believe that this reported method for implementing robust DOPC systems will broaden the practical utility of DOPC systems. PMID:24977504

Method for auto-alignment of digital optical phase conjugation systems based on digital propagation.

PubMed

Jang, Mooseok; Ruan, Haowen; Zhou, Haojiang; Judkewitz, Benjamin; Yang, Changhuei

2014-06-16

Optical phase conjugation (OPC) has enabled many optical applications such as aberration correction and image transmission through fiber. In recent years, implementation of digital optical phase conjugation (DOPC) has opened up the possibility of its use in biomedical optics (e.g. deep-tissue optical focusing) due to its ability to provide greater-than-unity OPC reflectivity (the power ratio of the phase conjugated beam and input beam to the OPC system) and its flexibility to accommodate additional wavefront manipulations. However, the requirement for precise (pixel-to-pixel matching) alignment of the wavefront sensor and the spatial light modulator (SLM) limits the practical usability of DOPC systems. Here, we report a method for auto-alignment of a DOPC system by which the misalignment between the sensor and the SLM is auto-corrected through digital light propagation. With this method, we were able to accomplish OPC playback with a DOPC system with gross sensor-SLM misalignment by an axial displacement of up to~1.5 cm, rotation and tip/tilt of ~5° and in-plane displacement of ~5 mm (dependent on the physical size of the sensor and the SLM). Our auto-alignment method robustly achieved a DOPC playback peak-to-background ratio (PBR) corresponding to more than ~30 % of the theoretical maximum. As an additional advantage, the auto-alignment procedure can be easily performed at will and, as such, allows us to correct for small mechanical drifts within the DOPC systems, thus overcoming a previously major DOPC system vulnerability. We believe that this reported method for implementing robust DOPC systems will broaden the practical utility of DOPC systems.

Solidification of arsenic and heavy metal containing tailings using cement and blast furnace slag.

PubMed

Kim, Jung-Wook; Jung, Myung Chae

2011-01-01

The objective of this study is to examine the solidification of toxic elements in tailings by the use of cement and blast furnace slag. Tailings samples were taken at an Au-Ag mine in Korea. To examine the best mixing ratio of tailings and the mixture of ordinary Portland cement (OPC) and blast furnace slag (SG) of 5:5, 6:6, 7:3, and 8:2, the 7:3 ratio of tailings and OPC+SG was adapted. In addition, the mixing ratios of water and OPC + SG were applied to 10, 20, and 30 wt%. After 7, 14, and 28 days' curing, the UCS test was undertaken. A relatively high strength of solidified material (137.2 kg cm⁻² in average of 3 samples) at 28 days' curing was found in 20 wt% of water content (WC). This study also examined the leachability of arsenic and heavy metals (Cd, Cu, Pb, and Zn) under the Korean Standard Leaching Test, and it showed that the reductions in leachabilities of As and heavy metals of solidified samples were ranged from 76 to 99%. Thus, all the solidified samples were within the guidelines for special and hazardous waste materials by the Waste Management Act in Korea. In addition, the result of freeze-thaw cycle test of the materials indicated that the durability of the materials was sufficient. In conclusion, solidification using a 7:3 mixing ratio of tailings and a 1:1 mixture of OPC + SG with 20% of WC is one of the best methods for the remediation of arsenic and heavy metals in tailings and other contaminated materials.

OPC care-area feedforwarding to MPC

NASA Astrophysics Data System (ADS)

Dillon, Brian; Peng, Yi-Hsing; Hamaji, Masakazu; Tsunoda, Dai; Muramatsu, Tomoyuki; Ohara, Shuichiro; Zou, Yi; Arnoux, Vincent; Baron, Stanislas; Zhang, Xiaolong

2016-10-01

Demand for mask process correction (MPC) is growing for leading-edge process nodes. MPC was originally intended to correct CD linearity for narrow assist features difficult to resolve on a photomask without any correction, but it has been extended to main features as process nodes have been shrinking. As past papers have observed, MPC shows improvements in photomask fidelity. Using advanced shape and dose corrections could give more improvements, especially at line-ends and corners. However, there is a dilemma on using such advanced corrections on full mask level because it increases data volume and run time. In addition, write time on variable shaped beam (VSB) writers also increases as the number of shots increases. Optical proximity correction (OPC) care-area defines circuit design locations that require high mask fidelity under mask writing process variations such as energy fluctuation. It is useful for MPC to switch its correction strategy and permit the use of advanced mask correction techniques in those local care-areas where they provide maximum wafer benefits. The use of mask correction techniques tailored to localized post-OPC design can result in similar desired level of data volume, run time, and write time. ASML Brion and NCS have jointly developed a method to feedforward the care-area information from Tachyon LMC to NDE-MPC to provide real benefit for improving both mask writing and wafer printing quality. This paper explains the detail of OPC care-area feedforwarding to MPC between ASML Brion and NCS, and shows the results. In addition, improvements on mask and wafer simulations are also shown. The results indicate that the worst process variation (PV) bands are reduced up to 37% for a 10nm tech node metal case.

65nm OPC and design optimization by using simple electrical transistor simulation

NASA Astrophysics Data System (ADS)

Trouiller, Yorick; Devoivre, Thierry; Belledent, Jerome; Foussadier, Franck; Borjon, Amandine; Patterson, Kyle; Lucas, Kevin; Couderc, Christophe; Sundermann, Frank; Urbani, Jean-Christophe; Baron, Stanislas; Rody, Yves; Chapon, Jean-Damien; Arnaud, Franck; Entradas, Jorge

2005-05-01

In the context of 65nm logic technology where gate CD control budget requirements are below 5nm, it is mandatory to properly quantify the impact of the 2D effects on the electrical behavior of the transistor [1,2]. This study uses the following sequence to estimate the impact on transistor performance: 1) A lithographic simulation is performed after OPC (Optical Proximity Correction) of active and poly using a calibrated model at best conditions. Some extrapolation of this model can also be used to assess marginalities due to process window (focus, dose, mask errors, and overlay). In our case study, we mainly checked the poly to active misalignment effects. 2) Electrical behavior of the transistor (Ion, Ioff, Vt) is calculated based on a derivative spice model using the simulated image of the gate as an input. In most of the cases Ion analysis, rather than Vt or leakage, gives sufficient information for patterning optimization. We have demonstrated the benefit of this approach with two different examples: -design rule trade-off : we estimated the impact with and without misalignment of critical rules like poly corner to active distance, active corner to poly distance or minimum space between small transistor and big transistor. -Library standard cell debugging: we applied this methodology to the most critical one hundred transistors of our standard cell libraries and calculate Ion behavior with and without misalignment between active and poly. We compared two scanner illumination modes and two OPC versions based on the behavior of the one hundred transistors. We were able to see the benefits of one illumination, and also the improvement in the OPC maturity.

Baseline peripheral blood leukocytosis: Biological marker predicts outcome in oropharyngeal cancer, regardless of HPV-status.

PubMed

Gouw, Zeno A R; Paul de Boer, Jan; Navran, Arash; van den Brekel, Michiel W M; Sonke, Jan-Jakob; Al-Mamgani, Abrahim

2018-03-01

To study the prognostic value of abnormalities in baseline complete blood count in patients with oropharyngeal cancer (OPC) treated with (chemo) radiation. The prognostic value of baseline complete blood count on outcome in 234 patients with OPC treated between 2010 and 2015 was examined in multivariate analysis together with other conventional prognostic variables including HPV-status, tumor stage, tumor and nodal size. The 3-year overall survival (OS), disease-free survival (DFS), locoregional control (LRC), and distant control (DC) of the whole group were 74%, 64%, 79%, and 88%, respectively. Leukocytosis and HPV-status were the only significant prognosticators for OS and DFS at the multivariate analysis. Patients without leukocytosis had a significantly better DC compared to those with leukocytosis (92% and 70%, respectively, p < 0.001). Patients with HPV-negative OPC had significantly worse LRC compared to HPV-positive patients (67% and 90%, respectively, p < 0.001). The 3-year OS in HPV-positive group with leukocytosis compared to those without leukocytosis were 69% and 95%, respectively (p < 0.001). The figures for HPV-negative patients were 41% vs. 61%, respectively (p = 0.010). This is the first study to date reporting the independent impact of leukocytosis and HPV-status on outcome of patients with OPC. The poor outcome of patients with leukocytosis is mainly caused by the worse DC. The significant impact of leukocytosis on outcome was even more pronounced in HPV-positive patients. These biomarkers could help identifying patients with poor prognosis at baseline requiring intensification of local and/or systemic treatment while treatment de-intensification might be offered to the low-risk group. Copyright © 2018 Elsevier Ltd. All rights reserved.

Stereotactic Body Radiotherapy: A Promising Treatment Option for the Boost of Oropharyngeal Cancers Not Suitable for Brachytherapy: A Single-Institutional Experience

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

Al-Mamgani, Abrahim, E-mail: a.al-mamgani@erasmusmc.nl; Tans, Lisa; Teguh, David N.

2012-03-15

Purpose: To prospectively assess the outcome and toxicity of frameless stereotactic body radiotherapy (SBRT) as a treatment option for boosting primary oropharyngeal cancers (OPC) in patients who not suitable for the standard brachytherapy boost (BTB). Methods and Materials: Between 2005 and 2010, 51 patients with Stage I to IV biopsy-proven OPC who were not suitable for BTB received boosts by means of SBRT (3 times 5.5 Gy, prescribed to the 80% isodose line), after 46 Gy of IMRT to the primary tumor and neck (when indicated). Endpoints of the study were local control (LC), disease-free survival (DFS), overall survival (OS),more » and acute and late toxicity. Results: After a median follow-up of 18 months (range, 6-65 months), the 2-year actuarial rates of LC, DFS, and OS were 86%, 80%, and 82%, respectively, and the 3-year rates were 70%, 66%, and 54%, respectively. The treatment was well tolerated, as there were no treatment breaks and no Grade 4 or 5 toxicity reported, either acute or chronic. The overall 2-year cumulative incidence of Grade {>=}2 late toxicity was 28%. Of the patients with 2 years with no evidence of disease (n = 20), only 1 patient was still feeding tube dependent and 2 patients had Grade 3 xerostomia. Conclusions: According to our knowledge, this study is the first report of patients with primary OPC who received boosts by means of SBRT. Patients with OPC who are not suitable for the standard BTB can safely and effectively receive boosts by SBRT. With this radiation technique, an excellent outcome was achieved. Furthermore, the SBRT boost did not have a negative impact regarding acute and late side effects.« less