Effects of lines of progress and semilogarithmic charts on ratings of charted data

PubMed Central

Bailey, Donald B.

1984-01-01

The extent to which interrater agreement and ratings of significance on both changes in level and trend are affected by lines of progress and semilogarithmic charts was investigated. Thirteen graduate students rated four sets of charts, each set containing 19 phase changes. Set I data were plotted on equal interval charts. In Set II a line of progress was drawn through each phase on each chart. In Set III data points were replotted on semilogarithmic charts. In Set IV a line of progress was drawn through each phase of each Set III chart. A significant main effect on interrater agreement was found for lines of progress as well as a significant 2-way interaction between lines of progress and change type. Three main effects (chart type, lines of progress, and type of change) and a significant 3-way interaction were found for ratings of significance. Implications of these data for visual analysis of charted data are discussed. PMID:16795676

System and method for determining stability of a neural system

NASA Technical Reports Server (NTRS)

Curtis, Steven A. (Inventor)

2011-01-01

Disclosed are methods, systems, and computer-readable media for determining stability of a neural system. The method includes tracking a function world line of an N element neural system within at least one behavioral space, determining whether the tracking function world line is approaching a psychological stability surface, and implementing a quantitative solution that corrects instability if the tracked function world line is approaching the psychological stability surface.

Implementation of an Outer Can Welding System for Savannah River Site FB-Line

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

Howard, S.R.

2003-03-27

This paper details three phases of testing to confirm use of a Gas Tungsten Arc (GTA) system for closure welding the 3013 outer container used for stabilization/storage of plutonium metals and oxides. The outer container/lid closure joint was originally designed for laser welding, but for this application, the gas tungsten arc (GTA) welding process has been adapted. The testing progressed in three phases: (1) system checkout to evaluate system components for operational readiness, (2) troubleshooting to evaluate high weld failure rates and develop corrective techniques, and (3) pre-installation acceptance testing.

Yield performance and stability of CMS-based triticale hybrids.

PubMed

Mühleisen, Jonathan; Piepho, Hans-Peter; Maurer, Hans Peter; Reif, Jochen Christoph

2015-02-01

CMS-based triticale hybrids showed only marginal midparent heterosis for grain yield and lower dynamic yield stability compared to inbred lines. Hybrids of triticale (×Triticosecale Wittmack) are expected to possess outstanding yield performance and increased dynamic yield stability. The objectives of the present study were to (1) examine the optimum choice of the biometrical model to compare yield stability of hybrids versus lines, (2) investigate whether hybrids exhibit a more pronounced grain yield performance and yield stability, and (3) study optimal strategies to predict yield stability of hybrids. Thirteen female and seven male parental lines and their 91 factorial hybrids as well as 30 commercial lines were evaluated for grain yield in up to 20 environments. Hybrids were produced using a cytoplasmic male sterility (CMS)-inducing cytoplasm that originated from Triticumtimopheevii Zhuk. We found that the choice of the biometrical model can cause contrasting results and concluded that a group-by-environment interaction term should be added to the model when estimating stability variance of hybrids and lines. midparent heterosis for grain yield was on average 3 % with a range from -15.0 to 11.5 %. No hybrid outperformed the best inbred line. Hybrids had, on average, lower dynamic yield stability compared to the inbred lines. Grain yield performance of hybrids could be predicted based on midparent values and general combining ability (GCA)-predicted values. In contrast, stability variance of hybrids could be predicted only based on GCA-predicted values. We speculated that negative effects of the used CMS cytoplasm might be the reason for the low performance and yield stability of the hybrids. For this purpose a detailed study on the reasons for the drawback of the currently existing CMS system in triticale is urgently required comprising also the search of potentially alternative hybridization systems.

Cell subpopulation deconvolution reveals breast cancer heterogeneity based on DNA methylation signature.

PubMed

Wen, Yanhua; Wei, Yanjun; Zhang, Shumei; Li, Song; Liu, Hongbo; Wang, Fang; Zhao, Yue; Zhang, Dongwei; Zhang, Yan

2017-05-01

Tumour heterogeneity describes the coexistence of divergent tumour cell clones within tumours, which is often caused by underlying epigenetic changes. DNA methylation is commonly regarded as a significant regulator that differs across cells and tissues. In this study, we comprehensively reviewed research progress on estimating of tumour heterogeneity. Bioinformatics-based analysis of DNA methylation has revealed the evolutionary relationships between breast cancer cell lines and tissues. Further analysis of the DNA methylation profiles in 33 breast cancer-related cell lines identified cell line-specific methylation patterns. Next, we reviewed the computational methods in inferring clonal evolution of tumours from different perspectives and then proposed a deconvolution strategy for modelling cell subclonal populations dynamics in breast cancer tissues based on DNA methylation. Further analysis of simulated cancer tissues and real cell lines revealed that this approach exhibits satisfactory performance and relative stability in estimating the composition and proportions of cellular subpopulations. The application of this strategy to breast cancer individuals of the Cancer Genome Atlas's identified different cellular subpopulations with distinct molecular phenotypes. Moreover, the current and potential future applications of this deconvolution strategy to clinical breast cancer research are discussed, and emphasis was placed on the DNA methylation-based recognition of intra-tumour heterogeneity. The wide use of these methods for estimating heterogeneity to further clinical cohorts will improve our understanding of neoplastic progression and the design of therapeutic interventions for treating breast cancer and other malignancies. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Liquid-bridge stability and breakup on surfaces with contact-angle hysteresis.

PubMed

Akbari, Amir; Hill, Reghan J

2016-08-10

We study the stability and breakup of liquid bridges with a free contact line on surfaces with contact-angle hysteresis (CAH) under zero-gravity conditions. Non-ideal surfaces exhibit CAH because of surface imperfections, by which the constraints on three-phase contact lines are influenced. Given that interfacial instabilities are constraint-sensitive, understanding how CAH affects the stability and breakup of liquid bridges is crucial for predicting the drop size in contact-drop dispensing. Unlike ideal surfaces on which contact lines are always free irrespective of surface wettability, contact lines may undergo transitions from pinned to free and vice versa during drop deposition on non-ideal surfaces. Here, we experimentally and theoretically examine how stability and breakup are affected by CAH, highlighting cases where stability is lost during a transition from a pinned-pinned (more constrained) to pinned-free (less constrained) interface-rather than a critical state. This provides a practical means of expediting or delaying stability loss. We also demonstrate how the dynamic contact angle can control the contact-line radius following stability loss.

Bevacizumab continuation versus no continuation after first-line chemotherapy plus bevacizumab in patients with metastatic colorectal cancer: a randomized phase III non-inferiority trial (SAKK 41/06).

PubMed

Koeberle, D; Betticher, D C; von Moos, R; Dietrich, D; Brauchli, P; Baertschi, D; Matter, K; Winterhalder, R; Borner, M; Anchisi, S; Moosmann, P; Kollar, A; Saletti, P; Roth, A; Frueh, M; Kueng, M; Popescu, R A; Schacher, S; Hess, V; Herrmann, R

2015-04-01

Chemotherapy plus bevacizumab is a standard option for first-line treatment in metastatic colorectal cancer (mCRC) patients. We assessed whether no continuation is non-inferior to continuation of bevacizumab after completing first-line chemotherapy. In an open-label, phase III multicentre trial, patients with mCRC without disease progression after 4-6 months of standard first-line chemotherapy plus bevacizumab were randomly assigned to continuing bevacizumab at a standard dose or no treatment. CT scans were done every 6 weeks until disease progression. The primary end point was time to progression (TTP). A non-inferiority limit for hazard ratio (HR) of 0.727 was chosen to detect a difference in TTP of 6 weeks or less, with a one-sided significance level of 10% and a statistical power of 85%. The intention-to-treat population comprised 262 patients: median follow-up was 36.7 months. The median TTP was 4.1 [95% confidence interval (CI) 3.1-5.4] months for bevacizumab continuation versus 2.9 (95% CI 2.8-3.8) months for no continuation; HR 0.74 (95% CI 0.58-0.96). Non-inferiority could not be demonstrated. The median overall survival was 25.4 months for bevacizumab continuation versus 23.8 months (HR 0.83; 95% CI 0.63-1.1; P = 0.2) for no continuation. Severe adverse events were uncommon in the bevacizumab continuation arm. Costs for bevacizumab continuation were estimated to be ∼30,000 USD per patient. Non-inferiority could not be demonstrated for treatment holidays versus continuing bevacizumab monotheray, after 4-6 months of standard first-line chemotherapy plus bevacizumab. Based on no impact on overall survival and increased treatment costs, bevacizumab as a single agent is of no meaningful therapeutic value. More efficient treatment approaches are needed to maintain control of stabilized disease following induction therapy. ClinicalTrials.gov, number NCT00544700. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

29 CFR 1604.3 - Separate lines of progression and seniority systems.

Code of Federal Regulations, 2014 CFR

2014-07-01

... GUIDELINES ON DISCRIMINATION BECAUSE OF SEX § 1604.3 Separate lines of progression and seniority systems. (a... lines of progression or separate seniority lists based on sex where this would adversely affect any employee unless sex is a bona fide occupational qualification for that job. Accordingly, employment...

DEC1 regulates breast cancer cell proliferation by stabilizing cyclin E protein and delays the progression of cell cycle S phase

PubMed Central

Bi, H; Li, S; Qu, X; Wang, M; Bai, X; Xu, Z; Ao, X; Jia, Z; Jiang, X; Yang, Y; Wu, H

2015-01-01

Breast cancer that is accompanied by a high level of cyclin E expression usually exhibits poor prognosis and clinical outcome. Several factors are known to regulate the level of cyclin E during the cell cycle progression. The transcription factor DEC1 (also known as STRA13 and SHARP2) plays an important role in cell proliferation and apoptosis. Nevertheless, the mechanism of its role in cell proliferation is poorly understood. In this study, using the breast cancer cell lines MCF-7 and T47D, we showed that DEC1 could inhibit the cell cycle progression of breast cancer cells independently of its transcriptional activity. The cell cycle-dependent timing of DEC1 overexpression could affect the progression of the cell cycle through regulating the level of cyclin E protein. DEC1 stabilized cyclin E at the protein level by interacting with cyclin E. Overexpression of DEC1 repressed the interaction between cyclin E and its E3 ligase Fbw7α, consequently reducing the level of polyunbiquitinated cyclin E and increased the accumulation of non-ubiquitinated cyclin E. Furthermore, DEC1 also promoted the nuclear accumulation of Cdk2 and the formation of cyclin E/Cdk2 complex, as well as upregulating the activity of the cyclin E/Cdk2 complex, which inhibited the subsequent association of cyclin A with Cdk2. This had the effect of prolonging the S phase and suppressing the growth of breast cancers in a mouse xenograft model. These events probably constitute the essential steps in DEC1-regulated cell proliferation, thus opening up the possibility of a protein-based molecular strategy for eliminating cancer cells that manifest a high-level expression of cyclin E. PMID:26402517

Spatially Developing Secondary Instabilities and Attachment Line Instability in Supersonic Boundary Layers

NASA Technical Reports Server (NTRS)

Li, Fei; Choudhari, Meelan M.

2008-01-01

This paper reports on progress towards developing a spatial stability code for compressible shear flows with two inhomogeneous directions, such as crossflow dominated swept-wing boundary layers and attachment line flows. Certain unique aspects of formulating a spatial, two-dimensional eigenvalue problem for the secondary instability of finite amplitude crossflow vortices are discussed. A primary test case used for parameter study corresponds to the low-speed, NLF-0415(b) airfoil configuration as tested in the ASU Unsteady Wind Tunnel, wherein a spanwise periodic array of roughness elements was placed near the leading edge in order to excite stationary crossflow modes with a specified fundamental wavelength. The two classes of flow conditions selected for this analysis include those for which the roughness array spacing corresponds to either the naturally dominant crossflow wavelength, or a subcritical wavelength that serves to reduce the growth of the naturally excited dominant crossflow modes. Numerical predictions are compared with the measured database, both as indirect validation for the spatial instability analysis and to provide a basis for comparison with a higher Reynolds number, supersonic swept-wing configuration. Application of the eigenvalue analysis to the supersonic configuration reveals that a broad spectrum of stationary crossflow modes can sustain sufficiently strong secondary instabilities as to potentially cause transition over this configuration. Implications of this finding for transition control in swept wing boundary layers are examined. Finally, extension of the spatial stability analysis to supersonic attachment line flows is also considered.

29 CFR 1604.3 - Separate lines of progression and seniority systems.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 29 Labor 4 2011-07-01 2011-07-01 false Separate lines of progression and seniority systems. 1604.3 Section 1604.3 Labor Regulations Relating to Labor (Continued) EQUAL EMPLOYMENT OPPORTUNITY COMMISSION GUIDELINES ON DISCRIMINATION BECAUSE OF SEX § 1604.3 Separate lines of progression and seniority systems. (a...

29 CFR 1604.3 - Separate lines of progression and seniority systems.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 4 2010-07-01 2010-07-01 false Separate lines of progression and seniority systems. 1604.3 Section 1604.3 Labor Regulations Relating to Labor (Continued) EQUAL EMPLOYMENT OPPORTUNITY COMMISSION GUIDELINES ON DISCRIMINATION BECAUSE OF SEX § 1604.3 Separate lines of progression and seniority systems. (a...

29 CFR 1604.3 - Separate lines of progression and seniority systems.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 29 Labor 4 2013-07-01 2013-07-01 false Separate lines of progression and seniority systems. 1604.3 Section 1604.3 Labor Regulations Relating to Labor (Continued) EQUAL EMPLOYMENT OPPORTUNITY COMMISSION GUIDELINES ON DISCRIMINATION BECAUSE OF SEX § 1604.3 Separate lines of progression and seniority systems. (a...

29 CFR 1604.3 - Separate lines of progression and seniority systems.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 29 Labor 4 2012-07-01 2012-07-01 false Separate lines of progression and seniority systems. 1604.3 Section 1604.3 Labor Regulations Relating to Labor (Continued) EQUAL EMPLOYMENT OPPORTUNITY COMMISSION GUIDELINES ON DISCRIMINATION BECAUSE OF SEX § 1604.3 Separate lines of progression and seniority systems. (a...

The effect of Zhangfei/CREBZF on cell growth, differentiation, apoptosis, migration, and the unfolded protein response in several canine osteosarcoma cell lines.

PubMed

Zhang, Rui; Thamm, Douglas H; Misra, Vikram

2015-02-07

We had previously shown that the bLZip domain-containing transcription factor, Zhangfei/CREBZF inhibits the growth and the unfolded protein response (UPR) in cells of the D-17 canine osteosarcoma (OS) line and that the effects of Zhangfei are mediated by it stabilizing the tumour suppressor protein p53. To determine if our observations with D-17 cells applied more universally to canine OS, we examined three other independently isolated canine OS cell lines--Abrams, McKinley and Gracie. Like D-17, the three cell lines expressed p53 proteins that were capable of activating promoters with p53 response elements on their own, and synergistically with Zhangfei. Furthermore, as with D-17 cells, Zhangfei suppressed the growth and UPR-related transcripts in the OS cell lines. Zhangfei also induced the activation of osteocalcin expression, a marker of osteoblast differentiation and triggered programmed cell death. Osteosarcomas are common malignancies in large breeds of dogs. Although there has been dramatic progress in their treatment, these therapies often fail, leading to recurrence of the tumour and metastatic spread. Our results indicate that induction of the expression of Zhangfei in OS, where p53 is functional, may be an effective modality for the treatment of OS.

Magnetotail Reconnection

NASA Astrophysics Data System (ADS)

Petrukovich, A.; Artemyev, A.; Nakamura, R.

Reconnection is the key process responsible for the magnetotail dynamics. Driven reconnection in the distant tail is not sufficient to support global magnetospheric convection and the near Earth neutral line spontaneously forms to restore the balance. Mechanisms of initiation of such near-Earth magnetotail reconnection still represent one of major unresolved issues in space physics. We review the progress in this topic during the last decade. Recent theoretical advances suggest several variants of overcoming the famous tearing stability problem. Multipoint spacecraft observations reveal detailed structure of pre-onset current sheet of and reconnection zone down to ion larmor scale, supporting the importance of unstable state development through internal magnetotail reconfiguration.

Recent progress in online ultrasonic process monitoring

NASA Astrophysics Data System (ADS)

Wen, Szu-Sheng L.; Chen, Tzu-Fang; Ramos-Franca, Demartonne; Nguyen, Ky T.; Jen, Cheng-Kuei; Ihara, Ikuo; Derdouri, A.; Garcia-Rejon, Andres

1998-03-01

On-line ultrasonic monitoring of polymer co-extrusion and gas-assisted injection molding are presented. During the co- extrusion of high density polyethylene and Santoprene ultrasonic sensors consisting of piezoelectric transducers and clad ultrasonic buffer rods are used to detect the interface between these two polymers and the stability of the extrusion. The same ultrasonic sensor also measures the surface temperature of the extruded polymer. The results indicate that temperature measurements using ultrasound have a faster response time than those obtained by conventional thermocouple. In gas-assisted injection molding the polymer and gas flow front positions are monitored simultaneously. This information may be used to control the plunger movement.

The ubiquitin ligase TRIM25 inhibits hepatocellular carcinoma progression by targeting metastasis associated 1 protein.

PubMed

Zang, Hong-Liang; Ren, Sheng-Nan; Cao, Hong; Tian, Xiao-Feng

2017-10-01

Metastasis associated 1 protein (MTA1) is one of the prime facilitators of metastatic progression in all solid tumors including hepatocellular carcinoma (HCC). However, the underlying regulatory mechanism of MTA1 expression in HCC is not clear. In this study, we evaluated MTA1 transcript and protein expression in HCC and normal hepatic cell lines. The results revealed that MTA1 protein expression had a significantly increase in HCC cell line, HuH6, compared with that in normal hepatic cell line, THLE-2. Determination of protein half-life using cycloheximide (CHX) treatment did not reveal any statistically significant difference in protein turn-over rates between THLE-2 (3.3 ± 0.25 h) and HuH6 (3.6 ± 0.15 h) cell lines. MTA1 protein level was stabilized in THLE-2 cells after treatment with MG-132 to levels similar to those observed in HuH6 cells. Mass spectrometric analysis of FLAG immunoprecipitates of FLAG-MTA1 transfected THLE-2 cells after MG-132 treated revealed candidate ubiquitin ligases that were interacting with MTA1. RNAi-mediated silencing of each prospective ubiquitin ligase in THLE-2 cells indicated that knockdown of TRIM25 resulted in stabilization of MTA1 protein, indicating TRIM25 as a putative E3 ligase for MTA1. Coimmunoprecipitation of FLAG-tagged MTA1, but not IgG, in MG-132 treated and untreated THLE-2 cells cotransfected with either FLAG-MTA1 or Myc-TRIM25 revealed robust polyubiquitinated MTA1, confirming that the TRIM25 is the ubiquitin ligase for MTA1 degradation. Overexpression of TRIM25 in HuH6 and RNAi mediated silencing of TRIM25 in THLE-2 cells inhibited and increased the cell migration and invasion, respectively. Analysis of The Cancer Genome Atlas data for assessment of TRIM25 transcript level and MTA1 protein expression in 25 HCC patients confirmed an inverse correlation between the expression of TRIM25 and MTA1. Cumulatively, our data reveal a novel mechanism of post-translational to regulate MTA1 expression in normal hepatic cells, which is repressed in HCC. © 2017 IUBMB Life, 69(10):795-801, 2017. © 2017 International Union of Biochemistry and Molecular Biology.

Extensive retreat and re-advance of the West Antarctic Ice Sheet during the Holocene.

PubMed

Kingslake, J; Scherer, R P; Albrecht, T; Coenen, J; Powell, R D; Reese, R; Stansell, N D; Tulaczyk, S; Wearing, M G; Whitehouse, P L

2018-06-01

To predict the future contributions of the Antarctic ice sheets to sea-level rise, numerical models use reconstructions of past ice-sheet retreat after the Last Glacial Maximum to tune model parameters 1 . Reconstructions of the West Antarctic Ice Sheet have assumed that it retreated progressively throughout the Holocene epoch (the past 11,500 years or so) 2-4 . Here we show, however, that over this period the grounding line of the West Antarctic Ice Sheet (which marks the point at which it is no longer in contact with the ground and becomes a floating ice shelf) retreated several hundred kilometres inland of today's grounding line, before isostatic rebound caused it to re-advance to its present position. Our evidence includes, first, radiocarbon dating of sediment cores recovered from beneath the ice streams of the Ross Sea sector, indicating widespread Holocene marine exposure; and second, ice-penetrating radar observations of englacial structure in the Weddell Sea sector, indicating ice-shelf grounding. We explore the implications of these findings with an ice-sheet model. Modelled re-advance of the grounding line in the Holocene requires ice-shelf grounding caused by isostatic rebound. Our findings overturn the assumption of progressive retreat of the grounding line during the Holocene in West Antarctica, and corroborate previous suggestions of ice-sheet re-advance 5 . Rebound-driven stabilizing processes were apparently able to halt and reverse climate-initiated ice loss. Whether these processes can reverse present-day ice loss 6 on millennial timescales will depend on bedrock topography and mantle viscosity-parameters that are difficult to measure and to incorporate into ice-sheet models.

Potentiation of antiproliferative drug activity by lonidamine in hepatocellular carcinoma cells.

PubMed

Ricotti, L; Tesei, A; De Paola, F; Milandri, C; Amadori, D; Frassineti, G L; Ulivi, P; Zoli, W

2003-10-01

The ability of lonidamine (LND), a derivative of indazole-carboxylic acid, to modulate the cytotoxic activity of anticancer drugs was investigated in two human hepatocarcinoma (HCC) cell lines. The cytotoxicity of drugs used singly, in association or in sequence was evaluated using the Sulforhodamine B (SRB) assay. LND did not appreciably potentiate the effect of antitumor drugs when given before or simultaneously, in either cell line. Conversely, a synergistic interaction was observed in both cell lines when LND was given after conventional drugs. LND produced a moderate decrease in S-phase cell fraction and did not induce apoptosis. Conversely, paclitaxel (TAX) induced an important block in G2 and an increase in apoptosis. Following a 48-h TAX wash out, a progressive passage of cells from G2 to M phase was observed with a corresponding increase in apoptotic cells. Post-treatment with LND increased the cytotoxicity of some antitumor drugs, especially TAX, in hepatocarcinoma cells, possibly by preventing, as an energolytic drug, cell damage repair or by producing an additional effect on microtubule stabilization.

Elevated O-GlcNAcylation stabilizes FOXM1 by its reduced degradation through GSK-3β inactivation in a human gastric carcinoma cell line, MKN45 cells.

PubMed

Inoue, Yosuke; Moriwaki, Kazumasa; Ueda, Yasuhiro; Takeuchi, Toshihisa; Higuchi, Kazuhide; Asahi, Michio

2018-01-08

O-GlcNAcylation is a dynamic post-translational modification of cytonuclear proteins for intracellular signaling. Elevated O-GlcNAcylation is a general feature of cancer and contributes to cancer progression, and recent studies indicate the contribution to increasing incidence of various types of cancer in diabetic patients. However, the role of O-GlcNAcylation in tumor progression is not fully elucidated. Forkhead box M1 (FOXM1), a master mitotic transcription factor, has been implicated in all major hallmarks of cancer, and is wildly expressed in solid tumors. Given that FOXM1 expression was reported to be elevated in gastric cancer, we examined the effect of high glucose or an inhibitor of O-GlcNAc hydrolase, Thiamet G (TMG), on FOXM1 protein expression in a human gastric cancer cell line, MKN45 cells, and confirmed that FOXM1 protein level and the cell proliferation were upregulated. To investigate the molecular mechanisms by which FOXM1 protein expression is regulated by O-GlcNAcylation, the effect of high glucose and TMG on FOXM1 ubiquitination was examined in MKN45 cells. As a result, the ubiquitination and degradation of FOXM1 protein were both suppressed by high glucose and TMG treatment. However, the O-GlcNAcylation was not detected on FOXM1 but not on GSK-3β. High glucose and TMG treatment increased phospho-serine 9 GSK-3β, an inactive form, and the degradation of FOXM1 protein was suppressed by treatment of GSK-3β inhibitors in MKN45 cells. Taken together, we suggest that high glucose and elevated O-GlcNAcylation stabilize FOXM1 protein by its reduced degradation via GSK-3β inactivation in MKN45 cells, suggesting that the higher risk of gastric cancer in diabetic patients could be partially due to O-GlcNAcylation-mediated FOXM1 stabilization. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparison and statistical analysis of four write stability metrics in bulk CMOS static random access memory cells

NASA Astrophysics Data System (ADS)

Qiu, Hao; Mizutani, Tomoko; Saraya, Takuya; Hiramoto, Toshiro

2015-04-01

The commonly used four metrics for write stability were measured and compared based on the same set of 2048 (2k) six-transistor (6T) static random access memory (SRAM) cells by the 65 nm bulk technology. The preferred one should be effective for yield estimation and help predict edge of stability. Results have demonstrated that all metrics share the same worst SRAM cell. On the other hand, compared to butterfly curve with non-normality and write N-curve where no cell state flip happens, bit-line and word-line margins have good normality as well as almost perfect correlation. As a result, both bit line method and word line method prove themselves preferred write stability metrics.

Amyloid-beta protofibrils differ from amyloid-beta aggregates induced in dilute hexafluoroisopropanol in stability and morphology.

PubMed

Nichols, Michael R; Moss, Melissa A; Reed, Dana Kim; Cratic-McDaniel, Stephanie; Hoh, Jan H; Rosenberry, Terrone L

2005-01-28

The brains of Alzheimer's disease (AD) patients contain large numbers of amyloid plaques that are rich in fibrils composed of 40- and 42-residue amyloid-beta (Abeta) peptides. Several lines of evidence indicate that fibrillar Abeta and especially soluble Abeta aggregates are important in the etiology of AD. Recent reports also stress that amyloid aggregates are polymorphic and that a single polypeptide can fold into multiple amyloid conformations. Here we demonstrate that Abeta-(1-40) can form soluble aggregates with predominant beta-structures that differ in stability and morphology. One class of aggregates involved soluble Abeta protofibrils, prepared by vigorous overnight agitation of monomeric Abeta-(1-40) at low ionic strength. Dilution of these aggregation reactions induced disaggregation to monomers as measured by size exclusion chromatography. Protofibril concentrations monitored by thioflavin T fluorescence decreased in at least two kinetic phases, with initial disaggregation (rate constant approximately 1 h(-1)) followed by a much slower secondary phase. Incubation of the reactions without agitation resulted in less disaggregation at slower rates, indicating that the protofibrils became progressively more stable over time. In fact, protofibrils isolated by size exclusion chromatography were completely stable and gave no disaggregation. A second class of soluble Abeta aggregates was generated rapidly (<10 min) in buffered 2% hexafluoroisopropanol (HFIP). These aggregates showed increased thioflavin T fluorescence and were rich in beta-structure by circular dichroism. Electron microscopy and atomic force microscopy revealed initial globular clusters that progressed over several days to soluble fibrous aggregates. When diluted out of HFIP, these aggregates initially were very unstable and disaggregated completely within 2 min. However, their stability increased as they progressed to fibers. Relative to Abeta protofibrils, the HFIP-induced aggregates seeded elongation by Abeta monomer deposition very poorly. The techniques used to distinguish these two classes of soluble Abeta aggregates may be useful in characterizing Abeta aggregates formed in vivo.

An Novel Continuation Power Flow Method Based on Line Voltage Stability Index

NASA Astrophysics Data System (ADS)

Zhou, Jianfang; He, Yuqing; He, Hongbin; Jiang, Zhuohan

2018-01-01

An novel continuation power flow method based on line voltage stability index is proposed in this paper. Line voltage stability index is used to determine the selection of parameterized lines, and constantly updated with the change of load parameterized lines. The calculation stages of the continuation power flow decided by the angle changes of the prediction of development trend equation direction vector are proposed in this paper. And, an adaptive step length control strategy is used to calculate the next prediction direction and value according to different calculation stages. The proposed method is applied clear physical concept, and the high computing speed, also considering the local characteristics of voltage instability which can reflect the weak nodes and weak area in a power system. Due to more fully to calculate the PV curves, the proposed method has certain advantages on analysing the voltage stability margin to large-scale power grid.

[Complications and postoperative therapeutic strategies in cross-linking].

PubMed

Kohlhaas, M

2017-08-01

The reduced corneal mechanical stability in keratoconus and similar collagen diseases can lead to a progressive and irregular corneal shape and decrease of visual acuity. A progression of keratectatic diseases can be shown with corneal topography. Keratoconus can be treated by photo-oxidative cross-linking of the corneal collagen. In order to achieve a high absorption of irradiation energy in the cornea, riboflavin at a concentration of 0.1% and UVA light at a wavelength of 370 nm corresponding to the relative maximum absorption of riboflavin (vitamin B2) are used. Evidence for corneal cross-linking are the increase of biomechanical stiffness, the increased resistance against enzymatic degradation, a higher shrinkage temperature, a lower swelling rate and an increased diameter of collagen fibers. The currently available data demonstrate that the therapeutic cross-linking procedure is safe when respecting the important theoretical and clinical parameters and that a progression of the keratoconus can be avoided. In 80% of cases an average levelling of the curvature of approximately 2 dpt can be achieved, which leads not only to stabilization but also to an increase in visual acuity of approximately 1.2 lines. In a Cochrane review from 2015 publications about complications and results were reviewed. Complication rates ranged from 1-10% depending on the initial situation, comorbidities and stage of the keratoconus. The most important complications are early epithelial wound healing problems as well as extremely rare perforations. Corneal cross-linking is a well-established and safe procedure but is not free of complications.

Effect of Propellant Feed System Coupling and Hydraulic Parameters on Analysis of Chugging

NASA Technical Reports Server (NTRS)

Wood, Don J.; Dorsch, Robert G.

1967-01-01

A digital distributed parameter model was used to study the effects of propellant-feed- system coupling and various hydraulic parameters on the analytical prediction of chugging instabilities. Coupling between the combustion chamber and feed system was controlled by varying the compliance of the injector-dome region. The coupling with the feed system above the pump was varied by changing the amount of cavitation compliance at the pump inlet. The stability limits and chugging frequencies proved to be strongly dependent on the degree of feed-system coupling. The maximum stability condition occurred with intermediate coupling. Under conditions of a high degree of feed-system-combustor coupling, the stability limits and chugging frequencies were primarily dependent on the feed-system characteristics; the responses were characterized by beating patterns. For the system analyzed, the pump suction line had little effect on the stability limits or chugging frequencies. Beating, present under the condition of near zero injector -dome compliance, was eliminated when the suction line was decoupled by employing a sufficiently high value of pump-inlet compliance. Under conditions of maximum feed-system coupling, the magnitude and distribution of line losses in the discharge line had a significant effect on the stability limits but had negligible effect on the chugging frequency and beating characteristics. Also, the length of the discharge line greatly affected the stability limits, chugging frequency, and beating characteristics. The length of the suction line, however, had little effect on the stability limits and chugging frequency but did influence the beating pattern. A resistive-shunt device attached to the pump discharge line to suppress chugging was investigated. The analysis showed that the device was effective under conditions of high feed-system coupling.

Economic outcomes of maintenance gefitinib for locally advanced/metastatic non-small-cell lung cancer with unknown EGFR mutations: a semi-Markov model analysis.

PubMed

Zeng, Xiaohui; Li, Jianhe; Peng, Liubao; Wang, Yunhua; Tan, Chongqing; Chen, Gannong; Wan, Xiaomin; Lu, Qiong; Yi, Lidan

2014-01-01

Maintenance gefitinib significantly prolonged progression-free survival (PFS) compared with placebo in patients from eastern Asian with locally advanced/metastatic non-small-cell lung cancer (NSCLC) after four chemotherapeutic cycles (21 days per cycle) of first-line platinum-based combination chemotherapy without disease progression. The objective of the current study was to evaluate the cost-effectiveness of maintenance gefitinib therapy after four chemotherapeutic cycle's stand first-line platinum-based chemotherapy for patients with locally advanced or metastatic NSCLC with unknown EGFR mutations, from a Chinese health care system perspective. A semi-Markov model was designed to evaluate cost-effectiveness of the maintenance gefitinib treatment. Two-parametric Weibull and Log-logistic distribution were fitted to PFS and overall survival curves independently. One-way and probabilistic sensitivity analyses were conducted to assess the stability of the model designed. The model base-case analysis suggested that maintenance gefitinib would increase benefits in a 1, 3, 6 or 10-year time horizon, with incremental $184,829, $19,214, $19,328, and $21,308 per quality-adjusted life-year (QALY) gained, respectively. The most sensitive influential variable in the cost-effectiveness analysis was utility of PFS plus rash, followed by utility of PFS plus diarrhoea, utility of progressed disease, price of gefitinib, cost of follow-up treatment in progressed survival state, and utility of PFS on oral therapy. The price of gefitinib is the most significant parameter that could reduce the incremental cost per QALY. Probabilistic sensitivity analysis indicated that the cost-effective probability of maintenance gefitinib was zero under the willingness-to-pay (WTP) threshold of $16,349 (3 × per-capita gross domestic product of China). The sensitivity analyses all suggested that the model was robust. Maintenance gefitinib following first-line platinum-based chemotherapy for patients with locally advanced/metastatic NSCLC with unknown EGFR mutations is not cost-effective. Decreasing the price of gefitinib may be a preferential choice for meeting widely treatment demands in China.

Slope evolution at the Calvert Cliffs, Maryland -- measuring the change from eroding bluffs to stable slopes

USGS Publications Warehouse

Herzog, Martha; Larsen, Curtis E.; McRae, Michele

2002-01-01

Despite a long history of geomorphic studies, it is difficult to ascertain the time required for slopes to change from near vertical exposures to relatively stable slopes due to inadequate age control. Actively eroding coastal bluffs along the western shore of the Chesapeake Bay provide a key for understanding the centennial-scale development of stable slopes from eroding bluff faces. The Calvert Cliffs are composed of sandy silts, silty sands, and clayey silts of Miocene-age. Active wave erosion at the bluff toes encourages rapid sloughing from bluff faces and maintains slope angles of 70-80 degrees and relatively constant bluff-retreat rates. Naturally stabilized slopes are preserved as a fossil bluff line inland from a prograding cuspate foreland at Cove Point. The foreland is migrating southward at a rate of ca. 1.5 m/yr. As it moves south, it progressively protects bluffs from wave action as new beaches are deposited at their toes. Wave erosion is reinitiated at the northern end of the complex as the landform passes. An incremental record of slope change is preserved along the fossil bluff line. 14C dating of swales between beach ridges shows the complex to span 1700 years of progressive migration history. We hypothesized that slopes would change from steep, eroding faces to low-angle slopes covered with vegetation and sought to document the rate of change. Our team measured slope angles at intervals along the fossil bluff line and dated profiles by interpolating 14C ages of adjacent beach ridges. There was no progressive decrease in slope with age. All slopes along the fossil bluff line were 30-40 degrees with a mean of 35 degrees. Constancy in slope angle suggests that steep, actively eroding bluffs were quickly changed to stable slopes by landslides and slumping once they were protected. Given the accuracy of our age control, we conclude that the time required to attain a stable slope under natural processes is less than one century. This indicates that once toe erosion is ended (naturally or through engineering) slopes are reduced to 35-degrees over a period of decades and not centuries.

Decreased RECQL5 correlated with disease progression of osteosarcoma

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

Wu, Junlong; Zhi, Liqiang; Dai, Xin

Human RecQ helicase family, consisting of RECQL, RECQL4, RECQL5, BLM and WRN, has critical roles in genetic stability and tumorigenesis. Although RECQL5 has been reported to correlate with the susceptibility to malignances including osteosarcoma, the specific effect on tumor genesis and progression is not yet clarified. Here we focused on the relationship between RECQL5 expression and osteosarcoma disease progression, and further investigated the function of RECQL5 on MG-63 cell proliferation and apoptosis. By immunohistochemical analysis, qRT-PCR and western blot, we found that RECQL5 expression was downregulated in osteosarcoma tissues and cells. Patients with advanced tumor stage and low grade expressedmore » lower RECQL5. To construct a stable RECQL5 overexpression osteosarcoma cell line (MG-63-RECQL5), RECQL5 gene was inserted into the human AAVS1 safe harbor by CRISPR/Cas9 system. The overexpression of RECQL5 was verified by qRT-PCR and western blot. Cell proliferation, cell cycle and apoptosis assay revealed that RECQL5 overexpression inhibited proliferation, induced G1-phase arrest and promoted apoptosis in MG-63 cells. Collectively, our results suggested RECQL5 as a tumor suppressor in osteosarcoma and may be a potential therapeutic target for osteosarcoma treatment. - Highlights: • The expression of RECQL5 was downregulated in osteosarcoma tissues and cells. • Decreased RECQL5 correlated with osteosarcoma Enneking surgical classification. • We constructed a stable RECQL5 overexpression cell line by CRISPR/Cas9 system. • RECQL5 overexpression inhibited proliferation of MG-63 cells. • RECQL5 overexpression promoted apoptosis of MG-63 cells.« less

Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) as second-line chemotherapy in HER2-negative, taxane-pretreated metastatic breast cancer patients: prospective evaluation of activity, safety, and quality of life.

PubMed

Palumbo, Raffaella; Sottotetti, Federico; Trifirò, Giuseppe; Piazza, Elena; Ferzi, Antonella; Gambaro, Anna; Spinapolice, Elena Giulia; Pozzi, Emma; Tagliaferri, Barbara; Teragni, Cristina; Bernardo, Antonio

2015-01-01

A prospective, multicenter trial was undertaken to assess the activity, safety, and quality of life of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) as second-line chemotherapy in HER2-negative, taxane-pretreated metastatic breast cancer (MBC). Fifty-two women with HER2-negative MBC who were candidates for second-line chemotherapy for the metastatic disease were enrolled and treated at three centers in Northern Italy. All patients had previously received taxane-based chemotherapy in the adjuvant or first-line metastatic setting. Single-agent nab-paclitaxel was given at the dose of 260 mg/m(2) as a 30-minute intravenous infusion on day 1 each treatment cycle, which lasted 3 weeks, in the outpatient setting. No steroid or antihistamine premedication was provided. Treatment was stopped for documented disease progression, unacceptable toxicity, or patient refusal. All of the enrolled patients were evaluable for the study endpoints. The objective response rate was 48% (95% CI, 31.5%-61.3%) and included complete responses from 13.5%. Disease stabilization was obtained in 19 patients and lasted >6 months in 15 of them; the overall clinical benefit rate was 77%. The median time to response was 70 days (range 52-86 days). The median progression-free survival time was 8.9 months (95% CI, 8.0-11.6 months, range 5-21+ months). The median overall survival point has not yet been reached. Toxicities were expected and manageable with good patient compliance and preserved quality of life in patients given long-term treatment. Our results showed that single-agent nab-paclitaxel 260 mg/m(2) every 3 weeks is an effective and well tolerated regimen as second-line chemotherapy in HER2-negative, taxane-pretreated MBC patients, and that it produced interesting values of objective response rate and progression-free survival without the concern of significant toxicity. Specifically, the present study shows that such a regimen is a valid therapeutic option for that 'difficult to treat' patient population represented by women who at the time of disease relapse have already received the most active agents in the adjuvant and/or metastatic setting (ie, conventional taxanes).

Zoledronic acid in metastatic osteosarcoma: encouraging progression free survival in four consecutive patients.

PubMed

Conry, Robert M; Rodriguez, Michael G; Pressey, Joseph G

2016-01-01

Zoledronic acid (ZA) is a third-generation bisphosphonate in widespread clinical use to reduce pain and skeletal events in patients from a variety of malignancies with bone metastases. Pre-clinical studies indicate that ZA inhibits osteosarcoma through direct anti-proliferative effects, immune activation and anti-angiogenic activity. The purpose of this study was to evaluate the antitumor efficacy of ZA at standard dose until progression in patients with stage IV osteosarcoma lacking a standard of care treatment option proven to influence survival. Researchers retrospectively reviewed medical records of all patients at our institution with high-grade osteosarcoma presumed to be incurable due to metastases progressive after primary combination chemotherapy who received single agent ZA in an effort to delay progression. In our four-patient cohort following initiation of ZA, the median progression-free survival was 19 months, and median overall survival was 56+ months. Two of four patients have remained progression-free since starting ZA. The other two initially progressed after 18-20 months on ZA followed by metastasectomy of lung or dural metastases and further stability for over a year following resumption of ZA. After a 20-month progression-free interval on ZA alone, one patient had partial response following addition of pazopanib to ZA that likely contributed to long term disease control. The four patients experienced no significant toxicities despite protracted dosing of ZA for up to 5 years, and none have required chemotherapy since beginning ZA. Single agent ZA was associated with encouraging progression-free survival in four consecutive patients with metastatic osteosarcoma. Prospective trials of single agent ZA are warranted as protracted maintenance therapy in surgically incurable osteosarcoma relapsed or refractory to first line combination chemotherapy with radiographically measurable metastases.

Final results of the TANIA randomised phase III trial of bevacizumab after progression on first-line bevacizumab therapy for HER2-negative locally recurrent/metastatic breast cancer.

PubMed

Vrdoljak, E; Marschner, N; Zielinski, C; Gligorov, J; Cortes, J; Puglisi, F; Aapro, M; Fallowfield, L; Fontana, A; Inbar, M; Kahan, Z; Welt, A; Lévy, C; Brain, E; Pivot, X; Putzu, C; González Martín, A; de Ducla, S; Easton, V; von Minckwitz, G

2016-11-01

The randomised phase III TANIA trial demonstrated that continuing bevacizumab with second-line chemotherapy for locally recurrent/metastatic breast cancer (LR/mBC) after progression on first-line bevacizumab-containing therapy significantly improved progression-free survival (PFS) compared with chemotherapy alone [hazard ratio (HR) = 0.75, 95% confidence interval (CI) 0.61-0.93]. We report final results from the TANIA trial, including overall survival (OS) and health-related quality of life (HRQoL). Patients with HER2-negative LR/mBC that had progressed on or after first-line bevacizumab plus chemotherapy were randomised to receive standard second-line chemotherapy either alone or with bevacizumab. At second progression, patients initially randomised to bevacizumab continued bevacizumab with their third-line chemotherapy, but those randomised to chemotherapy alone were not allowed to cross over to receive third-line bevacizumab. The primary end point was second-line PFS; secondary end points included third-line PFS, combined second- and third-line PFS, OS, HRQoL and safety. Of the 494 patients randomised, 483 received second-line therapy; 234 patients (47% of the randomised population) continued to third-line study treatment. The median duration of follow-up at the final analysis was 32.1 months in the chemotherapy-alone arm and 30.9 months in the bevacizumab plus chemotherapy arm. There was no statistically significant difference between treatment arms in third-line PFS (HR = 0.79, 95% CI 0.59-1.06), combined second- and third-line PFS (HR = 0.85, 95% CI 0.68-1.05) or OS (HR = 0.96, 95% CI 0.76-1.21). Third-line safety results showed increased incidences of proteinuria and hypertension with bevacizumab, consistent with safety results for the second-line treatment phase. No differences in HRQoL were detected. In this trial, continuing bevacizumab beyond first and second progression of LR/mBC improved second-line PFS, but no improvement in longer term efficacy was observed. The second-line PFS benefit appears to be achieved without detrimentally affecting quality of life. NCT01250379. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Heterotypic mouse models of canine osteosarcoma recapitulate tumor heterogeneity and biological behavior

PubMed Central

Tomiyasu, Hirotaka; Garbe, John R.; Cornax, Ingrid; Amaya, Clarissa; O'Sullivan, M. Gerard; Subramanian, Subbaya

2016-01-01

ABSTRACT Osteosarcoma (OS) is a heterogeneous and rare disease with a disproportionate impact because it mainly affects children and adolescents. Lamentably, more than half of patients with OS succumb to metastatic disease. Clarification of the etiology of the disease, development of better strategies to manage progression, and methods to guide personalized treatments are among the unmet health needs for OS patients. Progress in managing the disease has been hindered by the extreme heterogeneity of OS; thus, better models that accurately recapitulate the natural heterogeneity of the disease are needed. For this study, we used cell lines derived from two spontaneous canine OS tumors with distinctly different biological behavior (OS-1 and OS-2) for heterotypic in vivo modeling that recapitulates the heterogeneous biology and behavior of this disease. Both cell lines demonstrated stability of the transcriptome when grown as orthotopic xenografts in athymic nude mice. Consistent with the behavior of the original tumors, OS-2 xenografts grew more rapidly at the primary site and had greater propensity to disseminate to lung and establish microscopic metastasis. Moreover, OS-2 promoted formation of a different tumor-associated stromal environment than OS-1 xenografts. OS-2-derived tumors comprised a larger percentage of the xenograft tumors than OS-1-derived tumors. In addition, a robust pro-inflammatory population dominated the stromal cell infiltrates in OS-2 xenografts, whereas a mesenchymal population with a gene signature reflecting myogenic signaling dominated those in the OS-1 xenografts. Our studies show that canine OS cell lines maintain intrinsic features of the tumors from which they were derived and recapitulate the heterogeneous biology and behavior of bone cancer in mouse models. This system provides a resource to understand essential interactions between tumor cells and the stromal environment that drive the progression and metastatic propensity of OS. PMID:27874835

Metastatic extraskeletal Ewing's sarcoma treated with trabectedin: A case report.

PubMed

Hernando-Cubero, Jorge; Sanz-Moncasi, Pilar; Hernández-García, Alba; Pajares-Bernard, Isabel; Martínez-Trufero, Javier

2016-10-01

The Ewing's sarcoma family of tumors (ESFT) comprises a number of rare malignant tumors. Standard first-line treatment for patients with these tumors includes chemotherapy with a five-drug regimen of vincristine, doxorubicin (Adriamycin ® ) and cyclophosphamide, alternating with ifosfamide and etoposide (VAC/IE). In cases of inadequate response, there are a number of second-line regimens available. However, further treatment options are required for those patients with disease unresponsive to standard treatment. Trabectedin is a novel treatment option for patients with ESFT. The present study reports the case of a Caucasian 69-year-old female patient who presented with a soft tissue mass on the chest wall that had developed 7 months earlier. A computed tomography scan revealed a 9×8×7-cm mass on the anterior chest wall above the pectoral muscle. Histopathological evaluations and molecular analysis indicated that it was consistent with a metastatic extraskeletal Ewing's sarcoma. The patient was treated with an alternating VAC/IE regimen; however, an inadequate response was observed. The patient received second-line treatment with a gemcitabine and dacarbazine combination regimen, but the disease progressed. Subsequently, treatment with trabectedin (1.5 mg/m 2 as a 24-h continuous infusion every 3 weeks) was initiated. Trabectedin treatment resulted in long-lasting (18 months) progression-free survival. It is vital that novel drugs continue to being developed for patients with ESFT following progression subsequent to standard chemotherapy. The current report presents a case of a patient with metastatic, pre-treated Ewing's sarcoma achieving disease stabilization with trabectedin. Based on these results and the observed tolerability profile, trabectedin represents an alternative treatment for patients with ESFT. Further studies are required in order to determine the efficacy of trabectedin as monotherapy or in combination with other drugs. It is also important to identify which tumor subtypes, specific translocations and patient profiles will benefit the most from treatment with trabectedin.

Heterotypic mouse models of canine osteosarcoma recapitulate tumor heterogeneity and biological behavior.

PubMed

Scott, Milcah C; Tomiyasu, Hirotaka; Garbe, John R; Cornax, Ingrid; Amaya, Clarissa; O'Sullivan, M Gerard; Subramanian, Subbaya; Bryan, Brad A; Modiano, Jaime F

2016-12-01

Osteosarcoma (OS) is a heterogeneous and rare disease with a disproportionate impact because it mainly affects children and adolescents. Lamentably, more than half of patients with OS succumb to metastatic disease. Clarification of the etiology of the disease, development of better strategies to manage progression, and methods to guide personalized treatments are among the unmet health needs for OS patients. Progress in managing the disease has been hindered by the extreme heterogeneity of OS; thus, better models that accurately recapitulate the natural heterogeneity of the disease are needed. For this study, we used cell lines derived from two spontaneous canine OS tumors with distinctly different biological behavior (OS-1 and OS-2) for heterotypic in vivo modeling that recapitulates the heterogeneous biology and behavior of this disease. Both cell lines demonstrated stability of the transcriptome when grown as orthotopic xenografts in athymic nude mice. Consistent with the behavior of the original tumors, OS-2 xenografts grew more rapidly at the primary site and had greater propensity to disseminate to lung and establish microscopic metastasis. Moreover, OS-2 promoted formation of a different tumor-associated stromal environment than OS-1 xenografts. OS-2-derived tumors comprised a larger percentage of the xenograft tumors than OS-1-derived tumors. In addition, a robust pro-inflammatory population dominated the stromal cell infiltrates in OS-2 xenografts, whereas a mesenchymal population with a gene signature reflecting myogenic signaling dominated those in the OS-1 xenografts. Our studies show that canine OS cell lines maintain intrinsic features of the tumors from which they were derived and recapitulate the heterogeneous biology and behavior of bone cancer in mouse models. This system provides a resource to understand essential interactions between tumor cells and the stromal environment that drive the progression and metastatic propensity of OS. © 2016. Published by The Company of Biologists Ltd.

Systemic treatment in advanced biliary cancers: A multicenter Australian analysis and review.

PubMed

Brungs, Daniel; Aghmesheh, Morteza; Sjoquist, Katrin; Goldstein, David

2017-10-01

While first-line palliative chemotherapy (CT1) improves survival and quality of life in advanced biliary cancer (ABC), there is no randomized evidence to support second-line chemotherapy (CT2) in ABC. We aim to explore to role of CT2 in ABC. We performed a retrospective review of all patients who received one or more lines of chemotherapy for ABC at four Australian cancer centers between 2008 and 2011. A Cox proportional hazard model was developed to determine the impact of clinicopathologic variables on overall survival (OS) from time of progression on CT1. We identified 73 patients who received palliative chemotherapy for ABC. Twenty-five patients (34%) received two or more lines of chemotherapy. Patients with a preserved performance status on progression on first-line chemotherapy (CT1) were more likely to receive second-line chemotherapy (CT2) (P < 0.001). Disease control rate with CT2 was 36%, and mean progression-free survival was 3.2 months (95% confidence interval 1.5-4.9 months). The following variables were significant in the univariate analysis of OS from time of progression on CT1: lines of chemotherapy (P = 0.0001), Eastern Cooperative Oncology Group performance status at progression on CT1 (P < 0.0001) and disease control with CT1 (P = 0.027). Lines of chemotherapy received and performance status remained significant in the multivariate analysis for OS from progression on CT1. Second-line chemotherapy is feasible in a subset of patients with ABC. Even after accounting for confounding variables, CT2 appears to increase OS in ABC, although we are unable to exclude other unmeasured factors such as tumor biology. These findings warrant further evaluation with prospective trials. © 2016 John Wiley & Sons Australia, Ltd.

Metrological properties of {CO 2}/{OsO 4} optical frequency standard

NASA Astrophysics Data System (ADS)

Acef, O.

1997-02-01

Recent progress on the metrological performance of the BNM-LPTF {CO 2}/{OsO 4} frequency standards in the {28}/{29}THz range, using OsO 4 molecular transitions as a frequency reference is reported. Significant improvements in terms of both short-term stability ( {6.6×10 -14}/{τup to τ=300s }) and long-term stability (4 × 10 -15 up to τ = 1 000 s, Δν ˜ 0.1 Hz) are obtained. Long term reproducibility (over more than 18 months) of about 3 × 10 -13 has been achieved. This high level enables the transfer, in terms of absolute frequency at the 3 × 10 -13 level of uncertainty, from primary frequency standards in the microwave domain to near infrared and visible domains, using frequency chains with {CO 2}/{OsO 4} as a transfer frequency standard. Preliminary estimates of the main effects which may shift the OsO 4 center line are reported.

E2-EPF UCP targets pVHL for degradation and associates with tumor growth and metastasis.

PubMed

Jung, Cho-Rok; Hwang, Kyung-Sun; Yoo, Jinsang; Cho, Won-Kyung; Kim, Jin-Man; Kim, Woo Ho; Im, Dong-Soo

2006-07-01

The von Hippel-Lindau tumor suppressor, pVHL, forms part of an E3 ubiquitin ligase complex that targets specific substrates for degradation, including hypoxia-inducible factor-1alpha (HIF-1alpha), which is involved in tumor progression and angiogenesis. It remains unclear, however, how pVHL is destabilized. Here we show that E2-EPF ubiquitin carrier protein (UCP) associates with and targets pVHL for ubiquitin-mediated proteolysis in cells, thereby stabilizing HIF-1alpha. UCP is detected coincidently with HIF-1alpha in human primary liver, colon and breast tumors, and metastatic cholangiocarcinoma and colon cancer cells. UCP level correlates inversely with pVHL level in most tumor cell lines. In vitro and in vivo, forced expression of UCP boosts tumor-cell proliferation, invasion and metastasis through effects on the pVHL-HIF pathway. Our results suggest that UCP helps stabilize HIF-1alpha and may be a new molecular target for therapeutic intervention in human cancers.

Performance of a Nanometer Resolution BPM System

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

Walston, S.; Chung, C.; Fitsos, P.

2007-04-24

International Linear Collider (ILC) interaction region beam sizes and component position stability requirements will be as small as a few nanometers. It is important to the ILC design effort to demonstrate that these tolerances can be achieved ideally using beam-based stability measurements. It has been estimated that RF cavity beam position monitors (BPMs) could provide position measurement resolutions of less than one nanometer and could form the basis of the desired beam-based stability measurement. We have developed a high resolution RF cavity BPM system. A triplet of these BPMs has been installed in the extraction line of the KEK Acceleratormore » Test Facility (ATF) for testing with its ultra-low emittance beam. The three BPMs are rigidly mounted inside an alignment frame on variable-length struts which allow movement in position and angle. We have developed novel methods for extracting the position and tilt information from the BPM signals including a calibration algorithm which is immune to beam jitter. To date, we have been able to demonstrate a resolution of approximately 20 nm over a dynamic range of +/- 20 microns. We report on the progress of these ongoing tests.« less

Post-Progression Survival Associated with Overall Survival in Patients with Advanced Non-Small-Cell Lung Cancer Receiving Docetaxel Monotherapy as Second-Line Chemotherapy.

PubMed

Kotake, Mie; Miura, Yosuke; Imai, Hisao; Mori, Keita; Sakurai, Reiko; Kaira, Kyoichi; Tomizawa, Yoshio; Minato, Koichi; Saito, Ryusei; Hisada, Takeshi

2017-01-01

In patients with non-small-cell lung cancer (NSCLC), the effects of second-line chemotherapy on overall survival (OS) might be confounded by subsequent therapies. Therefore, using individual-level data, we aimed to determine the relationships between progression-free survival (PFS) and post-progression survival (PPS) with OS in patients with advanced NSCLC treated with docetaxel monotherapy as second-line chemotherapy. Between April 2002 and December 2014, data from 86 patients with advanced NSCLC who underwent second-line docetaxel monotherapy following first-line treatment with platinum combination chemotherapy were analyzed. The relationships of PFS and PPS with OS were analyzed at the individual level. Spearman rank correlation and linear regression analyses showed that PPS was strongly associated with OS (r = 0.86, p < 0.05, R2 = 0.93), whereas PFS was moderately correlated with OS (r = 0.50, p < 0.05, R2 = 0.21). Performance status at the end of second-line treatment and the number of regimens after progression beyond second-line chemotherapy were significantly associated with PPS (p < 0.05). In patients with advanced NSCLC with unknown oncogenic driver mutations undergoing docetaxel monotherapy as second-line chemotherapy, when compared with PFS, PPS had a stronger association with OS. This finding suggests that subsequent treatment after disease progression following second-line docetaxel monotherapy has a significant influence on OS. © 2017 S. Karger AG, Basel.

REHABILITATION FOLLOWING MEDIAL PATELLOFEMORAL LIGAMENT RECONSTRUCTION FOR PATELLAR INSTABILITY

PubMed Central

Prohaska, Daniel

2017-01-01

Patellar instability is a common problem seen by physical therapists, athletic trainers and orthopedic surgeons. Although following an acute dislocation, conservative rehabilitation is usually the first line of defense; refractory cases exist that may require surgical intervention. Substantial progress has been made in the understanding of the medial patellofemoral ligament (MPFL) and its role as the primary stabilizer to lateral patellar displacement. Medial patellofemoral ligament disruption is now considered to be the essential lesion following acute patellar dislocation due to significantly high numbers of ruptures following this injury. Evidence is now mounting that demonstrates the benefits of early reconstruction with a variety of techniques. Recently rehabilitation has become more robust and progressive due to our better understanding of soft tissue reconstruction and repair techniques. The purpose of this manuscript is to describe the etiology of patellar instability, the anatomy and biomechanics and examination of patellofemoral instability, and to describe surgical intervention and rehabilitation following MPFL rupture. Level of Evidence 5 PMID:28593102

A unified mechanism for the stability of surface nanobubbles: contact line pinning and supersaturation.

PubMed

Liu, Yawei; Zhang, Xianren

2014-10-07

In this paper, we apply the molecular dynamics simulation method to study the stability of surface nanobubbles in both pure fluids and gas-liquid mixtures. First, we demonstrate with molecular simulations, for the first time, that surface nanobubbles can be stabilized in superheated or gas supersaturated liquid by the contact line pinning caused by the surface heterogeneity. Then, a unified mechanism for nanobubble stability is put forward here that stabilizing nanobubbles require both the contact line pinning and supersaturation. In the mechanism, the supersaturation refers to superheating for pure fluids and gas supersaturation or superheating for the gas-liquid mixtures, both of which exert the same effect on nanobubble stability. As the level of supersaturation increases, we found a Wenzel or Cassie wetting state for undersaturated and saturated fluids, stable nanobubbles at moderate supersaturation with decreasing curvature radius and contact angle, and finally the liquid-to-vapor phase transition at high supersaturation.

Design of rapid prototype of UAV line-of-sight stabilized control system

NASA Astrophysics Data System (ADS)

Huang, Gang; Zhao, Liting; Li, Yinlong; Yu, Fei; Lin, Zhe

2018-01-01

The line-of-sight (LOS) stable platform is the most important technology of UAV (unmanned aerial vehicle), which can reduce the effect to imaging quality from vibration and maneuvering of the aircraft. According to the requirement of LOS stability system (inertial and optical-mechanical combined method) and UAV's structure, a rapid prototype is designed using based on industrial computer using Peripheral Component Interconnect (PCI) and Windows RTX to exchange information. The paper shows the control structure, and circuit system including the inertial stability control circuit with gyro and voice coil motor driven circuit, the optical-mechanical stability control circuit with fast-steering-mirror (FSM) driven circuit and image-deviation-obtained system, outer frame rotary follower, and information-exchange system on PC. Test results show the stability accuracy reaches 5μrad, and prove the effectiveness of the combined line-of-sight stabilization control system, and the real-time rapid prototype runs stable.

High beta and second stability region transport and stability analysis: Technical progress report

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

Hughes, M.H.; Phillips, M.W.

1995-03-01

This report summarizes MHD equilibrium and stability studies carried out at Northrop Grumman`s Advanced Technology and Development Center during the 12 month period starting March 1, 1994. Progress is reported in both ideal and resistive MHD modeling of TFTR plasmas. The development of codes to calculate the significant effects of highly anisotropic pressure distributions is discussed along with results from this model.

Towards attosecond synchronization of remote mode-locked lasers using stabilized transmission of optical comb frequencies

NASA Astrophysics Data System (ADS)

Wilcox, R. B.; Byrd, J. M.; Doolittle, L. R.; Holzwarth, R.; Huang, G.

2011-09-01

We propose a method of synchronizing mode-locked lasers separated by hundreds of meters with the possibility of achieving sub-fs performance by locking the phases of corresponding lines in the optical comb spectrum. The optical phase from one comb line is transmitted to the remote laser over an interferometrically stabilized link by locking a single frequency laser to a comb line with high phase stability. We describe how these elements are integrated into a complete system and estimate the potential performance.

Borderline Personality Disorder: Bipolarity, Mood Stabilizers and Atypical Antipsychotics in Treatment

PubMed Central

Belli, Hasan; Ural, Cenk; Akbudak, Mahir

2012-01-01

In this article, it is aimed to review the efficacies of mood stabilizers and atypical antipsychotics, which are used commonly in psychopharmacological treatments of bipolar and borderline personality disorders. In this context, common phenomenology between borderline personality and bipolar disorders and differential features of clinical diagnosis will be reviewed in line with the literature. Both disorders can demonstrate common features in the diagnostic aspect, and can overlap phenomenologically. Concomitance rate of both disorders is quite high. In order to differentiate these two disorders from each other, quality of mood fluctuations, impulsivity types and linear progression of disorders should be carefully considered. There are various studies in mood stabilizer use, like lithium, carbamazepine, oxcarbazepine, sodium valproate and lamotrigine, in the treatment of borderline personality disorder. Moreover, there are also studies, which have revealed efficacies of risperidone, olanzapine and quetiapine as atypical antipsychotics. It is not easy to differentiate borderline personality disorder from the bipolar disorders. An intensively careful evaluation should be performed. This differentiation may be helpful also for the treatment. There are many studies about efficacy of valproate and lamotrigine in treatment of borderline personality disorder. However, findings related to other mood stabilizers are inadequate. Olanzapine and quetiapine are reported to be more effective among atypical antipsychotics. No drug is approved for the treatment of borderline personality disorder by the entitled authorities, yet. Psychotherapeutic approaches have preserved their significant places in treatment of borderline personality disorder. Moreover, symptom based approach is recommended in use of mood stabilizers and atypical antipsychotics. PMID:23024731

Resistive edge mode instability in stellarator and tokamak geometries

NASA Astrophysics Data System (ADS)

Mahmood, M. Ansar; Rafiq, T.; Persson, M.; Weiland, J.

2008-09-01

Geometrical effects on linear stability of electrostatic resistive edge modes are investigated in the three-dimensional Wendelstein 7-X stellarator [G. Grieger et al., Plasma Physics and Controlled Nuclear Fusion Research 1990 (International Atomic Energy Agency, Vienna, 1991), Vol. 3, p. 525] and the International Thermonuclear Experimental Reactor [Progress in the ITER Physics Basis, Nucl. Fusion 7, S1, S285 (2007)]-like equilibria. An advanced fluid model is used for the ions together with the reduced Braghinskii equations for the electrons. Using the ballooning mode representation, the drift wave problem is set as an eigenvalue equation along a field line and is solved numerically using a standard shooting technique. A significantly larger magnetic shear and a less unfavorable normal curvature in the tokamak equilibrium are found to give a stronger finite-Larmor radius stabilization and a more narrow mode spectrum than in the stellarator. The effect of negative global magnetic shear in the tokamak is found to be stabilizing. The growth rate on a tokamak magnetic flux surface is found to be comparable to that on a stellarator surface with the same global magnetic shear but the eigenfunction in the tokamak is broader than in the stellarator due to the presence of large negative local magnetic shear (LMS) on the tokamak surface. A large absolute value of the LMS in a region of unfavorable normal curvature is found to be stabilizing in the stellarator, while in the tokamak case, negative LMS is found to be stabilizing and positive LMS destabilizing.

Evaluating plyometric exercises using time to stabilization.

PubMed

Ebben, William P; Vanderzanden, Tyler; Wurm, Bradley J; Petushek, Erich J

2010-02-01

Plyometric exercises are frequently used in strength and conditioning and rehabilitation programs because the landing phase of these exercises requires dynamic stabilization. This study examined the differences in landing stability of a variety of plyometric exercises by assessing time to stabilization (TTS), its reliability, and sex differences therein. Forty-nine men and women performed a variety of plyometric exercises thought to represent a continuum of difficulty of dynamic stabilization during landing. Plyometric exercises included line hops, cone hops, squat jumps, tuck jumps, countermovement jumps, dumbbell countermovement jumps, and single leg countermovement jumps, each performed for 3 repetitions on a force platform. A 2-way mixed analysis of covariance with repeated measures for plyometric exercise type was used to evaluate the main effects for plyometric exercise type and the interaction between plyometric exercise type and sex for TTS. Subject jumping ability was evaluated as a covariate. Results revealed significant main effects for plyometric exercise type (p < or = 0.001) and for the interaction between plyometric exercise type and sex (p = 0.002). Bonferroni adjusted post hoc analysis demonstrated differences in TTS between a number of plyometric exercises for men and women. Reliability analysis revealed intraclass correlation coefficients ranging from 0.51 to 0.86 with no significant difference between trials (p > 0.05). Practitioners who use plyometrics to train dynamic stability should create programs that progress the intensity of the exercises based on the results of this study. This study also demonstrated that TTS is moderately to highly reliable for a variety of jumping conditions for both men and women.

Surrogate endpoints for overall survival in advanced non-small-cell lung cancer patients with mutations of the epidermal growth factor receptor gene.

PubMed

Yoshino, Reiko; Imai, Hisao; Mori, Keita; Takei, Kousuke; Tomizawa, Mai; Kaira, Kyoichi; Yoshii, Akihiro; Tomizawa, Yoshio; Saito, Ryusei; Yamada, Masanobu

2014-09-01

Subsequent therapies confound the ability to discern the effect of first-line chemotherapy on overall survival (OS). We investigated whether progression-free survival (PFS), post-progression survival (PPS) and tumor response were valid surrogate endpoints for OS following first-line chemotherapy in individual patients with advanced non-small-cell lung cancer (NSCLC) harboring sensitive epidermal growth factor receptor gene mutations. We retrospectively analyzed 35 patients with advanced NSCLC treated with first-line gefitinib. The associations of PFS, PPS and tumor response with OS were analyzed. PPS was found to be strongly correlated with OS, unlike PFS and tumor shrinkage. The factors significantly associated with PPS were performance status (PS) after first-line treatment, best response to second-line treatment and number of regimens used after disease progression. PPS may be a surrogate for OS in this patient population and further therapy after disease progression following first-line chemotherapy may significantly affect OS. However, a larger study is required to validate these results.

Fiber-optic delay-line stabilization of heterodyne optical signal generator and method using same

NASA Technical Reports Server (NTRS)

Logan, Ronald T. (Inventor)

1997-01-01

The present invention is a laser heterodyne frequency generator system with a stabilizer for use in the microwave and millimeter-wave frequency ranges utilizing a photonic mixer as a photonic phase detector in a stable optical fiber delay-line. Phase and frequency fluctuations of the heterodyne laser signal generators are stabilized at microwave and millimeter wave frequencies by a delay line system operating as a frequency discriminator. The present invention is free from amplifier and mixer 1/.function. noise at microwave and millimeter-wave frequencies that typically limit phase noise performance in electronic cavity stabilized electronic oscillators. Thus, 1/.function. noise due to conventional mixers is eliminated and stable optical heterodyne generation of electrical signals is achieved.

Determining stability in connected speech in primary progressive aphasia and Alzheimer's disease.

PubMed

Beales, Ashleigh; Whitworth, Anne; Cartwright, Jade; Panegyres, Peter K; Kane, Robert T

2018-03-08

Using connected speech to assess progressive language disorders is confounded by uncertainty around whether connected speech is stable over successive sampling, and therefore representative of an individual's performance, and whether some contexts and/or language behaviours show greater stability than others. A repeated measure, within groups, research design was used to investigate stability of a range of behaviours in the connected speech of six individuals with primary progressive aphasia and three individuals with Alzheimer's disease. Stability was evaluated, at a group and individual level, across three samples, collected over 3 weeks, involving everyday monologue, narrative and picture description, and analysed for lexical content, fluency and communicative informativeness and efficiency. Excellent and significant stability was found on the majority of measures, at a group and individual level, across all genres, with isolated measures (e.g. nouns use, communicative efficiency) showing good, but greater variability, within one of the three genres. Findings provide evidence of stability on measures of lexical content, fluency and communicative informativeness and efficiency. While preliminary evidence suggests that task selection is influential when considering stability of particular connected speech measures, replication over a larger sample is necessary to reproduce findings.

An MHD variational principle that admits reconnection

NASA Technical Reports Server (NTRS)

Rilee, M. L.; Sudan, R. N.; Pfirsch, D.

1997-01-01

The variational approach of Pfirsch and Sudan's averaged magnetohydrodynamics (MHD) to the stability of a line-tied current layer is summarized. The effect of line-tying on current sheets that might arise in line-tied magnetic flux tubes by estimating the growth rates of a resistive instability using a variational method. The results show that this method provides a potentially new technique to gauge the stability of nearly ideal magnetohydrodynamic systems. The primary implication for the stability of solar coronal structures is that tearing modes are probably constant at work removing magnetic shear from the solar corona.

Integrating molecular mechanisms and clinical evidence in the management of trastuzumab resistant or refractory HER-2⁺ metastatic breast cancer.

PubMed

Wong, Hilda; Leung, Roland; Kwong, Ava; Chiu, Joanne; Liang, Raymond; Swanton, Charles; Yau, Thomas

2011-01-01

Human epidermal growth factor receptor (HER)-2(+) breast cancer is a distinct molecular and clinical entity, the prognosis of which is improved by trastuzumab. However, primary resistance to trastuzumab is observed in >50% of patients with HER-2(+) advanced breast cancer, and the majority of patients who initially respond to treatment eventually develop disease progression. To facilitate crosstrial comparisons and the understanding of resistance mechanisms, we propose a unifying definition of trastuzumab resistance as progression at first radiological reassessment at 8-12 weeks or within 3 months after first-line trastuzumab in the metastatic setting or new recurrences diagnosed during or within 12 months after adjuvant trastuzumab. In contrast, we define trastuzumab-refractory breast cancer as disease progression after two or more lines of trastuzumab-containing regimens that initially achieved disease response or stabilization at first radiological assessment. We review mechanisms of trastuzumab resistance mediated by p95HER-2 overexpression, phosphoinositide 3-kinase pathway activation, and signaling pathway activation driven by HER-3, epidermal growth factor receptor, and insulin-like growth factor 1 receptor. We distinguish in vitro from in vivo evidence, highlighting that most data describing trastuzumab resistance are derived from preclinical studies or small retrospective patient cohorts, and discuss targeted therapeutic approaches to overcome resistance. Prospective analysis through clinical trials with robust tissue collection procedures, prior to and following acquisition of resistance, integrated with next-generation tumor genome sequencing technologies, is identified as a priority area for development. The identification of predictive biomarkers is of paramount importance to optimize health economic costs and enhance stratification of anti-HER-2 targeted therapies.

On the stability of an infinite swept attachment line boundary layer

NASA Technical Reports Server (NTRS)

Hall, P.; Mallik, M. R.; Poll, D. I. A.

1984-01-01

The instability of an infinite swept attachment line boundary layer is considered in the linear regime. The basic three dimensional flow is shown to be susceptible to travelling wave disturbances which propagate along the attachment line. The effect of suction on the instability is discussed and the results suggest that the attachment line boundary layer on a swept wing can be significantly stabilized by extremely small amounts of suction. The results obtained are in excellent agreement with the available experimental observations.

Progress in theoretical and numerical modeling of RF/MHD coupling using NIMROD

NASA Astrophysics Data System (ADS)

Jenkins, Thomas G.; Schnack, Dalton D.; Hegna, Chris C.; Callen, James D.; Sovinec, Carl R.; Held, Eric D.; Ji, Jeong-Young; Kruger, Scott E.

2007-11-01

Preliminary work relevant to the development of a general framework for the self-consistent inclusion of RF effects in fluid codes is presented; specifically, the stabilization of neoclassical and conventional tearing modes by electron cyclotron current drive is considered. For this particular problem, the effects of the RF drive can be formally captured by a quasilinear diffusion operator which enters the fluid equations on the same footing as the collision operator. Furthermore, a Chapman-Enskog-like method can be used to determine the consequent effects of the RF drive on the fluid closures for the parallel heat flow and stress. We summarize our recent research along these lines and discuss issues relevant to its implementation in the NIMROD code.

The Structure and Dynamics of the Solar Corona and Inner Heliosphere

NASA Technical Reports Server (NTRS)

Mikic, Zoran

2002-01-01

This report covers technical progress during the second quarter of the first year of NASA Sun-Earth Connections Theory Program (SECTP) contract 'The Structure and Dynamics of the Solar Corona and Inner Heliosphere,' NAS5-99188, between NASA and Science Applications International Corporation. and covers the period November 16, 1999 to February 15, 2000. Under this contract SAIC and the University of California, Irvine (UCI) have conducted research into theoretical modeling of active regions, the solar corona, and the inner heliosphere, using the MHD (magnetohydrodynamic) model. The topics studied include: the effect of emerging flux on the stability of helmet streamers, coronal loops and streamers, the solar magnetic field, the solar wind, and open magnetic field lines.

The E3 ligase for metastasis associated 1 protein, TRIM25, is targeted by microRNA-873 in hepatocellular carcinoma.

PubMed

Li, Yu-Hui; Zhong, Ming; Zang, Hong-Liang; Tian, Xiao-Feng

2018-07-01

Tumor metastasis accounts for 90% of all cancer-related deaths. Epithelial to mesenchymal transition (EMT) considered to be centrally important in acquired resistance to chemotherapy and in progression of tumors to secondary organs. One of the important mediators of metastatic progression in hepatocellular carcinoma (HCC) is the metastasis associated protein 1 (MTA-1). We have earlier shown that in the context of HCC and normal liver cell lines, MTA-1 protein is actively stabilized in HCC cell lines and actively degraded in normal liver cells. We have also shown that TRIM25 is the E3 ligase that interacts with and degrades MTA-1 protein. The identity of the factor regulating expression of TRIM25 in normal liver cells and HCC is unknown. In the current work we elucidate that microRNA (miR)- 873 targets TRIM25 in HCC cells. Both metagenomic analysis and quantification of miR-873 and TRIM25 in 25 HCC patients revealed an inverse correlation between the two in HCC patients with high miR-873 and low TRIM25 expression, respectively. The expression pattern was mimicked in the normal liver cells THLE-2 and the HCC cell line, HuH6. In vitro luciferase reporter assays confirmed TRIM25 as the target of miR-873. Transient transfection of HuH6 cells with an anti-miR-873 antagomir significantly decreased both transwell motility in these cells. Furthermore, in in vivo xenograft assays treatment with anti-miR-873 antagomir significantly decreased hepatic nodules formation. Cumulatively, our data indicate that suppression of TRIM25 expression by high levels of miR-873 dictates MTA1 protein upregulation in HCC. Copyright © 2018 Elsevier Inc. All rights reserved.

Enzyme replacement therapy in Fabry disease: influence on cardiac manifestations.

PubMed

Caballero, L; Climent, V; Hernández-Romero, D; Quintanilla, M A; de la Morena, G; Marín, F

2010-01-01

Fabry disease (FD) is an X-linked glycosphingolipid storage disorder caused by deficient activity of the lysosomal enzyme alpha-galactosidase A. This leads to a progressive accumulation of globotriaosylceramide (Gb3) in the lysosomes of different cells and tissues, causing principally ventricular hypertrophy, renal failure and cerebrovascular accidents, reducing lifespan both in hemizygous males and heterozygous females. Residual enzyme activity might lead to slow progression of the disease and result in the so-called cardiac or renal variants with delayed presentation. Two different forms of alpha-galactosidase A enzyme replacement therapies (ERT) are available for the treatment of FD, one genetically engineered in human cell line (agalsidase alfa, Replagal, Shire) and the other produced in a Chinese hamster ovary cell line (agalsidase beta, Fabrazyme, Genzyme). Although both proteins are structurally and functionally very similar, with the same amino acid sequence as the native human enzyme, they differ in the pattern of glycosilation of the protein depending on the originating cell line. Studies with both preparations have described a reduction in plasma, urinary sediment and tissue levels of Gb3, a decrease in the frequency of pain crisis and a reduction in left ventricular mass and improvement or stabilization of renal function. Studies have generally shown the greatest benefit when treatment is started at an early stage of the disease before extensive fibrosis or other irreversible tissue damage takes place. However, more data are needed to document long-term treatment outcomes. The aim of the present review is to provide an update overview of the two different forms of ERT for FD, their clinical effects in cardiac manifestations and their possible differences in terms of efficacy, side effects and safety profiles.

Trapped particle stability for the kinetic stabilizer

NASA Astrophysics Data System (ADS)

Berk, H. L.; Pratt, J.

2011-08-01

A kinetically stabilized axially symmetric tandem mirror (KSTM) uses the momentum flux of low-energy, unconfined particles that sample only the outer end-regions of the mirror plugs, where large favourable field-line curvature exists. The window of operation is determined for achieving magnetohydrodynamic (MHD) stability with tolerable energy drain from the kinetic stabilizer. Then MHD stable systems are analysed for stability of the trapped particle mode. This mode is characterized by the detachment of the central-cell plasma from the kinetic-stabilizer region without inducing field-line bending. Stability of the trapped particle mode is sensitive to the electron connection between the stabilizer and the end plug. It is found that the stability condition for the trapped particle mode is more constraining than the stability condition for the MHD mode, and it is challenging to satisfy the required power constraint. Furthermore, a severe power drain may arise from the necessary connection of low-energy electrons in the kinetic stabilizer to the central region.

Performance of a Nanometer Resolution BPM System

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

Vogel, V; Hayano, H; Honda, Y

2005-10-14

International Linear Collider (ILC) interaction region beam sizes and component position stability requirements will be as small as a few nanometers. it is important to the ongoing ILC design effort to demonstrate that these tolerances can be achieved--ideally using beam-based stability measurements. It has been estimated that an RF cavity BPM with modern waveform processing could provide a position measurement resolution of less than one nanometer. Such a system could form the basis of the desired beam-based stability measurement, as well as be used for other specialized purposes. They have developed a high resolution RF cavity BPM and associated electronics.more » A triplet comprised of these BPMs has been installed in the extraction line of the KEK Accelerator Test Facility (ATF) for testing with its ultra-low emittance beam. The three BPMs are rigidly mounted inside an alignment frame on six variable-length struts which can be used to move the BPMs in position and angle. they have developed novel methods for extracting the position and tilt information from the BPM signals including a robust calibration algorithm which is immune to beam jitter. To date, they have been able to demonstrate a resolution of approximately 20 nm over a dynamic range of {+-} 20 {micro}m. They report on the progress of these ongoing tests.« less

Recombinase-mediated cassette exchange (RMCE) for monoclonal antibody expression in the commercially relevant CHOK1SV cell line.

PubMed

Zhang, Lin; Inniss, Mara C; Han, Shu; Moffat, Mark; Jones, Heather; Zhang, Baohong; Cox, Wendy L; Rance, James R; Young, Robert J

2015-01-01

To meet product quality and cost parameters for therapeutic monoclonal antibody (mAb) production, cell lines are required to have excellent growth, stability, and productivity characteristics. In particular, cell line generation stability is critical to the success of a program, especially where high cell line generation numbers are required for large in-market supply. However, a typical process for developing such cell lines is laborious, lengthy, and costly. In this study, we applied a FLP/FRT recombinase-mediated cassette exchange (RMCE) system to build a site-specific integration (SSI) system for mAb expression in the commercially relevant CHOK1SV cell line. Using a vector with a FRT-flanked mAb expression cassette, we generated a clonal cell line with good productivity, long-term production stability, and low mAb gene-copy number indicating the vector was located in a 'hot-spot.' A SSI host cell line was made by removing the mAb genes from the 'hot-spot' by RMCE, creating a 'landing pad' containing two recombination cassettes that allow targeting of one or two copies of recombinant genes. Cell lines made from this host exhibited excellent growth and productivity profiles, and stability for at least 100 generations in the absence of selection agents. Importantly, while clones containing two copies had higher productivity than single copy clones, both were stable over many generations. Taken together, this study suggests the use of FLP-based RMCE to develop SSI host cells for mAb production in CHOK1SV offers significant savings in both resources and overall cell line development time, leading to a shortened 'time-to-clinic' for therapeutic mAbs. © 2015 American Institute of Chemical Engineers.

New diamidequat-type surfactants in fabrication of long-sustained theranostic nanocapsules: Colloidal stability, drug delivery and bioimaging.

PubMed

Bazylińska, Urszula; Zieliński, Wojciech; Kulbacka, Julita; Samoć, Marek; Wilk, Kazimiera A

2016-01-01

We report a new theranostic nanoformulation to transport both chemotherapeutic and imaging agents for successfully exterminating cancer cells. This strategy is based on encapsulation of colchicine (cytostatic drug) and coumarin-6 (fluorescent biomarker) in oil-core nanocarriers stabilized by diamidequat-type surfactants - N,N-dimethyl-N,N-bis[2-(N-alkylcarbamoyl) ethyl]ammonium methylsulfates (2xCnA-MS, n=8,10,12), and fabricated by the nanoprecipitation technique. The surfactants were synthesized using a technologically viable methodology and characterized. The potential of the encapsulated theranostic cargoes was evaluated in cytotoxicity studies as well as in imaging of intracellular localization, accumulation and distribution of cargoes delivered to well characterized human cancer cell lines - doxorubicin-sensitive breast (MCF-7/WT), alveolar basal epithelial (A549) and skin melanoma (MEWO) - performed by confocal laser scanning microscopy (CLSM). Backscattered profiles obtained by the turbidimetric technique were applied to evaluate physical stability of the obtained nanosystems. DLS measurements confirmed the particle diameter to be below 200nm, while AFM - its morphology and shape. Doppler electrophoresis provided a highly positive ζ-potential. UV-vis was applied to determine the encapsulation efficiencies (ca. 90%), and release profiles. The study demonstrates that the soft cationic diamidequat-type surfactants are suitable for the stabilization of theranostic nanodispersions, and they can constitute a new functional class of stabilizers of nanoparticles and have a progressive impact onto development of formulations. Furthermore, our results demonstrate excellent biocompatibility of the studied long-sustained monodisperse oil-core nanocapsules, stabilized by 2xCnA-MS, which makes them promising for cell imaging. Copyright © 2015 Elsevier B.V. All rights reserved.

46 CFR 35.20-7 - Verification of vessel compliance with applicable stability requirements-TB/ALL.

Code of Federal Regulations, 2011 CFR

2011-10-01

... the vessels's trim and stability book, stability letter, Certificate of Inspection, and Load Line.... (b) When determining compliance with applicable stability requirements the vessel's draft, trim, and...

46 CFR 35.20-7 - Verification of vessel compliance with applicable stability requirements-TB/ALL.

Code of Federal Regulations, 2010 CFR

2010-10-01

... the vessels's trim and stability book, stability letter, Certificate of Inspection, and Load Line.... (b) When determining compliance with applicable stability requirements the vessel's draft, trim, and...

Overview of transport and MHD stability study: focusing on the impact of magnetic field topology in the Large Helical Device

NASA Astrophysics Data System (ADS)

Ida, K.; Nagaoka, K.; Inagaki, S.; Kasahara, H.; Evans, T.; Yoshinuma, M.; Kamiya, K.; Ohdach, S.; Osakabe, M.; Kobayashi, M.; Sudo, S.; Itoh, K.; Akiyama, T.; Emoto, M.; Dinklage, A.; Du, X.; Fujii, K.; Goto, M.; Goto, T.; Hasuo, M.; Hidalgo, C.; Ichiguchi, K.; Ishizawa, A.; Jakubowski, M.; Kawamura, G.; Kato, D.; Morita, S.; Mukai, K.; Murakami, I.; Murakami, S.; Narushima, Y.; Nunami, M.; Ohno, N.; Pablant, N.; Sakakibara, S.; Seki, T.; Shimozuma, T.; Shoji, M.; Tanaka, K.; Tokuzawa, T.; Todo, Y.; Wang, H.; Yokoyama, M.; Yamada, H.; Takeiri, Y.; Mutoh, T.; Imagawa, S.; Mito, T.; Nagayama, Y.; Watanabe, K. Y.; Ashikawa, N.; Chikaraishi, H.; Ejiri, A.; Furukawa, M.; Fujita, T.; Hamaguchi, S.; Igami, H.; Isobe, M.; Masuzaki, S.; Morisaki, T.; Motojima, G.; Nagasaki, K.; Nakano, H.; Oya, Y.; Suzuki, C.; Suzuki, Y.; Sakamoto, R.; Sakamoto, M.; Sanpei, A.; Takahashi, H.; Tsuchiya, H.; Tokitani, M.; Ueda, Y.; Yoshimura, Y.; Yamamoto, S.; Nishimura, K.; Sugama, H.; Yamamoto, T.; Idei, H.; Isayama, A.; Kitajima, S.; Masamune, S.; Shinohara, K.; Bawankar, P. S.; Bernard, E.; von Berkel, M.; Funaba, H.; Huang, X. L.; T., Ii; Ido, T.; Ikeda, K.; Kamio, S.; Kumazawa, R.; Kobayashi, T.; Moon, C.; Muto, S.; Miyazawa, J.; Ming, T.; Nakamura, Y.; Nishimura, S.; Ogawa, K.; Ozaki, T.; Oishi, T.; Ohno, M.; Pandya, S.; Shimizu, A.; Seki, R.; Sano, R.; Saito, K.; Sakaue, H.; Takemura, Y.; Tsumori, K.; Tamura, N.; Tanaka, H.; Toi, K.; Wieland, B.; Yamada, I.; Yasuhara, R.; Zhang, H.; Kaneko, O.; Komori, A.; Collaborators

2015-10-01

The progress in the understanding of the physics and the concurrent parameter extension in the large helical device since the last IAEA-FEC, in 2012 (Kaneko O et al 2013 Nucl. Fusion 53 095024), is reviewed. Plasma with high ion and electron temperatures (Ti(0) ˜ Te(0) ˜ 6 keV) with simultaneous ion and electron internal transport barriers is obtained by controlling recycling and heating deposition. A sign flip of the nondiffusive term of impurity/momentum transport (residual stress and convection flow) is observed, which is associated with the formation of a transport barrier. The impact of the topology of three-dimensional magnetic fields (stochastic magnetic fields and magnetic islands) on heat momentum, particle/impurity transport and magnetohydrodynamic stability is also discussed. In the steady state operation, a 48 min discharge with a line-averaged electron density of 1 × 1019 m-3 and with high electron and ion temperatures (Ti(0) ˜ Te(0) ˜ 2 keV), resulting in 3.36 GJ of input energy, is achieved.

Parkin-Dependent Degradation of the F-Box Protein Fbw7β Promotes Neuronal Survival in Response to Oxidative Stress by Stabilizing Mcl-1

PubMed Central

Ekholm-Reed, Susanna; Goldberg, Matthew S.; Schlossmacher, Michael G.

2013-01-01

Parkinson's disease (PD) is characterized by progressive loss of midbrain dopaminergic neurons resulting in motor dysfunction. While most PD is sporadic in nature, a significant subset can be linked to either dominant or recessive germ line mutations. PARK2, encoding the ubiquitin ligase parkin, is the most frequently mutated gene in hereditary Parkinson's disease. Here, we present evidence for a neuronal ubiquitin ligase cascade involving parkin and the multisubunit ubiquitin ligase SCFFbw7β. Specifically, parkin targets the SCF substrate adapter Fbw7β for proteasomal degradation. Furthermore, we show that the physiological role of parkin-mediated regulation of Fbw7β levels is the stabilization of the mitochondrial prosurvival factor Mcl-1, an SCFFbw7β target in neurons. We show that neurons depleted of parkin become acutely sensitive to oxidative stress due to an inability to maintain adequate levels of Mcl-1. Therefore, loss of parkin function through biallelic mutation of PARK2 may lead to death of dopaminergic neurons through unregulated SCFFbw7β-mediated ubiquitylation-dependent proteolysis of Mcl-1. PMID:23858059

All Inorganic Halide Perovskites Nanosystem: Synthesis, Structural Features, Optical Properties and Optoelectronic Applications.

PubMed

Li, Xiaoming; Cao, Fei; Yu, Dejian; Chen, Jun; Sun, Zhiguo; Shen, Yalong; Zhu, Ying; Wang, Lin; Wei, Yi; Wu, Ye; Zeng, Haibo

2017-03-01

The recent success of organometallic halide perovskites (OHPs) in photovoltaic devices has triggered lots of corresponding research and many perovskite analogues have been developed to look for devices with comparable performance but better stability. Upon the preparation of all inorganic halide perovskite nanocrystals (IHP NCs), research activities have soared due to their better stability, ultrahigh photoluminescence quantum yield (PL QY), and composition dependent luminescence covering the whole visible region with narrow line-width. They are expected to be promising materials for next generation lighting and display, and many other applications. Within two years, a lot of interesting results have been observed. Here, the synthesis of IHPs is reviewed, and their progresses in optoelectronic devices and optical applications, such as light-emitting diodes (LEDs), photodetectors (PDs), solar cells (SCs), and lasing, is presented. Information and recent understanding of their crystal structures and morphology modulations are addressed. Finally, a brief outlook is given, highlighting the presently main problems and their possible solutions and future development directions. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Stream Channel Stability Assessment

DOT National Transportation Integrated Search

1982-01-01

Channel instability is manifested as lateral bank erosion, progressive degradation of the streambed, or natural scour and fill of the streambed. Lateral stability is related to stream type, and four major stream types having different stability chara...

Preparation, characterization, and banking of clinical-grade cells for neural transplantation: Scale up, fingerprinting, and genomic stability of stem cell lines.

PubMed

Natalwala, Ammar; Kunath, Tilo

2017-01-01

Parkinson's disease is a complex and progressive neurodegenerative condition that is characterized by the severe loss of midbrain dopaminergic (mDA) neurons, which innervate the striatum. Cell transplantation therapies to rebuild this dopaminergic network have been attempted for over 30 years. The most promising outcomes were observed when human fetal mesencephalic tissue was used as the source of cells for transplantation. However, reliance on terminations for a Parkinson's therapy presents significant logistical and ethical hurdles. An alternative source of transplantable mDA neurons is urgently needed, and the solution may come from human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs). Protocols to differentiate hESCs/iPSCs toward mDA neurons are now robust and efficient, and upon grafting the cells rescue preclinical animal models of Parkinson's disease. The challenge now is to apply Good Manufacturing Practice (GMP) to the academic discoveries and protocols to produce clinical-grade transplantable mDA cells. Major technical and logistical considerations include (i) source of hESC or iPSC line, (ii) GMP compliance of the differentiation protocol and all reagents, (iii) characterization of the cell product in terms of identity, safety, and efficacy, (iv) characterization of genomic state and stability, and (v) banking of a transplantation-ready cell product. Approaches and solutions to these challenges are reviewed here. © 2017 Elsevier B.V. All rights reserved.

Re-challenge with pemetrexed in advanced mesothelioma: a multi-institutional experience

PubMed Central

2012-01-01

Background Although first-line therapy for patients affected by advanced mesothelioma is well established, there is a lack of data regarding the impact of second-line treatment. Methods We retrospectively collected data of patients affected by advanced mesothelioma, already treated with first-line therapy based on pemetrexed and platin, with a response (partial response or stable disease) lasting at least 6 months, and re-treated with a pemetrexed-based therapy at progression. The primary objective was to describe time to progression and overall survival after re-treatment. Results Overall across several Italian oncological Institutions we found 30 patients affected by advanced mesothelioma, in progression after a 6-month lasting clinical benefit following a first-line treatment with cisplatin and pemetrexed, and re-challenged with a pemetrexed-based therapy. In these patients we found a disease control rate of 66%, with reduction of pain in 43% of patients. Overall time to progression and survival were promising for a second-line setting of patients with advanced mesothelioma, being 5.1 and 13.6 months, respectively. Conclusions In our opinion, when a patient has a long-lasting benefit from previous treatment with pemetrexed combined with a platin compound, the same treatment should be offered at progression. PMID:22943698

GTSE1 tunes microtubule stability for chromosome alignment and segregation by inhibiting the microtubule depolymerase MCAK

PubMed Central

Bendre, Shweta; Hall, Conrad; Lin, Yu-Chih

2016-01-01

The dynamic regulation of microtubules (MTs) during mitosis is critical for accurate chromosome segregation and genome stability. Cancer cell lines with hyperstabilized kinetochore MTs have increased segregation errors and elevated chromosomal instability (CIN), but the genetic defects responsible remain largely unknown. The MT depolymerase MCAK (mitotic centromere-associated kinesin) can influence CIN through its impact on MT stability, but how its potent activity is controlled in cells remains unclear. In this study, we show that GTSE1, a protein found overexpressed in aneuploid cancer cell lines and tumors, regulates MT stability during mitosis by inhibiting MCAK MT depolymerase activity. Cells lacking GTSE1 have defects in chromosome alignment and spindle positioning as a result of MT instability caused by excess MCAK activity. Reducing GTSE1 levels in CIN cancer cell lines reduces chromosome missegregation defects, whereas artificially inducing GTSE1 levels in chromosomally stable cells elevates chromosome missegregation and CIN. Thus, GTSE1 inhibition of MCAK activity regulates the balance of MT stability that determines the fidelity of chromosome alignment, segregation, and chromosomal stability. PMID:27881713

Spectral and temporal characterization of a fused-quartz-microresonator optical frequency comb

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

Papp, Scott B.; Diddams, Scott A.

2011-11-15

We report on the fabrication of high-Q, fused-quartz microresonators and the parametric generation of a frequency comb with 36-GHz line spacing using them. We have characterized the intrinsic stability of the comb in both the time and frequency domains to assess its suitability for future precision metrology applications. Intensity autocorrelation measurements and line-by-line comb control reveal near-transform-limited picosecond pulse trains that are associated with good relative phase and amplitude stability of the comb lines. The comb's 36-GHz line spacing can be readily photodetected, which enables measurements of its intrinsic and absolute phase fluctuations.

Study on the new technology of removing gangue and retaining roadway in complicated roof condition

NASA Astrophysics Data System (ADS)

Chen, Yanhao; Jiang, Cong

2018-04-01

This article in view of the complex roof conditions was carried on study about the new technology of removing gangue and retaining roadway, and tells a method of progressive reinforced concrete wall segment with gangue to keep the roadway, the roadway beside the support system is mainly composed of the lining, waste rock wall and the outer wall, the wall and the outer wall of concrete material width to build the strength of the progressive type filling body, waste rock wall with woven bag with waste rock assembled, paragraphs geological survey on the actual distance should be based on working face. This method relies on the interior of the gangue wall to make the pressure control and allow the roof to sink. In this paper, the finite deformation control of the roof is realized by the gangue wall and the high strength filling body. This method has the characteristics of low entry cost, good forming of roadway, high security and good stability, and can be applied to complex geological conditions such as hard roof.

Evaluation of Hose in Hose Transfer Line Service Life for Hanfords Interim Stabilization Program

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

TORRES, T.D.

RPP-6153, Engineering Task Plan for Hose-in-Hose Transfer System for the Interim Stabilization Program (Torres, 2000a), defines the programmatic goals, functional requirements, and technical criteria for the development and subsequent installation of waste transfer line equipment to support Hanford's Interim Stabilization Program. RPP-6028, Specification for Hose in Hose Transfer Lines for Hanford's Interim Stabilization Program (Torres, 2000b), has been issued to define the specific requirements for the design, manufacture, and verification of transfer line assemblies for specific waste transfer applications associated with Interim Stabilization. Included in RPP-6028 are tables defining the chemical constituents of concern to which transfer lines will bemore » exposed. Current Interim Stabilization Program planning forecasts that the at-grade transfer lines will be required to convey pumpable waste for as much as three years after commissioning, RPP-6028 Section 3.2.7. Performance Incentive Number ORP-05 requires that all the Single Shell Tanks be Interim Stabilized by September 30, 2003. The Tri-Party Agreement (TPA) milestone M-41-00, enforced by a federal consent decree, requires all the Single Shell Tanks to be Interim stabilized by September 30, 2004. By meeting the Performance Incentive the TPA milestone is met. Prudent engineering dictates that the equipment used to transfer waste have a life in excess of the forecasted operational time period, with some margin to allow for future adjustments to the planned schedule. This document evaluates the effective service life of the Hose-in-Hose Transfer Lines, based on information submitted by the manufacturer, published literature and calculations. The effective service life of transfer line assemblies is a function of several factors. Foremost among these are the hose material's resistance to the harmful effects of process fluid characteristics, ambient environmental conditions, exposure to ionizing radiation and the manufacturer's stated shelf life. In order to determine the transfer line service life this evaluation examines the certification of shelf life, the certification of chemical compatibility with waste, catalog information of ambient ratings and published literature on the effects of exposure to ionizing radiation on the mechanical properties of elastomeric materials. During initial hose procurements, the hose-in-hose transfer line vendor River Bend Hose Specialty (RBHS) submitted a letter, dated 6/8/00, which recommended the service and shelf life of the hose to be seven years. In submittals for later hose procurements, RBHS submitted a letter, dated 11/6/00, which recommended the service life of the hose to be three years. This submittal was followed by documentation, on 2/14/01, which submitted new storage requirements and restated the seven year shelf life. RBHS revised their original hose service life estimate to a more conservative three years due to concerns over the effects of chemicals in transferred waste. The above mentioned submittals from RBHS are the primary drivers of the three year service life limit established by this document.« less

On-Line Robust Modal Stability Prediction using Wavelet Processing

NASA Technical Reports Server (NTRS)

Brenner, Martin J.; Lind, Rick

1998-01-01

Wavelet analysis for filtering and system identification has been used to improve the estimation of aeroservoelastic stability margins. The conservatism of the robust stability margins is reduced with parametric and nonparametric time- frequency analysis of flight data in the model validation process. Nonparametric wavelet processing of data is used to reduce the effects of external disturbances and unmodeled dynamics. Parametric estimates of modal stability are also extracted using the wavelet transform. Computation of robust stability margins for stability boundary prediction depends on uncertainty descriptions derived from the data for model validation. The F-18 High Alpha Research Vehicle aeroservoelastic flight test data demonstrates improved robust stability prediction by extension of the stability boundary beyond the flight regime. Guidelines and computation times are presented to show the efficiency and practical aspects of these procedures for on-line implementation. Feasibility of the method is shown for processing flight data from time- varying nonstationary test points.

Discovery of 2-(1H-indol-5-ylamino)-6-(2,4-difluorophenylsulfonyl)-8-methylpyrido[2,3-d]pyrimidin-7(8H)-one (7ao) as a potent selective inhibitor of Polo like kinase 2 (PLK2)

PubMed Central

Reddy, M. V. Ramana; Akula, Balireddy; Jatiani, Shashidhar; Vasquez-Del Carpio, Rodrigo; Billa, Vinay K.; Mallireddigari, Muralidhar R.; Cosenza, Stephen C.; Subbaiah, D. R. C. Venkata; Bharathi, E. Vijaya; Pallela, Venkat R.; Ramkumar, Poornima; Jain, Rinku; Aggarwal, Aneel K.; Reddy, E. Premkumar

2018-01-01

Several families of protein kinases have been shown to play a critical role in the regulation of cell cycle progression, particularly progression through mitosis. These kinase families include the Aurora kinases, the Mps1 gene product and the Polo Like family of protein kinases (PLKs). The PLK family consists of five members and of these, the role of PLK1 in human cancer is well documented. PLK2 (SNK), which is highly homologous to PLK1, has been shown to play a critical role in centriole duplication and is also believed to play a regulatory role in the survival pathway by physically stabilizing the TSC1/2 complex in tumor cells under hypoxic conditions. As a part of our research program, we have developed a library of novel ATP mimetic chemotypes that are cytotoxic against a panel of cancer cell lines. We show that one of these chemotypes, the 6-arylsulfonyl pyridopyrimidinones, induces apoptosis of human tumor cell lines in nanomolar concentrations. The most potent of these compounds, 7ao, was found to be a highly specific inhibitor of PLK2 when profiled against a panel of 288 wild type, 55 mutant and 12 lipid kinases. Here, we describe the synthesis, structure activity relationship, in vitro kinase specificity and biological activity of the lead compound, 7ao. PMID:26762835

Discovery of 2-(1H-indol-5-ylamino)-6-(2,4-difluorophenylsulfonyl)-8-methylpyrido[2,3-d]pyrimidin-7(8H)-one (7ao) as a potent selective inhibitor of Polo like kinase 2 (PLK2).

PubMed

Reddy, M V Ramana; Akula, Balireddy; Jatiani, Shashidhar; Vasquez-Del Carpio, Rodrigo; Billa, Vinay K; Mallireddigari, Muralidhar R; Cosenza, Stephen C; Venkata Subbaiah, D R C; Bharathi, E Vijaya; Pallela, Venkat R; Ramkumar, Poornima; Jain, Rinku; Aggarwal, Aneel K; Reddy, E Premkumar

2016-02-15

Several families of protein kinases have been shown to play a critical role in the regulation of cell cycle progression, particularly progression through mitosis. These kinase families include the Aurora kinases, the Mps1 gene product and the Polo Like family of protein kinases (PLKs). The PLK family consists of five members and of these, the role of PLK1 in human cancer is well documented. PLK2 (SNK), which is highly homologous to PLK1, has been shown to play a critical role in centriole duplication and is also believed to play a regulatory role in the survival pathway by physically stabilizing the TSC1/2 complex in tumor cells under hypoxic conditions. As a part of our research program, we have developed a library of novel ATP mimetic chemotypes that are cytotoxic against a panel of cancer cell lines. We show that one of these chemotypes, the 6-arylsulfonyl pyridopyrimidinones, induces apoptosis of human tumor cell lines in nanomolar concentrations. The most potent of these compounds, 7ao, was found to be a highly specific inhibitor of PLK2 when profiled against a panel of 288 wild type, 55 mutant and 12 lipid kinases. Here, we describe the synthesis, structure activity relationship, in vitro kinase specificity and biological activity of the lead compound, 7ao. Copyright © 2015 Elsevier Ltd. All rights reserved.

Comparison of 5-year progression of retinitis pigmentosa involving the posterior pole among siblings by means of SD-OCT: a retrospective study.

PubMed

Colombo, Leonardo; Montesano, Giovanni; Sala, Barbara; Patelli, Fabio; Maltese, Paolo; Abeshi, Andi; Bertelli, Matteo; Rossetti, Luca

2018-06-26

The aim of this study is to analyze and compare the progression of photoreceptor atrophy among siblings affected by retinitis pigmentosa by means of spectral SD-OCT. Fifty three eyes of 27 patients belonging to 12 family clusters were analyzed. To assess the annual progression rate of photoreceptor atrophy, the ellipsoid zone (EZ) line was measured in OCT sections through the fovea. We used multivariate generalized mixed effects to model the rate of progression and its relation to the initial ellipsoid zone line width. During our 4.84 years (± 1.44) mean follow up time (range 3-7) 53 eyes were examined. The ellipsoid zone line width declined with a yearly average rate of 76.4 μm (4.16% / year) (p-value < 0.0001). Progression rates were poorly correlated within family clusters (p-value = 0.23) and showed statistical difference between affected siblings (p-value = 0.007). There was no correlation between inter-familiar progression rate and mode of inheritance (p-value = 0.98) as well as between age and ellipsoid zone line width among siblings (p-value = 0.91). RP could be extremely heterogeneous even among siblings: an accurate and sensitive method to follow the progression of the disease is fundamental for future development of clinical trials and therapy strategies.

Gas6 Induces Growth, β-Catenin Stabilization, and T-Cell Factor Transcriptional Activation in Contact-Inhibited C57 Mammary Cells

PubMed Central

Goruppi, Sandro; Chiaruttini, Cristina; Ruaro, Maria Elisabetta; Varnum, Brian; Schneider, Claudio

2001-01-01

Gas6 is a growth factor related to protein S that was identified as the ligand for the Axl receptor tyrosine kinase (RTK) family. In this study, we show that Gas6 induces a growth response in a cultured mammalian mammary cell line, C57MG. The presence of Gas6 in the medium induces growth after confluence and similarly causes cell cycle reentry of density-inhibited C57MG cells. We show that Axl RTK but not Rse is efficiently activated by Gas6 in density-inhibited C57MG cells. We have analyzed the signaling required for the Gas6 proliferative effect and found a requirement for PI3K-, S6K-, and Ras-activated pathways. We also demonstrate that Gas6 activates Akt and concomitantly inhibits GSK3 activity in a wortmannin-dependent manner. Interestingly, Gas6 induces up-regulation of cytosolic β-catenin, while membrane-associated β-catenin remains unaffected. Stabilization of β-catenin in C57MG cells is correlated with activation of a T-cell factor (TCF)-responsive transcriptional element. We thus provide evidence that Gas6 is mitogenic and induces β-catenin proto-oncogene stabilization and subsequent TCF/Lef transcriptional activation in a mammary system. These results suggest that Gas6-Axl interaction, through stabilization of β-catenin, may have a role in mammary development and/or be involved in the progression of mammary tumors. PMID:11154277

Recent progress in degradation and stabilization of organic solar cells

NASA Astrophysics Data System (ADS)

Cao, Huanqi; He, Weidong; Mao, Yiwu; Lin, Xiao; Ishikawa, Ken; Dickerson, James H.; Hess, Wayne P.

2014-10-01

Stability is of paramount importance in organic semiconductor devices, especially in organic solar cells (OSCs). Serious degradation in air limits wide applications of these flexible, light-weight and low-cost power-generation devices. Studying the stability of organic solar cells will help us understand degradation mechanisms and further improve the stability of these devices. There are many investigations into the efficiency and stability of OSCs. The efficiency and stability of devices even of the same photoactive materials are scattered in different papers. In particular, the extrinsic degradation that mainly occurs near the interface between the organic layer and the cathode is a major stability concern. In the past few years, researchers have developed many new cathodes and cathode buffer layers, some of which have astonishingly improved the stability of OSCs. In this review article, we discuss the recent developments of these materials and summarize recent progresses in the study of the degradation/stability of OSCs, with emphasis on the extrinsic degradation/stability that is related to the intrusion of oxygen and water. The review provides detailed insight into the current status of research on the stability of OSCs and seeks to facilitate the development of highly-efficient OSCs with enhanced stability.

Simulation and comparison of progression-free survival among patients with non-squamous non-small-cell lung cancer receiving sequential therapy.

PubMed

Walzer, Stefan; Chouaid, Christos; Lister, Johanna; Gultyaev, Dmitry; Vergnenegre, Alain; de Marinis, Filippo; Meng, Jie; de Castro Carpeno, Javier; Crott, Ralph; Kleman, Martin; Ngoh, Charles

2015-01-01

In recent years, the treatment landscape in advanced non-squamous non-small-cell lung cancer (nsNSCLC) has changed. New therapies (e.g., bevacizumab indicated in first line) have become available and other therapies (e.g., pemetrexed in first line and second line) moved into earlier lines in the treatment paradigm. While there has been an expansion of the available treatment options, it is still a key research question which therapy sequence results in the best survival outcomes for patients with nsNSCLC. A therapy-sequencing disease model that approximates treatment outcomes in up to five lines of treatment was developed for patients with nsNSCLC. The primary source of data for progression-free survival (PFS) and time to death was published pivotal trial data. All patients were treatment-naïve and in the PFS state, received first-line treatment with either bevacizumab-based therapy or doublet chemotherapy (including the option of pemetrexed + cisplatin). Patients would then progress to a subsequent line of therapy, remain in PFS or die. In case of progression, it was assumed that each survivor would receive a subsequent line of therapy, based on EMA licensed therapies. Weibull distribution curves were fitted to the data. All bevacizumab-based first-line therapy sequences analyzed achieved total PFS of around 15 months. Bevacizumab + carboplatin + paclitaxel (first line) → pemetrexed (second line) → erlotinib (third line) → docetaxel (fourth line) resulted in total mean PFS time of 15.7 months, for instance. Sequences with pemetrexed in combination with cisplatin in first line achieved total PFS times between 12.6 and 12.8 months with a slightly higher total PFS time achieved when assuming pemetrexed continuation therapy in maintenance after pemetrexed + cisplatin in first-line induction. Overall survival results followed the same trend as PFS. The model suggests that treatment-sequencing strategies starting with a bevacizumab-based combination in first line yield better survival outcomes than those starting with pemetrexed-based combinations, a result that is attributable to the possibility of one further line of treatment with first-line bevacizumab-based treatment sequences.

Disease-related mortality exceeds treatment-related mortality in patients with chronic myeloid leukemia on second-line or later therapy.

PubMed

Pearson, Edward; McGarry, Lisa; Gala, Smeet; Nieset, Christopher; Nanavaty, Merena; Mwamburi, Mkaya; Levy, Yair

2016-04-01

Treatment of newly-diagnosed patients with chronic-phase chronic myeloid leukemia (CP-CML) with tyrosine kinase inhibitors (TKIs) results in near-normal life expectancy. However, CP-CML patients resistant to initial TKIs face a poorer prognosis and significantly higher CML-related mortality. We conducted a systematic literature review to evaluate the specific causes of deaths (diseases progression versus drug-related) in CP-CML patients receiving second- or third-line therapy. We identified eight studies based on our criteria that reported causes of death. Overall, 5% of second-line and 10% of third-line patients died during the study follow-up period. For second-line, (7 studies, n=1926), mortality was attributed to disease progression for 41% of deaths, 2% to treatment-related causes, 3% were treatment-unrelated, and 50% were unspecified adverse events (AEs), not likely related to study drug. In third-line, (2 studies, n=144), 71% deaths were attributed to disease progression, 7% treatment-related AEs, 14% treatment-unrelated and 7% unspecified AEs. Annual death rates for second- and third-line therapy were significantly higher than for general population in similar age group. Our findings suggest death attributed to disease progression is approximately 10 times that due to treatment-related AEs in patients with CP-CML receiving second- or third-line therapy. Therefore, the potential benefits of effective treatment for these patients with the currently available TKIs outweigh the risks of treatment-induced AEs. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cockayne syndrome group A and B proteins converge on transcription-linked resolution of non-B DNA.

PubMed

Scheibye-Knudsen, Morten; Tseng, Anne; Borch Jensen, Martin; Scheibye-Alsing, Karsten; Fang, Evandro Fei; Iyama, Teruaki; Bharti, Sanjay Kumar; Marosi, Krisztina; Froetscher, Lynn; Kassahun, Henok; Eckley, David Mark; Maul, Robert W; Bastian, Paul; De, Supriyo; Ghosh, Soumita; Nilsen, Hilde; Goldberg, Ilya G; Mattson, Mark P; Wilson, David M; Brosh, Robert M; Gorospe, Myriam; Bohr, Vilhelm A

2016-11-01

Cockayne syndrome is a neurodegenerative accelerated aging disorder caused by mutations in the CSA or CSB genes. Although the pathogenesis of Cockayne syndrome has remained elusive, recent work implicates mitochondrial dysfunction in the disease progression. Here, we present evidence that loss of CSA or CSB in a neuroblastoma cell line converges on mitochondrial dysfunction caused by defects in ribosomal DNA transcription and activation of the DNA damage sensor poly-ADP ribose polymerase 1 (PARP1). Indeed, inhibition of ribosomal DNA transcription leads to mitochondrial dysfunction in a number of cell lines. Furthermore, machine-learning algorithms predict that diseases with defects in ribosomal DNA (rDNA) transcription have mitochondrial dysfunction, and, accordingly, this is found when factors involved in rDNA transcription are knocked down. Mechanistically, loss of CSA or CSB leads to polymerase stalling at non-B DNA in a neuroblastoma cell line, in particular at G-quadruplex structures, and recombinant CSB can melt G-quadruplex structures. Indeed, stabilization of G-quadruplex structures activates PARP1 and leads to accelerated aging in Caenorhabditis elegans In conclusion, this work supports a role for impaired ribosomal DNA transcription in Cockayne syndrome and suggests that transcription-coupled resolution of secondary structures may be a mechanism to repress spurious activation of a DNA damage response.

Vitiligo in a patient with lung adenocarcinoma treated with nivolumab: A case report.

PubMed

Uenami, Takeshi; Hosono, Yuki; Ishijima, Mikako; Kanazu, Masaki; Akazawa, Yuki; Yano, Yukihiro; Mori, Masahide; Yamaguchi, Toshihiko; Yokota, Soichiro

2017-07-01

Nivolumab, an anti-programmed cell death-1 protein monoclonal antibody, is effective for treating patients with late-stage non-small-cell lung cancer. Immune checkpoint inhibitors such as nivolumab induce various kinds of immune-related adverse events, including vitiligo. Vitiligo has been reported in patients with melanoma but not lung cancer. We describe a 75-year-old man with lung adenocarcinoma, stage 4 with pleural and pericardial effusion, that progressed after first-line chemotherapy. Subsequently, he was treated with nivolumab as second-line therapy. After 6days of administering nivolumab, he developed vitiligo suddenly on the trunk of his body. Except for vitiligo, his physical examination was normal, and treatment with nivolumab was well tolerated. Therefore, this treatment was continued without further development or expansion of vitiligo. A computed tomography scan showed a reduction in the size of the lung nodule and stabilization of the pleural and pericardial effusion. This is the first case of vitiligo associated with the use of nivolumab in a patient with lung adenocarcinoma. Copyright © 2017. Published by Elsevier B.V.

Matching technique yields optimum LNA performance. [Low Noise Amplifiers

NASA Technical Reports Server (NTRS)

Sifri, J. D.

1986-01-01

The present article is concerned with a case in which an optimum noise figure and unconditional stability have been designed into a 2.385-GHz low-noise preamplifier via an unusual method for matching the input with a suspended line. The results obtained with several conventional line-matching techniques were not satisfactory. Attention is given to the minimization of thermal noise, the design procedure, requirements for a high-impedance line, a sampling of four matching networks, the noise figure of the single-line matching network as a function of frequency, and the approaches used to achieve unconditional stability.

Recovery of Posture Stability at Different Foot Placements in Patients Who Underwent Minimally Invasive Total Hip Arthroplasty: A One-Year Follow-Up Study.

PubMed

Chang, Chun-Ju; Lin, Na-Ling; Lee, Mel S; Chern, Jen-Suh

2015-01-01

To understand the progression of recovery in postural stability and physical functioning after patients received the minimally invasive total hip arthroplasty (MTHA), we monitor the pain level, functional capacity, and postural stability before and after operation within one year. In total of 23 subjects in our study, we found out that MTHA was effective in relieving pain in first 2 weeks and restoring the hip joint integrity, but the postural stability was influenced especially in tandem stand in both anterior-posterior and medial-lateral directions. The recovery of postural stability and functional capacity in one year duration fluctuated and no consistent improvement tendency was found. We suggested clinicians designing postsurgery rehabilitation program for consistent and progressive long-term recovery of postural stability and fall prevention to optimize surgical results and prevent undesired postoperative consequences.

Evaluating competing forces constraining glacial grounding-line stability (Invited)

NASA Astrophysics Data System (ADS)

Powell, R. D.

2013-12-01

Stability of grounding lines of marine-terminating glaciers and ice sheets is of concern due to their importance in governing rates of ice mass loss and consequent sea level rise during global warming. Although processes are similar at tidewater and floating grounding zones their relative magnitudes in terms of their influence on grounding-line stability vary between these two end members. Processes considered Important for this discussion are ice dynamics, ice surface melting and crevassing, ocean dynamics, subglacial sediment and water dynamics, and subglacial bed geometries. Models have continued to improve in their representation of these complex interactions but reliable field measurements and data continue to be hard earned and too few to properly constrain the range of boundary conditions in this complicated system. Some data will be presented covering a range of regimes from Alaska, Svalbard and Antarctica. Certainly more data are required on subglacial sediment/water dynamics and fluxes to fully represent the spectrum of glacial regimes and to assess the significance of grounding-zone sediment systems in counteracting the other processes to force grounding-line stability. Especially important here is constraining the duration of the stability that could be maintained by sediment flux - present data appear to show that it is likely to be a limited period.

Antiangiogenic therapy for patients with aggressive or refractory advanced non-small cell lung cancer in the second-line setting.

PubMed

Reck, Martin; Garassino, Marina Chiara; Imbimbo, Martina; Shepherd, Frances A; Socinski, Mark A; Shih, Jin-Yuan; Tsao, Anne; Lee, Pablo; Winfree, Katherine B; Sashegyi, Andreas; Cheng, Rebecca; Varea, Rocio; Levy, Benjamin; Garon, Edward

2018-06-01

A majority of patients with advanced or metastatic non-small cell lung cancer (NSCLC) will experience disease progression after first-line therapy. Patients who have advanced NSCLC that is especially aggressive, which is defined as disease that rapidly progresses on first-line treatment or disease that is refractory to first-line treatment, have a critical unmet medical need. These patients have a poor prognosis in the second-line setting. Several studies have recently shown that treatment with an antiangiogenic therapy may benefit these patients. This review summarizes the approved antiangiogenic therapies for the treatment of patients with advanced NSCLC in the second-line setting, specifically focusing on the outcomes from subgroups of patients with rapidly progressing or refractory disease. Several antiangiogenic agents, as monotherapy or in combination with other treatments, have been or are currently being studied in patients with advanced NSCLC. Antiangiogenics that are approved for use in patients with advanced NSCLC are limited to bevacizumab in combination with chemotherapy (nonsquamous NSCLC), ramucirumab in combination with docetaxel (all histologies), and nintedanib in combination with docetaxel (adenocarcinoma histology). This review focuses on the efficacy, safety, and quality of life outcomes in the subpopulation of patients with rapidly progressing or refractory NSCLC treated with approved antiangiogenic therapies in the second-line setting. We also discuss the impact of newly approved immunotherapy agents on the outcomes of patients with aggressive or refractory disease. Studies in progress and planned future research will determine if combination treatment with antiangiogenics and immunotherapies will benefit patients with aggressive, advanced NSCLC. Copyright © 2018. Published by Elsevier B.V.

Direct Simulation of Evolution and Control of Three-Dimensional Instabilities in Attachment-Line Boundary Layers

NASA Technical Reports Server (NTRS)

Joslin, Ronald D.

1995-01-01

The spatial evolution of three-dimensional disturbances in an attachment-line boundary layer is computed by direct numerical simulation of the unsteady, incompressible Navier-Stokes equations. Disturbances are introduced into the boundary layer by harmonic sources that involve unsteady suction and blowing through the wall. Various harmonic- source generators are implemented on or near the attachment line, and the disturbance evolutions are compared. Previous two-dimensional simulation results and nonparallel theory are compared with the present results. The three-dimensional simulation results for disturbances with quasi-two-dimensional features indicate growth rates of only a few percent larger than pure two-dimensional results; however, the results are close enough to enable the use of the more computationally efficient, two-dimensional approach. However, true three-dimensional disturbances are more likely in practice and are more stable than two-dimensional disturbances. Disturbances generated off (but near) the attachment line spread both away from and toward the attachment line as they evolve. The evolution pattern is comparable to wave packets in at-plate boundary-layer flows. Suction stabilizes the quasi-two-dimensional attachment-line instabilities, and blowing destabilizes these instabilities; these results qualitatively agree with the theory. Furthermore, suction stabilizes the disturbances that develop off the attachment line. Clearly, disturbances that are generated near the attachment line can supply energy to attachment-line instabilities, but suction can be used to stabilize these instabilities.

PARTIAL RESTRAINING FORCE INTRODUCTION METHOD FOR DESIGNING CONSTRUCTION COUNTERMESURE ON ΔB METHOD

NASA Astrophysics Data System (ADS)

Nishiyama, Taku; Imanishi, Hajime; Chiba, Noriyuki; Ito, Takao

Landslide or slope failure is a three-dimensional movement phenomenon, thus a three-dimensional treatment makes it easier to understand stability. The ΔB method (simplified three-dimensional slope stability analysis method) is based on the limit equilibrium method and equals to an approximate three-dimensional slope stability analysis that extends two-dimensional cross-section stability analysis results to assess stability. This analysis can be conducted using conventional spreadsheets or two-dimensional slope stability computational software. This paper describes the concept of the partial restraining force in-troduction method for designing construction countermeasures using the distribution of the restraining force found along survey lines, which is based on the distribution of survey line safety factors derived from the above-stated analysis. This paper also presents the transverse distributive method of restraining force used for planning ground stabilizing on the basis of the example analysis.

Laser heterodyne spectrometer for helioseismology

NASA Technical Reports Server (NTRS)

Glenar, D. A.; Deming, D.; Espenak, F.; Kostiuk, T.; Mumma, M. J.

1986-01-01

The technique of laser heterodyne spectroscopy has been applied to the measurement of solar oscillations. Coherent mixing of solar radiation with the output of a frequency-stabilized CO2 laser permits the measurement of fully resolved profiles of solar absorption lines with high spectral purity and excellent frequency stability. This technique has been used to measure OH pure rotation lines in the infrared solar spectrum. Power spectra of these line frequency measurements show the well-known 5-min oscillations as well as significant velocity power at shorter periods.

A Comparative Study of Discovery Learning Scientific Community Laboratories and Traditional Laboratories in Physics at an Independent University, Florida, U. S

NASA Astrophysics Data System (ADS)

Reinhard, Karl E.

Electric power is fully interwoven into the fabric of American life. Its loss for extended periods has profound impacts upon public safety, health and welfare. The power system has been termed the most complex machine built by man. Not surprisingly, the measures to address the range of power system downtime causes are as diverse as the causes themselves. One important arc of effort is providing power system operators with full knowledge of the system's operating state, timely warning when changing conditions threaten system stability, and tools guiding control actions to maintain stable operations. This research is motivated, in part, by the need to explore opportunities for leveraging nascent synchrophasor data streams against known power system stability challenges. Over the past half-decade, power system operators have aggressively installed large networks of phasor measurement units (PMUs) and phasor data concentrators (PDCs) across the United States and Canada. Today, the synchrophasor data network has reached a state of maturity that opens the door to useful application. This dissertation investigates power system stability along three lines of effort. The first two efforts address steady-state power system stability--specifically methods for assessing system vulnerabilities arising from the phase angle difference between two buses connected by a transmission line. The third effort investigates the information that can be gleaned from synchrophasor measurements during a system's dynamic system response to changing system conditions. The first line of investigation extends steady-state distribution factor theory. Distribution factors are computed from a known non-linear power system load flow solution. They provide a computationally light method for estimating new system conditions under different operating circumstances. Distribution factors are extremely useful for very rapidly screening the impact of unexpected changes in power system configuration--e.g. a transmission line dropping out of service due to environmental conditions. The Line Outage Angle Factor (LOAF) developed herein provides a method for fast computation of bus voltage angle changes after a line outage. The Line Outage Generator Factor (LOGF) modifies the simulated circuit topology to include synchronous machine transient reactances, enabling rapid screening of operating states in which line opening (or re-closure) risks damaging equipment. The LOAF and LOGF provide promising results in MATLAB simulation of the Western System Coordinating Council 3-Machine, 9-Bus System. The second investigative line seeks to develop a Thevenin equivalent model to be used in tandem with synchrophasor data streams to provide real-time bus angle difference information for buses connected by a transmission line. The appeal is that real-time bus angle difference information could be computed on-site and very rapidly--and significantly, independent of other network bus measurements. The results show that developing a Thevenin equivalent that provides a useful angle difference measure often works well on paper, but is challenging using actual synchrophasor data. Efforts to develop a Thevenin equivalent using Monte Carlo methods show promise, but require further investigation. The third line of effort shifts to investigate the useful information that a PMU can produce during a power system disturbance event. A synchrophasor is defined at a specific frequency, i.e. the system steady-state operating frequency. Thus a PMU produces a data stream recording power system changes progressing slower than the nominal system frequency; consequently, this is an "off-label" synchrophasor data application. The test system is a generator with electrical and mechanical controls connected by a pair of identical transmission lines to an infinite bus. The synchronous generator is modeled as a three-damper-winding synchronous machine. A MATLAB simulation was written to simulate both the full 14 dynamic state and the reduced order 11 dynamic state system models. A Real-Time Digital Simulator (RTDS) simulation emulating the test system provides the capability to produce real-time analog generator terminal waveforms to be sampled by a commercial off-the-shelf PMU to produce synchrophasor data. We find that the RTDS generated synchrophasor data stream is similar to the MATLAB reduced order model voltage and current generator terminal data in the dqo reference frame--reflecting parallel, but distinct, filtering processes.

Altered Fibroblast Growth Factor Receptor 4 Stability Promotes Prostate Cancer Progression1

PubMed Central

Wang, Jianghua; Yu, Wendong; Cai, Yi; Ren, Chengxi; Ittmann, Michael M

2008-01-01

Fibroblast growth factor receptor 4 (FGFR-4) is expressed at significant levels in almost all human prostate cancers, and expression of its ligands is ubiquitous. A common polymorphism of FGFR-4 in which arginine (Arg388) replaces glycine (Gly388) at amino acid 388 is associated with progression in human prostate cancer. We show that the FGFR-4 Arg388 polymorphism, which is present in most prostate cancer patients, results in increased receptor stability and sustained receptor activation. In patients bearing the FGFR-4 Gly388 variant, expression of Huntingtin-interacting protein 1 (HIP1), which occurs in more than half of human prostate cancers, also results in FGFR-4 stabilization. This is associated with enhanced proliferation and anchorage-independent growth in vitro. Our findings indicate that increased receptor stability and sustained FGFR-4 signaling occur in most human prostate cancers due to either the presence of a common genetic polymorphism or the expression of a protein that stabilizes FGFR-4. Both of these alterations are associated with clinical progression in patients with prostate cancer. Thus, FGFR-4 signaling and receptor turnover are important potential therapeutic targets in prostate cancer. PMID:18670643

A Ground-Based 2-Micron DIAL System to Profile Tropospheric CO2 and Aerosol Distributions for Atmospheric Studies

NASA Technical Reports Server (NTRS)

Ismail, Syed; Koch, Grady; Abedin, Nurul; Refaat, Tamer; Rubio, Manuel; Davis, Kenneth; Miller, Charles; Singh, Upendra

2006-01-01

System will operate at a temperature insensitive CO2 line (2050.967 nm) with side-line tuning and off-set locking. Demonstrated an order of magnitude improvement in laser line locking needed for high precision measurements, side-line operation, and simultaneously double pulsing and line locking. Detector testing of phototransistor has demonstrated sensitivity to aerosol features over long distances in the atmosphere and resolve features approx. 100m. Optical systems that collect light onto small area detectors work well. Receiver optical designs are being optimized and data acquisition systems developed. CO2 line parameter characterization in progress In situ sensor calibration in progress for validation of DIAL CO2 system.

Regulation of hypoxia-inducible factor-1alpha by nitric oxide through mitochondria-dependent and -independent pathways.

PubMed Central

Mateo, Jesús; García-Lecea, Marta; Cadenas, Susana; Hernández, Carlos; Moncada, Salvador

2003-01-01

Nitric oxide (NO) has been reported both to promote and to inhibit the activity of the transcription factor hypoxia-inducible factor-1 (HIF-1). In order to avoid the pitfalls associated with the use of NO donors, we have developed a human cell line (Tet-iNOS 293) that expresses the inducible NO synthase (iNOS) under the control of a tetracycline-inducible promoter. Using this system to generate finely controlled amounts of NO, we have demonstrated that the stability of the alpha-subunit of HIF-1 is regulated by NO through two separate mechanisms, only one of which is dependent on a functional respiratory chain. HIF-1alpha is unstable in cells maintained at 21% O(2), but is progressively stabilized as the O(2) concentration decreases, resulting in augmented HIF-1 DNA-binding activity. High concentrations of NO (>1 microM) stabilize HIF-1alpha at all O(2) concentrations tested. This effect does not involve the respiratory chain, since it is preserved in cells lacking functional mitochondria (rho(0)-cells) and is not reproduced by other inhibitors of the cytochrome c oxidase. By contrast, lower concentrations of NO (<400 nM) cause a rapid decrease in HIF-1alpha stabilized by exposure of the cells to 3% O(2). This effect of NO is dependent on the inhibition of mitochondrial respiration, since it is mimicked by other inhibitors of mitochondrial respiration, including those not acting at cytochrome c oxidase. We suggest that, although stabilization of HIF-1alpha by high concentrations of NO might have implications in pathophysiological processes, the inhibitory effect of lower NO concentrations is likely to be of physiological relevance. PMID:14531732

Towards an optimal treatment algorithm for metastatic pancreatic ductal adenocarcinoma (PDA)

PubMed Central

Uccello, M.; Moschetta, M.; Mak, G.; Alam, T.; Henriquez, C. Murias; Arkenau, H.-T.

2018-01-01

Chemotherapy remains the mainstay of treatment for advanced pancreatic ductal adenocarcinoma (pda). Two randomized trials have demonstrated superiority of the combination regimens folfirinox (5-fluorouracil, leucovorin, oxaliplatin, and irinotecan) and gemcitabine plus nab-paclitaxel over gemcitabine monotherapy as a first-line treatment in adequately fit subjects. Selected pda patients progressing to first-line therapy can receive secondline treatment with moderate clinical benefit. Nevertheless, the optimal algorithm and the role of combination therapy in second-line are still unclear. Published second-line pda clinical trials enrolled patients progressing to gemcitabine-based therapies in use before the approval of nab-paclitaxel and folfirinox. The evolving scenario in second-line may affect the choice of the first-line treatment. For example, nanoliposomal irinotecan plus 5-fluouracil and leucovorin is a novel second-line option which will be suitable only for patients progressing to gemcitabine-based therapy. Therefore, clinical judgement and appropriate patient selection remain key elements in treatment decision. In this review, we aim to illustrate currently available options and define a possible algorithm to guide treatment choice. Future clinical trials taking into account sequential treatment as a new paradigm in pda will help define a standard algorithm. PMID:29507500

Second-line chemotherapy in advanced biliary cancer progressed to first-line platinum-gemcitabine combination: a multicenter survey and pooled analysis with published data.

PubMed

Fornaro, Lorenzo; Vivaldi, Caterina; Cereda, Stefano; Leone, Francesco; Aprile, Giuseppe; Lonardi, Sara; Silvestris, Nicola; Santini, Daniele; Milella, Michele; Caparello, Chiara; Musettini, Gianna; Pasquini, Giulia; Falcone, Alfredo; Brandi, Giovanni; Sperduti, Isabella; Vasile, Enrico

2015-12-23

After progression to a standard first-line platinum and gemcitabine combination (GP), there is no established second-line therapy for patients with advanced biliary tract cancers (aBTC). Indeed, literature data suggest limited activity of most second-line agents evaluated so far. We collected a large retrospective series of aBTC patients treated with second-line chemotherapy after progression to a first-line GP regimen at different Italian institutions. We then pooled the data with those reported in previous studies, which were identified with a Medline search and the on-line abstract datasets of major international oncology meetings. A total of 174 patients were included in the multicenter survey: response rate (RR) with second-line chemotherapy was low (3.4 %), with median PFS and OS of 3.0 months and 6.6 months, respectively. At multivariate analysis, preserved performance status, low CA19.9 levels and absence of distant metastases were favorable prognostic factors. Data from other five presented or published series were identified, for a total of 499 patients included in the pooled analysis. The results confirmed marginal activity of second-line chemotherapy (RR: 10.2 %), with limited efficacy in unselected patient populations (median PFS: 3.1 months; median OS: 6.3 months). The current analysis highlights the limited value of second-line chemotherapy after a first-line GP combination in aBTC. While waiting for effective biologic agents in this setting, ongoing randomized trials will identify the optimal second-line chemotherapy regimen and validate prognostic factors for individual patient management.

Direct Simulation of Evolution and Control of Nonlinear Instabilities in Attachment-Line Boundary Layers

NASA Technical Reports Server (NTRS)

Joslin, Ronald D.

2004-01-01

The unsteady, incompressible Navier-Stokes equations are used for the direct numerical simulation (DNS) of spatially evolving disturbances in a three-dimensional (3-D) attachment-line boundary layer. Two-dimensional (2-D) disturbances are introduced either by forcing at the in ow or by harmonic-source generators at the wall; 3-D disturbances are introduced by harmonic-source generators at the wall. The DNS results are in good agreement with both 2-D non-parallel theory (for small-amplitude disturbances) and weakly nonlinear theory (for finite-amplitude disturbances), which validates the two theories. The 2-D DNS results indicate that nonlinear disturbance growth occurs near branch II of the neutral stability curve; however, steady suction can be used to stabilize this disturbance growth. For 3-D instabilities that are generated o the attachment line, spreading both toward and away from the attachment line causes energy transfer to the attachment-line and downstream instabilities; suction stabilizes these instabilities. Furthermore, 3-D instabilities are more stable than 2-D or quasi-2-D instabilities.

Cytogenetic damage, oncogenic transformation and p53 induction in human epithelial cells in response to irradiation

NASA Astrophysics Data System (ADS)

Armitage, Mark

Ionizing radiation can have several different effects on cells, some are almost instantaneous such as the generation of DNA damage, other cellular responses take a matter of minutes or hours - DNA repair protein induction/activation, and others may take months or even years to be manifested - carcinogenesis. Human epithelial cell lines derived from both normal, non-neoplastic tissues and from a malignant source were cultured in order to examine several effects of ionizing radiation on such cell types. Cells not from a malignant source were previously immortalized by viral infection or by transfection with viral sequences. Simian virus 40 immortalised uroepithelial cells (SV-HUC) were found to be approximately a factor of two fold more radioresistant than cells of malignant origin (T24) in terms of unrepaired clastogenic damage i.e. assessment of micronuclei levels following irradiation. SV-HUC lines unlike T24 cells are non-tumourigenic when inoculated into nude athymic mice. SV-HUC lines proved very resistant to full oncogenic transformation using radiation and chemical carcinogens. However, morphological alterations and decreased anchorage dependant growth was observed in post carcinogen treated cells after appropriate cell culture conditions were utilized. The progression from this phenotype to a fully tumourigenic one was not recorded in this study. The ability of ionizing radiation to induce increased levels of the nuclear phosphoprotein p53 was also assessed using several different cell lines. SV- HUC and T24 cell lines failed to exhibit any increased p53 stabilization following irradiation. One cell line, a human papilloma virus transformed line (HPV) did show an approximate two fold increase of the wild type p53 protein after treatment with radiation. Only the cell line HPV showed any cell cycle delay, resulting in accumulation of cells in the G2/M compartment in post irradiation cell cycle analysis. The status of p53 was also assessed i.e. wild type or mutant conformation in all the above cells lines and two other control lines HOS (a human osteosarcoma cell line) and H Tori-3 (SV40 immortalised thyroid epithelial cells).

Simulation of Nonlinear Instabilities in an Attachment-Line Boundary Layer

NASA Technical Reports Server (NTRS)

Joslin, Ronald D.

1996-01-01

The linear and the nonlinear stability of disturbances that propagate along the attachment line of a three-dimensional boundary layer is considered. The spatially evolving disturbances in the boundary layer are computed by direct numerical simulation (DNS) of the unsteady, incompressible Navier-Stokes equations. Disturbances are introduced either by forcing at the in ow or by applying suction and blowing at the wall. Quasi-parallel linear stability theory and a nonparallel theory yield notably different stability characteristics for disturbances near the critical Reynolds number; the DNS results con rm the latter theory. Previously, a weakly nonlinear theory and computations revealed a high wave-number region of subcritical disturbance growth. More recent computations have failed to achieve this subcritical growth. The present computational results indicate the presence of subcritically growing disturbances; the results support the weakly nonlinear theory. Furthermore, an explanation is provided for the previous theoretical and computational discrepancy. In addition, the present results demonstrate that steady suction can be used to stabilize disturbances that otherwise grow subcritically along the attachment line.

Apoptosis induction and anti-cancer activity of LeciPlex formulations.

PubMed

Dhawan, Vivek V; Joshi, Ganesh V; Jain, Ankitkumar S; Nikam, Yuvraj P; Gude, Rajiv P; Mulherkar, Rita; Nagarsenker, Mangal S

2014-10-01

Cationic agents have been reported to possess anti-neoplastic properties against various cancer cell types. However, their complexes with lipids appear to interact differently with different cancer cells. The purpose of this study was to (i) design and generate novel cationic lecithin nanoparticles, (ii) assess and understand the mechanism underlying their putative cytotoxicity and (iii) test their effect on cell cycle progression in various cancer-derived cell lines. In addition, we aimed to evaluate the in vivo potential of these newly developed nanoparticles in oral anti-cancer delivery. Cationic lecithin nanoparticles were generated using a single step nanoprecipitation method and they were characterized for particle size, zeta potential, stability and in vitro release. Their cytotoxic potential was assessed using a sulforhodamine B assay, and their effect on cell cycle progression was evaluated using flow cytometry. The nanoparticle systems were also tested in vivo for their anti-tumorigenic potential. In contrast to cationic agents alone, the newly developed nanoformulations showed a specific toxicity against cancer cells. The mechanism of toxic cell death included apoptosis, S and G2/M cell cycle phase arrest, depending on the type of cationic agent and the cancer-derived cell line used. Both blank and drug-loaded systems exhibited significant anti-cancer activity, suggesting a synergistic anti-tumorigenic effect of the drug and its delivery system. Both in vitro and in vivo data indicate that cationic agents themselves exhibit broad anti-neoplastic activities. Complex formation of the cationic agents with phospholipids was found to provide specificity to the anti-cancer activity. These formulations thus possess potential for the design of effective anti-cancer delivery systems.

Efficacy and safety of the third-generation chloroethylnitrosourea fotemustine for the treatment of chemorefractory T-cell lymphomas

PubMed Central

Corazzelli, Gaetano; Frigeri, Ferdinando; Arcamone, Manuela; Aloj, Luigi; Capobianco, Gaetana; Becchimanzi, Cristina; Morelli, Emanuela; Volzone, Francesco; Marcacci, Gianpaolo; Russo, Filippo; De Filippi, Rosaria; Lastoria, Secondo; Pinto, Antonio

2011-01-01

Patients with recurring T-cell non-Hodgkin lymphoma (T-NHL) are incurable and candidate for investigational agents. Here, we report on five patients with T-NHL refractory to multiple chemotherapy lines, including in all cases alkylators and gemcitabine, who received the third-generation chloroethylnitrosourea fotemustine at a dose of 120 mg/m2 every 21 d, up to eight courses. Median actual dose intensity was 79%; toxicity was manageable and mainly hematological. One complete remission, one partial remission, two protracted disease stabilization, and one transient, minor response were achieved. Time to progression ranged from 48 to 240+ d. This is the first evidence ever reporting the activity of fotemustine in end-stage T-NHL. Formal studies with this agent are warranted in T-cell malignancies. PMID:21752099

Flexible Launch Vehicle Stability Analysis Using Steady and Unsteady Computational Fluid Dynamics

NASA Technical Reports Server (NTRS)

Bartels, Robert E.

2012-01-01

Launch vehicles frequently experience a reduced stability margin through the transonic Mach number range. This reduced stability margin can be caused by the aerodynamic undamping one of the lower-frequency flexible or rigid body modes. Analysis of the behavior of a flexible vehicle is routinely performed with quasi-steady aerodynamic line loads derived from steady rigid aerodynamics. However, a quasi-steady aeroelastic stability analysis can be unconservative at the critical Mach numbers, where experiment or unsteady computational aeroelastic analysis show a reduced or even negative aerodynamic damping.Amethod of enhancing the quasi-steady aeroelastic stability analysis of a launch vehicle with unsteady aerodynamics is developed that uses unsteady computational fluid dynamics to compute the response of selected lower-frequency modes. The response is contained in a time history of the vehicle line loads. A proper orthogonal decomposition of the unsteady aerodynamic line-load response is used to reduce the scale of data volume and system identification is used to derive the aerodynamic stiffness, damping, and mass matrices. The results are compared with the damping and frequency computed from unsteady computational aeroelasticity and from a quasi-steady analysis. The results show that incorporating unsteady aerodynamics in this way brings the enhanced quasi-steady aeroelastic stability analysis into close agreement with the unsteady computational aeroelastic results.

Linearized blade row compression component model. Stability and frequency response analysis of a J85-3 compressor

NASA Technical Reports Server (NTRS)

Tesch, W. A.; Moszee, R. H.; Steenken, W. G.

1976-01-01

NASA developed stability and frequency response analysis techniques were applied to a dynamic blade row compression component stability model to provide a more economic approach to surge line and frequency response determination than that provided by time-dependent methods. This blade row model was linearized and the Jacobian matrix was formed. The clean-inlet-flow stability characteristics of the compressors of two J85-13 engines were predicted by applying the alternate Routh-Hurwitz stability criterion to the Jacobian matrix. The predicted surge line agreed with the clean-inlet-flow surge line predicted by the time-dependent method to a high degree except for one engine at 94% corrected speed. No satisfactory explanation of this discrepancy was found. The frequency response of the linearized system was determined by evaluating its Laplace transfer function. The results of the linearized-frequency-response analysis agree with the time-dependent results when the time-dependent inlet total-pressure and exit-flow function amplitude boundary conditions are less than 1 percent and 3 percent, respectively. The stability analysis technique was extended to a two-sector parallel compressor model with and without interstage crossflow and predictions were carried out for total-pressure distortion extents of 180 deg, 90 deg, 60 deg, and 30 deg.

Noise properties of an optical frequency comb from a SESAM-mode-locked 1.5-μm solid-state laser stabilized to the 10-13 level

NASA Astrophysics Data System (ADS)

Schilt, S.; Dolgovskiy, V.; Bucalovic, N.; Schori, C.; Stumpf, M. C.; Di Domenico, G.; Pekarek, S.; Oehler, A. E. H.; Südmeyer, T.; Keller, U.; Thomann, P.

2012-11-01

We present a detailed investigation of the noise properties of an optical frequency comb generated from a femtosecond diode-pumped solid-state laser operating in the 1.5-μm spectral region. The stabilization of the passively mode-locked Er:Yb:glass laser oscillator, referred to as ERGO, is achieved using pump power modulation for the control of the carrier envelope offset (CEO) frequency and by adjusting the laser cavity length for the control of the repetition rate. The stability and the noise of the ERGO comb are characterized in free-running and in phase-locked operation by measuring the noise properties of the CEO, of the repetition rate, and of a comb line at 1558 nm. The comb line is analyzed from the heterodyne beat signal with a cavity-stabilized ultra-narrow-linewidth laser using a frequency discriminator. Two different schemes to stabilize the comb to a radio-frequency (RF) reference are compared. The comb properties (phase noise, frequency stability) are limited in both cases by the RF oscillator used to stabilize the repetition rate, while the contribution of the CEO is negligible at all Fourier frequencies, as a consequence of the low-noise characteristics of the CEO-beat. A linewidth of ≈150 kHz and a fractional frequency instability of 4.2×10-13 at 1 s are obtained for an optical comb line at 1558 nm. Improved performance is obtained by stabilizing the comb to an optical reference, which is a cavity-stabilized ultra-narrow linewidth laser at 1558 nm. The fractional frequency stability of 8×10-14 at 1 s, measured in preliminary experiments, is limited by the reference oscillator used in the frequency comparison.

Selection of early-occurring mutations dictates hormone-independent progression in mouse mammary tumor lines.

PubMed

Gattelli, Albana; Zimberlin, María N; Meiss, Roberto P; Castilla, Lucio H; Kordon, Edith C

2006-11-01

Mice harboring three mouse mammary tumor virus (MMTV) variants develop pregnancy-dependent (PD) tumors that progress to pregnancy-independent (PI) behavior through successive passages. Herein, we identified 10 predominant insertions in PI transplants from 8 independent tumor lines. These mutations were also detected in small cell populations in the early PD passages. In addition, we identified a new viral insertion upstream of the gene Rspo3, which is overexpressed in three of the eight independent tumor lines and codes for a protein very similar to the recently described protein encoded by Int7. This study suggests that during progression towards hormone independence, clonal expansion of cells with specific mutations might be more relevant than the occurrence of new MMTV insertions.

Effect of intrinsic curvature and edge tension on the stability of binary mixed-membrane three-junctions

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

Gardner, Jasmine M.; Abrams, Cameron F.; Deserno, Markus

We use a combination of coarse-grained molecular dynamics simulations and theoretical modeling to examine three-junctions in mixed lipid bilayer membranes. These junctions are localized defect lines in which three bilayers merge in such a way that each bilayer shares one monolayer with one of the other two bilayers. The resulting local morphology is non-lamellar, resembling the threefold symmetric defect lines in inverse hexagonal phases, but it regularly occurs during membrane fission and fusion events. We realize a system of junctions by setting up a honeycomb lattice, which in its primitive cell contains two hexagons and four three-line junctions, permitting usmore » to study their stability as well as their line tension. We specifically consider the effects of lipid composition and intrinsic curvature in binary mixtures, which contain a fraction of negatively curved lipids in a curvature-neutral background phase. Three-junction stability results from a competition between the junction and an open edge, which arises if one of the three bilayers detaches from the other two. We show that the stable phase is the one with the lower defect line tension. The strong and opposite monolayer curvatures present in junctions and edges enhance the mole fraction of negatively curved lipids in junctions and deplete it in edges. This lipid sorting affects the two line tensions and in turn the relative stability of the two phases. It also leads to a subtle entropic barrier for the transition between junction and edge that is absent in uniform membranes.« less

Individual patient data analysis of progression-free survival versus overall survival as a first-line end point for metastatic colorectal cancer in modern randomized trials: findings from the analysis and research in cancers of the digestive system database.

PubMed

Shi, Qian; de Gramont, Aimery; Grothey, Axel; Zalcberg, John; Chibaudel, Benoist; Schmoll, Hans-Joachim; Seymour, Matthew T; Adams, Richard; Saltz, Leonard; Goldberg, Richard M; Punt, Cornelis J A; Douillard, Jean-Yves; Hoff, Paulo M; Hecht, Joel Randolph; Hurwitz, Herbert; Díaz-Rubio, Eduardo; Porschen, Rainer; Tebbutt, Niall C; Fuchs, Charles; Souglakos, John; Falcone, Alfredo; Tournigand, Christophe; Kabbinavar, Fairooz F; Heinemann, Volker; Van Cutsem, Eric; Bokemeyer, Carsten; Buyse, Marc; Sargent, Daniel J

2015-01-01

Progression-free survival (PFS) has previously been established as a surrogate for overall survival (OS) for first-line metastatic colorectal cancer (mCRC). Because mCRC treatment has advanced in the last decade with extended OS, this surrogacy requires re-examination. Individual patient data from 16,762 patients were available from 22 first-line mCRC studies conducted from 1997 to 2006; 12 of those studies tested antiangiogenic and/or anti-epidermal growth factor receptor agents. The relationship between PFS (first event of progression or death) and OS was evaluated by using R(2) statistics (the closer the value is to 1, the stronger the correlation) from weighted least squares regression of trial-specific hazard ratios estimated by using Cox and Copula models. Forty-four percent of patients received a regimen that included biologic agents. Median first-line PFS was 8.3 months, and median OS was 18.2 months. The correlation between PFS and OS was modest (R(2), 0.45 to 0.69). Analyses limited to trials that tested treatments with biologic agents, nonstrategy trials, or superiority trials did not improve surrogacy. In modern mCRC trials, in which survival after the first progression exceeds time to first progression, a positive but modest correlation was observed between OS and PFS at both the patient and trial levels. This finding demonstrates the substantial variability in OS introduced by the number of lines of therapy and types of effective subsequent treatments and the associated challenge to the use of OS as an end point to assess the benefit attributable to a single line of therapy. PFS remains an appropriate primary end point for first-line mCRC trials to detect the direct treatment effect of new agents. © 2014 by American Society of Clinical Oncology.

Individual Patient Data Analysis of Progression-Free Survival Versus Overall Survival As a First-Line End Point for Metastatic Colorectal Cancer in Modern Randomized Trials: Findings From the Analysis and Research in Cancers of the Digestive System Database

PubMed Central

Shi, Qian; de Gramont, Aimery; Grothey, Axel; Zalcberg, John; Chibaudel, Benoist; Schmoll, Hans-Joachim; Seymour, Matthew T.; Adams, Richard; Saltz, Leonard; Goldberg, Richard M.; Punt, Cornelis J.A.; Douillard, Jean-Yves; Hoff, Paulo M.; Hecht, Joel Randolph; Hurwitz, Herbert; Díaz-Rubio, Eduardo; Porschen, Rainer; Tebbutt, Niall C.; Fuchs, Charles; Souglakos, John; Falcone, Alfredo; Tournigand, Christophe; Kabbinavar, Fairooz F.; Heinemann, Volker; Van Cutsem, Eric; Bokemeyer, Carsten; Buyse, Marc; Sargent, Daniel J.

2015-01-01

Purpose Progression-free survival (PFS) has previously been established as a surrogate for overall survival (OS) for first-line metastatic colorectal cancer (mCRC). Because mCRC treatment has advanced in the last decade with extended OS, this surrogacy requires re-examination. Methods Individual patient data from 16,762 patients were available from 22 first-line mCRC studies conducted from 1997 to 2006; 12 of those studies tested antiangiogenic and/or anti–epidermal growth factor receptor agents. The relationship between PFS (first event of progression or death) and OS was evaluated by using R2 statistics (the closer the value is to 1, the stronger the correlation) from weighted least squares regression of trial-specific hazard ratios estimated by using Cox and Copula models. Results Forty-four percent of patients received a regimen that included biologic agents. Median first-line PFS was 8.3 months, and median OS was 18.2 months. The correlation between PFS and OS was modest (R2, 0.45 to 0.69). Analyses limited to trials that tested treatments with biologic agents, nonstrategy trials, or superiority trials did not improve surrogacy. Conclusion In modern mCRC trials, in which survival after the first progression exceeds time to first progression, a positive but modest correlation was observed between OS and PFS at both the patient and trial levels. This finding demonstrates the substantial variability in OS introduced by the number of lines of therapy and types of effective subsequent treatments and the associated challenge to the use of OS as an end point to assess the benefit attributable to a single line of therapy. PFS remains an appropriate primary end point for first-line mCRC trials to detect the direct treatment effect of new agents. PMID:25385741

Prismatic displacement effect of progressive multifocal glasses on reaction time and accuracy in elderly people.

PubMed

Ellison, Ashton C; Campbell, A John; Robertson, M Clare; Sanderson, Gordon F

2014-01-01

Multifocal glasses (bifocals, trifocals, and progressives) increase the risk of falling in elderly people, but how they do so is unclear. To explain why glasses with progressive addition lenses increase the risk of falls and whether this can be attributed to false projection, this study aimed to 1) map the prismatic displacement of a progressive lens, and 2) test whether this displacement impaired reaction time and accuracy. The reaction times of healthy ≥75-year-olds (31 participants) were measured when grasping for a bar and touching a black line. Participants performed each test twice, wearing their progressives and new, matched single vision (distance) glasses in random order. The line and bar targets were positioned according to the maximum and minimum prismatic displacement effect through the progressive lens, mapped using a focimeter. Progressive spectacle lenses have large areas of prismatic displacement in the central visual axis and edges. Reaction time was faster for progressives compared with single vision glasses with a centrally-placed horizontal grab bar (mean difference 101 ms, P=0.011 [repeated measures analysis]) and a horizontal black line placed 300 mm below center (mean difference 80 ms, P=0.007). There was no difference in accuracy between the two types of glasses. Older people appear to adapt to the false projection of progressives in the central visual axis. This adaptation means that swapping to new glasses or a large change in prescription may lead to a fall. Frequently updating glasses may be more beneficial.

MHD Stability of Axisymmetric Plasmas In Closed Line Magnetic Fields

NASA Astrophysics Data System (ADS)

Simakov, Andrei N.; Catto, Peter J.; Ramos, Jesus J.; Hastie, R. J.

2003-04-01

The stability of axisymmetric plasmas confined by closed poloidal magnetic field lines is considered. The results are relevant to plasmas in the dipolar fields of stars and planets, as well as the Levitated Dipole Experiment, multipoles, Z pinches and field reversed configurations. The ideal MHD energy principle is employed to study stability of pressure driven Alfvén modes. A point dipole is considered in detail to demonstrate that equilibria exist, which are MHD stable for arbitrary beta. Effects of sound waves and plasma resistivity are investigated next for point dipole equilibria by means of resistive MHD theory.

p21 stability: linking chaperones to a cell cycle checkpoint.

PubMed

Liu, Geng; Lozano, Guillermina

2005-02-01

Progression through the cell cycle is regulated by numerous proteins, one of which is the cyclin-dependent kinase inhibitor, p21. A new study identifies a novel protein complex that stabilizes p21. The stability of this complex is critical in effecting the p53-mediated cell cycle checkpoint.

The tumor suppressor SirT2 regulates cell cycle progression and genome stability by modulating the mitotic deposition of H4K20 methylation

USDA-ARS?s Scientific Manuscript database

The establishment of the epigenetic mark H4K20me1 (monomethylation of H4K20) by PR-Set7 during G2/M directly impacts S-phase progression and genome stability. However, the mechanisms involved in the regulation of this event are not well understood. Here we show that SirT2 regulates H4K20me1 depositi...

On-line determination of transient stability status using multilayer perceptron neural network

NASA Astrophysics Data System (ADS)

Frimpong, Emmanuel Asuming; Okyere, Philip Yaw; Asumadu, Johnson

2018-01-01

A scheme to predict transient stability status following a disturbance is presented. The scheme is activated upon the tripping of a line or bus and operates as follows: Two samples of frequency deviation values at all generator buses are obtained. At each generator bus, the maximum frequency deviation within the two samples is extracted. A vector is then constructed from the extracted maximum frequency deviations. The Euclidean norm of the constructed vector is calculated and then fed as input to a trained multilayer perceptron neural network which predicts the stability status of the system. The scheme was tested using data generated from the New England test system. The scheme successfully predicted the stability status of all two hundred and five disturbance test cases.

Field-Line Localized Destabilization of Ballooning Modes in Three-Dimensional Tokamaks

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

Willensdorfer, M.; Cote, T. B.; Hegna, C. C.

2017-08-25

Field-line localized ballooning modes have been observed at the edge of high confinement mode plasmas in ASDEX Upgrade with rotating 3D perturbations induced by an externally applied n ¼ 2 error field and during a moderate level of edge localized mode mitigation. The observed ballooning modes are localized to the field lines which experience one of the two zero crossings of the radial flux surface displacement during one rotation period. The localization of the ballooning modes agrees very well with the localization of the largest growth rates from infinite-n ideal ballooning stability calculations using a realistic 3D ideal magnetohydrodynamic equilibrium.more » This analysis predicts a lower stability with respect to the axisymmetric case. The primary mechanism for the local lower stability is the 3D distortion of the local magnetic shear.« less

Apatinib + CPT-11 + S-1 for treatment of refractory brain metastases in patient with triple-negative breast cancer: Case report and literature review.

PubMed

Hu, Ting; Liu, Cuiwei; Li, Qiuhui; Xiong, Jie; Ma, Yuxi; Wu, Gang; Zhao, Yanxia

2018-04-01

Brain metastasis (BM) is a rising challenge in forward-looking oncology, as its treatment choices are very limited, especially, after the failure of local treatment schemes. We report on a 39-year-old Chinese woman who was diagnosed with stage IV triple-negative breast cancer(TNBC) with multiple brain, lung, and bone metastases. She had previously, undergone whole-brain radiation therapy. Paclitaxel, platinum, UTD1, capecitabine, gemcitabine, vinorelbine, and single-agent apatinib were then administered as first- to fifth-line therapies. She exhibited progression each time after a short period of disease stabilization. Triple-negative breast cancer. The patient chose treatment with apatinib+CPT-11+S-1 as the sixth-line therapy. A remarkable response of the brain, and lung metastases, and alleviation of the brain edema were achieved, and these effects persisted for 7 months. We describe the significant anti-tumor effect of apatinib + CPT-11 + S-1 against BMs from breast cancer. This report is the first to suggest potential approaches to BM treatment using this scheme and describes the effects of an apatinib-containing regimen on BMs.

Apatinib + CPT-11 + S-1 for treatment of refractory brain metastases in patient with triple-negative breast cancer

PubMed Central

Hu, Ting; Liu, Cuiwei; Li, Qiuhui; Xiong, Jie; Ma, Yuxi; Wu, Gang; Zhao, Yanxia

2018-01-01

Abstract Rationale: Brain metastasis (BM) is a rising challenge in forward-looking oncology, as its treatment choices are very limited, especially, after the failure of local treatment schemes. Patient concerns: We report on a 39-year-old Chinese woman who was diagnosed with stage IV triple-negative breast cancer(TNBC) with multiple brain, lung, and bone metastases. She had previously, undergone whole-brain radiation therapy. Paclitaxel, platinum, UTD1, capecitabine, gemcitabine, vinorelbine, and single-agent apatinib were then administered as first- to fifth-line therapies. She exhibited progression each time after a short period of disease stabilization. Diagnoses: Triple-negative breast cancer. Interventions: The patient chose treatment with apatinib+CPT-11+S-1 as the sixth-line therapy. Outcomes: A remarkable response of the brain, and lung metastases, and alleviation of the brain edema were achieved, and these effects persisted for 7 months. Lessons: We describe the significant anti-tumor effect of apatinib + CPT-11 + S-1 against BMs from breast cancer. This report is the first to suggest potential approaches to BM treatment using this scheme and describes the effects of an apatinib-containing regimen on BMs. PMID:29642175

Antarctic grounding-line migration

NASA Astrophysics Data System (ADS)

Slater, T.; Konrad, H.; Shepherd, A.; Gilbert, L.; Hogg, A.; McMillan, M.; Muir, A. S.

2017-12-01

Knowledge of grounding-line position is critical for quantifying ice discharge into the ocean, as a boundary condition for numerical models of ice flow, and as an indicator of ice sheet stability. Although geological investigations have documented extensive grounding-line retreat since the period of the Last Glacial Maximum, observations of grounding line migration during the satellite era are restricted to a handful of locations. We combine satellite altimeter observations of ice-elevation change and airborne measurements of ice geometry to track movement of the Antarctic Ice Sheet grounding line. Based on these data, we estimate that 22%, 3%, and 10% of the West Antarctic, East Antarctic, and Antarctic Peninsula ice sheet grounding lines are retreating at rates faster than the typical pace since the Last Glacial Maximum, and that the continent loses over 200 km2 of grounded-ice area per year. Although by far the fastest rates of retreat occurred in the Amundsen Sea Sector, the Pine Island Glacier grounding line has stabilized - likely as a consequence of abated ocean forcing during the survey period.

The Evolving Treatment Landscape of Advanced Renal Cell Carcinoma in Patients Progressing after VEGF Inhibition

PubMed Central

Barata, Pedro C.; Ornstein, Moshe C.

2017-01-01

Despite significant changes in the therapeutic landscape of renal cell carcinoma, the majority of patients with metastatic disease eventually progress after first-line treatment with vascular endothelial growth factor receptors (VEGFR) tyrosine kinase inhibitor (TKI) therapy. Understanding existing data on subsequent therapies is crucial to define an optimal treatment sequence following first-line failure. This review examines the data supporting currently approved agents in this setting and provides a framework for decision-making regarding treatment sequencing beyond first-line therapy with VEGFR TKIs. PMID:28725539

Comparative study of resist stabilization techniques for metal etch processing

NASA Astrophysics Data System (ADS)

Becker, Gerry; Ross, Matthew F.; Wong, Selmer S.; Minter, Jason P.; Marlowe, Trey; Livesay, William R.

1999-06-01

This study investigates resist stabilization techniques as they are applied to a metal etch application. The techniques that are compared are conventional deep-UV/thermal stabilization, or UV bake, and electron beam stabilization. The electron beam tool use din this study, an ElectronCure system from AlliedSignal Inc., ELectron Vision Group, utilizes a flood electron source and a non-thermal process. These stabilization techniques are compared with respect to a metal etch process. In this study, two types of resist are considered for stabilization and etch: a g/i-line resist, Shipley SPR-3012, and an advanced i-line, Shipley SPR 955- Cm. For each of these resist the effects of stabilization on resist features are evaluated by post-stabilization SEM analysis. Etch selectivity in all cases is evaluated by using a timed metal etch, and measuring resists remaining relative to total metal thickness etched. Etch selectivity is presented as a function of stabilization condition. Analyses of the effects of the type of stabilization on this method of selectivity measurement are also presented. SEM analysis was also performed on the features after a compete etch process, and is detailed as a function of stabilization condition. Post-etch cleaning is also an important factor impacted by pre-etch resist stabilization. Results of post- etch cleaning are presented for both stabilization methods. SEM inspection is also detailed for the metal features after resist removal processing.

Combination Therapy with Capecitabine and Cisplatin as Second-Line Chemotherapy for Advanced Biliary Tract Cancer.

PubMed

Jung, Jang Han; Lee, Hee Seung; Jo, Jung Hyun; Cho, In Rae; Chung, Moon Jae; Bang, Seungmin; Park, Seung Woo; Song, Si Young; Park, Jeong Youp

2017-01-01

Palliative chemotherapy is the main treatment for advanced biliary tract cancer (BTC). However, there is a lack of established second-line chemotherapy to treat disease progression after first-line chemotherapy. We examined combination therapy with capecitabine and cisplatin for advanced BTC as a second-line regimen. We analyzed the medical records of 40 patients diagnosed with BTC who received palliative second-line chemotherapy with capecitabine and cisplatin. The median overall survival from the start of second-line chemotherapy was 6.3 months. The median overall survival from diagnosis was 17.9 months. The median progression-free survival during second-line chemotherapy was 2.3 months. Nine (30%) patients experienced adverse events of grade ≥3. Eastern Cooperative Oncology Group performance score was an independent predictor of adverse events. Combination therapy with capecitabine and cisplatin may be an option for second-line chemotherapy in some of patients with advanced BTC. © 2017 S. Karger AG, Basel.

LINE-1 couples EMT programming with acquisition of oncogenic phenotypes in human bronchial epithelial cells.

PubMed

Reyes-Reyes, Elsa M; Aispuro, Ivan; Tavera-Garcia, Marco A; Field, Matthew; Moore, Sara; Ramos, Irma; Ramos, Kenneth S

2017-11-28

Although several lines of evidence have established the central role of epithelial-to-mesenchymal-transition (EMT) in malignant progression of non-small cell lung cancers (NSCLCs), the molecular events connecting EMT to malignancy remain poorly understood. This study presents evidence that Long Interspersed Nuclear Element-1 (LINE-1) retrotransposon couples EMT programming with malignancy in human bronchial epithelial cells (BEAS-2B). This conclusion is supported by studies showing that: 1) activation of EMT programming by TGF-β1 increases LINE-1 mRNAs and protein; 2) the lung carcinogen benzo(a)pyrene coregulates TGF-β1 and LINE-1 mRNAs, with LINE-1 positioned downstream of TGF-β1 signaling; and, 3) forced expression of LINE-1 in BEAS-2B cells recapitulates EMT programming and induces malignant phenotypes and tumorigenesis in vivo . These findings identify a TGFβ1-LINE-1 axis as a critical effector pathway that can be targeted for the development of precision therapies during malignant progression of intractable NSCLCs.

Multimodal imaging of central retinal disease progression in a 2 year mean follow up of Retinitis Pigmentosa

PubMed Central

Sujirakul, Tharikarn; Lin, Michael K.; Duong, Jimmy; Wei, Ying; Lopez-Pintado, Sara; Tsang, Stephen H.

2015-01-01

Purpose To determine the rate of progression and optimal follow up time in patients with advanced stage retinitis pigmentosa (RP) comparing the use of fundus autofluorescence imaging and spectral domain optical coherence tomography. Design Retrospective analysis of progression rate. Methods Longitudinal imaging follow up in 71 patients with retinitis pigmentosa was studied using the main outcome measurements of hyperautofluoresent ring horizontal diameter and vertical diameter along with ellipsoid zone line width from spectral domain optical coherence tomography. Test-retest reliability and the rate of progression were calculated. The interaction between the progression rates was tested for sex, age, mode of inheritance, and baseline measurement size. Symmetry of left and right eye progression rate was also tested. Results Significant progression was observed in >75% of patients during the 2 year mean follow up. The mean annual progression rates of ellipsoid zone line, and hyperautofluorescent ring horizontal diameter and vertical diameter were 0.45° (4.9%), 0.51° (4.1%), and 0.42° (4.0%), respectively. The e llipsoid zone line width, and hyperautofluorescent ring horizontal diameter and vertical diameter had low test-retest variabilities of 8.9%, 9.5% and 9.6%, respectively. This study is the first to demonstrate asymmetrical structural progression rate between right and left eye, which was found in 19% of patients. The rate of progression was significantly slower as the disease approached the fovea, supporting the theory that RP progresses in an exponential fashion. No significant interaction between progression rate and patient age, sex, or mode of inheritance was observed. Conclusions Fundus autofluorescence and optical coherence tomography detect progression in patients with RP reliably and with strong correlation. These parameters may be useful alongside functional assessments as the outcome measurements for future therapeutic trials. Follow-up at 1 year intervals should be adequate to efficiently detect progression. PMID:26164827

Computer Programs for Calculating and Plotting the Stability Characteristics of a Balloon Tethered in a Wind

NASA Technical Reports Server (NTRS)

Bennett, R. M.; Bland, S. R.; Redd, L. T.

1973-01-01

Computer programs for calculating the stability characteristics of a balloon tethered in a steady wind are presented. Equilibrium conditions, characteristic roots, and modal ratios are calculated for a range of discrete values of velocity for a fixed tether-line length. Separate programs are used: (1) to calculate longitudinal stability characteristics, (2) to calculate lateral stability characteristics, (3) to plot the characteristic roots versus velocity, (4) to plot the characteristic roots in root-locus form, (5) to plot the longitudinal modes of motion, and (6) to plot the lateral modes for motion. The basic equations, program listings, and the input and output data for sample cases are presented, with a brief discussion of the overall operation and limitations. The programs are based on a linearized, stability-derivative type of analysis, including balloon aerodynamics, apparent mass, buoyancy effects, and static forces which result from the tether line.

Propagation and stability characteristics of a 500-m-long laser-based fiducial line for high-precision alignment of long-distance linear accelerators.

PubMed

Suwada, Tsuyoshi; Satoh, Masanori; Telada, Souichi; Minoshima, Kaoru

2013-09-01

A laser-based alignment system with a He-Ne laser has been newly developed in order to precisely align accelerator units at the KEKB injector linac. The laser beam was first implemented as a 500-m-long fiducial straight line for alignment measurements. We experimentally investigated the propagation and stability characteristics of the laser beam passing through laser pipes in vacuum. The pointing stability at the last fiducial point was successfully obtained with the transverse displacements of ±40 μm level in one standard deviation by applying a feedback control. This pointing stability corresponds to an angle of ±0.08 μrad. This report contains a detailed description of the experimental investigation for the propagation and stability characteristics of the laser beam in the laser-based alignment system for long-distance linear accelerators.

How nanobubbles lose stability: Effects of surfactants

NASA Astrophysics Data System (ADS)

Xiao, Qianxiang; Liu, Yawei; Guo, Zhenjiang; Liu, Zhiping; Zhang, Xianren

2017-09-01

In contrast to stability theories of nanobubbles, the molecular mechanism of how nanobubbles lose stability is far from being understood. In this work, we try to interpret recent experimental observations that the addition of surfactants destabilizes nanobubbles with an unclear mechanism. Using molecular dynamics simulations, we identify two surfactant-induced molecular mechanisms for nanobubbles losing stability, either through depinning of a contact line or reducing vapor-liquid surface tension. One corresponds to the case with significant adsorption of surfactants on the substrates, which causes depinning of the nanobubble contact line and thus leads to nanobubble instability. The other stresses surfactant adsorption on the vapor-liquid interface of nanobubbles, especially for insoluble surfactants, which reduces the surface tension of the interface and leads to an irreversible liquid-to-vapor phase transition. Our finding can help improve our understanding in nanobubble stability, and the insight presented here has implications for surface nanobubbles involving with other amphiphilic molecules, such as proteins and contaminations.

Quadrupole mass filter: design and performance for operation in stability zone 3.

PubMed

Syed, Sarfaraz U A H; Hogan, Thomas J; Antony Joseph, Mariya J; Maher, Simon; Taylor, Stephen

2013-10-01

The predicted performance of a quadrupole mass filter (QMF) operating in Mathieu stability zone 3 is described in detail using computer simulations. The investigation considers the factors that limit the ultimate maximum resolution (Rmax) and percentage transmission (%Tx), which can be obtained for a given QMF for a particular scan line of operation. The performance curve (i.e., the resolution (R) versus number (N) of radio frequency (rf) cycles experienced by the ions in the mass filter) has been modeled for the upper and lower tip of stability zone 3. The saturation behavior of the performance curve observed in practice for zone 3 is explained. Furthermore, new design equations are presented by examining the intersection of the scan line with stability zone 3. Resolution versus transmission characteristics of stability zones 1 and 3 are compared and the dependence of performance for zones 1 and 3 is related to particular instrument operating parameters.

Propagation and stability characteristics of a 500-m-long laser-based fiducial line for high-precision alignment of long-distance linear accelerators

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

Suwada, Tsuyoshi; Satoh, Masanori; Telada, Souichi

2013-09-15

A laser-based alignment system with a He-Ne laser has been newly developed in order to precisely align accelerator units at the KEKB injector linac. The laser beam was first implemented as a 500-m-long fiducial straight line for alignment measurements. We experimentally investigated the propagation and stability characteristics of the laser beam passing through laser pipes in vacuum. The pointing stability at the last fiducial point was successfully obtained with the transverse displacements of ±40 μm level in one standard deviation by applying a feedback control. This pointing stability corresponds to an angle of ±0.08 μrad. This report contains a detailedmore » description of the experimental investigation for the propagation and stability characteristics of the laser beam in the laser-based alignment system for long-distance linear accelerators.« less

Flow Range of Centrifugal Compressor Being Extended

NASA Technical Reports Server (NTRS)

Skoch, Gary J.

2001-01-01

General Aviation will benefit from turbine engines that are both fuel-efficient and reliable. Current engines fall short of their potential to achieve these attributes. The reason is compressor surge, which is a flow stability problem that develops when the compressor is subjected to conditions that are outside of its operating range. Compressor surge can occur when fuel flow to the engine is increased, temporarily back pressuring the compressor and pushing it past its stability limit, or when the compressor is subjected to inlet flow-field distortions that may occur during takeoff and landing. Compressor surge can result in the loss of an aircraft. As a result, engine designers include a margin of safety between the operating line of the engine and the stability limit line of the compressor. Unfortunately, the most efficient operating line for the compressor is usually closer to its stability limit line than it is to the line that provides an adequate margin of safety. A wider stable flow range will permit operation along the most efficient operating line of the compressor, improving the specific fuel consumption of the engine and reducing emissions. The NASA Glenn Research Center is working to extend the stable flow range of the compressor. Significant extension has been achieved in axial compressors by injecting air upstream of the compressor blade rows. Recently, the technique was successfully applied to a 4:1 pressure ratio centrifugal compressor by injecting streams of air into the diffuser. Both steady and controlled unsteady injection were used to inject air through the diffuser shroud surface and extend the range. Future work will evaluate the effect of air injection through the diffuser hub surface and diffuser vanes with the goal of maximizing the range extension while minimizing the amount of injected air that is required.

Prismatic displacement effect of progressive multifocal glasses on reaction time and accuracy in elderly people

PubMed Central

Ellison, Ashton C; Campbell, A John; Robertson, M Clare; Sanderson, Gordon F

2014-01-01

Background Multifocal glasses (bifocals, trifocals, and progressives) increase the risk of falling in elderly people, but how they do so is unclear. To explain why glasses with progressive addition lenses increase the risk of falls and whether this can be attributed to false projection, this study aimed to 1) map the prismatic displacement of a progressive lens, and 2) test whether this displacement impaired reaction time and accuracy. Methods The reaction times of healthy ≥75-year-olds (31 participants) were measured when grasping for a bar and touching a black line. Participants performed each test twice, wearing their progressives and new, matched single vision (distance) glasses in random order. The line and bar targets were positioned according to the maximum and minimum prismatic displacement effect through the progressive lens, mapped using a focimeter. Results Progressive spectacle lenses have large areas of prismatic displacement in the central visual axis and edges. Reaction time was faster for progressives compared with single vision glasses with a centrally-placed horizontal grab bar (mean difference 101 ms, P=0.011 [repeated measures analysis]) and a horizontal black line placed 300 mm below center (mean difference 80 ms, P=0.007). There was no difference in accuracy between the two types of glasses. Conclusion Older people appear to adapt to the false projection of progressives in the central visual axis. This adaptation means that swapping to new glasses or a large change in prescription may lead to a fall. Frequently updating glasses may be more beneficial. PMID:24872674

Amyloid-beta aggregates formed at polar-nonpolar interfaces differ from amyloid-beta protofibrils produced in aqueous buffers.

PubMed

Nichols, Michael R; Moss, Melissa A; Reed, Dana Kim; Hoh, Jan H; Rosenberry, Terrone L

2005-07-01

The deposition of aggregated amyloid-beta (Abeta) peptides in the brain as senile plaques is a pathological hallmark of Alzheimer's disease (AD). Several lines of evidence indicate that fibrillar and, in particular, soluble aggregates of these 40- and 42-residue peptides are important in the etiology of AD. Recent studies also stress that amyloid aggregates are polymorphic and that a single polypeptide can fold into multiple amyloid conformations. Here we review our recent reports that Abeta(1-40) in vitro can form soluble aggregates with predominant beta-structures that differ in stability and morphology. One class of aggregates involved soluble Abeta protofibrils, prepared by vigorous overnight agitation of monomeric Abeta(1-40) in low ionic strength buffers. These aggregates were quite stable and disaggregated to only a limited extent on dilution. A second class of soluble Abeta aggregates was generated at polar-nonpolar interfaces. Aggregation in a two-phase system of buffer over chloroform occurred more rapidly than in buffer alone. In buffered 2% hexafluoroisopropanol (HFIP), microdroplets of HFIP were formed and the half-time for aggregation was less than 10 minutes. Like Abeta protofibrils, these interfacial aggregates showed increased thioflavin T fluorescence and were rich in beta-structure by circular dichroism. However, electron microscopy and atomic force microscopy revealed very different morphologies. The HFIP aggregates formed initial globular clusters that progressed over several days to soluble fibrous aggregates. When diluted out of HFIP these aggregates initially were very unstable and disaggregated completely within 2 minutes. However, their stability increased as they progressed to fibers. It is important to determine whether similar interfacial Abeta aggregates are produced in vivo.

ZEB1 induces LOXL2-mediated collagen stabilization and deposition in the extracellular matrix to drive lung cancer invasion and metastasis.

PubMed

Peng, D H; Ungewiss, C; Tong, P; Byers, L A; Wang, J; Canales, J R; Villalobos, P A; Uraoka, N; Mino, B; Behrens, C; Wistuba, I I; Han, R I; Wanna, C A; Fahrenholtz, M; Grande-Allen, K J; Creighton, C J; Gibbons, D L

2017-04-06

Lung cancer is the leading cause of cancer-related deaths, primarily due to distant metastatic disease. Metastatic lung cancer cells can undergo an epithelial-to-mesenchymal transition (EMT) regulated by various transcription factors, including a double-negative feedback loop between the microRNA-200 (miR-200) family and ZEB1, but the precise mechanisms by which ZEB1-dependent EMT promotes malignancy remain largely undefined. Although the cell-intrinsic effects of EMT are important for tumor progression, the reciprocal dynamic crosstalk between mesenchymal cancer cells and the extracellular matrix (ECM) is equally critical in regulating invasion and metastasis. Investigating the collaborative effect of EMT and ECM in the metastatic process reveals increased collagen deposition in metastatic tumor tissues as a direct consequence of amplified collagen gene expression in ZEB1-activated mesenchymal lung cancer cells. In addition, collagen fibers in metastatic lung tumors exhibit greater linearity and organization as a result of collagen crosslinking by the lysyl oxidase (LOX) family of enzymes. Expression of the LOX and LOXL2 isoforms is directly regulated by miR-200 and ZEB1, respectively, and their upregulation in metastatic tumors and mesenchymal cell lines is coordinated to that of collagen. Functionally, LOXL2, as opposed to LOX, is the principal isoform that crosslinks and stabilizes insoluble collagen deposition in tumor tissues. In turn, focal adhesion formation and FAK/SRC signaling is activated in mesenchymal tumor cells by crosslinked collagen in the ECM. Our study is the first to validate direct regulation of LOX and LOXL2 by the miR-200/ZEB1 axis, defines a novel mechanism driving tumor metastasis, delineates collagen as a prognostic marker, and identifies LOXL2 as a potential therapeutic target against tumor progression.

ZEB1 Induces LOXL2-Mediated Collagen Stabilization and Deposition in the Extracellular Matrix to Drive Lung Cancer Invasion and Metastasis

PubMed Central

Peng, David H.; Ungewiss, Christin; Tong, Pan; Byers, Lauren A.; Wang, Jing; Canales, Jaime Rodriguez; Villalobos, Pamela A.; Uraoka, Naohiro; Mino, Barbara; Behrens, Carmen; Wistuba, Ignacio I.; Han, Richard I; Wanna, Charles A.; Fahrenholtz, Monica; Grande-Allen, Kathryn Jane; Creighton, Chad J.; Gibbons, Don L.

2016-01-01

Lung cancer is the leading cause of cancer-related death, primarily due to distant metastatic disease. Metastatic lung cancer cells can undergo an epithelial-to-mesenchymal transition (EMT) regulated by many transcription factors, including double-negative feedback loop between the microRNA-200 (miR-200) family and ZEB1, but the precise mechanisms by which ZEB1-dependent EMT promotes malignancy remain largely undefined. While the cell-intrinsic effects of EMT are important for tumor progression, the reciprocal dynamic crosstalk between mesenchymal cancer cells and the extracellular matrix (ECM) is equally critical in regulating invasion and metastasis. Investigating the collaborative effect of EMT and ECM in the metastatic process reveals increased collagen deposition in metastatic tumor tissues as a direct consequence of amplified collagen gene expression in ZEB1-activated mesenchymal lung cancer cells. Additionally, collagen fibers in metastatic lung tumors exhibit greater linearity and organization as a result of collagen crosslinking by the lysyl oxidase (LOX) family of enzymes. Expression of the LOX and LOXL2 isoforms is directly regulated by miR-200 and ZEB1, respectively, and their upregulation in metastatic tumors and mesenchymal cell lines is coordinated to that of collagen. Functionally, LOXL2, as opposed to LOX, is the principle isoform that crosslinks and stabilizes insoluble collagen deposition in tumor tissues. In turn, focal adhesion formation and FAK/SRC signaling is activated in mesenchymal tumor cells by crosslinked collagen in the ECM. Our study is the first to validate direct regulation of LOX and LOXL2 by the miR-200/ZEB1 axis, defines a novel mechanism driving tumor metastasis, delineates collagen as a prognostic marker, and identifies LOXL2 as a potential therapeutic target against tumor progression. PMID:27694892

Somatostatin Analogues according to Ki67 index in neuroendocrine tumours: an observational retrospective-prospective analysis from real life

PubMed Central

Faggiano, Antongiulio; Carratù, Anna Chiara; Guadagno, Elia; Tafuto, Salvatore; Tatangelo, Fabiana; Riccardi, Ferdinando; Mocerino, Carmela; Palmieri, Giovannella; Damiano, Vincenzo; Siciliano, Roberta; Leo, Silvana; Mauro, Annamaria; Tozzi, Lucia Franca; Battista, Claudia; De Rosa, Gaetano; Colao, Annamaria

2016-01-01

Somatostatin analogues (SSAs) have shown limited and variable antiproliferative effects in neuroendocrine tumours (NETs). Whether tumour control by SSAs depends on grading based on the 2010 WHO NET classification is still unclear. The aim of this study is to evaluate the efficacy of long-acting SSAs in NETs according to Ki67 index. An observational Italian multicentre study was designed to collect data in patients with gastro-entero-pancreatic or thoracic NETs under SSA treatment. Both retrospective and prospective data were included and they were analysed in line with Ki67 index, immunohistochemically evaluated in tumour samples and graded according to WHO classification (G1 = Ki67 index 0-2%, G2 = Ki67 index 3-20%, G3 = Ki67 index > 20%). Among 601 patients with NET, 140 with a histologically confirmed gastro-entero-pancreatic or thoracic NET or NET with unknown primary were treated with lanreotide autogel or octreotide LAR. An objective tumour response was observed in 11%, stability in 58% and progression in 31%. Objective response and tumour stability were not significantly different between G1 and G2 NETs. Progression free survival was longer but not significantly different in G1 than G2 NETs (median: 89 vs 43 months, p = 0.15). The median PFS was significantly longer in NETs showing Ki67 < 5% than in those showing Ki67 ≥5% (89 vs 35 months, p = 0.005). SSA therapy shows significant antiproliferative effects in well differentiated low/intermediate-proliferating NETs, not only G1 but also in G2 type. A Ki67 index of 5% seems to work better than 3% to select the best candidates for SSA therapy. PMID:26701729

Somatostatin analogues according to Ki67 index in neuroendocrine tumours: an observational retrospective-prospective analysis from real life.

PubMed

Faggiano, Antongiulio; Carratù, Anna Chiara; Guadagno, Elia; Tafuto, Salvatore; Tatangelo, Fabiana; Riccardi, Ferdinando; Mocerino, Carmela; Palmieri, Giovannella; Damiano, Vincenzo; Siciliano, Roberta; Leo, Silvana; Mauro, Annamaria; Tozzi, Lucia Franca; Battista, Claudia; De Rosa, Gaetano; Colao, Annamaria

2016-02-02

Somatostatin analogues (SSAs) have shown limited and variable antiproliferative effects in neuroendocrine tumours (NETs). Whether tumour control by SSAs depends on grading based on the 2010 WHO NET classification is still unclear. The aim of this study is to evaluate the efficacy of long-acting SSAs in NETs according to Ki67 index. An observational Italian multicentre study was designed to collect data in patients with gastro-entero-pancreatic or thoracic NETs under SSA treatment. Both retrospective and prospective data were included and they were analysed in line with Ki67 index, immunohistochemically evaluated in tumour samples and graded according to WHO classification (G1 = Ki67 index 0-2%, G2 = Ki67 index 3-20%, G3 = Ki67 index > 20%). Among 601 patients with NET, 140 with a histologically confirmed gastro-entero-pancreatic or thoracic NET or NET with unknown primary were treated with lanreotide autogel or octreotide LAR. An objective tumour response was observed in 11%, stability in 58% and progression in 31%. Objective response and tumour stability were not significantly different between G1 and G2 NETs. Progression free survival was longer but not significantly different in G1 than G2 NETs (median: 89 vs 43 months, p = 0.15). The median PFS was significantly longer in NETs showing Ki67 < 5% than in those showing Ki67 ≥ 5% (89 vs 35 months, p = 0.005). SSA therapy shows significant antiproliferative effects in well differentiated low/intermediate-proliferating NETs, not only G1 but also in G2 type. A Ki67 index of 5% seems to work better than 3% to select the best candidates for SSA therapy.

The Freedmen’s Bureau, Politics, and Stability Operations during Reconstruction in the South

DTIC Science & Technology

2009-06-12

Movement in the 1960s. 15. SUBJECT TERMS Freedmen‘s Bureau, Stability Operations, Andrew Johnson, Reconstruction 16. SECURITY CLASSIFICATION OF...Mercer Langston (1829-1897) [on-line]; available from http://www. oberlin.edu /external/ EOG /OYTT-images/JMLangston.html; Internet; accessed 26 March...by sentiment more in line with the South‘s old ruling class view of labor, society, and governance. 53 Democratic victories of 1874 signaled a

Ten-year stability and variability, drinking patterns, and impairment in community youth with diagnostic orphan status of alcohol dependence.

PubMed

Grabitz, Maike; Behrendt, Silke; Klotsche, Jens; Buehringer, Gerhard; Lieb, Roselind; Wittchen, Hans-Ullrich

2012-04-01

Some adolescents and young adults who do not fulfill criteria for DSM-IV alcohol abuse (AA) report symptoms of DSM-IV alcohol dependence (AD) below the diagnostic threshold (diagnostic orphans, DOs; 1 or 2 symptoms). Contemporarily, little is known on the long-term stability, risk of progression to AD, impairment, and drinking patterns possibly associated with this status in the first decades of life. (1) To identify prevalence rates of the DO status from adolescence to early adulthood. To investigate (2) stability and variability of the DO status over time and (3) associations between DO status, drinking patterns and impairment in comparison to subjects with AA, with AD, or without any symptoms. N=2039 community subjects (aged 14-24 years at baseline) were assessed at baseline and at about four and ten years after baseline. DSM-IV AUD diagnoses were obtained with the DIA-X/M-CIDI. About 11-12% of the sample was classified as DOs at all waves. Over a period of ten years, 18% of DOs were stable in their diagnosis and additional 10% progressed to AD. DOs were comparable to subjects with AA in drinking patterns, impairment and stability of diagnostic status. DOs progressed to AD significantly more often than AA. AD was associated with highest levels in all outcomes of interest. The DO status in adolescence and early adulthood is associated with considerable stability, risk of progression and problematic alcohol intake. In consequence, it can be meaningful for the timely identification of early stages of clinically relevant alcohol problems. For subjects with DO status early specific interventions are required. Copyright © 2011 Elsevier Ltd. All rights reserved.

Utilizing Flight Data to Update Aeroelastic Stability Estimates

NASA Technical Reports Server (NTRS)

Lind, Rick; Brenner, Marty

1997-01-01

Stability analysis of high performance aircraft must account for errors in the system model. A method for computing flutter margins that incorporates flight data has been developed using robust stability theory. This paper considers applying this method to update flutter margins during a post-flight or on-line analysis. Areas of modeling uncertainty that arise when using flight data with this method are investigated. The amount of conservatism in the resulting flutter margins depends on the flight data sets used to update the model. Post-flight updates of flutter margins for an F/A-18 are presented along with a simulation of on-line updates during a flight test.

Survival after failure of first-line chemotherapy in advanced gastric cancer patients: differences between Japan and the rest of the world.

PubMed

Takashima, Atsuo; Iizumi, Sakura; Boku, Narikazu

2017-07-01

In this review, we focus on post-progression survival after first-line chemotherapy of advanced gastric cancer, and particularly the differences between Japan and the rest of the world. We reviewed 15 recent phase III trials of which 4 were solely recruited from Japanese and 11 from rest of the world. The patient characteristics age, performance status, previous gastrectomy and the number of metastatic sites were similar in Japan and rest of the world. However, the diffuse histological type was more common in Japan. While overall survival was longer in Japan (10.5-14.1 vs. 7.9-12.2 months), progression-free survival tended to be shorter in Japan (3.6-6.0 vs. 3.1-7.4 months). Post-progression survival calculated as the difference between median overall survival and progression-free survival was clearly longer in Japan (6.9-8.6 vs. 2.4-6.2 months). The proportion of patients receiving second-line chemotherapy (%2nd-CX) was quite different in Japan and rest of the world (69-85% vs. 11-59%). Correlations between %2nd-CX and post-progression survival were strong (Spearman's rank correlation coefficient; ρ = 0.86, P < 0.001). Correlations between %2nd-CX and ratio of post-progression survival to total overall survival were also strong (ρ = 0.84, P < 0.001). Because a survival benefit of second-CX was documented in several phase III trials, it can be concluded that higher %2nd-CX partly contributed to extended post-progression survival. However, considering that second-CX increased survival only by ~1.5 months at median, other factors such as third-line chemotherapy may have some influences to prolonged post-progression survival. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A Long DNA Segment in a Linear Nanoscale Paul Trap

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

Joseph, Sony nmn; Guan, Weihau; Reed, Mark A

2009-01-01

We study the dynamics of a linearly distributed line charge such as single stranded DNA (ssDNA) in a nanoscale, linear 2D Paul trap in vacuum. Using molecular dynamics simulations we show that a line charge can be trapped effectively in the trap for a well defined range of stability parameters. We investigated (i) a flexible bonded string of charged beads and (ii) a ssDNA polymer of variable length, for various trap parameters. A line charge undergoes oscillations or rotations as it moves, depending on its initial angle, the position of the center of mass and the velocity. The stability regionmore » for a strongly bonded line of charged beads is similar to that of a single ion with the same charge to mass ratio. Single stranded DNA as long as 40 nm does not fold or curl in the Paul trap, but could undergo rotations about the center of mass. However, we show that a stretching field in the axial direction can effectively prevent the rotations and increase the confinement stability.« less

Progression of Neurovisceral Storage Disease With Supranuclear Ophthalmoplegia Following Orthotopic Liver Transplantation

PubMed Central

Gartner, J. Carlton; Bergman, Ira; Malatack, J. Jeffrey; Zitelli, Basil J.; Jaffe, Ronald; Watkins, John B.; Shaw, Byers W.; Iwatsuki, Shunzaburo; Starzl, Thomas E.

2011-01-01

A 7-year-old girl with progressive ataxia, spasticity, supranuclear ophthalmoplegia, and sea-blue histiocytes in her bone marrow underwent orthotopic liver transplantation for hepatocellular carcinoma. After an initial period of stabilization, she has shown progression of neurologic symptoms with recurrence of storage material in the transplanted liver. PMID:2999691

Amplification of anharmonicities in multiphoton vibrational action spectra.

PubMed

Calvo, F; Parneix, P

2012-01-16

The influence of one or several infrared laser pulses on the stability of bare and argon-tagged sodium chloride clusters is investigated theoretically by a combination of computational methods involving explicit molecular dynamics and properly calibrated unimolecular rate theories. The fragmentation spectra obtained by varying the laser frequency in the far-IR range is compared to the linear absorption spectrum resulting from the dipole moment autocorrelation function. Under appropriate laser field parameters, the action spectra are found to resemble the absorption spectra quite accurately in terms of positions, line widths, and even relative intensities. However, the action spectra exhibit residual and systematic redshifts of a few percent, which are partly due to the finite spectral bandwidth but are amplified by the progressive heating by the laser. A quantitative analysis suggests that these anharmonicity effects should generally arise upon multiple photon absorption. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Novel Approaches to the Production of Higher Alcohols From Synthesis Gas. Quarterly report, January 1 - March 31, 1997

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

Roberts, George W

1998-12-11

A modified analytical system was assembled and calibrated, in preparation for a second run with cesium (Cs)-promoted "zinc chromite" catalyst. A new column for the on-line gas chromatography (GC) was purchased for the analysis of various light olefin and paraffin isomers. A run was carried out in the continuous stirred autoclave using the Cs-promoted catalyst. Decahydronaphfialene was used as the slurry liquid. Reaction conditions were 375°C, 2000 psig total pressure, 0.5 H₂/CO ratio, and 5000 sL/Kg (cat.)-hr. Analysis of the data from this run is in progress. A manuscript on the thermal stability of potential slurry liquids was submitted tomore » 'Industrial and Engineering Chemistry Research,' and a paper was presented at the 1997 Spring National Meeting of the American Institute of Chemical Engineers, Houston, Texas.« less

Integrated function nonimaging concentrating collector tubes for solar thermal energy

NASA Astrophysics Data System (ADS)

Winston, R.; Ogallagher, J. J.

1982-09-01

A substantial improvement in optical efficiency over contemporary external reflector evacuated tube collectors has been achieved by integrating the reflector surface into the outer glass envelope. Described are the design fabrication and test results for a prototype collector based on this concept. A comprehensive test program to measure performance and operational characteristics of a 2 sq m panel (45 tubes) has been completed. Efficiencies above 50% relative to beam at 200 C have been repeatedly demonstrated. Both the instantaneous and long term average performance of this totally stationary solar collector are comparable to those for tracking line focus parabolic troughs. The yield, reliability and stability of performance achieved have been excellent. Subcomponent assemblies and fabrication procedures have been used which are expected to be compatible with high volume production. The collector has a wide variety of applications in the 100 to 300 C range including industrial progress heat, air conditioning and Rankine engine operation.

Efficacy and safety of the third-generation chloroethylnitrosourea fotemustine for the treatment of chemorefractory T-cell lymphomas.

PubMed

Corazzelli, Gaetano; Frigeri, Ferdinando; Arcamone, Manuela; Aloj, Luigi; Capobianco, Gaetana; Becchimanzi, Cristina; Morelli, Emanuela; Volzone, Francesco; Marcacci, Gianpaolo; Russo, Filippo; De Filippi, Rosaria; Lastoria, Secondo; Pinto, Antonio

2011-12-01

Patients with recurring T-cell non-Hodgkin lymphoma (T-NHL) are incurable and candidate for investigational agents. Here, we report on five patients with T-NHL refractory to multiple chemotherapy lines, including in all cases alkylators and gemcitabine, who received the third-generation chloroethylnitrosourea fotemustine at a dose of 120 mg/m(2) every 21 d, up to eight courses. Median actual dose intensity was 79%; toxicity was manageable and mainly hematological. One complete remission, one partial remission, two protracted disease stabilization, and one transient, minor response were achieved. Time to progression ranged from 48 to 240+ d. This is the first evidence ever reporting the activity of fotemustine in end-stage T-NHL. Formal studies with this agent are warranted in T-cell malignancies. © 2011 John Wiley & Sons A/S.

New HIF2α inhibitors: potential implications as therapeutics for advanced pheochromocytomas and paragangliomas.

PubMed

Toledo, Rodrigo Almeida

2017-09-01

Two recent independent studies published in Nature show robust responses of clear cell renal cell carcinoma (ccRCC) cell lines, preclinical ccRCC xenograft models and, remarkably, a patient with progressive ccRCC despite receiving multiple lines of treatment, to the long-awaited, recently developed inhibitors of hypoxia-inducible factor 2-alpha (HIF2α). This commentary published in Endocrine-Related Cancer is based on the recognition of similar molecular drivers in ccRCC and the endocrine neoplasias pheochromocytomas and paragangliomas (PPGLs), ultimately leading to stabilization of HIFs. HIF-stabilizing mutations have been detected in the von Hippel-Lindau (VHL) gene, as well as in other genes, such as succinate dehydrogenase (SDHx), fumarate hydratase (FH) and transcription elongation factor B subunit 1 (TCEB1), as well as the gene that encodes HIF2α itself: EPAS1 HIF2α Importantly, the recent discovery of EPAS1 mutations in PPGLs and the results of comprehensive in vitro and in vivo studies revealing their oncogenic roles characterized a hitherto unknown direct mechanism of HIF2α activation in human cancer. The now available therapeutic opportunity to successfully inhibit HIF2α pharmacologically with PT2385 and PT2399 will certainly spearhead a series of investigations in several types of cancers, including patients with SDHB -related metastatic PPGL for whom limited therapeutic options are currently available. Future studies will determine the efficacy of these promising drugs against the hotspot EPAS1 mutations affecting HIF2α amino acids 529-532 (in PPGLs) and amino acids 533-540 (in erythrocytosis type 4), as well as against HIF2α protein activated by VHL , SDHx and FH mutations in PPGL-derived chromatin cells. © 2017 Society for Endocrinology.

Stabilization in early adult-onset myopia with corneal refractive therapy.

PubMed

González-Méijome, José M; Carracedo, Gonzalo; Lopes-Ferreira, Daniela; Faria-Ribeiro, Miguel A; Peixoto-de-Matos, Sofia C; Queirós, António

2016-02-01

To describe the stabilization of early adult-onset myopia in three university students after initiating orthokeratology treatment with corneal refractive therapy contact lenses. Three Caucasian early adult-onset progressing myopic subjects (1 male, 2 females) were fitted with corneal refractive therapy lenses to correct myopia between -1.50 and -2.50 D of sphere using Paragon CRT (Paragon Vision Sciences, Mesa, AZ) lenses for overnight orthokeratology. The pre-treatment refractive history from 2005 as well as refraction and axial length after treatment onset are reported over a period of 3 years between December 2009 and January 2013 with an additional year of follow-up after treatment discontinuation (January-December 2013). The peripheral refractive patterns and topographic changes are also reported individually. Treatment was successful in all three subjects achieving uncorrected visual acuity of 20/20 or better monocularly. During a period of 3 years of follow-up the subjects did not experience progression in their refractive error, nor in their axial length (measured during the last 2 years of treatment and 1 year after discontinuation). Furthermore, the subjects recovered to their baseline refraction and did not progressed further over the following year after lens wear discontinuation. We cannot attribute a causative effect to the orthokeratology treatment alone as underlying mechanism for myopia stabilization in this 3 patients. However, the present report points to the possibility of stabilization of early adult-onset myopia progression in young adults using corneal refractive therapy treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

Field Verification of Undercut Criteria and Alternatives for Subgrade Stabilization-Coastal Plain

DOT National Transportation Integrated Search

2012-06-01

The North Carolina Department of Transportation (NCDOT) is progressing toward developing quantitative and systematic : criteria that address the implementation of undercutting as a subgrade stabilization measure. As part of this effort, a : laborator...

Common Progress Monitoring Graph Omissions: Missing Goal and Goal Line. Progress Monitoring Brief #2

ERIC Educational Resources Information Center

National Center on Response to Intervention, 2013

2013-01-01

Progress monitoring assessment is one of the four essential components of Response to Intervention (RTI), as defined by the National Center on Response to Intervention (NCRTI). Progress data allow teachers to evaluate the academic performance of students over time, quantify rates of improvement or responsiveness to instruction, and evaluate…

Serum LDH predicts benefit from bevacizumab beyond progression in metastatic colorectal cancer.

PubMed

Marmorino, Federica; Salvatore, Lisa; Barbara, Cecilia; Allegrini, Giacomo; Antonuzzo, Lorenzo; Masi, Gianluca; Loupakis, Fotios; Borelli, Beatrice; Chiara, Silvana; Banzi, Maria Chiara; Miraglio, Emanuela; Amoroso, Domenico; Dargenio, Francesco; Bonetti, Andrea; Martignetti, Angelo; Paris, Myriam; Tomcikova, Daniela; Boni, Luca; Falcone, Alfredo; Cremolini, Chiara

2017-01-01

Different antiangiogenics are currently indicated in the second-line treatment of metastatic colorectal cancer (mCRC), following a first-line bevacizumab-containing treatment. The magnitude of benefit is limited, but no predictors of benefit have been identified. A total of 184 mCRC patients progressing to a first-line bevacizumab-containing treatment were randomised in the BEBYP study to continue or not the antiangiogenic in combination with a second-line chemotherapy. A subgroup analysis according to baseline serum lactate dehydrogenase (LDH) levels was carried out. A significant interaction effect between LDH levels and treatment was found in terms of progression-free survival (PFS; P=0.002). Although patients with low LDH levels achieved significant PFS benefit from the continuation of bevacizumab (HR: 0.39 (95% CI: 0.23-0.65)), patients with high levels did not (HR: 1.10 (95% CI: 0.74-1.64)). Consistent results were reported in overall survival (OS; P=0.075). As preclinical evidence suggests that serum LDH may be a marker of tumour angiogenesis activation, low levels may indicate that bevacizumab is still efficacious in inhibiting angiogenesis. Validation of present results in subgroup analyses of other randomised trials of second-line angiogenesis inhibitors is warranted.

First-line treatment with capecitabine combined with irinotecan in patients with advanced colorectal carcinoma: a phase II study.

PubMed

Assy, Nimer; Basher, Walid; Chetver, Lika; Shnaider, Julia; Zidan, Jamal

2012-04-01

To evaluate the efficacy and toxicity of capecitabine with irinotecan as first-line treatment in metastatic colorectal cancer. The addition of irinotecan to infusional 5 fluorouracil and leucovorin significantly improves the response rate and survival compared with 5 fluorouracil/leucovorin alone in metastatic colorectal cancer. Capecitabine with irinoteacan was reported to yield comparable results in phase II studies. Patients older than 75 years, Eastern Cooperative Oncology Group ≤0 to 3, with measurable disease, no previous treatment for advanced disease, previous adjuvant chemotherapy >6 months, and adequate hepatic, renal, and hematological function were included. The treatment protocol included capecitabine 1000 mg/m twice daily given for 14 days (days 1 to 14) and irinotecan (100 mg/m) given on days 1 and 8. Treatment was repeated on day 21. Thirty patients were included. All were assessable for response and toxicity. Average age was 64 years, male/female ratio 20/10. Fifteen had liver metastases; 9 had abdominal metastases; 5 had liver and lymph nodes metastases; and 1 had lung metastases. The median number of cycles was 8. Grades III and IV diarrheas were observed in 20%, mild vomiting in 20%, grades III and IV leukopenia in 23%, and hand and foot syndrome grade III in 1 patient (3%). A complete response was achieved in 3 (10%) patients, a partial response in 16 (53%), disease stabilization in 6 (20%), and tumor progression in 5 (17%). Progression-free survival was 8.4 months. Overall survival was 19.3 months. This regimen was provided on an outpatient basis with significant antitumor activity and without the need for indwelling catheters and seems to be feasible for patients of all ages, with acceptable toxicity.

Progressive hemifacial atrophy (Parry-Romberg syndrome). Case report.

PubMed

Mazzeo, N; Fisher, J G; Mayer, M H; Mathieu, G P

1995-01-01

Progressive hemifacial atrophy (Parry-Romberg syndrome) is a slowly progressing facial atrophy of subcutaneous fat and the wasting of associated skin, cartilage, and bone. This disorder includes an active progressive phase (2 to 10 years) followed by a burning out of the atrophic process with subsequent stability. This article presents a review of the literature and a case report with unique dental involvement as a result of this disease process.

Oncogenic LINE-1 Retroelements Sustain Prostate Tumor Cells and Promote Metastatic Progression

DTIC Science & Technology

2015-10-01

elements in prostate cancer contribute to its progression by activating oncogenic DNA sequences, or silencing tumor suppressor like sequences. We have...prostate cancer cells. Experiments are ongoing to determine if PIWIL-1 expression in prostate cancer cells will reduce their growth, thereby providing...proof of principle for future gene-based therapeutics for this cancer . 15. SUBJECT TERMS Prostate cancer , LINE-1, PIWIL-1, retrotransposons 16

Coupled Directional Stability of Multiple Ship Formations

DTIC Science & Technology

2013-06-01

Papoulias, “Bifurcation analysis of line of sight vehicle guidance using sliding modes ,” Int. J. of Bifurcation and Chaos, vol. 1, p.4, 1991. [12] F...DISTRIBUTION CODE 13. ABSTRACT (maximum 200 words) This thesis addresses the problem of coordinated motion control and the stability loss of surface...plane with no side slip. A state feedback control law is coupled with a line of sight guidance law to provide path control . A string of three vehicles

Completely optical orientation determination for an unstabilized aerial three-line camera

NASA Astrophysics Data System (ADS)

Wohlfeil, Jürgen

2010-10-01

Aerial line cameras allow the fast acquisition of high-resolution images at low costs. Unfortunately the measurement of the camera's orientation with the necessary rate and precision is related with large effort, unless extensive camera stabilization is used. But also stabilization implicates high costs, weight, and power consumption. This contribution shows that it is possible to completely derive the absolute exterior orientation of an unstabilized line camera from its images and global position measurements. The presented approach is based on previous work on the determination of the relative orientation of subsequent lines using optical information from the remote sensing system. The relative orientation is used to pre-correct the line images, in which homologous points can reliably be determined using the SURF operator. Together with the position measurements these points are used to determine the absolute orientation from the relative orientations via bundle adjustment of a block of overlapping line images. The approach was tested at a flight with the DLR's RGB three-line camera MFC. To evaluate the precision of the resulting orientation the measurements of a high-end navigation system and ground control points are used.

Adaptability and stability of soybean genotypes in off-season cultivation.

PubMed

Batista, R O; Hamawaki, R L; Sousa, L B; Nogueira, A P O; Hamawaki, O T

2015-08-14

The oil and protein contents of soybean grains are important quantitative traits for use in breeding. However, few breeding programs perform selection based on these traits in different environments. This study assessed the adaptability and stability of 14 elite early soybean breeding lines in off-season cultivation with respect to yield, and oil and protein contents. A range of statistical methods was applied and these analyses indicated that for off-season cultivation, the lines UFUS 5 and UFUS 10 could be recommended due to their superior performance in grain yield, oil content, and specific adaptability to unfavorable environments along with high stability in these characteristics. Also recommended were UFUS 06, which demonstrated superior performance in all three tested characteristics and showed adaptation to favorable environments, and UFUS 13, which showed high adaptability and stability and a superior performance for protein content.

Expression profiling in progressive stages of fumarate-hydratase deficiency: the contribution of metabolic changes to tumorigenesis.

PubMed

Ashrafian, Houman; O'Flaherty, Linda; Adam, Julie; Steeples, Violetta; Chung, Yuen-Li; East, Phil; Vanharanta, Sakari; Lehtonen, Heli; Nye, Emma; Hatipoglu, Emine; Miranda, Melroy; Howarth, Kimberley; Shukla, Deepa; Troy, Helen; Griffiths, John; Spencer-Dene, Bradley; Yusuf, Mohammed; Volpi, Emanuela; Maxwell, Patrick H; Stamp, Gordon; Poulsom, Richard; Pugh, Christopher W; Costa, Barbara; Bardella, Chiara; Di Renzo, Maria Flavia; Kotlikoff, Michael I; Launonen, Virpi; Aaltonen, Lauri; El-Bahrawy, Mona; Tomlinson, Ian; Pollard, Patrick J

2010-11-15

Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is caused by mutations in the Krebs cycle enzyme fumarate hydratase (FH). It has been proposed that "pseudohypoxic" stabilization of hypoxia-inducible factor-α (HIF-α) by fumarate accumulation contributes to tumorigenesis in HLRCC. We hypothesized that an additional direct consequence of FH deficiency is the establishment of a biosynthetic milieu. To investigate this hypothesis, we isolated primary mouse embryonic fibroblast (MEF) lines from Fh1-deficient mice. As predicted, these MEFs upregulated Hif-1α and HIF target genes directly as a result of FH deficiency. In addition, detailed metabolic assessment of these MEFs confirmed their dependence on glycolysis, and an elevated rate of lactate efflux, associated with the upregulation of glycolytic enzymes known to be associated with tumorigenesis. Correspondingly, Fh1-deficient benign murine renal cysts and an advanced human HLRCC-related renal cell carcinoma manifested a prominent and progressive increase in the expression of HIF-α target genes and in genes known to be relevant to tumorigenesis and metastasis. In accord with our hypothesis, in a variety of different FH-deficient tissues, including a novel murine model of Fh1-deficient smooth muscle, we show a striking and progressive upregulation of a tumorigenic metabolic profile, as manifested by increased PKM2 and LDHA protein. Based on the models assessed herein, we infer that that FH deficiency compels cells to adopt an early, reversible, and progressive protumorigenic metabolic milieu that is reminiscent of that driving the Warburg effect. Targets identified in these novel and diverse FH-deficient models represent excellent potential candidates for further mechanistic investigation and therapeutic metabolic manipulation in tumors. Copyright © 2010 AACR.

Characterization of a spontaneous disease of white leghorn chickens resembling progressive systemic sclerosis (scleroderma)

PubMed Central

1981-01-01

University of California, Davis (UCD) line 200 White Leghorn Chickens spontaneously develop a syndrome that has many analogous features to human progressive systemic sclerosis. This syndrome is characterized by progressive involution of comb, dermal fibrosis, and distal polyarthritis. These three features occur within 6 wk after hatching, and are accompanied by a 40% mortality as a result of vaso-occlusive disease, with development of secondary infection of peripheral gangrenous lesions. Birds that survive greater than 2 mo after hatching progressively develop fibrosis of the esophagous and mononuclear infiltration of heart and kidney, with prominent occlusion of small and medium sized blood vessels. In addition, line 200 chickens develop rheumatoid factors, antinuclear antibodies, and antibodies to collagen, but do not have antibodies to thymocytes, DNA, or extractable nuclear antigens. Moreover, antinuclear antibodies when studied using HEp-2 cells as substrate demonstrate predominantly a speckled pattern. This syndrome of line 200 chickens is not detectable in F1 crosses to several UCD inbred lines. F1 X parental line BC1 backcrosses have an approximately 50% incidence of disease, suggesting that this syndrome is inherited as autosomal recessive. However, only 4% of F2 generation birds show abnormal symptoms, suggesting the presence of modifying genes. There is no appearance of IgG deposition, as determined by immunofluorescence, in either skin, blood vessels, esophagus, or heart. However, approximately 20% of chickens have a glomerulonephritis; this feature appears to be a terminal event and does not appear clinically significant. Although this syndrome of line 200 chickens has several features that are in sharp distinction to human scleroderma, the presence of common immunologic and pathologic denominators suggest that this spontaneous disease may be an appropriate model to develop a better understanding of autoimmune connective tissue diseases. PMID:7252423

14 CFR 25.231 - Longitudinal stability and control.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Longitudinal stability and control. 25.231... Characteristics § 25.231 Longitudinal stability and control. (a) Landplanes may have no uncontrollable tendency to... on concrete, to maintain any attitude up to thrust line level, at 75 percent of V SR 1. (b) For...

14 CFR 25.231 - Longitudinal stability and control.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Longitudinal stability and control. 25.231... Characteristics § 25.231 Longitudinal stability and control. (a) Landplanes may have no uncontrollable tendency to... on concrete, to maintain any attitude up to thrust line level, at 75 percent of V SR 1. (b) For...

14 CFR 25.231 - Longitudinal stability and control.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Longitudinal stability and control. 25.231... Characteristics § 25.231 Longitudinal stability and control. (a) Landplanes may have no uncontrollable tendency to... on concrete, to maintain any attitude up to thrust line level, at 75 percent of V SR 1. (b) For...

14 CFR 25.231 - Longitudinal stability and control.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Longitudinal stability and control. 25.231... Characteristics § 25.231 Longitudinal stability and control. (a) Landplanes may have no uncontrollable tendency to... on concrete, to maintain any attitude up to thrust line level, at 75 percent of V SR 1. (b) For...

46 CFR 172.065 - Damage stability.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 7 2014-10-01 2014-10-01 false Damage stability. 172.065 Section 172.065 Shipping COAST... § 172.065 Damage stability. (a) Definitions. As used in this section, Length or L means load line length... paragraph (c) of this section, assuming the damage specified in paragraph (d) of this section. (c...

46 CFR 172.065 - Damage stability.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 7 2012-10-01 2012-10-01 false Damage stability. 172.065 Section 172.065 Shipping COAST... § 172.065 Damage stability. (a) Definitions. As used in this section, Length or L means load line length... paragraph (c) of this section, assuming the damage specified in paragraph (d) of this section. (c...

46 CFR 172.065 - Damage stability.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 7 2013-10-01 2013-10-01 false Damage stability. 172.065 Section 172.065 Shipping COAST... § 172.065 Damage stability. (a) Definitions. As used in this section, Length or L means load line length... paragraph (c) of this section, assuming the damage specified in paragraph (d) of this section. (c...

Constructing Hopf bifurcation lines for the stability of nonlinear systems with two time delays

NASA Astrophysics Data System (ADS)

Nguimdo, Romain Modeste

2018-03-01

Although the plethora real-life systems modeled by nonlinear systems with two independent time delays, the algebraic expressions for determining the stability of their fixed points remain the Achilles' heel. Typically, the approach for studying the stability of delay systems consists in finding the bifurcation lines separating the stable and unstable parameter regions. This work deals with the parametric construction of algebraic expressions and their use for the determination of the stability boundaries of fixed points in nonlinear systems with two independent time delays. In particular, we concentrate on the cases for which the stability of the fixed points can be ascertained from a characteristic equation corresponding to that of scalar two-delay differential equations, one-component dual-delay feedback, or nonscalar differential equations with two delays for which the characteristic equation for the stability analysis can be reduced to that of a scalar case. Then, we apply our obtained algebraic expressions to identify either the parameter regions of stable microwaves generated by dual-delay optoelectronic oscillators or the regions of amplitude death in identical coupled oscillators.

46 CFR 171.015 - Location of margin line.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 7 2010-10-01 2010-10-01 false Location of margin line. 171.015 Section 171.015 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) SUBDIVISION AND STABILITY SPECIAL RULES PERTAINING TO VESSELS CARRYING PASSENGERS General § 171.015 Location of margin line. (a) A vessel with a...

Developmental changes in consistency of autobiographical memories: adolescents' and young adults' repeated recall of recent and distance events.

PubMed

Larkina, Marina; Merrill, Natalie A; Bauer, Patricia J

2017-09-01

Autobiographical memories contribute continuity and stability to one's self yet they also are subject to change: they can be forgotten or be inconsistently remembered and reported. In the present research, we compared the consistency of two reports of recent and distant personal events in adolescents (12- to 14-year-olds) and young adults (18- to 23-year-olds). In line with expectations of greater mnemonic consistency among young adults relative to adolescents, adolescents reported the same events 80% of the time compared with 90% consistency among young adults; the significant difference disappeared after taking into consideration narrative characteristics of individual memories. Neither age group showed high levels of content consistency (30% vs. 36%); young adults were more consistent than adolescents even after controlling for other potential predictors of content consistency. Adolescents and young adults did not differ in consistency of estimating when their past experiences occurred. Multilevel modelling indicated that the level of thematic coherence of the initial memory report and ratings of event valence significantly predicted memory consistency at the level of the event. Thematic coherence was a significant negative predictor of content consistency. The findings suggest a developmental progression in the robustness and stability of personal memories between adolescence and young adulthood.

Actin-Binding Protein Requirement for Cortical Stability and Efficient Locomotion

NASA Astrophysics Data System (ADS)

Cunningham, C. Casey; Gorlin, Jed B.; Kwiatkowski, David J.; Hartwig, John H.; Janmey, Paul A.; Randolph Byers, H.; Stossel, Thomas P.

1992-01-01

Three unrelated tumor cell lines derived from human malignant melanomas lack actin-binding protein (ABP), which cross-links actin filaments in vitro and connects these filaments to plasma membrane glycoproteins. The ABP-deficient cells have impaired locomotion and display circumferential blebbing of the plasma membrane. Expression of ABP in one of the lines after transfection restored translocational motility and reduced membrane blebbing. These findings establish that ABP functions to stabilize cortical actin in vivo and is required for efficient cell locomotion.

Prevention and Treatment of ER-Negative Breast Cancer

DTIC Science & Technology

2005-10-01

human breast epithelial cell lines that express several levels of P13 kinase and AKT activity. These lines will be characterized with respect to...cancer. (4)Defined a putative role for psoriasin in breast tumor progression. (5) Progress in the analysis of the role of NFkappaB signaling in ER...press.. 9 PREVENTION AND TREATMENT OF ER-NEGATIVE BREAST CANCERPrincipal Investigator: Brown, Mvles A. 4) IGF-1 Receptor and the Akt protein kinase Akt

Stability and Control Characteristics of a Complete Airplane Model Having a Wing with Quarter-chord Line Swept Back 40 Degrees, Aspect Ratio 2.50, and Taper Ratio 0.42

NASA Technical Reports Server (NTRS)

Schulderfrei, Marvin; Comisarow, Paul; Goodson, Kenneth W

1951-01-01

An investigation has been made of a complete airplane model having a wing with the quarter-chord line swept back 40 degrees, aspect ratio 2.50, and taper ratio 0.42 to determine its low-speed stability and control characteristics. The longitudinal stability investigation included stabilizer and tail-off tests with different wing dihedral angles (Gamma = 0 degrees and Gamma = -10 degrees) over an angle-of-attack range for the cruising and landing configurations and tests. with a high horizontal-tail location (Gamma = -10 degrees) for the cruising configuration. Tests were made of the wing alone and to determine the effect of wing end plates in pitch. Lateral stability characteristics were determined for the airplane with different geometric wing dihedrals, with end plates, and with several dorsal modifications. Tests were made with ailerons and spoilers to determine control characteristics.

A gimbal platform stabilization for topographic applications

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

Michele, Mangiameli, E-mail: michele.mangiameli@dica.unict.it; Giuseppe, Mussumeci

2015-03-10

The aim of this work is the stabilization of a Gimbal platform for optical sensors acquisitions in topographic applications using mobile vehicles. The stabilization of the line of sight (LOS) consists in tracking the command velocity in presence of nonlinear noise due to the external environment. The hardware architecture is characterized by an Ardupilot platform that allows the control of both the mobile device and the Gimbal. Here we developed a new approach to stabilize the Gimbal platform, which is based on neural network. For the control system, we considered a plant that represents the transfer function of the servomore » system control model for an inertial stabilized Gimbal platform. The transductor used in the feed-back line control is characterized by the Rate Gyro transfer function installed onboard of Ardupilot. For the simulation and investigation of the system performance, we used the Simulink tool of Matlab. Results show that the hardware/software approach is efficient, reliable and cheap for direct photogrammetry, as well as for general purpose applications using mobile vehicles.« less

Nano-Bio-Mechanics of Neuroblastoma Cells Using AFM

NASA Astrophysics Data System (ADS)

Bastatas, Lyndon; Matthews, James; Kang, Min; Park, Soyeun

2011-10-01

We have conducted an in vitro study to determine the elastic moduli of neurobalstoma cell lines using atomic force microscopy. Using a panel of cell lines established from neuroblastoma patients at different stages of disease progress and treatment, we have investigated the differences in elastic moduli during a course of cancer progression and chemotherapy. The cells were grown on the hard substrates that are chemically functionalized to enhance adhesion. We have performed the AFM indentation experiments with different applied forces from the AFM probe. For the purpose of the comparison between cell lines, the indentations were performed only on cell centers. The obtained force-distance curves were analyzed using the Hertz model in order to extract the elastic moduli. We have found that the elastic moduli of human neuroblastoma cells significantly varied during the disease progression. We postulate that the observed difference might be affected by the treatment and chemotherapy.

AIM1 and LINE-1 Epigenetic Aberrations In Tumor and Serum Relate to Melanoma Progression and Disease Outcome

PubMed Central

Hoshimoto, Sojun; Kuo, Christine; Chong, Kelly; Takeshima, Ling; Takei, Yoshiki; Li, Michelle; Huang, Sharon; Sim, Myung-Shin; Morton, Donald L.; Hoon, Dave S.B.

2012-01-01

Aberrations in the methylation status of non-coding genomic repeat DNA sequences and specific gene promoter region are important epigenetic events in melanoma progression. Promoter methylation status in LINE-1 and Absent in melanoma-1(AIM1;6q21) associated with melanoma progression and disease outcome was assessed. LINE-1 and AIM1 methylation status was assessed in paraffin-embedded archival tissues(PEAT)(n=133) and melanoma patients’ serum(n=56). LINE-1 U-Index(hypomethylation) and AIM1 were analyzed in microdissected melanoma PEAT sections. The LINE-1 U-Index of melanoma(n=100) was significantly higher than that of normal skin(n=14) and nevi(n=12)(P=0.0004). LINE-1 U-Index level was elevated with increasing AJCC stage(P<0.0001). AIM1 promoter hypermethylation was found in higher frequency(P=0.005) in metastatic melanoma(65%) than in primary melanomas(38%). When analyzed, high LINE-1 U-Index and/or AIM1 methylation in melanomas were associated with disease-free survival(DFS) and overall survival(OS) in Stage I/II patients (P=0.017, 0.027; respectively). In multivariate analysis, melanoma AIM1 methylation status was a significant prognostic factor of OS(P=0.032). Furthermore, serum unmethylated LINE-1 was at higher levels in both stage III(n=20) and stage IV(n=36) patients compared to healthy donors(n=14)(P=0.022). Circulating methylated AIM1 was detected in patients’ serum and was predictive of OS in Stage IV patients (P=0.009). LINE-1 hypomethylation and AIM1 hypermethylation have prognostic utility in both melanoma patients’ tumors and serum. PMID:22402438

Downregulation of indoleamine-2,3-dioxygenase in cervical cancer cells suppresses tumor growth by promoting natural killer cell accumulation

PubMed Central

SATO, NAOTO; SAGA, YASUSHI; MIZUKAMI, HIROAKI; WANG, DONGDONG; TAKAHASHI, SUZUYO; NONAKA, HIROAKI; FUJIWARA, HIROYUKI; TAKEI, YUJI; MACHIDA, SHIZUO; TAKIKAWA, OSAMU; OZAWA, KEIYA; SUZUKI, MITSUAKI

2012-01-01

This study examined the role of the immunosuppressive enzyme indoleamine-2,3-dioxygenase (IDO) in cervical cancer progression and the possible use of this enzyme for cervical cancer therapy. We analyzed IDO protein expression in 9 cervical cancer cell lines (SKG-I, -II, -IIIa, -IIIb, SiHa, CaSki, BOKU, HCS-2 and ME-180) stimulated with interferon-γ. IDO expression was observed in all cell lines except for SKG-IIIb. We transfected the human cervical cancer cell line CaSki that constitutively expresses IDO with a short hairpin RNA vector targeting IDO, and established an IDO-downregulated cell line to determine whether inhibition of IDO mediates cervical cancer progression. IDO downregulation suppressed tumor growth in vivo, without influencing cancer cell growth in vitro. Moreover, IDO downregulation enhanced the sensitivity of cervical cancer cells to natural killer (NK) cells in vitro and promoted NK cell accumulation in the tumor stroma in vivo. These findings indicate that downregulation of IDO controls cervical cancer progression by activating NK cells, suggesting IDO as a potential therapy for cervical cancer. PMID:22923135

Use of near-isogenic wheat lines to determine the glutenin composition and functionality requirements for flour tortillas.

PubMed

Mondal, Suchismita; Tilley, Michael; Alviola, Juma Novi; Waniska, Ralph D; Bean, Scott R; Glover, Karl D; Hays, Dirk B

2008-01-09

In wheat ( Triticum aestivum L), the synthesis of high molecular weight (HMW) glutenins (GS) is controlled by three heterologous genetic loci present on the long arms of group 1 wheat chromosomes. The loci Glu-A1, Glu-B1, and Glu-D1 and their allelic variants play important roles in the functional properties of wheat flour. This study focused on understanding the functionality of these protein subunits on tortilla quality. Near-isogenic wheat lines in which one or more of these loci were absent or deleted were used. Tortillas were prepared from each deletion line and the parent lines. The elimination of certain HMW-GS alleles alter distinct but critical aspects of tortilla quality such as diameter, shelf stability, and overall quality. Two deletion lines possessing HMW-GS 17 + 18 at Glu-B1 and deletions in Glu-A1 and Glu-D1 had significantly larger tortilla diameters, yet tortilla shelf life was compromised or unchanged from the parent lines used to develop the deletion lines or the commercial tortilla flour used as a control. Alternatively, a deletion line possessing Glu-A1 and Glu-D1 (HMW-GS 1, 5 + 10) and a deletion in Glu-B1 also significantly improved tortilla diameters. Whereas the increase in diameter was less than the line possessing only HMW-GS 17 + 18 at Glu-B1, the stability of the tortillas were, however, maintained and improved as compared to the parent lines containing a full compliment of HMW-GS. Thus, the presence of subunits 5 + 10 at Glu-D1 alone or in combination with subunit 1 at Glu-A1 appears to provide a compromise of improvement in dough extensibility for improved tortilla diameters while also providing sufficient gluten strength to maintain ideal shelf stability.

Development of stable, narrow spectral line-width, fiber delivered laser source for spin exchange optical pumping

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

Liu, Bo; Tong, Xin; Jiang, Chenyang

2015-06-05

In this study, we developed a stable, narrow spectral line-width, fiber delivered laser source for spin exchange optical pumping. An optimized external cavity equipped with an off-the-shelf volume holographic grating narrowed the spectral line-width of a 100 W high-power diode laser and stabilized the laser spectrum. The laser spectrum showed a high side mode suppression ratio of >30 dB and good long-term stability (center wavelength drifting within ±0.002 nm during 220 h of operation). Finally, our laser is delivered by a multimode fiber with power ~70 W, center wavelength of 794.77 nm, and spectral bandwidth of ~0.12 nm.

Track Generator.

DTIC Science & Technology

provided for periodically inserting a new line of data in place of the oldest data line only, whereby a historical display is maintained while also showing progression of parameters represented by the data.

Improving the stability of coal slurries. Quarterly progress report, March 15-June 15, 1986. [Sedimentation tests in the presence and absence of gum tragacanth

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

Fogler, H.S.

1986-01-01

In this report, we will describe the progress of our research in two key areas. The twin objectives of this research are: (a) to examine the effectiveness of hydrocolloids as stabilizers of coal-water slurries and (b) to gain an understanding of the mechanism of stabilization through the use of monodisperse polystyrene lattices as model systems. Sedimentation tests with ultrafine ground coal in presence and absence of gum tragacanth have been carried out. An isotherm of gum tragacanth binding to coal surface has been generated. We have also conducted rheological studies to characterize the stabilized coal-water slurries. Similar experiments with -200more » mesh coal are currently under way. In the case of model system studies, the effect of article size on the gum tragacanth induced stability has been studied. Initial experiments on the effects of increased electrolyte concentration and the addition of nonsolvents like ethanol to the continuous phase have been undertaken. 9 refs., 16 figs., 1 tab.« less

Third-line therapy in recurrent glioblastoma: is it another chance for bevacizumab?

PubMed

Franceschi, Enrico; Lamberti, Giuseppe; Paccapelo, Alexandro; Di Battista, Monica; Genestreti, Giovenzio; Minichillo, Santino; Mura, Antonella; Bartolini, Stefania; Agati, Raffaele; Brandes, Alba A

2018-04-18

Standard glioblastoma therapy is long-lasting. Among second-line therapy, choices could be bevacizumab and nitrosoureas depending on National Agencies approval. There is no consensus on 3rd line therapy or clinical trials specifically designed for this setting. We reviewed our institutional database on all consecutive patients who received 3rd line therapy for glioblastoma. Data on 168 out of 1337 (12.6%) glioblastoma patients who underwent 3rd line therapy treatment were collected. Third line treatments were bevacizumab or chemotherapy (nitrosourea, temozolomide or carboplatin plus etoposide). Median progression free survival was 2.9 months and median survival time was 6.6 months from the start of 3rd line therapy. Bevacizumab significantly improved progression-free survival (4.7 vs. 2.6 months, p = .020) and survival from 3rd line start (8.0 vs. 6.0 months, p = .014) in respect to chemotherapy. Toxicity of grade ≥ 3 occurred in 13.7% of patients. In multivariate analysis, survival in 3rd line treatment depends on MGMT methylation (p = .006) and treatment with Bevacizumab (p = .011). Third line therapy in selected glioblastoma patients may be feasible and well tolerated. Bevacizumab improved outcome in 3rd line in respect to chemotherapy.

Optimal placement of unified power flow controllers to improve dynamic voltage stability using power system variable based voltage stability indices.

PubMed

Albatsh, Fadi M; Ahmad, Shameem; Mekhilef, Saad; Mokhlis, Hazlie; Hassan, M A

2015-01-01

This study examines a new approach to selecting the locations of unified power flow controllers (UPFCs) in power system networks based on a dynamic analysis of voltage stability. Power system voltage stability indices (VSIs) including the line stability index (LQP), the voltage collapse proximity indicator (VCPI), and the line stability index (Lmn) are employed to identify the most suitable locations in the system for UPFCs. In this study, the locations of the UPFCs are identified by dynamically varying the loads across all of the load buses to represent actual power system conditions. Simulations were conducted in a power system computer-aided design (PSCAD) software using the IEEE 14-bus and 39- bus benchmark power system models. The simulation results demonstrate the effectiveness of the proposed method. When the UPFCs are placed in the locations obtained with the new approach, the voltage stability improves. A comparison of the steady-state VSIs resulting from the UPFCs placed in the locations obtained with the new approach and with particle swarm optimization (PSO) and differential evolution (DE), which are static methods, is presented. In all cases, the UPFC locations given by the proposed approach result in better voltage stability than those obtained with the other approaches.

Optimal Placement of Unified Power Flow Controllers to Improve Dynamic Voltage Stability Using Power System Variable Based Voltage Stability Indices

PubMed Central

Albatsh, Fadi M.; Ahmad, Shameem; Mekhilef, Saad; Mokhlis, Hazlie; Hassan, M. A.

2015-01-01

This study examines a new approach to selecting the locations of unified power flow controllers (UPFCs) in power system networks based on a dynamic analysis of voltage stability. Power system voltage stability indices (VSIs) including the line stability index (LQP), the voltage collapse proximity indicator (VCPI), and the line stability index (Lmn) are employed to identify the most suitable locations in the system for UPFCs. In this study, the locations of the UPFCs are identified by dynamically varying the loads across all of the load buses to represent actual power system conditions. Simulations were conducted in a power system computer-aided design (PSCAD) software using the IEEE 14-bus and 39- bus benchmark power system models. The simulation results demonstrate the effectiveness of the proposed method. When the UPFCs are placed in the locations obtained with the new approach, the voltage stability improves. A comparison of the steady-state VSIs resulting from the UPFCs placed in the locations obtained with the new approach and with particle swarm optimization (PSO) and differential evolution (DE), which are static methods, is presented. In all cases, the UPFC locations given by the proposed approach result in better voltage stability than those obtained with the other approaches. PMID:25874560

Learning curve for the management of tyrosine kinase inhibitors as the first line of treatment for patients with metastatic renal cancer.

PubMed

Lendínez-Cano, G; Osman García, I; Congregado Ruiz, C B; Conde Sánchez, J M; Medina López, R A

2018-03-07

To analyse the learning curve for the management of tyrosine kinase inhibitors as the first line of treatment for patients with metastatic renal cancer. We evaluated 32 consecutive patients treated in our department for metastatic renal cancer with tyrosine kinase inhibitors (pazopanib or sunitinib) as first-line treatment between September 2012 and November 2015. We retrospectively analysed this sample. We measured the time to the withdrawal of the first-line treatment, the time to progression and overall survival using Kaplan-Meier curves. The learning curve was analysed with the cumulative sum (CUSUM) methodology. In our series, the median time to the withdrawal of the first-line treatment was 11 months (95% CI 4.9-17.1). The mean time to progression was 30.4 months (95% CI 22.7-38.1), and the mean overall survival was 34.9 months (95% CI 27.8-42). By applying the CUSUM methodology, we obtained a graph for the CUSUM value of the time to withdrawal of the first-line treatment (CUSUM TW), observing 3 well-differentiated phases: phase 1 or initial learning phase (1-15), phase 2 (16-26) in which the management of the drug progressively improved and phase 3 (27-32) of maximum experience or mastery of the management of these drugs. The number of treated patients needed to achieve the proper management of these patients was estimated at 15. Despite the limitations of the sample size and follow-up time, we estimated (in 15 patients) the number needed to reach the necessary experience in the management of these patients with tyrosine kinase inhibitors. We observed no relationship between the time to the withdrawal of the first-line treatment for any cause and progression. Copyright © 2018 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

[Online endpoint detection algorithm for blending process of Chinese materia medica].

PubMed

Lin, Zhao-Zhou; Yang, Chan; Xu, Bing; Shi, Xin-Yuan; Zhang, Zhi-Qiang; Fu, Jing; Qiao, Yan-Jiang

2017-03-01

Blending process, which is an essential part of the pharmaceutical preparation, has a direct influence on the homogeneity and stability of solid dosage forms. With the official release of Guidance for Industry PAT, online process analysis techniques have been more and more reported in the applications in blending process, but the research on endpoint detection algorithm is still in the initial stage. By progressively increasing the window size of moving block standard deviation (MBSD), a novel endpoint detection algorithm was proposed to extend the plain MBSD from off-line scenario to online scenario and used to determine the endpoint in the blending process of Chinese medicine dispensing granules. By online learning of window size tuning, the status changes of the materials in blending process were reflected in the calculation of standard deviation in a real-time manner. The proposed method was separately tested in the blending processes of dextrin and three other extracts of traditional Chinese medicine. All of the results have shown that as compared with traditional MBSD method, the window size changes according to the proposed MBSD method (progressively increasing the window size) could more clearly reflect the status changes of the materials in blending process, so it is suitable for online application. Copyright© by the Chinese Pharmaceutical Association.

Single stage reduction and stabilization of basilar invagination after failed prior fusion surgery in children with Down's syndrome.

PubMed

Hedequist, Daniel; Bekelis, Kimon; Emans, John; Proctor, Mark R

2010-02-15

We describe an innovative single-stage reduction and stabilization technique using modern cervical instrumentation. We hypothesis modern instrumentation has made more aggressive surgical corrections possible and has reduced the need for transoral resection of the odontoid and traction reduction in children with basilar invagination. Craniocervical junction abnormalities, including atlantoaxial instability and progressive basilar invagination, are relatively common phenomenon in Down's syndrome patients, and can lead to chronic progressive neurologic deficits, catastrophic injury, and death. This patient population also can be a difficult one in which to perform successful stabilization and fusion. We reviewed the records and films on 2 children with Down's syndrome and atlantoaxial instability who had undergone prior occipital-cervical fusion and then presented with symptomatic progressive basilar invagination due to atlantoaxial displacement. In both cases, the children had progressive symptoms of spinal cord and brain stem compression. Multiple approaches for surgical correction, including preoperative traction and transoral odontoid resection, were considered, but ultimately it was elected to perform a single stage posterior operation. In both patients, we performed fusion takedown, intraoperative realignment with reduction of the basilar invagination, and stabilization using modern occipito-cervical instrumentation. In both children, excellent cranio-cervical realignment was achieved; along with successful fusion and improvement in clinical symptoms. In this article we will discuss the clinical cases and review the background of craniocervical junction abnormalities in Down's syndrome patients. We hypothesis modern instrumentation has made more aggressive surgical corrections possible and has reduced the need for transoral resection of the odontoid and traction reduction in children with basilar invagination.

Rapidly progressive Scheuermann's disease in an adolescent after pectus bar placement treated with posterior vertebral-column resection: case report and review of the literature.

PubMed

Sugrue, Patrick A; OʼShaughnessy, Brian A; Blanke, Kathy M; Lenke, Lawrence G

2013-02-15

Case report and review of the literature. This case illustrates the importance of the costosternal complex in maintaining the stability and alignment of the thoracic spine. The patient was iatrogenically destabilized by placement of a pectus bar leading to rapid symptomatic progression of his Scheuermann's kyphosis, ultimately requiring surgical correction. Scheuermann's kyphosis is a disease process defined by strict radiographical and clinical criteria. Surgical treatment is generally recommended for curves greater than 75°. This case demonstrates the critical role of the costosternal complex in maintaining the stability of the thoracic spine. The patient described in this report underwent placement of a pectus bar for correction of symptomatic pectus excavatum. He subsequently developed a progressive symptomatic Scheuermann's kyphosis as a result of the destabilization of his costosternal complex. This patient ultimately required removal of the pectus bar and posterior instrumented kyphosis correction. Progressive symptomatic Scheuermann's kyphosis (105°) corrected by removal of the pectus bar, T11 posterior vertebral-column resection and T4-L3 instrumented posterior spinal fusion. The patient had an uneventful immediate postoperative course. He was discharged neurologically intact with dramatic kyphosis correction and significant symptomatic improvement. Radiographs obtained 3 years postoperatively reveal stable thoracolumbar correction. The costosternal complex plays a critically important role in the intrinsic stability of the thoracic spine. Iatrogenic disruption of the costosternal complex can result in rapid progression of thoracic/thoracolumbar kyphosis in the setting of Scheuermann's disease.

Differential Nanos 2 protein stability results in selective germ cell accumulation in the sea urchin

PubMed Central

Oulhen, Nathalie; Wessel, Gary M.

2016-01-01

Nanos is a translational regulator required for the survival and maintenance of primordial germ cells. In the sea urchin, Strongylocentrotus purpuratus (Sp), Nanos 2 mRNA is broadly transcribed but accumulates specifically in the small micromere (sMic) lineage, in part because of the 3′UTR element GNARLE leads to turnover in somatic cells but retention in the sMics. Here we found that the Nanos 2 protein is also selectively stabilized; it is initially translated throughout the embryo but turned over in the future somatic cells and retained only in the sMics, the future germ line in this animal. This differential stability of Nanos protein is dependent on the open reading frame (ORF), and is independent of the sumoylation and ubiquitylation pathways. Manipulation of the ORF indicates that 68 amino acids in the N terminus of the Nanos protein are essential for its stability in the sMics whereas a 45 amino acid element adjacent to the zinc fingers targets its degradation. Further, this regulation of Nanos protein is cell autonomous, following formation of the germ line. These results are paradigmatic for the unique presence of Nanos in the germ line by a combination of selective RNA retention, distinctive translational control mechanisms (Oulhen et al., 2013), and now also by defined Nanos protein stability. PMID:27424271

Differential Nanos 2 protein stability results in selective germ cell accumulation in the sea urchin.

PubMed

Oulhen, Nathalie; Wessel, Gary M

2016-10-01

Nanos is a translational regulator required for the survival and maintenance of primordial germ cells. In the sea urchin, Strongylocentrotus purpuratus (Sp), Nanos 2 mRNA is broadly transcribed but accumulates specifically in the small micromere (sMic) lineage, in part because of the 3'UTR element GNARLE leads to turnover in somatic cells but retention in the sMics. Here we found that the Nanos 2 protein is also selectively stabilized; it is initially translated throughout the embryo but turned over in the future somatic cells and retained only in the sMics, the future germ line in this animal. This differential stability of Nanos protein is dependent on the open reading frame (ORF), and is independent of the sumoylation and ubiquitylation pathways. Manipulation of the ORF indicates that 68 amino acids in the N terminus of the Nanos protein are essential for its stability in the sMics whereas a 45 amino acid element adjacent to the zinc fingers targets its degradation. Further, this regulation of Nanos protein is cell autonomous, following formation of the germ line. These results are paradigmatic for the unique presence of Nanos in the germ line by a combination of selective RNA retention, distinctive translational control mechanisms (Oulhen et al., 2013), and now also by defined Nanos protein stability. Copyright © 2016 Elsevier Inc. All rights reserved.

Kinetic measures of restabilisation during volitional stepping reveal age-related alterations in the control of mediolateral dynamic stability.

PubMed

Singer, Jonathan C; McIlroy, William E; Prentice, Stephen D

2014-11-07

Research examining age-related changes in dynamic stability during stepping has recognised the importance of the restabilisation phase, subsequent to foot-contact. While regulation of the net ground reaction force (GRFnet) line of action is believed to influence dynamic stability during steady-state locomotion, such control during restabilisation remains unknown. This work explored the origins of age-related decline in mediolateral dynamic stability by examining the line of action of GRFnet relative to the centre of mass (COM) during restabilisation following voluntary stepping. Healthy younger and older adults (n=20 per group) performed three single-step tasks (varying speed and step placement), altering the challenge to stability control. Age-related differences in magnitude and intertrial variability of the angle of divergence of GRFnet line of action relative to the COM were quantified, along with the peak mediolateral and vertical GRFnet components. The angle of divergence was further examined at discrete points during restabilisation, to uncover events of potential importance to stability control. Older adults exhibited a reduced angle of divergence throughout restabilisation. Temporal and spatial constraints on stepping increased the magnitude and intertrial variability of the angle of divergence, although not differentially among the older adults. Analysis of the time-varying angle of divergence revealed age-related reductions in magnitude, with increases in timing and intertrial timing variability during the later phase of restabilisation. This work further supports the idea that age-related challenges in lateral stability control emerge during restabilisation. Age-related alterations during the later phase of restabilisation may signify challenges with reactive control. Copyright © 2014 Elsevier Ltd. All rights reserved.

Design and Synthesis of 2-Heterocyclyl-3-arylthio-1H-indoles as Potent Tubulin Polymerization and Cell Growth Inhibitors with Improved Metabolic Stability

PubMed Central

La Regina, Giuseppe; Bai, Ruoli; Rensen, Willeke; Coluccia, Antonio; Piscitelli, Francesco; Gatti, Valerio; Bolognesi, Alessio; Lavecchia, Antonio; Granata, Ilaria; Porta, Amalia; Maresca, Bruno; Soriani, Alessandra; Iannitto, Maria Luisa; Mariani, Marisa; Santoni, Angela; Brancale, Andrea; Ferlini, Cristiano; Dondio, Giulio; Varasi, Mario; Mercurio, Ciro; Hamel, Ernest; Lavia, Patrizia; Novellino, Ettore; Silvestri, Romano

2011-01-01

New arylthioindoles (ATIs) were obtained by replacing the 2-alkoxycarbonyl group with a bioisosteric 5-membered heterocycle nucleus. The new ATIs 5, 8, and 10 inhibited tubulin polymerization, reduced cell growth of a panel of human transformed cell lines, and showed higher metabolic stability than the reference ester 3. These compounds induced mitotic arrest and apoptosis at a similar level as combretastatin A-4 and vinblastine and triggered caspase-3 expression in a significant fraction of cells in both p53-proficient and p53-defective cell lines. Importantly, ATIs 5, 8, and 10 were more effective than vinorelbine, vinblastine, and paclitaxel as growth inhibitors of the P-glycoprotein-overexpressing cell line NCI/ADR-RES. Compound 5 was shown to have medium metabolic stability in both human and mouse liver microsomes, in contrast to the rapidly degraded reference ester 3, and a pharmacokinetic profile in the mouse characterized by a low systemic clearance and excellent oral bioavailability. PMID:22044164

Tunable Microcavity-Stabilized Quantum Cascade Laser for Mid-IR High-Resolution Spectroscopy and Sensing.

PubMed

Borri, Simone; Siciliani de Cumis, Mario; Insero, Giacomo; Bartalini, Saverio; Cancio Pastor, Pablo; Mazzotti, Davide; Galli, Iacopo; Giusfredi, Giovanni; Santambrogio, Gabriele; Savchenkov, Anatoliy; Eliyahu, Danny; Ilchenko, Vladimir; Akikusa, Naota; Matsko, Andrey; Maleki, Lute; De Natale, Paolo

2016-02-17

The need for highly performing and stable methods for mid-IR molecular sensing and metrology pushes towards the development of more and more compact and robust systems. Among the innovative solutions aimed at answering the need for stable mid-IR references are crystalline microresonators, which have recently shown excellent capabilities for frequency stabilization and linewidth narrowing of quantum cascade lasers with compact setups. In this work, we report on the first system for mid-IR high-resolution spectroscopy based on a quantum cascade laser locked to a CaF₂ microresonator. Electronic locking narrows the laser linewidth by one order of magnitude and guarantees good stability over long timescales, allowing, at the same time, an easy way for finely tuning the laser frequency over the molecular absorption line. Improvements in terms of resolution and frequency stability of the source are demonstrated by direct sub-Doppler recording of a molecular line.

Tunable Microcavity-Stabilized Quantum Cascade Laser for Mid-IR High-Resolution Spectroscopy and Sensing

PubMed Central

Borri, Simone; Siciliani de Cumis, Mario; Insero, Giacomo; Bartalini, Saverio; Cancio Pastor, Pablo; Mazzotti, Davide; Galli, Iacopo; Giusfredi, Giovanni; Santambrogio, Gabriele; Savchenkov, Anatoliy; Eliyahu, Danny; Ilchenko, Vladimir; Akikusa, Naota; Matsko, Andrey; Maleki, Lute; De Natale, Paolo

2016-01-01

The need for highly performing and stable methods for mid-IR molecular sensing and metrology pushes towards the development of more and more compact and robust systems. Among the innovative solutions aimed at answering the need for stable mid-IR references are crystalline microresonators, which have recently shown excellent capabilities for frequency stabilization and linewidth narrowing of quantum cascade lasers with compact setups. In this work, we report on the first system for mid-IR high-resolution spectroscopy based on a quantum cascade laser locked to a CaF2 microresonator. Electronic locking narrows the laser linewidth by one order of magnitude and guarantees good stability over long timescales, allowing, at the same time, an easy way for finely tuning the laser frequency over the molecular absorption line. Improvements in terms of resolution and frequency stability of the source are demonstrated by direct sub-Doppler recording of a molecular line. PMID:26901199

Serum LDH predicts benefit from bevacizumab beyond progression in metastatic colorectal cancer

PubMed Central

Marmorino, Federica; Salvatore, Lisa; Barbara, Cecilia; Allegrini, Giacomo; Antonuzzo, Lorenzo; Masi, Gianluca; Loupakis, Fotios; Borelli, Beatrice; Chiara, Silvana; Banzi, Maria Chiara; Miraglio, Emanuela; Amoroso, Domenico; Dargenio, Francesco; Bonetti, Andrea; Martignetti, Angelo; Paris, Myriam; Tomcikova, Daniela; Boni, Luca; Falcone, Alfredo; Cremolini, Chiara

2017-01-01

Background: Different antiangiogenics are currently indicated in the second-line treatment of metastatic colorectal cancer (mCRC), following a first-line bevacizumab-containing treatment. The magnitude of benefit is limited, but no predictors of benefit have been identified. Methods: A total of 184 mCRC patients progressing to a first-line bevacizumab-containing treatment were randomised in the BEBYP study to continue or not the antiangiogenic in combination with a second-line chemotherapy. A subgroup analysis according to baseline serum lactate dehydrogenase (LDH) levels was carried out. Results: A significant interaction effect between LDH levels and treatment was found in terms of progression-free survival (PFS; P=0.002). Although patients with low LDH levels achieved significant PFS benefit from the continuation of bevacizumab (HR: 0.39 (95% CI: 0.23–0.65)), patients with high levels did not (HR: 1.10 (95% CI: 0.74–1.64)). Consistent results were reported in overall survival (OS; P=0.075). Conclusions: As preclinical evidence suggests that serum LDH may be a marker of tumour angiogenesis activation, low levels may indicate that bevacizumab is still efficacious in inhibiting angiogenesis. Validation of present results in subgroup analyses of other randomised trials of second-line angiogenesis inhibitors is warranted. PMID:28081548

Anti-HER2 Therapy Beyond Second-Line for HER2-Positive Metastatic Breast Cancer: A Short Review and Recommendations for Several Clinical Scenarios from a Spanish Expert Panel

PubMed Central

Martínez-Jañez, Noelia; Chacón, Ignacio; de Juan, Ana; Cruz-Merino, Luis; del Barco, Sònia; Fernández, Isaura; García-Teijido, Paula; Gómez-Bernal, Amalia; Plazaola, Arrate; Ponce, José; Servitja, Sonia; Zamora, Pilar

2016-01-01

Summary Background The aim of this project was to provide an expert opinion regarding anti-human epidermal growth factor receptor 2 (HER2) therapy beyond second-line treatment of metastatic breast cancer (mBC). Methods A group of experts discussed specific issues concerning anti-HER2 therapy in late-line settings in mBC. Results Trastuzumab emtansine (T-DM1) or dual HER2 blockade appeared to be good options for HER2-positive mBC after ≥ 2 HER2-targeted therapies. Once an objective response has been achieved with anti-HER2-containing therapy, the anti-HER2 agent can be continued until progression of the disease, unacceptable toxicity or patient decision. mBC treated with ≥ 3 consecutive lines of anti-HER therapy, ≥ 1 being a dual HER2 blockade and with early progression of disease during a fourth or later-line treatment, are clinically resistant to anti-HER therapy. For progression of metastasis in the brain after anti-HER2 therapy, lapatinib and chemotherapy appear to be a good alternative after best local treatment. Conclusions Further clinical trials are needed to provide valuable knowledge about the best treatment options in the later settings of mBC. PMID:27239176

Thermostability analysis of line-tension-associated nucleation at a gas-liquid interface.

PubMed

Singha, Sanat Kumar; Das, Prasanta Kumar; Maiti, Biswajit

2017-01-01

The influence of line tension on the thermostability of a droplet nucleated from an oversaturated vapor at the interface of the vapor and another immiscible liquid is investigated. Along with the condition of mechanical equilibrium, the notion of extremization of the reversible work of formation is considered to obtain the critical parameters related to heterogeneous nucleation. From the energetic formulation, the critical reversible work of formation is found to be greater than that of homogeneous nucleation for high value of the positive line tension. On the other hand, for high value of the negative line tension, the critical reversible work of formation becomes negative. Therefore, these thermodynamic instabilities under certain substrate wettability situations necessitate a free-energetics-based stability of the nucleated droplet, because the system energy is not minimized under these conditions. This thermostability is analogous to the transition-based stability proposed by Widom [B. Widom, J. Phys. Chem. 99, 2803 (1995)]10.1021/j100009a041 in the case of partial wetting phenomena along with the positive line tension. The thermostability analysis limits the domain of the solution space of the present critical-value problem as the thermodynamic transformation in connection with homogeneous and workless nucleation is considered. Within the stability range of the geometry-based wetting parameters, three limiting modes of nucleation, i.e., total-dewetting-related homogeneous nucleation, and total-wetting-associated and total-submergence-associated workless nucleation scenarios, are identified. Either of the two related limiting wetting scenarios of workless nucleation, namely, total wetting and total submergence, is found to be favorable depending on the geometry-based wetting conditions. The line-tension-associated nucleation on a liquid surface can be differentiated from that on a rigid substrate, as in the former, the stability based on mechanical equilibrium and a typical case of workless nucleation with complete submergence are observed.

The taccalonolides: microtubule stabilizers that circumvent clinically relevant taxane resistance mechanisms.

PubMed

Risinger, April L; Jackson, Evelyn M; Polin, Lisa A; Helms, Gregory L; LeBoeuf, Desiree A; Joe, Patrick A; Hopper-Borge, Elizabeth; Ludueña, Richard F; Kruh, Gary D; Mooberry, Susan L

2008-11-01

The taccalonolides are a class of structurally and mechanistically distinct microtubule-stabilizing agents isolated from Tacca chantrieri. A crucial feature of the taxane family of microtubule stabilizers is their susceptibility to cellular resistance mechanisms including overexpression of P-glycoprotein (Pgp), multidrug resistance protein 7 (MRP7), and the betaIII isotype of tubulin. The ability of four taccalonolides, A, E, B, and N, to circumvent these multidrug resistance mechanisms was studied. Taccalonolides A, E, B, and N were effective in vitro against cell lines that overexpress Pgp and MRP7. In addition, taccalonolides A and E were highly active in vivo against a doxorubicin- and paclitaxel-resistant Pgp-expressing tumor, Mam17/ADR. An isogenic HeLa-derived cell line that expresses the betaIII isotype of tubulin was generated to evaluate the effect of betaIII-tubulin on drug sensitivity. When compared with parental HeLa cells, the betaIII-tubulin-overexpressing cell line was less sensitive to paclitaxel, docetaxel, epothilone B, and vinblastine. In striking contrast, the betaIII-tubulin-overexpressing cell line showed greater sensitivity to all four taccalonolides. These data cumulatively suggest that the taccalonolides have advantages over the taxanes in their ability to circumvent multiple drug resistance mechanisms. The ability of the taccalonolides to overcome clinically relevant mechanisms of drug resistance in vitro and in vivo confirms that the taccalonolides represent a valuable addition to the family of microtubule-stabilizing compounds with clinical potential.

The Long Non-Coding RNA MIR503HG Enhances Proliferation of Human ALK-Negative Anaplastic Large-Cell Lymphoma.

PubMed

Huang, Po-Shuan; Chung, I-Hsiao; Lin, Yang-Hsiang; Lin, Tzu-Kang; Chen, Wei-Jan; Lin, Kwang-Huei

2018-05-14

Anaplastic lymphoma kinase (ALK)-negative anaplastic large-cell lymphoma (ALCL) is a rare type of highly malignant, non-Hodgkin lymphoma. Currently, only a few gene rearrangements have been linked to ALK-negative ALCL progression. However, the specific molecular mechanisms underlying the growth of ALK-negative ALCL tumors remain unclear. Here, we investigated aberrantly expressed, long non-coding RNAs (lncRNAs) in ALK-negative ALCL and assessed their potential biological function. MIR503HG ( miR-503 host gene) was highly expressed in ALK-negative cell lines and was significantly upregulated in tumors in mice formed from ALK-negative ALCL cell lines. Depletion of MIR503HG suppressed tumor cell proliferation in vivo and in vitro; conversely, its overexpression enhanced tumor cell growth. MIR503HG -induced proliferation was mediated by the induction of microRNA-503 ( miR - 503 ) and suppression of Smurf2, resulting in stabilization of the tumor growth factor-β receptor (TGFBR) and enhanced tumor cell growth. Collectively, these findings support a potential role for MIR503HG in cancer cell proliferation through the miR-503 /Smurf2/TGFBR axis and indicate that MIR503HG is a potential marker in ALK-negative ALCL.

APELA promotes tumour growth and cell migration in ovarian cancer in a p53-dependent manner.

PubMed

Yi, Yuyin; Tsai, Shu-Huei; Cheng, Jung-Chien; Wang, Evan Y; Anglesio, Michael S; Cochrane, Dawn R; Fuller, Megan; Gibb, Ewan A; Wei, Wei; Huntsman, David G; Karsan, Aly; Hoodless, Pamela A

2017-12-01

APELA is a small, secreted peptide that can function as a ligand for the G-protein coupled receptor, Apelin Receptor (APLNR, APJ). APELA plays an essential role in endoderm differentiation and cardiac development during embryogenesis. We investigated whether APELA exerts any functions in cancer progression. The Cancer Genome Atlas (TCGA) RNA sequencing datasets, microarray from an OCCC mouse model, and RNA isolated from fresh frozen and FFPE patient tissue were used to assess APELA expression. APELA knockout ovarian clear cell carcinoma (OCCC) cell lines were generated using CRISPR/Cas9. APELA was expressed in various ovarian cancer histotypes and was especially elevated in OCCC. Disruption of APELA expression in OCCC cell lines suppressed cell growth and migration, and altered cell-cycle progression. Moreover, addition of human recombinant APELA peptide to the OCCC cell line OVISE promoted cell growth and migration. Interestingly, OVISE cells do not express APLNR, suggesting that APELA can function through an APLNR-independent pathway. Furthermore, APELA affected cell growth and cell cycle progression in a p53-dependent manner. In addition, APELA knockdown induced p53 expression in cancer cell lines. Our findings uncover a potential oncogenic role for APELA in promoting ovarian tumour progression and provide a possible therapeutic strategy in ovarian cancer by targeting APELA. Copyright © 2017 Elsevier Inc. All rights reserved.

Direct inkjet printing of miniaturized luminescent YAG:Er3+ from sol-gel precursor

NASA Astrophysics Data System (ADS)

Hong, Yuzhe; Chen, Zhaoxi; Trofimov, Artem A.; Lei, Jincheng; Chen, Jie; Yuan, Lei; Zhu, Wenge; Xiao, Hai; Xu, Dong; Jacobsohn, Luiz G.; Kornev, Konstantin G.; Bordia, Rajendra K.; Peng, Fei

2017-06-01

This work focuses on demonstrating the fabrication of miniaturized scintillators based on rare earth activated YAG ceramics using the direct inkjet printing method. Erbium was chosen as the activator, and YAG sol-gel precursor inks were prepared under precise hydrolysis and polycondensation reactions. The precursors showed excellent control over rheology and surface tension, resulting in good printability. One of the most important challenges of inkjet printing of lines is the stability of lines. Line stability during printing is highly dependent on the printing frequency, drop spacing and substrate temperature. When a line was printed drop by drop, bulges were always observed during printing at 25 °C. This instability was significantly suppressed when the substrates were slightly heated. Adding polyvinylpyrrolidone to the precursor helped eliminate pores and cracks during firing. Crack-free YAG lines with ∼200 nm thickness were obtained after firing. The photoluminescence of YAG:Er heat-treated at 1200 °C for 1 h was optimized for an Er concentration of 2 wt%. X-ray induced radioluminescence was dominated by emission lines at 398 and 567 nm.

Continued EGFR-TKI with concurrent radiotherapy to improve time to progression (TTP) in patients with locally progressive non-small cell lung cancer (NSCLC) after front-line EGFR-TKI treatment.

PubMed

Wang, Y; Li, Y; Xia, L; Niu, K; Chen, X; Lu, D; Kong, R; Chen, Z; Sun, J

2018-03-01

Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is the optimal treatment for EGFR-mutant advanced non-small cell lung cancer (NSCLC). However, most patients developed systemic or local progression due to acquired EGFR-TKI resistance. This retrospective study aimed to evaluate the feasibility of continued EGFR-TKI with concurrent radiotherapy (CTCRT) in patients with local progression after front-line EGFR-TKI treatment. Advanced NSCLC patients with active EGFR mutation who received EGFR-TKI were treated with CTCRT after local progression. Medical data were analyzed for time to progression (TTP), progression-free survival (PFS), tumor response rate, overall survival (OS) and adverse events. A total of 50 irradiated lesions from 44 patients were included. Median TTP and PFS of measurable lesions (n = 31) were both significantly prolonged after local radiotherapy (TTP1 + TTP2 vs. TTP1: 21.7 vs. 16.0 months, P = 0.010; PFS1 + PFS2 vs. PFS1: 21.3 vs. 16.0 months, P = 0.027). For all lesions (n = 50), objective response rate (ORR) and local tumor control rate (LCR) were 54.0 and 84.0%, respectively. Median OS was 26.6 months. There were no serious adverse events before or after radiotherapy. The treatment modality of CTCRT is considerable and effective for EGFR-mutant NSCLC patients even with local failure from front-line EGFR-TKI treatment.

Progressive Hearing Loss in Mice Carrying a Mutation in Usp53

PubMed Central

Kazmierczak, Marcin; Harris, Suzan L.; Kazmierczak, Piotr; Shah, Prahar; Starovoytov, Valentin; Ohlemiller, Kevin K.

2015-01-01

Disordered protein ubiquitination has been linked to neurodegenerative disease, yet its role in inner ear homeostasis and hearing loss is essentially unknown. Here we show that progressive hearing loss in the ethylnitrosourea-generated mambo mouse line is caused by a mutation in Usp53, a member of the deubiquitinating enzyme family. USP53 contains a catalytically inactive ubiquitin-specific protease domain and is expressed in cochlear hair cells and a subset of supporting cells. Although hair cell differentiation is unaffected in mambo mice, outer hair cells degenerate rapidly after the first postnatal week. USP53 colocalizes and interacts with the tight junction scaffolding proteins TJP1 and TJP2 in polarized epithelial cells, suggesting that USP53 is part of the tight junction complex. The barrier properties of tight junctions of the stria vascularis appeared intact in a biotin tracer assay, but the endocochlear potential is reduced in adult mambo mice. Hair cell degeneration in mambo mice precedes endocochlear potential decline and is rescued in cochlear organotypic cultures in low potassium milieu, indicating that hair cell loss is triggered by extracellular factors. Remarkably, heterozygous mambo mice show increased susceptibility to noise injury at high frequencies. We conclude that USP53 is a novel tight junction-associated protein that is essential for the survival of auditory hair cells and normal hearing in mice, possibly by modulating the barrier properties and mechanical stability of tight junctions. SIGNIFICANCE STATEMENT Hereditary hearing loss is extremely prevalent in the human population, but many genes linked to hearing loss remain to be discovered. Forward genetics screens in mice have facilitated the identification of genes involved in sensory perception and provided valuable animal models for hearing loss in humans. This involves introducing random mutations in mice, screening the mice for hearing defects, and mapping the causative mutation. Here, we have identified a mutation in the Usp53 gene that causes progressive hearing loss in the mambo mouse line. We demonstrate that USP53 is a catalytically inactive deubiquitinating enzyme and a novel component of tight junctions that is necessary for sensory hair cell survival and inner ear homeostasis. PMID:26609154

Direct Adaptive Aircraft Control Using Dynamic Cell Structure Neural Networks

NASA Technical Reports Server (NTRS)

Jorgensen, Charles C.

1997-01-01

A Dynamic Cell Structure (DCS) Neural Network was developed which learns topology representing networks (TRNS) of F-15 aircraft aerodynamic stability and control derivatives. The network is integrated into a direct adaptive tracking controller. The combination produces a robust adaptive architecture capable of handling multiple accident and off- nominal flight scenarios. This paper describes the DCS network and modifications to the parameter estimation procedure. The work represents one step towards an integrated real-time reconfiguration control architecture for rapid prototyping of new aircraft designs. Performance was evaluated using three off-line benchmarks and on-line nonlinear Virtual Reality simulation. Flight control was evaluated under scenarios including differential stabilator lock, soft sensor failure, control and stability derivative variations, and air turbulence.

Electrochemical oxidation coupled with liquid chromatography and mass spectrometry to study the oxidative stability of active pharmaceutical ingredients in solution: A comparison of off-line and on-line approaches.

PubMed

Torres, Susana; Brown, Roland; Zelesky, Todd; Scrivens, Garry; Szucs, Roman; Hawkins, Joel M; Taylor, Mark R

2016-11-30

Stability studies of pharmaceutical drug products and pharmaceutical active substances are important to research and development in order to fully understand and maintain product quality and safety throughout its shelf-life. Oxidative forced degradation studies are among the different types of stability studies performed by the pharmaceutical industry in order to understand the intrinsic stability of drug molecules. We have been comparing the use of electrochemistry as an alternative oxidative forced degradation method to traditional forced degradation and accelerated stability studies. Using the electrochemical degradation approach the substrate oxidation takes place in a commercially available electrochemical cell and the effluent of the cell can be either a) directly infused into the mass spectrometer or b) injected in a chromatographic column for separation of the different products formed prior to the mass spectrometry analysis. To enable the study of large numbers of different experimental conditions and molecules we developed a new dual pump automated electrochemical screening platform. This system used a HPLC pump and autosampler to load and wash the electrochemical cell and deliver the oxidized sample plug to a second injection loop. This system enabled the automatic sequential analyses of large numbers of different solutions under varied experimental conditions without need for operator intervention during the run sequence. Here we describe the system and evaluate its performance using a test molecule with well characterized stability and compare results to those obtained using an off-line electrochemistry approach. Copyright © 2016 Elsevier B.V. All rights reserved.

Progress toward ultra-stable lasers for use in space

NASA Technical Reports Server (NTRS)

Buoncristiani, A. M.; Sandford, S. P.; Amundsen, R. M.

1992-01-01

This is a summary of a research project that has come to be known as SUNLITE, initially standing for Stanford University - NASA laser in space technology experiment. It involves scientists from the NASA Langley Research Center (LaRC), Stanford University, the National Institute of Standards and Technology (NIST), and the Joint Institute for Laboratory Astrophysics (JILA), and a growing number of other institutions. The long range objective of the SUNLITE effort is to examine the fundamental linewidth and frequency stability limits of an actively stabilized laser oscillator in the microgravity and vibration-free environment of space. The ground-based SUNLITE activities supporting that objective will develop a space-qualified, self-contained and completely automated terahertz oscillator stabilized to a linewidth of less than 3 Hz, along with a measurement system capable of determining laser linewidth to one part in 10(exp 16). The purpose of this paper is to discuss the critical technologies needed to place stabilized lasers in space and to describe the progress made by the SUNLITE project to develop these technologies.

Atom Resonance Lines for Modeling Atmosphere: Studies of Pressure-Broadening of Alkali Atom Resonance Lines for Modeling Atmospheres of Extrasolar Giant Planets and Brown Dwarfs

NASA Technical Reports Server (NTRS)

Hasan, Hashima (Technical Monitor); Kirby, K.; Babb, J.; Yoshino, K.

2005-01-01

We report on progress made in a joint program of theoretical and experimental research to study the line-broadening of alkali atom resonance lines due to collisions with species such as helium and molecular hydrogen. Accurate knowledge of the line profiles of Na and K as a function of temperature and pressure will allow such lines to serve as valuable diagnostics of the atmospheres of brown dwarfs and extra-solar giant planets. A new experimental apparatus has been designed, built and tested over the past year, and we are poised to begin collecting data on the first system of interest, the potassium resonance lines perturbed by collisions with helium. On the theoretical front, calculations of line-broadening due to sodium collisions with helium are nearly complete, using accurate molecular potential energy curves and transition moments just recently computed for this system. In addition we have completed calculations of the three relevant potential energy curves and associated transition moments for K - He, using the MOLPRO quantum chemistry codes. Currently, calculations of the potential surfaces describing K-H2 are in progress.

Processed pseudogenes of human endogenous retroviruses generated by LINEs: their integration, stability, and distribution.

PubMed

Pavlícek, Adam; Paces, Jan; Elleder, Daniel; Hejnar, Jirí

2002-03-01

We report here the presence of numerous processed pseudogenes derived from the W family of endogenous retroviruses in the human genome. These pseudogenes are structurally colinear with the retroviral mRNA followed by a poly(A) tail. Our analysis of insertion sites of HERV-W processed pseudogenes shows a strong preference for the insertion motif of long interspersed nuclear element (LINE) retrotransposons. The genomic distribution, stability during evolution, and frequent truncations at the 5' end resemble those of the pseudogenes generated by LINEs. We therefore suggest that HERV-W processed pseudogenes arose by multiple and independent LINE-mediated retrotransposition of retroviral mRNA. These data document that the majority of HERV-W copies are actually nontranscribed promoterless pseudogenes. The current search for HERV-Ws associated with several human diseases should concentrate on a small subset of transcriptionally competent elements.

Employing static excitation control and tie line reactance to stabilize wind turbine generators

NASA Technical Reports Server (NTRS)

Hwang, H. H.; Mozeico, H. V.; Guo, T.

1978-01-01

An analytical representation of a wind turbine generator is presented which employs blade pitch angle feedback control. A mathematical model was formulated. With the functioning MOD-0 wind turbine serving as a practical case study, results of computer simulations of the model as applied to the problem of dynamic stability at rated load are also presented. The effect of the tower shadow was included in the input to the system. Different configurations of the drive train, and optimal values of the tie line reactance were used in the simulations. Computer results revealed that a static excitation control system coupled with optimal values of the tie line reactance would effectively reduce oscillations of the power output, without the use of a slip clutch.

Wavelength locking of CW and Q-switched Er(3+) microchip lasers to acetylene absorption lines using pump-power modulation.

PubMed

Brunel, Marc; Vallet, Marc

2007-02-19

We show that modulating the diode-pump power of a microchip solid-state laser enables to lock its wavelength to a reference molecular line. The method is applied to two different types of Er,Yb:glass monolithic microchip lasers operating at 1.53 microm. First, wavelength locking of a continuous-wave dual-polarization microchip laser to acetylene absorption lines is demonstrated, without using any additional modulator, internal or external. We then show that, remarkably, this simple method is also suitable for stabilizing a passively Q-switched microchip laser. A pulsed wavelength stability of 10(-8) over 1 hour is readily observed. Applications to lidars and to microwave photonics are discussed.

Habitable Exoplanet Imager Optical-Mechanical Design and Analysis

NASA Technical Reports Server (NTRS)

Gaskins, Jonathan; Stahl, H. Philip

2017-01-01

The Habitable Exoplanet Imager (HabEx) is a space telescope currently in development whose mission includes finding and spectroscopically characterizing exoplanets. Effective high-contrast imaging requires tight stability requirements of the mirrors to prevent issues such as line of sight and wavefront errors. PATRAN and NASTRAN were used to model updates in the design of the HabEx telescope and find how those updates affected stability. Most of the structural modifications increased first mode frequencies and improved line of sight errors. These studies will be used to help define the baseline HabEx telescope design.

Possible stabilization of the frequency of a CO/sub 2/ laser using an external Stark cell containing 1-1 difluoroethane

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

Avtonomov, V.P.; Alexandrescu, R.; Dumitras, D.

1979-02-01

Results are presented of measurements of the Stark modulation index and absorption coefficient of CO/sub 2/ laser radiation due to the P (24) line by 1-1 difluorethane (C/sub 2/H/sub 4/F/sub 2/). The possibility of stabilizing the CO/sub 2/ laser frequency using a Stark cell is demonstrated and the laser frequency tuning efficiency within the P (24) line of the 00/sup 0/1--10/sup 0/0 transition is determined.

Co-simulation of heavy truck tire dynamics and electronic stability control systems (phase B).

DOT National Transportation Integrated Search

2010-07-01

In the past decade, electronic stability controls (ESC) have become increasingly common on vehicles operating in the United States. The acceptance of this technology has progressed to the point where all new passenger vehicles sold in the US are requ...

Determination of the elastic modulus of fly ash-based stabilizer applied in the trackbed

NASA Astrophysics Data System (ADS)

Lojda, Vít; Lidmila, Martin; Pýcha, Marek

2017-09-01

This paper describes a unique application of a fly ash-based stabilizer in the trackbed of a railway main line. The key goals of the stabilizer application are to protect the subgrade against the ingress of rain water, to increase the frost resistance and to remediate the natural ground constituted of weathered rock. The stabilizer was designed as a mixture of fly ash, generated as a waste material from coal plants, gypsum, calcium oxide and water. The mixture recipe was developed in a laboratory over several years. In 2005, a trial section of a railway line with subgrade consisting of clay limestone (weathered marlite) was built in the municipality of Smiřice. Since then, periodical measurements including collection of samples for laboratory evaluation of the fly ash-based stabilizer have taken place. Over the time span of the measurements, changes in mineral composition and development of fly ash transforming structures leading to the formation of C-A-S-H gel were detected. This paper describes the experimental laboratory investigation of the influence of dynamic loading on the elastic modulus of fly ash stabilizer samples and the development of permanent deformation of the samples with increasing number of loading cycles.

The stability of colorectal cancer mathematical models

NASA Astrophysics Data System (ADS)

Khairudin, Nur Izzati; Abdullah, Farah Aini

2013-04-01

Colorectal cancer is one of the most common types of cancer. To better understand about the kinetics of cancer growth, mathematical models are used to provide insight into the progression of this natural process which enables physicians and oncologists to determine optimal radiation and chemotherapy schedules and develop a prognosis, both of which are indispensable for treating cancer. This thesis investigates the stability of colorectal cancer mathematical models. We found that continuous saturating feedback is the best available model of colorectal cancer growth. We also performed stability analysis. The result shows that cancer progress in sequence of genetic mutations or epigenetic which lead to a very large number of cells population until become unbounded. The cell population growth initiate and its saturating feedback is overcome when mutation changes causing the net per-capita growth rate of stem or transit cells exceed critical threshold.

[Genetic improvement of cotton varieties in Huang-Huai region in China since 1950's. III. Improvement on agronomy properties, disease resistance and stability].

PubMed

Jiang, B G; Kong, F L; Zhang, Q Y; Yang, F X; Jiang, R Q

2000-01-01

Data from a set of 5-location and 2-year experiments on 10 representative historical cotton varieties and the data of Huang-Huai Regional Cotton Trials from 1973 to 1996 were analyzed to estimate the effects of genetic improvement in agronomy properties, disease resistance and stability of cotton in Huang-Huai Region in China. The results indicated that a great genetic progress of earliness and disease resistance had been achieved by breeding programs since 1950's. The maturity was shortened 3-5 days; The rate of preforst yield was increased about 7 percentages. The problem of resistance to Fususium wilt has been solved and the resistance to Verticillum wilt was improving. Some progress in stability of cotton varieties also has been achieved by breeding programs since 1950.

High beta and second stability region transport and stability analysis. Final report

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

Hughes, M.H.; Phillips, M.W.

1996-01-01

This report describes MHD equilibrium and stability studies carried out at Northrop Grumman`s Advanced Technology and Development Center during the period March 1 to December 31, 1995. Significant progress is reported in both ideal and resistive MHD modeling of TFTR plasmas. Specifically, attention is concentrated on analysis of Advanced Tokamak experiments at TFTR involving plasmas in which the q-profiles were non-monotonic.

[RESEARCH PROGRESS OF BIOMECHANICS OF PROXIMAL ROW CARPAL INSTABILITY].

PubMed

Guo, Jinhai; Huang, Fuguo

2015-01-01

To review the research progress of the biomechanics of proximal row carpal instability (IPRC). The related literature concerning IPRC was extensively reviewed. The biomechanical mechanism of the surrounding soft tissue in maintaining the stability of the proximal row carpal (PRC) was analyzed, and the methods to repair or reconstruct the stability and function of the PRC were summarized from two aspects including basic biomechanics and clinical biomechanics. The muscles and ligaments of the PRC are critical to its stability. Most scholars have reached a consensus about biomechanical mechanism of the PRC, but there are still controversial conclusions on the biomechanics mechanism of the surrounding soft tissue to stability of distal radioulnar joint when the triangular fibrocartilage complex are damaged and the biomechanics mechanism of the scapholunate ligament. At present, there is no unified standard about the methods to repair or reconstruct the stability and function of the PRC. So, it is difficult for clinical practice. Some strides have been made in the basic biomechanical study on muscle and ligament and clinical biomechanical study on the methods to repair or reconstruct the stability and function of PRC, but it will be needed to further study the morphology of carpal articular surface and the adjacent articular surface, the pressure of distal carpals to proximal carpal and so on.

Complete intracranial response to talimogene laherparepvec (T-Vec), pembrolizumab and whole brain radiotherapy in a patient with melanoma brain metastases refractory to dual checkpoint-inhibition.

PubMed

Blake, Zoë; Marks, Douglas K; Gartrell, Robyn D; Hart, Thomas; Horton, Patti; Cheng, Simon K; Taback, Bret; Horst, Basil A; Saenger, Yvonne M

2018-04-06

Immunotherapy, in particular checkpoint blockade, has changed the clinical landscape of metastatic melanoma. Nonetheless, the majority of patients will either be primary refractory or progress over follow up. Management of patients progressing on first-line immunotherapy remains challenging. Expanded treatment options with combination immunotherapy has demonstrated efficacy in patients previously unresponsive to single agent or alternative combination therapy. We describe the case of a patient with diffusely metastatic melanoma, including brain metastases, who, despite being treated with stereotactic radiosurgery and dual CTLA-4/PD-1 blockade (ipilimumab/nivolumab), developed systemic disease progression and innumerable brain metastases. This patient achieved a complete CNS response and partial systemic response with standard whole brain radiation therapy (WBRT) combined with Talimogene laherparepvec (T-Vec) and pembrolizumab. Patients who do not respond to one immunotherapy combination may respond during treatment with an alternate combination, even in the presence of multiple brain metastases. Biomarkers are needed to assist clinicians in evidence based clinical decision making after progression on first line immunotherapy to determine whether response can be achieved with second line immunotherapy.

Effects of Goal Line Feedback on Level, Slope, and Stability of Performance within Curriculum-Based Measurement.

ERIC Educational Resources Information Center

Fuchs, Lynn S.; And Others

1991-01-01

Nineteen special educators implemented Curriculum-Based Measurement with a total of 36 learning-disabled math pupils in grades 2-8 to examine the effects of goal line feedback. Results indicated comparable levels and slopes of student performance across treatment conditions, although goal line feedback was associated with greater performance…

Structural Stabilities of β-Ti Alloys Studied Using a New Mo Equivalent Derived from [ β/( α + β)] Phase-Boundary Slopes

NASA Astrophysics Data System (ADS)

Wang, Qing; Dong, Chuang; Liaw, Peter K.

2015-08-01

Structural stabilities of β-Ti alloys are generally investigated by an empirical Mo equivalent, which quantifies the stability contribution of each alloying element, M, in comparison to that of the major β-Ti stabilizer, Mo. In the present work, a new Mo equivalent (Moeq)Q is proposed, which uses the slopes of the boundary lines between the β and ( α + β) phase zones in binary Ti-M phase diagrams. This (Moeq)Q reflects a simple fact that the β-Ti stability is enhanced, when the β phase zone is enlarged by a β-Ti stabilizer. It is expressed as (Moeq)Q = 1.0 Mo + 0.74 V + 1.01 W + 0.23 Nb + 0.30 Ta + 1.23 Fe + 1.10 Cr + 1.09 Cu + 1.67 Ni + 1.81 Co + 1.42 Mn + 0.38 Sn + 0.34 Zr + 0.99 Si - 0.57 Al (at. pct), where the equivalent coefficient of each element is the slope ratio of the [ β/( α + β)] boundary line of the binary Ti-M phase diagram to that of the Ti-Mo. This (Moeq)Q is shown to reliably characterize the critical stability limit of multi-component β-Ti alloys with low Young's moduli, where the critical lower limit for β stabilization is (Moeq)Q = 6.25 at. pct or 11.8 wt pct Mo.

Nanobubbles in confined solution: Generation, contact angle, and stability.

PubMed

Wei, Jiachen; Zhang, Xianren; Song, Fan; Shao, Yingfeng

2018-02-14

The formation of gas bubbles presents a frequent challenge to microfluidic operations, for which fluids are geometrically confined to a microscale space. Here, to understand the mechanism of nucleating gas bubbles in microfluidic devices, we investigate the formation and stability of nanobubbles in confined solutions. Our molecular dynamics simulations show that while pinning of the contact line is a prerequisite for the stability of surface nanobubbles in open systems that can exchange gas with surrounding environment, in confined solutions, stable nanobubbles can exist even without pinning. In supersaturated condition, stable bubbles can be found in confined solutions with acute or obtuse contact angle, depending on the substrate hydrophobicity. We also demonstrate that when open to the bulk solution, the stable nanobubbles in closed systems would become unstable unless both supersaturation and pinning of the contact line are satisfied. Our results not only shed light on the design of novel heterogeneous surfaces for generating nanobubbles in confined space with controllable shape and stability but also address the crucial effect of gas exchange with the surroundings in determining the stability of nanobubbles.

Nanobubbles in confined solution: Generation, contact angle, and stability

NASA Astrophysics Data System (ADS)

Wei, Jiachen; Zhang, Xianren; Song, Fan; Shao, Yingfeng

2018-02-01

The formation of gas bubbles presents a frequent challenge to microfluidic operations, for which fluids are geometrically confined to a microscale space. Here, to understand the mechanism of nucleating gas bubbles in microfluidic devices, we investigate the formation and stability of nanobubbles in confined solutions. Our molecular dynamics simulations show that while pinning of the contact line is a prerequisite for the stability of surface nanobubbles in open systems that can exchange gas with surrounding environment, in confined solutions, stable nanobubbles can exist even without pinning. In supersaturated condition, stable bubbles can be found in confined solutions with acute or obtuse contact angle, depending on the substrate hydrophobicity. We also demonstrate that when open to the bulk solution, the stable nanobubbles in closed systems would become unstable unless both supersaturation and pinning of the contact line are satisfied. Our results not only shed light on the design of novel heterogeneous surfaces for generating nanobubbles in confined space with controllable shape and stability but also address the crucial effect of gas exchange with the surroundings in determining the stability of nanobubbles.

Absolute Transition Probabilities of Lines in the Spectra of Astrophysical Atoms, Molecules, and Ions

NASA Technical Reports Server (NTRS)

Parkinson, W. H.; Smith, P. L.; Yoshino, K.

1984-01-01

Progress in the investigation of absolute transition probabilities (A-values or F values) for ultraviolet lines is reported. A radio frequency ion trap was used for measurement of transition probabilities for intersystem lines seen in astronomical spectra. The intersystem line at 2670 A in Al II, which is seen in pre-main sequence stars and symbiotic stars, was studied.

33 CFR 157.21 - Subdivision and stability.

Code of Federal Regulations, 2014 CFR

2014-07-01

.... vessel must meet the following subdivision and damage stability criteria after assuming side and bottom damages, as defined in appendix B of this part. A U.S. vessel that meets the requirements in this section... account sinkage, heel, and trim, must be below the lower edge of an opening through which progressive...

33 CFR 157.21 - Subdivision and stability.

Code of Federal Regulations, 2012 CFR

2012-07-01

.... vessel must meet the following subdivision and damage stability criteria after assuming side and bottom damages, as defined in appendix B of this part. A U.S. vessel that meets the requirements in this section... account sinkage, heel, and trim, must be below the lower edge of an opening through which progressive...

33 CFR 157.21 - Subdivision and stability.

Code of Federal Regulations, 2013 CFR

2013-07-01

.... vessel must meet the following subdivision and damage stability criteria after assuming side and bottom damages, as defined in appendix B of this part. A U.S. vessel that meets the requirements in this section... account sinkage, heel, and trim, must be below the lower edge of an opening through which progressive...

Identification of differentially expressed proteins during human urinary bladder cancer progression.

PubMed

Memon, Ashfaque A; Chang, Jong W; Oh, Bong R; Yoo, Yung J

2005-01-01

Comparative proteome analysis was performed between RT4 (grade-1) and T24 (grade-3) bladder cancer cell lines, in an attempt to identify differentially expressed proteins during bladder cancer progression. Among those relatively abundant proteins, seven spots changed more than two-fold reproducibly and identified by peptide mass fingerprinting using mass spectrometry and database search. We found most extensive and reproducible down-regulation of NADP dependent isocitrate dehydrogenase cytoplasmic (IDPc) and peroxiredoxin-II (Prx-II), in poorly differentiated T24 compared to well-differentiated RT4 bladder cancer cell line. Subsequent Western blotting analysis of human biopsy samples from bladder cancer patient revealed significant loss of IDPc and Prx-II in more advance tumor samples, in agreement with data on cell lines. These results suggest that loss of IDPc and Prx-II during tumor development may involve in tumor progression and metastasis. However, additional investigations are needed on large number of human samples to further verify these findings.

Caffeine stabilizes Cdc25 independently of Rad3 in S chizosaccharomyces pombe contributing to checkpoint override

PubMed Central

Alao, John P; Sjölander, Johanna J; Baar, Juliane; Özbaki-Yagan, Nejla; Kakoschky, Bianca; Sunnerhagen, Per

2014-01-01

Cdc25 is required for Cdc2 dephosphorylation and is thus essential for cell cycle progression. Checkpoint activation requires dual inhibition of Cdc25 and Cdc2 in a Rad3-dependent manner. Caffeine is believed to override activation of the replication and DNA damage checkpoints by inhibiting Rad3-related proteins in both S chizosaccharomyces pombe and mammalian cells. In this study, we have investigated the impact of caffeine on Cdc25 stability, cell cycle progression and checkpoint override. Caffeine induced Cdc25 accumulation in S . pombe independently of Rad3. Caffeine delayed cell cycle progression under normal conditions but advanced mitosis in cells treated with replication inhibitors and DNA-damaging agents. In the absence of Cdc25, caffeine inhibited cell cycle progression even in the presence of hydroxyurea or phleomycin. Caffeine induces Cdc25 accumulation in S . pombe by suppressing its degradation independently of Rad3. The induction of Cdc25 accumulation was not associated with accelerated progression through mitosis, but rather with delayed progression through cytokinesis. Caffeine-induced Cdc25 accumulation appears to underlie its ability to override cell cycle checkpoints. The impact of Cdc25 accumulation on cell cycle progression is attenuated by Srk1 and Mad2. Together our findings suggest that caffeine overrides checkpoint enforcement by inducing the inappropriate nuclear localization of Cdc25. PMID:24666325

Detection of Prostate Cancer Progression by Serum DNA Integrity

DTIC Science & Technology

2010-04-01

qRT) Alu and direct qRT LINE1 is being optimized. We will also continue to develop circulating DNA methylated GSTP1 assay to complement the DNA...developed the LINE1 assay, assembled the manuscript on uLINE1, and performed preliminary analysis of circulating DNA GSTP1 methylation. The goal is to

Patterns in longitudinal growth of refraction in Southern Chinese children: cluster and principal component analysis.

PubMed

Chen, Yanxian; Chang, Billy Heung Wing; Ding, Xiaohu; He, Mingguang

2016-11-22

In the present study we attempt to use hypothesis-independent analysis in investigating the patterns in refraction growth in Chinese children, and to explore the possible risk factors affecting the different components of progression, as defined by Principal Component Analysis (PCA). A total of 637 first-born twins in Guangzhou Twin Eye Study with 6-year annual visits (baseline age 7-15 years) were available in the analysis. Cluster 1 to 3 were classified after a partitioning clustering, representing stable, slow and fast progressing groups of refraction respectively. Baseline age and refraction, paternal refraction, maternal refraction and proportion of two myopic parents showed significant differences across the three groups. Three major components of progression were extracted using PCA: "Average refraction", "Acceleration" and the combination of "Myopia stabilization" and "Late onset of refraction progress". In regression models, younger children with more severe myopia were associated with larger "Acceleration". The risk factors of "Acceleration" included change of height and weight, near work, and parental myopia, while female gender, change of height and weight were associated with "Stabilization", and increased outdoor time was related to "Late onset of refraction progress". We therefore concluded that genetic and environmental risk factors have different impacts on patterns of refraction progression.

Delayed Cell Cycle Progression and Apoptosis Induced by Hemicellulase-Treated Agaricus blazei

PubMed Central

Kasai, Hirotake

2007-01-01

We examined the effects of hemicellulase-treated Agaricus blazei (AB fraction H, ABH) on growth of several tumor cell lines. ABH inhibited the proliferation of some cell lines without cytotoxic effects. It markedly prolonged the S phase of the cell cycle. ABH also induced mitochondria-mediated apoptosis in different cell lines. However, it had no impact on the growth of other cell lines. ABH induced strong activation of p38 mitogen-activated protein kinase (MAPK) in the cells in which it evoked apoptosis. On the other hand, ABH showed only a weak p38 activation effect in those cell lines in which it delayed cell cycle progression with little induction of apoptosis. However, p38 MAPK-specific inhibitor inhibited both ABH-induced effects, and ABH also caused apoptosis in the latter cells under conditions of high p38 MAPK activity induced by combined treatment with TNF-α. These results indicate that the responsiveness of p38 MAPK to ABH, which differs between cell lines, determines subsequent cellular responses on cell growth. PMID:17342245

Combined line-of-sight error and angular position to generate feedforward control for a charge-coupled device-based tracking loop

NASA Astrophysics Data System (ADS)

Tang, Tao; Cai, Huaxiang; Huang, Yongmei; Ren, Ge

2015-10-01

A feedforward control based on data fusion is proposed to enhance closed-loop performance. The target trajectory as the observed value of a Kalman filter is recovered by synthesizing line-of-sight error and angular position from the encoder. A Kalman filter based on a Singer acceleration model is employed to estimate the target velocity. In this control scheme, the control stability is influenced by the bandwidth of the Kalman filter and time misalignment. The transfer function of the Kalman filter in the frequency domain is built for analyzing the closed loop stability, which shows that the Kalman filter is the major factor that affects the control stability. The feedforward control proposed here is verified through simulations and experiments.

Optimal line drop compensation parameters under multi-operating conditions

NASA Astrophysics Data System (ADS)

Wan, Yuan; Li, Hang; Wang, Kai; He, Zhe

2017-01-01

Line Drop Compensation (LDC) is a main function of Reactive Current Compensation (RCC) which is developed to improve voltage stability. While LDC has benefit to voltage, it may deteriorate the small-disturbance rotor angle stability of power system. In present paper, an intelligent algorithm which is combined by Genetic Algorithm (GA) and Backpropagation Neural Network (BPNN) is proposed to optimize parameters of LDC. The objective function proposed in present paper takes consideration of voltage deviation and power system oscillation minimal damping ratio under multi-operating conditions. A simulation based on middle area of Jiangxi province power system is used to demonstrate the intelligent algorithm. The optimization result shows that coordinate optimized parameters can meet the multioperating conditions requirement and improve voltage stability as much as possible while guaranteeing enough damping ratio.

Line-Tension Controlled Mechanism for Influenza Fusion

PubMed Central

Risselada, Herre Jelger; Smirnova, Yuliya G.; Grubmüller, Helmut; Marrink, Siewert Jan; Müller, Marcus

2012-01-01

Our molecular simulations reveal that wild-type influenza fusion peptides are able to stabilize a highly fusogenic pre-fusion structure, i.e. a peptide bundle formed by four or more trans-membrane arranged fusion peptides. We rationalize that the lipid rim around such bundle has a non-vanishing rim energy (line-tension), which is essential to (i) stabilize the initial contact point between the fusing bilayers, i.e. the stalk, and (ii) drive its subsequent evolution. Such line-tension controlled fusion event does not proceed along the hypothesized standard stalk-hemifusion pathway. In modeled influenza fusion, single point mutations in the influenza fusion peptide either completely inhibit fusion (mutants G1V and W14A) or, intriguingly, specifically arrest fusion at a hemifusion state (mutant G1S). Our simulations demonstrate that, within a line-tension controlled fusion mechanism, these known point mutations either completely inhibit fusion by impairing the peptide’s ability to stabilize the required peptide bundle (G1V and W14A) or stabilize a persistent bundle that leads to a kinetically trapped hemifusion state (G1S). In addition, our results further suggest that the recently discovered leaky fusion mutant G13A, which is known to facilitate a pronounced leakage of the target membrane prior to lipid mixing, reduces the membrane integrity by forming a ‘super’ bundle. Our simulations offer a new interpretation for a number of experimentally observed features of the fusion reaction mediated by the prototypical fusion protein, influenza hemagglutinin, and might bring new insights into mechanisms of other viral fusion reactions. PMID:22761674

Efficacy of Capecitabine Plus Oxaliplatin Combination Chemotherapy for Advanced Pancreatic Cancer after Failure of First-Line Gemcitabine-Based Therapy.

PubMed

Chung, Kwang Hyun; Ryu, Ji Kon; Son, Jun Hyuk; Lee, Jae Woo; Jang, Dong Kee; Lee, Sang Hyub; Kim, Yong-Tae

2017-03-15

Second-line chemotherapy in patients with advanced pancreatic ductal adenocarcinoma (PDAC) that progresses following gemcitabine-based treatment has not been established. This study aimed to investigate the efficacy and safety of second-line combination chemotherapy with capecitabine and oxaliplatin (XELOX) in these patients. Between August 2011 and May 2014, all patients who received at least one cycle of XELOX (capecitabine, 1,000 mg/m 2 twice daily for 14 days; oxaliplatin, 130 mg/m 2 on day 1 of a 3-week cycle) combination chemotherapy for unresectable or recurrent PDAC were retrospectively recruited. The response was evaluated every 9 weeks, and the tumor response rate, progression-free survival and overall survival, and adverse events were assessed. Sixty-two patients were included; seven patients (11.3%) had a partial tumor response, and 20 patients (32.3%) had stable disease. The median progression-free and overall survival were 88 days (range, 35.1 to 140.9 days) and 158 days (range, 118.1 to 197.9 days), respectively. Patients who remained stable longer with frontline therapy (≥120 days) exhibited significantly longer progression-free and overall survival. The most common grade 3 to 4 adverse events in patients were vomiting (8.1%) and anorexia (6.5%). There was one treatment-related mortality caused by severe neutropenia and typhlitis. Second-line XELOX combination chemotherapy demonstrated an acceptable response and survival rate in patients with advanced PDAC who had failed gemcitabine-based chemotherapy.

Rock mechanics. Practical use in civil engineering

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

Murakami, S.

1985-01-01

Because of the recent development of computer technology, a systematic analysis of the stability and behavior of rock is gradually progressing as rock mechanics. Although its progress is still behind that of engineering geology, the book aims to contribute to the systematization of the subject. Examples of design are given.

Nuclear waste management. Semiannual progress report, October 1982-March 1983

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

Chikalla, T.D.; Powell, J.A.

1983-06-01

This document is one of a series of technical progress reports designed to report radioactive waste management programs at the Pacific Northwest Laboratory. Accomplishments in the following programs are reported: waste stabilization; Materials Characterization Center; waste isolation; low-level waste management; remedial action; and supporting studies.

46 CFR 174.207 - Damaged stability criteria.

Code of Federal Regulations, 2013 CFR

2013-10-01

...) Permeability of spaces. The permeability of a floodable space must be as specified by Table 174.207(b) of this...) Equipped with arrangements, such as stop check-valves, to prevent progressive flooding of the spaces with... permit progressive flooding of the spaces with which they connect. (d) Buoyancy of superstructure. For...

46 CFR 174.207 - Damaged stability criteria.

Code of Federal Regulations, 2010 CFR

2010-10-01

...) Permeability of spaces. The permeability of a floodable space must be as specified by Table 174.207(b) of this...) Equipped with arrangements, such as stop check-valves, to prevent progressive flooding of the spaces with... permit progressive flooding of the spaces with which they connect. (d) Buoyancy of superstructure. For...

46 CFR 174.207 - Damaged stability criteria.

Code of Federal Regulations, 2014 CFR

2014-10-01

...) Permeability of spaces. The permeability of a floodable space must be as specified by Table 174.207(b) of this...) Equipped with arrangements, such as stop check-valves, to prevent progressive flooding of the spaces with... permit progressive flooding of the spaces with which they connect. (d) Buoyancy of superstructure. For...

46 CFR 174.207 - Damaged stability criteria.

Code of Federal Regulations, 2012 CFR

2012-10-01

...) Permeability of spaces. The permeability of a floodable space must be as specified by Table 174.207(b) of this...) Equipped with arrangements, such as stop check-valves, to prevent progressive flooding of the spaces with... permit progressive flooding of the spaces with which they connect. (d) Buoyancy of superstructure. For...

Evaluation of conditions along the grounding line of temperate marine glaciers: An example from Muir Inlet, Glacier Bay, Alaska

USGS Publications Warehouse

Seramur, K.C.; Powell, R.D.; Carlson, P.R.

1997-01-01

In the marine environment, stability of the glacier terminus and the location of subglacial streams are the dominant controls on the distribution of grounding-line deposits within morainal banks. A morainal bank complex in Muir Inlet, Glacier Bay, SE Alaska, is used to develop a model of terminus stability and location of subglacial streams along the grounding line of temperate marine glaciers. This model can be used to interpret former grounding-line conditions in other glacimarine settings from the facies architecture within morainal bank deposits. The Muir Inlet morainal bank complex was deposited between 1860 A.D. and 1899 A.D., and historical observations provide a record of terminus positions, glacial retreat rates and sedimentary sources. These data are used to reconstruct the depositional environment and to develop a correlation between sedimentary facies and conditions along the grounding line. Four seismic facies identified on the high-resolution seismic-reflection profiles are used to interpret sedimentary facies within the morainal bank complex. Terminus stability is interpreted from the distribution of sedimentary facies within three distinct submarine geomorphic features, a grounding-line fan; stratified ridges, and a field of push ridges. The grounding-line fan was deposited along a stable terminus and is represented on seismic-reflection profiles by two distinct seismic facies, a proximal and a distal fan facies. The proximal fan facies was deposited at the efflux of subglacial streams and indicates the location of former glacifluvial discharges into the sea. Stratified ridges formed as a result of the influence of a quasi-stable terminus on the distribution of sedimentary facies along the grounding line. A field of push ridges formed along the grounding line of an unstable terminus that completely reworked the grounding-line deposits through glacitectonic deformation. Between 1860 A.D. and 1899 A.D. (39 years), 8.96 x 108 m3 of sediment were deposited within the Muir Inlet morainal bank complex at an average annual sediment accumulation rate of 2.3 x 107 m3/a. This rate represents the annual sediment production capacity of the glacier when the Muir Inlet drainage basin is filled with glacial ice.

In line monitoring of the preparation of water-in-oil-in-water (W/O/W) type multiple emulsions via dielectric spectroscopy.

PubMed

Beer, Sebastian; Dobler, Dorota; Gross, Alexander; Ost, Martin; Elseberg, Christiane; Maeder, Ulf; Schmidts, Thomas Michael; Keusgen, Michael; Fiebich, Martin; Runkel, Frank

2013-01-30

Multiple emulsions offer various applications in a wide range of fields such as pharmaceutical, cosmetics and food technology. Two features are known to yield a great influence on multiple emulsion quality and utility as encapsulation efficiency and prolonged stability. To achieve a prolonged stability, the production of the emulsions has to be observed and controlled, preferably in line. In line measurements provide available parameters in a short time frame without the need for the sample to be removed from the process stream, thereby enabling continuous process control. In this study, information about the physical state of multiple emulsions obtained from dielectric spectroscopy (DS) is evaluated for this purpose. Results from dielectric measurements performed in line during the production cycle are compared to theoretically expected results and to well established off line measurements. Thus, a first step to include the production of multiple emulsions into the process analytical technology (PAT) guidelines of the Food and Drug Administration (FDA) is achieved. DS proved to be beneficial in determining the crucial stopping criterion, which is essential in the production of multiple emulsions. The stopping of the process at a less-than-ideal point can severely lower the encapsulation efficiency and the stability, thereby lowering the quality of the emulsion. DS is also expected to provide further information about the multiple emulsion like encapsulation efficiency. Copyright © 2012 Elsevier B.V. All rights reserved.

Level densities of residual nuclei from the reactions ^6Li on ^58Fe and ^7Li on ^57Fe

NASA Astrophysics Data System (ADS)

Oginni, Babatunde; Grimes, Steven; Voinov, Alexander; Adekola, Aderemi; Brune, Carl; Heinen, Zachary; Hornish, Michael; Massey, Thomas; Matei, Catalin; Carter, Don; O'Donnell, John

2008-04-01

The reactions ^6Li on ^58Fe and ^7Li on ^57Fe have been studied; these two reactions give the same compound nucleus, ^64Cu. The neutron, proton and alpha spectra were measured at backward angles, and the level densities of the residual nuclei from the particle evaporation spectra have been obtained. The contribution of the breakup mechanism to the reaction cross-section was studied from ^6Li on ^197Au reaction. The data obtained have been compared with Hauser Feshbach model calculations performed with HF and Empire codes. Three other reactions were also studied to see how level densities change as we move away from the nuclear stability line. These are: ^18O on ^64Ni reaction, this gives ^82Kr as compound nucleus which is on the stability line; ^24Mg on ^58Fe, this gives ^82Sr as compound nucleus and ^24Mg on ^58Ni which gives ^82Zr as compound nucleus; these are two and four steps away from the stability line respectively. Some results are presented.

Efficacy and safety of third-line molecular-targeted therapy in metastatic renal cell carcinoma resistant to first-line vascular endothelial growth factor receptor tyrosine kinase inhibitor and second-line therapy.

PubMed

Ishihara, Hiroki; Takagi, Toshio; Kondo, Tsunenori; Tachibana, Hidekazu; Yoshida, Kazuhiko; Omae, Kenji; Iizuka, Junpei; Kobayashi, Hirohito; Tanabe, Kazunari

2018-06-01

The number of studies evaluating the efficacy and safety of third-line molecular-targeted therapy for metastatic renal cell carcinoma (mRCC) is limited. The data for 48 patients with disease progression after first-line vascular endothelial growth factor receptor tyrosine kinase inhibitor (TKI) and second-line targeted therapy were evaluated. Patients with prior cytokine therapy were excluded. Overall survival (OS) after first- and second-line therapy initiation was compared between patients with and without third-line therapy. In addition, dose-limiting toxicities (DLTs) were evaluated. Twenty-two of 48 patients (45.8%) received third-line therapy, and TKI and mammalian target of rapamycin inhibitor were each administered in 11 patients (50%). Patients with third-line therapy had significantly longer median OS after first-line therapy (26.6 vs. 14.6 months, p = 0.0010) and second-line therapy (18.2 vs. 7.4 months, p < 0.0001) compared to those without third-line therapy. Multivariate analysis showed that the use of third-line therapy following second-line therapy was an independent prognosticator for longer OS (hazard ratio 0.29, 95% confidence interval 0.14-0.58, p = 0.0005). The median progression-free survival and OS after third-line therapy was 2.76 and 8.71 months, respectively. Although a high frequency of DLTs was observed (n = 10, 45.5%), the frequencies were similar among the sequential therapies. Third-line therapy has a beneficial therapeutic effect in patients with mRCC that is resistant to previous therapies. However, there is a need to evaluate in detail the high frequency of adverse events, including DLTs.

Performance prediction of optical image stabilizer using SVM for shaker-free production line

NASA Astrophysics Data System (ADS)

Kim, HyungKwan; Lee, JungHyun; Hyun, JinWook; Lim, Haekeun; Kim, GyuYeol; Moon, HyukSoo

2016-04-01

Recent smartphones adapt the camera module with optical image stabilizer(OIS) to enhance imaging quality in handshaking conditions. However, compared to the non-OIS camera module, the cost for implementing the OIS module is still high. One reason is that the production line for the OIS camera module requires a highly precise shaker table in final test process, which increases the unit cost of the production. In this paper, we propose a framework for the OIS quality prediction that is trained with the support vector machine and following module characterizing features : noise spectral density of gyroscope, optically measured linearity and cross-axis movement of hall and actuator. The classifier was tested on an actual production line and resulted in 88% accuracy of recall rate.

Real-World Treatment Patterns, Survival, and Prediction of CNS Progression in ALK-Positive Non-Small-Cell Lung Cancer Patients Treated with First-Line Crizotinib in Latin America Oncology Practices.

PubMed

Martín, Claudio; Cardona, Andrés F; Zatarain-Barrón, Zyanya Lucia; Ruiz-Patiño, Alejandro; Castillo, Omar; Oblitas, George; Corrales, Luis; Lupinacci, Lorena; Pérez, María Angelina; Rojas, Leonardo; González, Lisde; Chirinos, Luis; Ortíz, Carlos; Lema, Mauricio; Vargas, Carlos; Puparelli, Carmen; Carranza, Hernán; Otero, Jorge; Arrieta, Oscar

2018-01-01

This study describes the real-world characteristics, treatment sequencing, and outcomes among Hispanic patients with locally advanced/metastatic ALK-positive non-small-cell lung cancer (NSCLC) treated with crizotinib. A retrospective patient review was conducted for several centers in Latin America. Clinicians identified ALK-positive NSCLC patients who received crizotinib and reported their clinical characteristics, treatments, and survival. Overall survival and progression-free survival (PFS) were described. A Random Forest Tree (RFT) model was constructed to predict brain progression. A total of 73 patients were included; median age at diagnosis was 58 years, 60.3% were female, and 93.2% had adenocarcinoma. Eighty-nine percent of patients were never smokers/former smokers, 71.1% had ≥2 sites of metastasis, and 20.5% had brain metastases at diagnosis. The median PFS on first-line crizotinib was 7.07 months (95% CI 3.77-12.37) and the overall response rate was 52%. Of those who discontinued crizotinib, 55.9% progressed in the central nervous system (CNS). The RFT model reached a sensitivity of 100% and a specificity of 88% for prediction of CNS progression. The overall response rate and the PFS observed in Hispanic patients with ALK-positive NSCLC treated with first-line crizotinib were similar to those in previous reports. An RFT model is helpful in predicting CNS progression and can help clinicians tailor treatments in a resource-limited practice. © 2018 S. Karger AG, Basel.

Universal single level implicit algorithm for gasdynamics

NASA Technical Reports Server (NTRS)

Lombard, C. K.; Venkatapthy, E.

1984-01-01

A single level effectively explicit implicit algorithm for gasdynamics is presented. The method meets all the requirements for unconditionally stable global iteration over flows with mixed supersonic and supersonic zones including blunt body flow and boundary layer flows with strong interaction and streamwise separation. For hyperbolic (supersonic flow) regions the method is automatically equivalent to contemporary space marching methods. For elliptic (subsonic flow) regions, rapid convergence is facilitated by alternating direction solution sweeps which bring both sets of eigenvectors and the influence of both boundaries of a coordinate line equally into play. Point by point updating of the data with local iteration on the solution procedure at each spatial step as the sweeps progress not only renders the method single level in storage but, also, improves nonlinear accuracy to accelerate convergence by an order of magnitude over related two level linearized implicit methods. The method derives robust stability from the combination of an eigenvector split upwind difference method (CSCM) with diagonally dominant ADI(DDADI) approximate factorization and computed characteristic boundary approximations.

Silica-Coated Plasmonic Metal Nanoparticles in Action.

PubMed

Hanske, Christoph; Sanz-Ortiz, Marta N; Liz-Marzán, Luis M

2018-05-07

Hybrid colloids consisting of noble metal cores and metal oxide shells have been under intense investigation for over two decades and have driven progress in diverse research lines including sensing, medicine, catalysis, and photovoltaics. Consequently, plasmonic core-shell particles have come to play a vital role in a plethora of applications. Here, an overview is provided of recent developments in the design and utilization of the most successful class of such hybrid materials, silica-coated plasmonic metal nanoparticles. Besides summarizing common simple approaches to silica shell growth, special emphasis is put on advanced synthesis routes that either overcome typical limitations of classical methods, such as stability issues and undefined silica porosity, or grant access to particularly sophisticated nanostructures. Hereby, a description is given, how different types of silica can be used to provide noble metal particles with specific functionalities. Finally, applications of such nanocomposites in ultrasensitive analyte detection, theranostics, catalysts, and thin-film solar cells are reviewed. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Gamma Knife radiosurgery in pituitary adenomas: Why, who, and how to treat?

PubMed

Castinetti, Frederic; Brue, Thierry

2010-08-01

Pituitary adenomas are benign tumors that can be either secreting (acromegaly, Cushing's disease, prolactinomas) or non-secreting. Transsphenoidal neurosurgery is the gold standard treatment; however, it is not always effective. Gamma Knife radiosurgery is a specific modality of stereotactic radiosurgery, a precise radiation technique. Several studies reported the efficacy and low risk of adverse effects induced by this technique: in secreting pituitary adenomas, hypersecretion is controlled in about 50% of cases and tumor volume is stabilized or decreased in 80-90% of cases, making Gamma Knife a valuable adjunctive or first-line treatment. As hormone levels decrease progressively, the main drawback is the longer time to remission (12-60 months), requiring an additional treatment during this period. Hypopituitarism is the main side effect, observed in 20-40% cases. Gamma Knife is thus useful in the therapeutic algorithms of pituitary adenomas in well-defined indications, mainly low secreting small lesions well identified on magnetic resonance imaging (MRI).

Characterization of 193-nm resists for optical mask manufacturing

NASA Astrophysics Data System (ADS)

Fosshaug, Hans; Paulsson, Adisa; Berzinsh, Uldis; Magnusson, Helena

2004-12-01

The push for smaller linewidths and tighter critical dimension (CD) budgets forced manufacturers of optical pattern generators to move from traditional i-line to deep ultraviolet (DUV) resist processing. Entering the DUV area was not without pain. The process conditions, especially exposure times of a few hours, put very tough demands on the resist material itself. However, today 248nm laser writers are fully operating using a resist process that exhibits the requested resolution, CD uniformity and environmental stability. The continuous demands of CD performance made Micronic to investigate suitable resist candidate materials for the next generation optical writer using 193nm excimer laser exposure. This paper reports on resist benchmarking of one commercial as well as several newly developed resists. The resists were investigated using a wafer scanner. The data obtained illustrate the current performance of 193nm photoresists, and further demonstrate that despite good progress in resist formulation optimization, the status is still a bit from the required lithographic performance.

Inhibition of NEDD8-activating enzyme: a novel approach for the treatment of acute myeloid leukemia.

PubMed

Swords, Ronan T; Kelly, Kevin R; Smith, Peter G; Garnsey, James J; Mahalingam, Devalingam; Medina, Ernest; Oberheu, Kelli; Padmanabhan, Swaminathan; O'Dwyer, Michael; Nawrocki, Steffan T; Giles, Francis J; Carew, Jennifer S

2010-05-06

NEDD8 activating enzyme (NAE) has been identified as an essential regulator of the NEDD8 conjugation pathway, which controls the degradation of many proteins with important roles in cell-cycle progression, DNA damage, and stress responses. Here we report that MLN4924, a novel inhibitor of NAE, has potent activity in acute myeloid leukemia (AML) models. MLN4924 induced cell death in AML cell lines and primary patient specimens independent of Fms-like tyrosine kinase 3 expression and stromal-mediated survival signaling and led to the stabilization of key NAE targets, inhibition of nuclear factor-kappaB activity, DNA damage, and reactive oxygen species generation. Disruption of cellular redox status was shown to be a key event in MLN4924-induced apoptosis. Administration of MLN4924 to mice bearing AML xenografts led to stable disease regression and inhibition of NEDDylated cullins. Our findings indicate that MLN4924 is a highly promising novel agent that has advanced into clinical trials for the treatment of AML.

Isolation and characterisation of microcrystalline cellulose and cellulose nanocrystals from coffee husk and comparative study with rice husk.

PubMed

Collazo-Bigliardi, Sofía; Ortega-Toro, Rodrigo; Chiralt Boix, Amparo

2018-07-01

Cellulosic material from coffee husk has not been previously studied despite being a potential source of reinforcing agents for different applications. This material has been extracted and characterised from coffee husk, in parallel with previously studied rice husk. Samples have been analysed as to their ability to obtain cellulosic fibres and cellulose nanocrystals (CNC) by applying alkali and bleaching treatments and final sulphuric acid hydrolysis. Microstructural changes were analysed after treatments, and the size and aspect ratio of CNCs were determined. Crystallinity and thermal stability of both materials progressed in line with the enrichment in cellulosic compounds. The CNC aspect ratio was higher than 10, which confers good reinforcing properties. These were tested in thermoplastic starch films, whose elastic modulus increased by 186 and 121% when 1 wt% of CNCs from rice and coffee husks, respectively, was incorporated into the matrix. Coffee husk represents an interesting source of cellulosic reinforcing materials. Copyright © 2018 Elsevier Ltd. All rights reserved.

Green synthesis of Nerium oleander-conjugated gold nanoparticles and study of its in vitro anticancer activity on MCF-7 cell lines and catalytic activity

NASA Astrophysics Data System (ADS)

Barai, Abir Chandan; Paul, Koushik; Dey, Aditi; Manna, Subhankar; Roy, Somenath; Bag, Braja Gopal; Mukhopadhyay, Chiradeep

2018-04-01

The phytochemicals present in the stem bark extract of Nerium oleander (commonly known as Karabi) have been utilized for the green synthesis of stable gold-conjugated nanoparticles at room temperature under very mild conditions. The green synthesized gold-conjugated nanoparticles were characterized by surface plasmon resonance spectroscopy, High resolution transmission electron microscopy, X-ray diffraction studies and dynamic light scattering. A mechanism for the synthesis and stabilization of gold-conjugated nanoparticles (AuNPs) has been proposed. Anticancer activity of the stabilized AuNPs studied against MCF-7 breast cancer cell line revealed that the stabilized AuNPs were highly effective for the apoptosis of cancer cells selectively. The antioxidant activity of the stem bark extract of Nerium oleander has also been studied against a long lived 2,2-diphenylpicrylhydrazyl radical at room temperature. Moreover, the utilization of the stabilized AuNPs as a catalyst has also been demonstrated. [Figure not available: see fulltext.

Stability of surface nanobubbles

NASA Astrophysics Data System (ADS)

Maheshwari, Shantanu; van der Hoef, Martin; Zhang, Xuehua; Lohse, Detlef

2015-11-01

We have studied the stability and dissolution of surface nanobubbles on the chemical heterogenous surface by performing Molecular Dynamics (MD) simulations of binary mixture consists of Lennard-Jones (LJ) particles. Recently our group has derived the exact expression for equilibrium contact angle of surface nanobubbles as a function of oversaturation of the gas concentration in bulk liquid and the lateral length of bubble. It has been showed that the contact line pinning and the oversaturation of gas concentration in bulk liquid is crucial in the stability of surface nanobubbles. Our simulations showed that how pinning of the three-phase contact line on the chemical heterogenous surface lead to the stability of the nanobubble. We have calculated the equilibrium contact angle by varying the gas concentration in bulk liquid and the lateral length of the bubble. Our results showed that the equilibrium contact angle follows the expression derived analytically by our group. We have also studied the bubble dissolution dynamics and showed the ''stick-jump'' mechanism which was also observed experimentally in case of dissolution of nanodrops.

Frequency stabilization of a 1083 nm fiber laser to {sup 4}He transition lines with optical heterodyne saturation spectroscopies

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

Gong, W.; Peng, X., E-mail: xiangpeng@pku.edu.cn; Li, W.

2014-07-15

Two kinds of optical heterodyne saturation spectroscopies, namely, frequency modulation spectroscopy (FMS) and modulation transfer spectroscopy (MTS), are demonstrated for locking a fiber laser to the transition lines of metastable {sup 4}He atoms around 1083 nm. The servo-loop error signals of FMS and MTS for stabilizing laser frequency are optimized by studying the dependence of the peak-to-peak amplitude and slope on the optical power of pump and probe beams. A comparison of the stabilization performances of FMS/MTS and polarization spectroscopy (PS) is presented, which shows that MTS exhibits relatively superior performance with the least laser frequency fluctuation due to itsmore » flat-background dispersive signal, originated from the four-wave mixing process. The Allan deviation of the stabilized laser frequency is 5.4 × 10{sup −12}@100 s with MTS for data acquired in 1000 s, which is sufficiently applicable for fields like laser cooling, optical pumping, and optical magnetometry.« less

Green synthesis of Nerium oleander-conjugated gold nanoparticles and study of its in vitro anticancer activity on MCF-7 cell lines and catalytic activity.

PubMed

Barai, Abir Chandan; Paul, Koushik; Dey, Aditi; Manna, Subhankar; Roy, Somenath; Bag, Braja Gopal; Mukhopadhyay, Chiradeep

2018-01-01

The phytochemicals present in the stem bark extract of Nerium oleander (commonly known as Karabi) have been utilized for the green synthesis of stable gold-conjugated nanoparticles at room temperature under very mild conditions. The green synthesized gold-conjugated nanoparticles were characterized by surface plasmon resonance spectroscopy, High resolution transmission electron microscopy, X-ray diffraction studies and dynamic light scattering. A mechanism for the synthesis and stabilization of gold-conjugated nanoparticles (AuNPs) has been proposed. Anticancer activity of the stabilized AuNPs studied against MCF-7 breast cancer cell line revealed that the stabilized AuNPs were highly effective for the apoptosis of cancer cells selectively. The antioxidant activity of the stem bark extract of Nerium oleander has also been studied against a long lived 2,2-diphenylpicrylhydrazyl radical at room temperature. Moreover, the utilization of the stabilized AuNPs as a catalyst has also been demonstrated.

Colloids in food: ingredients, structure, and stability.

PubMed

Dickinson, Eric

2015-01-01

This article reviews progress in the field of food colloids with particular emphasis on advances in novel functional ingredients and nanoscale structuring. Specific aspects of ingredient development described here are the stabilization of bubbles and foams by the protein hydrophobin, the emulsifying characteristics of Maillard-type protein-polysaccharide conjugates, the structural and functional properties of protein fibrils, and the Pickering stabilization of dispersed droplets by food-grade nanoparticles and microparticles. Building on advances in the nanoscience of biological materials, the application of structural design principles to the fabrication of edible colloids is leading to progress in the fabrication of functional dispersed systems-multilayer interfaces, multiple emulsions, and gel-like emulsions. The associated physicochemical insight is contributing to our mechanistic understanding of oral processing and textural perception of food systems and to the development of colloid-based strategies to control delivery of nutrients during food digestion within the human gastrointestinal tract.

Oestradiol reduces Liver Receptor Homolog-1 mRNA transcript stability in breast cancer cell lines

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

Lazarus, Kyren A.; Environmental and Biotechnology Centre, Swinburne University, Hawthorn, Victoria 3122; Zhao, Zhe

2013-08-30

Highlights: •LRH-1 is an orphan nuclear receptor that regulates tumor proliferation. •In breast cancer, high mRNA expression is associated with ER+ status. •In ER−ve cells, despite very low mRNA, we found abundant LRH-1 protein. •Our data show distinctly different LRH-1 protein isoforms in ER− and ER+ breast cancer cells. •This is due to differences in LRH-1 mRNA and protein stability rates. -- Abstract: The expression of orphan nuclear receptor Liver Receptor Homolog-1 (LRH-1) is elevated in breast cancer and promotes proliferation, migration and invasion in vitro. LRH-1 expression is regulated by oestrogen (E{sub 2}), with LRH-1 mRNA transcript levels highermore » in oestrogen receptor α (ERα) positive (ER+) breast cancer cells compared to ER− cells. However, the presence of LRH-1 protein in ER− cells suggests discordance between mRNA transcript levels and protein expression. To understand this, we investigated the impact of mRNA and protein stability in determining LRH-1 protein levels in breast cancer cells. LRH-1 transcript levels were significantly higher in ER+ versus ER− breast cancer cells lines; however LRH-1 protein was expressed at similar levels. We found LRH-1 mRNA and protein was more stable in ER− compared to ER+ cell lines. The tumor-specific LRH-1 variant isoform, LRH-1v4, which is highly responsive to E{sub 2}, showed increased mRNA stability in ER− versus ER+ cells. In addition, in MCF-7 and T47-D cell lines, LRH-1 total mRNA stability was reduced with E{sub 2} treatment, this effect mediated by ERα. Our data demonstrates that in ER− cells, increased mRNA and protein stability contribute to the abundant protein expression levels. Expression and immunolocalisation of LRH-1 in ER− cells as well as ER− tumors suggests a possible role in the development of ER− tumors. The modulation of LRH-1 bioactivity may therefore be beneficial as a treatment option in both ER− and ER+ breast cancer.« less

Unsupervised Gaussian Mixture-Model With Expectation Maximization for Detecting Glaucomatous Progression in Standard Automated Perimetry Visual Fields.

PubMed

Yousefi, Siamak; Balasubramanian, Madhusudhanan; Goldbaum, Michael H; Medeiros, Felipe A; Zangwill, Linda M; Weinreb, Robert N; Liebmann, Jeffrey M; Girkin, Christopher A; Bowd, Christopher

2016-05-01

To validate Gaussian mixture-model with expectation maximization (GEM) and variational Bayesian independent component analysis mixture-models (VIM) for detecting glaucomatous progression along visual field (VF) defect patterns (GEM-progression of patterns (POP) and VIM-POP). To compare GEM-POP and VIM-POP with other methods. GEM and VIM models separated cross-sectional abnormal VFs from 859 eyes and normal VFs from 1117 eyes into abnormal and normal clusters. Clusters were decomposed into independent axes. The confidence limit (CL) of stability was established for each axis with a set of 84 stable eyes. Sensitivity for detecting progression was assessed in a sample of 83 eyes with known progressive glaucomatous optic neuropathy (PGON). Eyes were classified as progressed if any defect pattern progressed beyond the CL of stability. Performance of GEM-POP and VIM-POP was compared to point-wise linear regression (PLR), permutation analysis of PLR (PoPLR), and linear regression (LR) of mean deviation (MD), and visual field index (VFI). Sensitivity and specificity for detecting glaucomatous VFs were 89.9% and 93.8%, respectively, for GEM and 93.0% and 97.0%, respectively, for VIM. Receiver operating characteristic (ROC) curve areas for classifying progressed eyes were 0.82 for VIM-POP, 0.86 for GEM-POP, 0.81 for PoPLR, 0.69 for LR of MD, and 0.76 for LR of VFI. GEM-POP was significantly more sensitive to PGON than PoPLR and linear regression of MD and VFI in our sample, while providing localized progression information. Detection of glaucomatous progression can be improved by assessing longitudinal changes in localized patterns of glaucomatous defect identified by unsupervised machine learning.

PSI-Center Final Progress Report

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

Jarboe, Thomas R.; Shumlak, Uri; Sovinec, Carl

This is the Final Progress Report of the Plasma Science and Innovation Center (PSI-Center) covering March 2014 through February 2017. The Center has accomplished a great deal during this period. The PSI-Center is organized into four groups: Edge and Dynamic Neutrals; Transport and Kinetic Effects; Equilibrium, Stability, and Kinetic Effects in 3D Topologies; and Interface for Validation. Each group has made good progress and the results from each group are given in detail.

Production of higher quality bio-oils by in-line esterification of pyrolysis vapor

DOEpatents

Hilten, Roger Norris; Das, Keshav; Kastner, James R; Bibens, Brian P

2014-12-02

The disclosure encompasses in-line reactive condensation processes via vapor phase esterification of bio-oil to decease reactive species concentration and water content in the oily phase of a two-phase oil, thereby increasing storage stability and heating value. Esterification of the bio-oil vapor occurs via the vapor phase contact and subsequent reaction of organic acids with ethanol during condensation results in the production of water and esters. The pyrolysis oil product can have an increased ester content and an increased stability when compared to a condensed pyrolysis oil product not treated with an atomized alcohol.

BROWSER: An Automatic Indexing On-Line Text Retrieval System. Annual Progress Report.

ERIC Educational Resources Information Center

Williams, J. H., Jr.

The development and testing of the Browsing On-line With Selective Retrieval (BROWSER) text retrieval system allowing a natural language query statement and providing on-line browsing capabilities through an IBM 2260 display terminal is described. The prototype system contains data bases of 25,000 German language patent abstracts, 9,000 English…

HTLV-1 Tax upregulates early growth response protein 1 through nuclear factor-κB signaling.

PubMed

Huang, Qingsong; Niu, Zhiguo; Han, Jingxian; Liu, Xihong; Lv, Zhuangwei; Li, Huanhuan; Yuan, Lixiang; Li, Xiangping; Sun, Shuming; Wang, Hui; Huang, Xinxiang

2017-08-01

Human T cell leukemia virus type 1 (HTLV-1) is a complex retrovirus that causes adult T cell leukemia (ATL) in susceptible individuals. The HTLV-1-encoded oncoprotein Tax induces persistent activation of the nuclear factor-κB (NF-κB) pathway. Early growth response protein 1 (EGR1) is overexpressed in HTLV-1-infected T cell lines and ATL cells. Here, we showed that both Tax expression and HTLV-1 infection promoted EGR1 overexpression. Loss of the NF-κB binding site in the EGR1 promotor or inhibition of NF-κB activation reduced Tax-induced EGR1 upregulation. Tax mutants unable to activate NF-κB induced only slight EGR1 upregulation as compared with wild-type Tax, confirming NF-κB pathway involvement in EGR1 regulation. Tax also directly interacted with the EGR1 protein and increased endogenous EGR1 stability. Elevated EGR1 in turn promoted p65 nuclear translocation and increased NF-κB activation. These results demonstrate a positive feedback loop between EGR1 expression and NF-κB activation in HTLV-1-infected and Tax-expressing cells. Both NF-κB activation and Tax-induced EGR1 stability upregulated EGR1, which in turn enhanced constitutive NF-κB activation and facilitated ATL progression in HTLV-1-infected cells. These findings suggest EGR1 may be an effective anti-ATL therapeutic target.

Metastatic signet-ring cell cancer of the bladder responding to chemotherapy with capecitabine: case report and review of literature

PubMed Central

Michels, Jorg; Barbour, Sean; Cavers, Douglas; Chi, Kim N.

2010-01-01

Signet-ring cell cancers deriving from the bladder are rare entities and usually present with advanced incurable disease and associated poor outlook. No standard effective chemotherapeutic option has been described largely due to the rarity of this malignancy. We report a case of a patient with metastatic bladder cancer, signet-ring cell variant. The patient progressed rapidly on standard first-line bladder cancer chemotherapy with gemcitabine and carboplatin. He responded well to second-line capecitabine with a clinically meaningful progression-free survival. PMID:20368884

Design and progress in the fabrication of an EUV micro exposure tool optics for PREUVE

NASA Astrophysics Data System (ADS)

Geyl, Roland; Tanne, Jean-Francois

2001-12-01

SAGEM, through its REOSC product line, is participating since November 1999 to PREUVE, the French EUV initiative, and work within this program especially in the field of EUV illumination and projection optics. After a short description of the PREUVE main lines of activity, we will detail our contributions to this program and work progress. This is mainly focused on basic EUV optics fabrication technology in order to ensure the fabrication of the entire optics assembly of an EUV micro exposure tool.

Seeking stability for research and applied uses of entomopathogenic fungi as biological control agents

USDA-ARS?s Scientific Manuscript database

Future progress in research with entomopathogenic fungi depends on a number of diverse considerations that help to stabilize the state of knowledge while supporting research about the documentation of the biodiversity and systematics of these fungi as well as those studies about their actions as pat...

Longitudinal Stability and Control Characteristics from a Flight Investigation of a Cruciform Canard Missile Configuration Having an Exposed Wing-canard Area Ratio of 16:1

NASA Technical Reports Server (NTRS)

Moul, Martin T; Wineman, Andrew R

1952-01-01

A flight investigation has been made to determine the longitudinal stability and control characteristics of a 60 0 delta-wing-canard missile configuration with an exposed wing-canard area ratio of 16:1. The results presented include the longitudinal stability derivatives, control effectiveness, and drag characteristics for a Mach number range of 0.75 to 1.80 and are compared with the results of a similar configuration having larger 6ontrols. Stability characteristics are also presented from the flights of an interdigitated canard configuration at a Mach number of 2.08 and a wing-body configuration at Mach numbers of 1.25 to 1.45. The stability derivatives varied gradually with Mach number with the exception of the damping-in-pitch derivative. Aerodynamic damping in pitch decreased to a minimum at a Mach number of 1.0 3, then increased to a peak value at a Mach number of 1.26 followed by a gradual decrease at higher Mach numbers. The aerodynamic-center location of the in-line canard configuration shifted rearward 13 percent of the mean aerodynamic chord at transonic speeds. The pitching-moment curve slope was 25 percent greater for the model having no canards than for the in-line configuration. No large effects of interdigitation were noted in the stability derivatives. Pitching effectiveness of the in-line configuration was maintained throughout the Mach number range. A comparison of the stability and control characteristics of two canard configurations having different area controls showed that decreasing the control area 44 percent decreased the pitching effectiveness proportionally, shifted the aerodynamic-center location rearward 9 to 14 percent of the mean aerodynamic chord, and reduced the total hinge moments required for 10 trimmed flight about 50 percent at transonic speeds.

DNA Methylation as an Epigenetic Factor in the Development and Progression of Polycythemia Vera

DTIC Science & Technology

2008-10-01

vera and idiopathic myelofibrosis. Pathol Biol ( Paris ). 2001;49:164-166. 2. Spivak JL. Diagnosis of the myeloproliferative disorders: resolving...leukemia cell lines with different cellular origin (myeloid cell lines KG1, KG1a, HEL, K562, and TF1; T lymphoid cell lines CEM and JTAg; and B lymphoid...in the cell lines of lymphoid origin versus myeloid leukemia cell lines and a GM-CSF- Services Email this article to a friend Download to

Dynamic trunk stabilization: a conceptual back injury prevention program for volleyball athletes.

PubMed

Smith, Chad E; Nyland, John; Caudill, Paul; Brosky, Joseph; Caborn, David N M

2008-11-01

The sport of volleyball creates considerable dynamic trunk stability demands. Back injury occurs all too frequently in volleyball, particularly among female athletes. The purpose of this clinical commentary is to review functional anatomy, muscle coactivation strategies, assessment of trunk muscle performance, and the characteristics of effective exercises for the trunk or core. From this information, a conceptual progressive 3-phase volleyball-specific training program is presented to improve dynamic trunk stability and to potentially reduce the incidence of back injury among volleyball athletes. Phase 1 addresses low-velocity motor control, kinesthetic awareness, and endurance, with the clinician providing cues to teach achievement of biomechanically neutral spine alignment. Phase 2 focuses on progressively higher velocity dynamic multiplanar endurance, coordination, and strength-power challenges integrating upper and lower extremity movements, while maintaining neutral spine alignment. Phase 3 integrates volleyball-specific skill simulations by breaking down composite movement patterns into their component parts, with differing dynamic trunk stability requirements, while maintaining neutral spine alignment. Prospective research is needed to validate the efficacy of this program.

Postural Stability Margins as a Function of Support Surface Slopes.

PubMed

Dutt-Mazumder, Aviroop; Slobounov, Seymon M; Challis, John Henry; Newell, Karl Maxim

2016-01-01

This investigation examined the effects of slope of the surface of support (35°, 30°, 20°, 10° Facing(Toe) Down, 0° Flat and 10°, 20°, 25° Facing (Toe) Up) and postural orientation on the margins of postural stability in quiet standing of young adults. The findings showed that the center of pressure-CoP (displacement, area and length) had least motion at the baseline (0° Flat) platform condition that progressively increased as a function of platform angle in both facing up and down directions. The virtual time to collision (VTC) dynamics revealed that the spatio-temporal margins to the functional stability boundary were progressively smaller and the VTC time series also more regular (SampEn-Sample Entropy) as slope angle increased. Surface slope induces a restricted stability region with lower dimension VTC dynamics that is more constrained when postural orientation is facing down the slope. These findings provide further evidence that VTC acts as a control variable in standing posture that is influenced by the emergent dynamics of the individual-environment-task interaction.

Comparative study of a novel application of automated HR HPV assay and stability in a previously untested Preservative media.

PubMed

Morel, Mike E; McBride, Simon E; Gomez, Maria P

2017-12-01

The suitability and stability of cervical cells in Novaprep media (NHQ) for certain HPV assays is unknown. We evaluated the accuracy of an automated HPV assay (Abbott RealTime HR HPV) for cervical cells prepared in NHQ and NHQ with a pre-treatment to mimic a worst case clinical use, compared to the assay manufacturers media; repeatability and reproducibility of HPV results and the stability of detectable HPV in NHQ over time compared to CE marked liquid based cytology preservatives. Cell lines were used to simulate patient samples. Cells stored in NHQ produced accurate, repeatable and reproducible results. Stability in NHQ was comparable to the best performing LBC, with at least 7 months' stability at 18-25°C, 2-8°C, -20°C and -80°C; and at least 3 months' stability at 40°C. Similar results were obtained for pre-treated NHQ except only 3.5 months' stability at 18-25°C. Cell line samples in all media and concentrations tested were detected appropriately by the assay. Based on this first stage validation analytical study, cervical cells stored in NHQ are suitable for the Realtime HPV assay. There should be no reservations for inclusion of NHQ in any further validation and clinical performance evaluation of this assay. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

MULTIFUNCTION ENERGY PLATFORM (MFP) PILOT

EPA Science Inventory

• Multi-sector Baseline Survey:  A five-sector survey (agriculture, energy, water, health, and general - demogr...

• Stability and broad-sense heritaibility of mineral content in potato: copper and sulfur

  USDA-ARS?s Scientific Manuscript database

  Potato breeding lines and varieties in two separate trials were evaluated for copper and sulfur content by wet ashing and Inductively Coupled Argon Plasma Emission Spectrophotometer analysis. Stability and broad-sense heritability were determined. Copper contents ranged among genotypes between 2.0...

• Global Failure Modes in High Temperature Composite Structures

  NASA Technical Reports Server (NTRS)

  Knauss, W. G.

  1998-01-01

  Composite materials have been considered for many years as the major advance in the construction of energy efficient aerospace structures. Notable advances have been made in understanding the special design considerations that set composites apart from the usual "isotropic" engineering materials such as the metals. As a result, a number of significant engineering designs have been accomplished. However, one shortcoming of the currently favored composites is their relatively unforgiving behavior with respect to failure (brittleness) under seemingly mild impact conditions and large efforts are underway to rectify that situation, much along the lines of introducing thermoplastic matrix materials. Because of their relatively more pronounced (thermo) viscoelastic behavior these materials respond with "toughness" in fracture situations. From the point of view of applications requiring material strength, this property is highly desirable. This feature impacts several important and distinct engineering problems which have been' considered under this grant and cover the 1) effect of impact damage on structural (buckling) stability of composite panels, the 2) effect of time dependence on the progression of buckling instabilities, and the 3) evolution of damage and fracture at generic thickness discontinuities in structures. The latter topic has serious implications for structural stability problems (buckling failure in reinforced shell structures) as well as failure progression in stringer-reinforced shell structures. This grant has dealt with these issues. Polymer "toughness" is usually associated with uncrosslinked or thermo-plastic polymers. But, by comparison with their thermoset counterparts they tend to exhibit more pronounced time dependent material behavior; also, that time dependence can occur at lower temperatures which places restriction in the high temperature use of these "newer and tougher" materials that are not quite so serious with the thermoset matrix materials. From a structural point of view the implications of this material behavior are potentially severe in that structural failure characteristics are no longer readily observed in short term qualification tests so characteristic for aerospace structures built from typical engineering metals.

• Attitude dynamic of spin-stabilized satellites with flexible appendages

  NASA Technical Reports Server (NTRS)

  Renard, M. L.

  1973-01-01

  Equations of motion and computer programs have been developed for analyzing the motion of a spin-stabilized spacecraft having long, flexible appendages. Stability charts were derived, or can be redrawn with the desired accuracy for any particular set of design parameters. Simulation graphs of variables of interest are readily obtainable on line using program FLEXAT. Finally, applications to actual satellites, such as UK-4 and IMP-1 have been considered.

• Influence of in line monitored fluid bed granulation process parameters on the stability of Ethinylestradiol.

  PubMed

  Roßteuscher-Carl, Katrin; Fricke, Sabine; Hacker, Michael C; Schulz-Siegmund, Michaela

  2015-12-30

  Ethinylestradiol (EE) as a highly active and low dosed compound is prone to oxidative degradation. The stability of the drug substance is therefore a critical parameter that has to be considered during drug formulation. Beside the stability of the drug substance, granule particle size and moisture are critical quality attributes (CQA) of the fluid bed granulation process which influence the tableting ability of the resulting granules. Both CQA should therefore be monitored during the production process by process analytic technology (PAT) according to ICH Q8. This work focusses on the effects of drying conditions on the stability of EE in a fluid-bed granulation process. We quantified EE degradation products 6-alpha-hydroxy-EE, 6-beta-hydroxy-EE, 9(11)-dehydro-EE and 6-oxo-EE during long time storage and accelerated conditions. PAT-tools that monitor granule particle size (Spatial filtering technology) and granule moisture (Microwave resonance technology) were applied and compared with off-line methods. We found a relevant influence of residual granule moisture and thermic stress applied during granulation on the storage stability of EE, whereas no degradation was found immediately after processing. Hence we conclude that drying parameters have a relevant influence on long term EE stability. Copyright © 2015 Elsevier B.V. All rights reserved.

• Progress on plutonium stabilization

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

  Hurt, D.

  1996-05-01

  The Defense Nuclear Facilities Safety Board has safety oversight responsibility for most of the facilities where unstable forms of plutonium are being processed and packaged for interim storage. The Board has issued recommendations on plutonium stabilization and has has a considerable influence on DOE`s stabilization schedules and priorities. The Board has not made any recommendations on long-term plutonium disposition, although it may get more involved in the future if DOE develops plans to use defense nuclear facilities for disposition activities.

• Silicon Anode Consortium | Transportation Research | NREL

  Science.gov Websites

  Stabilization, Second Quarter Progress Report 2018 Next Generation Anodes for Lithium-Ion Batteries, Second 2018 Next Generation Anodes for Lithium-Ion Batteries, First Quarter Progress Report 2018 Contact For consortium focuses on understanding and eliminating barriers to implementing silicon-based anodes in Li-ion

• ICS classification system of infected osteosynthesis: Long-term results.

  PubMed

  Romanò, Carlo L; Morelli, Ilaria; Romanò, Delia; Meani, Enzo; Drago, Lorenzo

  2018-03-01

  The best treatment strategy for infected osteosyntheses is still debated. While hardware removal or eventually early device exchange may be necessary in most of the cases, temporary hardware retention until fracture healing can be a valid alternative option in others. Aim of the present study is to report the long-term results of 215 patients with infected osteosyntheses, treated according to the ICS (Infection, Callus, Stability) classification in two Italian hospitals. Patients classified as ICS Type 1 (N = 83) feature callus progression and hardware stability, in spite of the presence of infection; these patients were treated with suppressive antibiotic therapy coupled with local debridement in 18.1% of the cases, and no hardware removal until bone healing. Type 2 patients (N = 75) are characterized by the presence of infection and hardware stability, but no callus progression; these patients were treated as Type 1 patients, but with additional callus stimulation therapies. Type 3 patients (N = 57), showing infection, no callus progression and loss of hardware stability, underwent removal and exchange of the fixation device. Considering only the initial treatment, performed according to the ICS classification, at a minimum 5 years follow up, 89.3% achieved bone healing and 93.5% did not show infection recurrence. The ICS classification appears as a useful and reliable tool to help standardizing the decision-making process in treating infected osteosynthesis with the most conservative approach. Copyright © 2018 Elsevier Ltd. All rights reserved.

• Renovascular disease, microcirculation, and the progression of renal injury: role of angiogenesis

  PubMed Central

  2011-01-01

  Emerging evidence supports the pivotal role of renal microvascular disease as a determinant of tubulo-interstitial and glomerular fibrosis in chronic kidney disease. An intact microcirculation is vital to restore blood flow to the injured tissues, which is a crucial step to achieve a successful repair response. The purpose of this review is to discuss the impact and mechanisms of the functional and structural changes of the renal microvascular network, as well as the role of these changes in the progression and irreversibility of renal injury. Damage of the renal microcirculation and deterioration of the angiogenic response may constitute early steps in the complex pathways involved in progressive renal injury. There is limited but provocative evidence that stimulation of vascular proliferation and repair may stabilize renal function and slow the progression of renal disease. The feasibility of novel potential therapeutic interventions for stabilizing the renal microvasculature is also discussed. Targeted interventions to enhance endogenous renoprotective mechanisms focused on the microcirculation, such as cell-based therapy or the use of angiogenic cytokines have shown promising results in some experimental and clinical settings. PMID:21307362

βTrCP controls the lysosome-mediated degradation of CDK1, whose accumulation correlates with tumor malignancy.

PubMed

Herrero-Ruiz, Joaquín; Mora-Santos, Mar; Giráldez, Servando; Sáez, Carmen; Japón, Miguel A; Tortolero, Maria; Romero, Francisco

2014-09-15

In mammals, cell cycle progression is controlled by cyclin-dependent kinases, among which CDK1 plays important roles in the regulation of the G2/M transition, G1 progression and G1/S transition. CDK1 is highly regulated by its association to cyclins, phosphorylation and dephosphorylation, changes in subcellular localization, and by direct binding of CDK inhibitor proteins. CDK1 steady-state protein levels are held constant throughout the cell cycle by a coordinated regulation of protein synthesis and degradation. We show that CDK1 is ubiquitinated by the E3 ubiquitin ligase SCFβTrCP and degraded by the lysosome. Furthermore, we found that DNA damage not only triggers the stabilization of inhibitory phosphorylation sites on CDK1 and repression of CDK1 gene expression, but also regulates βTrCP-induced CDK1 degradation in a cell type-dependent manner. Specifically, treatment with the chemotherapeutic agent doxorubicin in certain cell lines provokes CDK1 degradation and induces apoptosis, whereas in others it inhibits destruction of the protein. These observations raise the possibility that different tumor types, depending on their pathogenic spectrum mutations, may display different sensitivity to βTrCP-induced CDK1 degradation after DNA damage. Finally, we found that CDK1 accumulation in patients' tumors shows a negative correlation with βTrCP and a positive correlation with the degree of tumor malignancy.

Phase II of oral gimatecan in patients with recurrent epithelial ovarian, fallopian tube or peritoneal cancer, previously treated with platinum and taxanes

PubMed Central

Pecorelli, S.; Ray-Coquard, I.; Tredan, O.; Colombo, N.; Parma, G.; Tisi, G.; Katsaròs, D.; Lhommé, C.; Lissoni, A. A.; Vermorken, J. B.; du Bois, A.; Poveda, A.; Frigerio, L.; Barbieri, P.; Carminati, P.; Brienza, S.; Guastalla, J. P.

2010-01-01

Background: A prospective phase II study was conducted to evaluate the efficacy and toxicity of oral gimatecan in patients with recurrent epithelial ovarian, fallopian tube or peritoneal cancer. Patients and methods: Patients had a maximum of three prior chemotherapy lines with no more than two prior platinum-containing regimens and a progression-free interval after the last dose of platinum <12 months. A total dose of 4 mg/m2/cycle (0.8 mg/m2/day from day 1 to day 5) was administered, repeated every 28 days. Results: From June 2005 to December 2005, 69 assessable patients were enrolled. The best overall response to study treatment by combined CA-125 and RECIST criteria was partial response in 17 patients (24.6%) and disease stabilization in 22 patients (31.9%). The median time to progression and overall survival were 3.8 and 16.2 months, respectively. A total of 312 cycles were administered. Neutropenia grade 4 and thrombocytopenia grade 4 occurred in 17.4% and 7.2% of patients, respectively. Diarrhea grade 4 was never observed. Asthenia and fatigue were reported by 36.2% and 18.8% of patients, but were all grade 2 or less. Conclusion: Gimatecan is a new active agent in previously treated ovarian cancer with myelosuppression as main toxicity. PMID:19906760

A pilot study with very low-intensity, intermediate-frequency electric fields in patients with locally advanced and/or metastatic solid tumors.

PubMed

Salzberg, Marc; Kirson, Eilon; Palti, Yoram; Rochlitz, Christoph

2008-07-01

The transmission of electric fields using insulated electrodes has demonstrated that very low-intensity, properly tuned, intermediate-frequency electric fields, termed tumor-treating fields (TTFields), selectively stunts tumor cell growth and is accompanied by a decrease in tumor angiogenesis. This open, prospective pilot study was designed to evaluate the safety, tolerability, and efficacy profile of TTFields treatment in patients with locally advanced and/or metastatic solid tumors using the NovoTTF100A(TM) device. All 6 patients were heavily pre-treated with several lines of therapy; no additional standard treatment option was available to them. TTFields treatment using continuous NovoTTF-100A lasted a minimum of 14 days and was very well tolerated. No related serious adverse events occurred. Outcomes showed 1 partial response of a treated skin metastasis from a primary breast cancer, 3 cases where tumor growth was arrested during treatment, and 1 case of disease progression. One mesothelioma patient experienced lesion regression near TTFields with simultaneous tumor stability or progression in distal areas. Although the number of patients in this study is small, the lack of therapy toxicity and the efficacy observed in data gathered to date indicate the potential of TTFields as a new treatment modality for solid tumors, definitely warranting further investigation. (c) 2008 S. Karger AG, Basel

INTENSITY AND GENERALIZATION OF TREADMILL-SLIP TRAINING: HIGH OR LOW; PROGRESSIVELY-INCREASE OR -DECREASE?

PubMed Central

Liu, Xuan; Bhatt, Tanvi; Pai, Yi-Chung (Clive)

2015-01-01

Very little is known how training intensity interacts with the generalization from treadmill-slip to overground slip. The purposes of this study were to determine whether treadmill-slip training improved center-of-mass stability, more so in the reactive than in the proactive control of stability, with high intensity (HI with a trial-to-trial-consistent acceleration of 12 m/s2) better than low intensity training (LO with a consistent acceleration of 6 m/s2), and progressively-increasing intensity (INCR with a block-to-block acceleration varied from 6 to 12 m/s2) better than progressively-decreasing intensity training (DECR with an acceleration varied from 12 to 6 m/s2) in such generalization. Thirty-six young subjects evenly assigned to one of four (HI, LO, INCR, DECR) groups underwent 24 treadmill-slips before their generalization test trial with a novel slip during overground walking. The controls (CTRL, n=9) from existing data only experienced the same novel overground slip without treadmill training but under otherwise identical condition. The results showed that treadmill-slip training did improved balance control on overground slip with a greater impact on subjects’ reactive (44.3%) than proactive control of stability (27.1%) in comparison to the CTRL. HI yielded stronger generalization than LO, while INCR was only marginally better than DECR. Finally, the group means of these four displayed a clear ascending order from CTRL, LO, DECR, INCR, to HI. The results suggested that higher training intensity on treadmill led to a better generalization, while a progressively-increase in intensity had advantage over the progressively-decrease or the low training strategy. (243 words) PMID:26159058

Ankyrin G expression is associated with androgen receptor stability, invasiveness, and lethal outcome in prostate cancer patients.

PubMed

Wang, Tingting; Abou-Ouf, Hatem; Hegazy, Samar A; Alshalalfa, Mohammed; Stoletov, Konstantin; Lewis, John; Donnelly, Bryan; Bismar, Tarek A

2016-12-01

Ankyrin G (ANK3) is a member of the Ankyrin family, which functions to provide cellular stability by anchoring the cytoskeleton to the plasma membrane. Deregulation of ANK3 expression has been observed in multiple human cancers but its mechanism remains unknown. ANK3 expression in relation to disease progression and patients' outcome was investigated in two cohorts of prostate cancer (PCA). Mechanistic studies were carried out in vitro and in vivo using several PCA cell lines and the avian embryo model. Silencing ANK3 resulted in significant reduction of cell proliferation through an AR-independent mechanism. Decreased ANK3 expression delayed S phase to G2/M cell cycle transition and reduced the expression of cyclins A and B. However, cells with knocked-down ANK3 exhibited significant increase in cell invasion through an AR-dependent mechanism. Furthermore, we found that ANK3 is a regulator of AR protein stability. ANK3 knockdown also promoted cancer cell invasion and extravasations in vivo using the avian embryo model (p < 0.01). In human samples, ANK3 expression was dramatically upregulated in high grade intraepithelial neoplasia (HGPIN) and localized PCA (p < 0.0001). However, it was downregulated castration resistant stage (p < 0.0001) and showed inverse relation to Gleason score (p < 0.0001). In addition, increased expression of ANK3 in cancer tissues was correlated with better cancer-specific survival of PCA patients (p = 0.012). Silencing ANK3 results in significant reduction of cell proliferation through an AR-independent mechanism. ANK3 knockdown results in significant increase in cell invasion through an AR-dependent mechanism. ANK3 is a regulator of AR protein stability. ANK3 knockdown also promotes cancer cell invasion and extravasation in vivo using the avian embryo model.

Sinorhizobium meliloti CtrA Stability Is Regulated in a CbrA-Dependent Manner That Is Influenced by CpdR1

PubMed Central

Schallies, Karla B.; Sadowski, Craig; Meng, Julia; Chien, Peter

2015-01-01

ABSTRACT CbrA is a DivJ/PleC-like histidine kinase of DivK that is required for cell cycle progression and symbiosis in the alphaproteobacterium Sinorhizobium meliloti. Loss of cbrA results in increased levels of CtrA as well as its phosphorylation. While many of the known Caulobacter crescentus regulators of CtrA phosphorylation and proteolysis are phylogenetically conserved within S. meliloti, the latter lacks the PopA regulator that is required for CtrA degradation in C. crescentus. In order to investigate whether CtrA proteolysis occurs in S. meliloti, CtrA stability was assessed. During exponential growth, CtrA is unstable and therefore likely to be degraded in a cell cycle-regulated manner. Loss of cbrA significantly increases CtrA stability, but this phenotype is restored to that of the wild type by constitutive ectopic expression of a CpdR1 variant that cannot be phosphorylated (CpdR1D53A). Addition of CpdR1D53A fully suppresses cbrA mutant cell cycle defects, consistent with regulation of CtrA stability playing a key role in mediating proper cell cycle progression in S. meliloti. Importantly, the cbrA mutant symbiosis defect is also suppressed in the presence of CpdR1D53A. Thus, regulation of CtrA stability by CbrA and CpdR1 is associated with free-living cell cycle outcomes and symbiosis. IMPORTANCE The cell cycle is a fundamental process required for bacterial growth, reproduction, and developmental differentiation. Our objective is to understand how a two-component signal transduction network directs cell cycle events during free-living growth and host colonization. The Sinorhizobium meliloti nitrogen-fixing symbiosis with plants is associated with novel cell cycle events. This study identifies a link between the regulated stability of an essential response regulator, free-living cell cycle progression, and symbiosis. PMID:25897034

Nanoscale pinning effect evaluated from deformed nanobubbles.

PubMed

Teshima, Hideaki; Nishiyama, Takashi; Takahashi, Koji

2017-01-07

Classical thermodynamics theory predicts that nanosized bubbles should disappear in a few hundred microseconds. The surprisingly long lifetime and stability of nanobubbles are therefore interesting research subjects. It has been proposed that the stability of nanobubbles arises through pinning of the three-phase contact line, which results from intrinsic nanoscale geometrical and chemical heterogeneities of the substrate. However, a definitive explanation of nanobubble stability is still lacking. In this work, we examined the stability mechanism by introducing a "pinning force." We investigated nanobubbles at a highly ordered pyrolytic graphite/pure water interface by peak force quantitative nano-mechanical mapping and estimated the pinning force and determined its maximum value. We then observed the shape of shrinking nanobubbles. Because the diameter of the shrinking nanobubbles was pinned, the height decreased and the contact angle increased. This phenomenon implies that the stability results from the pinning force, which flattens the bubble through the pinned three-phase contact line and prevents the Laplace pressure from increasing. The pinning force can also explain the metastability of coalesced nanobubbles, which have two semispherical parts that are joined to form a dumbbell-like shape. The pinning force of the semispherical parts was stronger than that of the joint region. This result demonstrates that the contact line of the semispherical parts is pinned strongly to keep the dumbbell-like shape. Furthermore, we proposed a nanobubble generation mechanism for the solvent-exchange method and explained why the pinning force of large nanobubbles was not initially at its maximum value, as it was for small nanobubbles.

Nanoscale pinning effect evaluated from deformed nanobubbles

NASA Astrophysics Data System (ADS)

Teshima, Hideaki; Nishiyama, Takashi; Takahashi, Koji

2017-01-01

Classical thermodynamics theory predicts that nanosized bubbles should disappear in a few hundred microseconds. The surprisingly long lifetime and stability of nanobubbles are therefore interesting research subjects. It has been proposed that the stability of nanobubbles arises through pinning of the three-phase contact line, which results from intrinsic nanoscale geometrical and chemical heterogeneities of the substrate. However, a definitive explanation of nanobubble stability is still lacking. In this work, we examined the stability mechanism by introducing a "pinning force." We investigated nanobubbles at a highly ordered pyrolytic graphite/pure water interface by peak force quantitative nano-mechanical mapping and estimated the pinning force and determined its maximum value. We then observed the shape of shrinking nanobubbles. Because the diameter of the shrinking nanobubbles was pinned, the height decreased and the contact angle increased. This phenomenon implies that the stability results from the pinning force, which flattens the bubble through the pinned three-phase contact line and prevents the Laplace pressure from increasing. The pinning force can also explain the metastability of coalesced nanobubbles, which have two semispherical parts that are joined to form a dumbbell-like shape. The pinning force of the semispherical parts was stronger than that of the joint region. This result demonstrates that the contact line of the semispherical parts is pinned strongly to keep the dumbbell-like shape. Furthermore, we proposed a nanobubble generation mechanism for the solvent-exchange method and explained why the pinning force of large nanobubbles was not initially at its maximum value, as it was for small nanobubbles.

Micromachined silicon acoustic delay line with improved structural stability and acoustic directivity for real-time photoacoustic tomography

NASA Astrophysics Data System (ADS)

Cho, Young; Kumar, Akhil; Xu, Song; Zou, Jun

2017-03-01

Recent studies have shown that micromachined silicon acoustic delay lines can provide a promising solution to achieve real-time photoacoustic tomography without the need for complex transducer arrays and data acquisition electronics. However, as its length increases to provide longer delay time, the delay line becomes more vulnerable to structural instability due to reduced mechanical stiffness. In addition, the small cross-section area of the delay line results in a large acoustic acceptance angle and therefore poor directivity. To address these two issues, this paper reports the design, fabrication, and testing of a new silicon acoustic delay line enhanced with 3D printed polymer micro linker structures. First, mechanical deformation of the silicon acoustic delay line (with and without linker structures) under gravity was simulated by using finite element method. Second, the acoustic crosstalk and acoustic attenuation caused by the polymer micro linker structures were evaluated with both numerical simulation and ultrasound transmission testing. The result shows that the use of the polymer micro linker structures significantly improves the structural stability of the silicon acoustic delay lines without creating additional acoustic attenuation and crosstalk. In addition, a new tapered design for the input terminal of the delay line was also investigate to improve its acoustic directivity by reducing the acoustic acceptance angle. These two improvements are expected to provide an effective solution to eliminate current limitations on the achievable acoustic delay time and out-of-plane imaging resolution of micromachined silicon acoustic delay line arrays.

Treatment of a patient with posterior cortical atrophy (PCA) with chiropractic manipulation and Dynamic Neuromuscular Stabilization (DNS): A case report.

PubMed

Francio, Vinicius T; Boesch, Ron; Tunning, Michael

2015-03-01

Posterior cortical atrophy (PCA) is a rare progressive neurodegenerative syndrome which unusual symptoms include deficits of balance, bodily orientation, chronic pain syndrome and dysfunctional motor patterns. Current research provides minimal guidance on support, education and recommended evidence-based patient care. This case reports the utilization of chiropractic spinal manipulation, dynamic neuromuscular stabilization (DNS), and other adjunctive procedures along with medical treatment of PCA. A 54-year-old male presented to a chiropractic clinic with non-specific back pain associated with visual disturbances, slight memory loss, and inappropriate cognitive motor control. After physical examination, brain MRI and PET scan, the diagnosis of PCA was recognized. Chiropractic spinal manipulation and dynamic neuromuscular stabilization were utilized as adjunctive care to conservative pharmacological treatment of PCA. Outcome measurements showed a 60% improvement in the patient's perception of health with restored functional neuromuscular pattern, improvements in locomotion, posture, pain control, mood, tolerance to activities of daily living (ADLs) and overall satisfactory progress in quality of life. Yet, no changes on memory loss progression, visual space orientation, and speech were observed. PCA is a progressive and debilitating condition. Because of poor awareness of PCA by physicians, patients usually receive incomplete care. Additional efforts must be centered on the musculoskeletal features of PCA, aiming enhancement in quality of life and functional improvements (FI). Adjunctive rehabilitative treatment is considered essential for individuals with cognitive and motor disturbances, and manual medicine procedures may be consider a viable option.

Pharmacokinetic drug evaluation of osimertinib for the treatment of non-small cell lung cancer.

PubMed

Rossi, Antonio; Muscarella, Lucia Anna; Di Micco, Concetta; Carbonelli, Cristiano; D'alessandro, Vito; Notarangelo, Stefano; Palomba, Giuseppe; Sanpaolo, Gerardo; Taurchini, Marco; Graziano, Paolo; Maiello, Evaristo

2017-12-01

First- and second-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib, erlotinib, icotinib, and afatinib are the standard-of-care for first-line therapy of non-small-cell lung cancer (NSCLC) harboring activating EGFR mutations. Unfortunately, after initial activity of an average 9-13 months, disease progression has been reported in the majority of patients. In about 50% of cases the progression is due to the onset of the T790M mutation in exon 20 of the EGFR gene. Third-generation EGFR-TKIs targeting this mutation were investigated, with osimertinib the only reaching clinical practice. Areas covered: A structured search of bibliographic databases for peer-reviewed research literature and of main meetings using a focused review question addressing osimertinib, was undertaken. Expert opinion: Osimertinib is the standard-of-care for EGFR-mutated patients progressing to first-line EGFR-TKIs due to the acquired EGFR T790M mutation. Results from the head-to-head first-line trial comparing osimertinib versus gefitinib or erlotinib in activating EGFR mutations might change the front-line approach. Osimertinib in combination regimens, such as immunotherapy, and in adjuvant setting are ongoing. Thus, the strategic approach for the management of EGFR-mutated NSCLC patients will change further in the next few years.

Is progression-free survival a more relevant endpoint than overall survival in first-line HR+/HER2- metastatic breast cancer?

PubMed

Forsythe, Anna; Chandiwana, David; Barth, Janina; Thabane, Marroon; Baeck, Johan; Shor, Anastasiya; Tremblay, Gabriel

2018-01-01

Hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), metastatic breast cancer (MBC) accounts for 73% of all MBCs. Endocrine therapy (ET) is the basis of first-line (1L) therapy for patients with HR+/HER2- MBC. Novel therapies have demonstrated improvements in progression-free survival (PFS) compared to ET. The clinical relevance of PFS is being debated, as there is no proven direct correlation with overall survival (OS) benefit to date. We reviewed studies of HR+/HER2- MBC to assess PFS and other factors that influence OS and treatment response, and health-related quality of life (HRQoL). The Embase ® , Medline ® , and Cochrane databases were systematically searched to identify studies in adult women with HR+/HER2- MBC, published between January 2006 and January 2017, and written in English. Phase II and III randomized controlled trials (RCTs), observational, and retrospective studies were included. Seventy-nine RCTs were identified: 58 (73%) in the 1L+ setting and 21 (27%) in second-line or greater settings. PFS hazard ratios (HRs) were reported in 61 (77%) studies; 31 (39%) reported significant PFS improvements. OS was reported in 44 (41%) studies; 12 (15%) reported significant OS improvements. Significant improvements in both PFS and OS were reported in only 6 (8%) studies (1 Phase II; 5 Phase III). Patients with HER2- MBC received, on average, ≥5 lines of therapy, with no consistent treatment pathway. Baseline characteristics, prior therapies, and the type and number of post-progression therapies significantly impacted OS. PFS, response rates, and HRQoL decreased with each line of therapy (EuroQol 5 Dimensions: 0.78 1L vs. 0.70 post-progression). Few RCTs in HR+/HER2- MBC have demonstrated significant improvements in OS. Factors other than choice of 1L therapy impact OS, including post-progression therapies, which cannot be controlled in RCTs. This study emphasizes the importance of PFS improvement in 1L treatment of HR+/HER2- MBC.

Human Fibronectin Extra-Domain B (EDB)-Specific Aptide (APTEDB) Radiolabelling with Technetium-99m as a Potent Targeted Tumour-Imaging Agent.

PubMed

Mohammadgholi, Mohsen; Sadeghzadeh, Nourollah; Erfani, Mostafa; Abediankenari, Saeid; Abedi, Seyed Mohammad; Emrarian, Iman; Jafari, Narjes; Behzadi, Ramezan

2018-01-01

Human fibronectin extra-domain B (EDB) is particularly expressed during angiogenesis progression. It is, thus, a promising marker of tumour growth. Aptides are a novel class of peptides with high-affinity binding to specific protein targets. APTEDB is an antagonist-like ligand that especially interacts with human fibronectin EDB. This study was the first attempt in which the hydrazinonicotinamide (HYNIC)-conjugated APTEDB was labelled with technetium-99m (99mTc) as an appropriate radiotracer and tricine/EDDA exchange labeling. Radiochemical purity, normal saline, and serum stability were evaluated by HPLC and radio-isotope TLC scanner. Other examinations, such as protein-binding calculation, dissociation radioligand binding assay, and partition coefficient constant determination, were also carried out. The cellular-specific binding of 99mTc- HYNIC-conjugated APTEDB was assessed in two EDB-positive (U87MG) and EDB-negative (U373MG) cell lines. Bio-distribution was investigated in normal mice as well as in U87MG and U373MG tumour-bearing mice. Eventually, the radiolabelled APTEDB was used for tumour imaging using planar SPECT. Radiolabelling was achieved with high purity (up to 97%) and accompanied by high solution (over 90% after overnight) and serum (80% after 2 hours) stability. The obtained cellular-specific binding ratio was greater than nine-fold. In-vivo experiments showed rapid blood clearance with mainly renal excretion and tumour uptake specificity (0.48±0.03% ID/g after 1h). The results of the imaging also confirmed considerable tumour uptake for EDB-positive cell line compared with the EDB-negative one. Aptides are considered to be a potent candidate for biopharmaceutical applications. They can be modified with imaging or therapeutic agents. This report shows the capability of 99mTc-HYNIC-APTEDB for human EDB-expressing tumours detection. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Genotype × Environment Interactions of Yield Traits in Backcross Introgression Lines Derived from Oryza sativa cv. Swarna/Oryza nivara

PubMed Central

Balakrishnan, Divya; Subrahmanyam, Desiraju; Badri, Jyothi; Raju, Addanki Krishnam; Rao, Yadavalli Venkateswara; Beerelli, Kavitha; Mesapogu, Sukumar; Surapaneni, Malathi; Ponnuswamy, Revathi; Padmavathi, G.; Babu, V. Ravindra; Neelamraju, Sarla

2016-01-01

Advanced backcross introgression lines (BILs) developed from crosses of Oryza sativa var. Swarna/O. nivara accessions were grown and evaluated for yield and related traits. Trials were conducted for consecutive three seasons in field conditions in a randomized complete block design with three replications. Data on yield traits under irrigated conditions were analyzed using the Additive Main Effect and Multiplicative Interaction (AMMI), Genotype and Genotype × Environment Interaction (GGE) and modified rank-sum statistic (YSi) for yield stability. BILs viz., G3 (14S) and G6 (166S) showed yield stability across the seasons along with high mean yield performance. G3 is early in flowering with high yield and has good grain quality and medium height, hence could be recommended for most of the irrigated locations. G6 is a late duration genotype, with strong culm strength, high grain number and panicle weight. G6 has higher yield and stability than Swarna but has Swarna grain type. Among the varieties tested DRRDhan 40 and recurrent parent Swarna showed stability for yield traits across the seasons. The component traits thousand grain weight, panicle weight, panicle length, grain number and plant height explained highest genotypic percentage over environment and interaction factors and can be prioritized to dissect stable QTLs/ genes. These lines were genotyped using microsatellite markers covering the entire rice genome and also using a set of markers linked to previously reported yield QTLs. It was observed that wild derived lines with more than 70% of recurrent parent genome were stable and showed enhanced yield levels compared to genotypes with higher donor genome introgressions. PMID:27807437

Immunomodulatory therapy in refractory/recurrent ovarian cancer.

PubMed

Chen, Chao-Yu; Lai, Chyong-Huey; Yang, Lan-Yan; Tang, Yun-Hsin; Chou, Hung-Hsueh; Chang, Chee-Jen; Lin, Cheng-Tao

2015-04-01

To investigate the efficacy and toxicity of immunomodulatory therapy (IMT) alone or as an add-on to palliative/salvage chemotherapy in patients with refractory/recurrent epithelial ovarian cancer (EOC). We retrospectively analyzed the efficacy and toxicity of IMT in 15 patients with refractory/recurrent EOC who had previously received multiple chemotherapy regimens. The median age of the patients was 56 years (range, 41-75 years). Three patients were platinum-sensitive, two were platinum-resistant, and the remaining 10 patients were refractory to platinum-based front-line chemotherapy. IMT consisted of picibanil (OK-432) on Day 1, interleukin-2 and/or interferon-α on Day 2 administered by subcutaneous injection (every week or 2-weekly). Five patients never received metronomic oral cyclophosphamide. After IMT, three patients achieved partial remission (PR, lasting for 11 months, ≥ 12 months, and 16 months), and six patients had stable disease (SD). The disease stabilizing rate (PR+SD) was 60% (3/3 in platinum-sensitive and 6/12 in platinum-resistant/refractory patients). The absolute lymphocyte count (ALC) at 1 month after IMT was significantly higher in the PR+SD group (median 1242.0/μL) than in the progression group (median 325.0/μL) (p = 0.012). No ≥ Grade 3 toxicities were observed. The median post-IMT survival time was 12 months (range, 2-39 months). IMT alone or add-on to palliative/salvage chemotherapy for refractory/recurrent EOC achieves a substantial disease stabilizing rate without severe toxicity, which might be a potential option in selected patients. The ALC 1 month after IMT could be an early indicator to disease stabilization. Copyright © 2015. Published by Elsevier B.V.

Prediction of Pork Longissimus Lean Color Stability Using VIS/NIR

USDA-ARS?s Scientific Manuscript database

Insufficient case-life is a costly problem facing pork processors. To assess Visible and Near-Infrared (VIS/NIR) spectroscopy as a technology to sort pork loins according to lean color stability, center-cut pork loins (n = 1208) were selected from the boning lines of four large-scale pork processor...

Cyclophosphamide-hydroxycamptothecin as second-line chemotherapy for advanced Ewing's sarcoma: experience of a single institution.

PubMed

Han, Kun; Sun, Yuanjue; Zhang, Jianjun; He, Aina; Zheng, Shui'er; Shen, Zan; Yao, Yang

2014-06-01

To investigate the feasibility and efficacy of cyclophosphamide (CTX)-hydroxycamptothecin (HCPT) as second-line chemotherapy on advanced Ewing's sarcoma. From April 2009 to November 2010, 27 patients with advanced Ewing's sarcoma who had progressive disease after the first-line chemotherapy regimen of vincristine, dactinomycin and cyclophosphamide and ifosfamide and etoposide were retrospectively reviewed in this analysis. CTX was given (0.6 g/m(2), i.v. push day 1) and HCPT (6 mg/m(2), i.v. drip days 1-5) as second-line chemotherapy every 3 weeks. The primary end-point was overall response rate, the secondary end-point included progression-free, overall survival, disease control rate and toxicities. A total of 134 cycles were given, median four cycles per patient (range 2-6). Overall response rate was 30% and disease control rate was 82%, with two complete response (8%), six partial remission (22%) and 14 stable disease (52%). The median time to progression and overall survival time were 7 months (95% CI 3-10) and 11 months (95% CI 5-18), respectively. Major severe toxicities (grade 3 and 4) were: nausea/vomiting (17%), alopecia (17%); leukopenia (27%) in total cycles. Mild toxicities (grade 1 or 2) were leukopenia (73%), nausea/vomiting (83%), hepatic lesion (14%) and anemia (44%). A CTX-HCPT regimen can control disease progression effectively and the side effects can be tolerable for Chinese advanced Ewing's sarcoma patients. Further assessment is necessary to confirm the safety and efficacy of this treatment. © 2012 Wiley Publishing Asia Pty Ltd.

[Optimization of Glycyrrhiza flavonoid and ferulic acid cream by reflect-line orthogonal simplex method].

PubMed

Liu, Sheng; Xie, Jun; Chen, Xiangqing; Yang, Liqiang; Su, Dan; Fang, Yan; Yu, Na; Fang, Wei

2010-02-01

To optimize the formula of Glycyrrhiza flavonoid and ferulic acid cream and set up its quality control parameters. Reflect-line orthogonal simplex method was used to optimize the main factors such as amount of Myrj52-glyceryl monostearate and dimethicone, based on the appearance, spreadability and stability of the cream. 9.0% Myrj52-glyceryl monostearate (3:2) and 2.5% dimethicone were chosen in prescription. The prepared cream presented a good stability after being placed 24 h at 5 degrees C, 25 degrees C and 37 degrees C respectively,and its spreadability suited with the property of semi-fluid cream. [corrected] The formula of Glycyrrhiza flavonoid and ferulic acid cream is suitable, and its quality is stable. The reflect-line orthogonal simplex method is suitable for the formula optimization of cream.

Single steady frequency and narrow-linewidth external-cavity semiconductor laser

NASA Astrophysics Data System (ADS)

Zhao, Weirui; Jiang, Pengfei; Xie, Fuzeng

2003-11-01

A single longitudinal mode and narrow line width external cavity semiconductor laser is proposed. It is constructed with a semiconductor laser, collimator, a flame grating, and current and temperature control systems. The one facet of semiconductor laser is covered by high transmission film, and another is covered by high reflection film. The flame grating is used as light feedback element to select the mode of the semiconductor laser. The temperature of the constructed external cavity semiconductor laser is stabilized in order of 10-3°C by temperature control system. The experiments have been carried out and the results obtained - the spectral line width of this laser is compressed to be less than 1.4MHz from its original line-width of more than 1200GHz and the output stability (including power and mode) is remarkably enhanced.

Selection of Early-Occurring Mutations Dictates Hormone-Independent Progression in Mouse Mammary Tumor Lines▿

PubMed Central

Gattelli, Albana; Zimberlin, María N.; Meiss, Roberto P.; Castilla, Lucio H.; Kordon, Edith C.

2006-01-01

Mice harboring three mouse mammary tumor virus (MMTV) variants develop pregnancy-dependent (PD) tumors that progress to pregnancy-independent (PI) behavior through successive passages. Herein, we identified 10 predominant insertions in PI transplants from 8 independent tumor lines. These mutations were also detected in small cell populations in the early PD passages. In addition, we identified a new viral insertion upstream of the gene Rspo3, which is overexpressed in three of the eight independent tumor lines and codes for a protein very similar to the recently described protein encoded by Int7. This study suggests that during progression towards hormone independence, clonal expansion of cells with specific mutations might be more relevant than the occurrence of new MMTV insertions. PMID:16971449

Chronic mild stress facilitates melanoma tumor growth in mouse lines selected for high and low stress-induced analgesia.

PubMed

Ragan, Agnieszka R; Lesniak, Anna; Bochynska-Czyz, Marta; Kosson, Anna; Szymanska, Hanna; Pysniak, Kazimiera; Gajewska, Marta; Lipkowski, Andrzej W; Sacharczuk, Mariusz

2013-09-01

Both chronic stress conditions and hyperergic reaction to environmental stress are known to enhance cancer susceptibility. We described two mouse lines that displayed high (HA) and low (LA) swim stress-induced analgesia (SSIA) to investigate the relationship between inherited differences in sensitivity to stress and proneness to an increased growth rate of subcutaneously inoculated melanoma. These lines display several genetic and physiological differences, among which distinct sensitivity to mutagens and susceptibility to cancer are especially noticeable. High analgesic mice display high proneness both to stress and a rapid local spread of B16F0 melanoma. However, stress-resistant LA mice do not develop melanoma tumors after inoculation, or if so, tumors regress spontaneously. We found that the chronic mild stress (CMS) procedure leads to enhanced interlinear differences in melanoma susceptibility. Tumors developed faster in stress conditions in both lines. However, LA mice still displayed a tendency for spontaneous regression, and 50% of LA mice did not develop a tumor, even under stressed conditions. Moreover, we showed that chronic stress, but not tumor progression, induces depressive behavior, which may be an important clue in cancer therapy. Our results clearly indicate how the interaction between genetic susceptibility to stress and environmental stress determine the risk and progression of melanoma. To our knowledge, HA/LA mouse lines are the first animal models of distinct melanoma progression mediated by inherited differences in stress reactivity.

Altered LINE-1 Methylation in Mothers of Children with Down Syndrome

PubMed Central

Babić Božović, Ivana; Stanković, Aleksandra; Živković, Maja; Vraneković, Jadranka; Kapović, Miljenko; Brajenović-Milić, Bojana

2015-01-01

Down syndrome (DS, also known as trisomy 21) most often results from chromosomal nondisjunction during oogenesis. Numerous studies sustain a causal link between global DNA hypomethylation and genetic instability. It has been suggested that DNA hypomethylation might affect the structure and dynamics of chromatin regions that are critical for chromosome stability and segregation, thus favouring chromosomal nondisjunction during meiosis. Maternal global DNA hypomethylation has not yet been analyzed as a potential risk factor for chromosome 21 nondisjunction. This study aimed to asses the risk for DS in association with maternal global DNA methylation and the impact of endogenous and exogenous factors that reportedly influence DNA methylation status. Global DNA methylation was analyzed in peripheral blood lymphocytes by quantifying LINE-1 methylation using the MethyLight method. Levels of global DNA methylation were significantly lower among mothers of children with maternally derived trisomy 21 than among control mothers (P = 0.000). The combination of MTHFR C677T genotype and diet significantly influenced global DNA methylation (R2 = 4.5%, P = 0.046). The lowest values of global DNA methylation were observed in mothers with MTHFR 677 CT+TT genotype and low dietary folate. Although our findings revealed an association between maternal global DNA hypomethylation and trisomy 21 of maternal origin, further progress and final conclusions regarding the role of global DNA methylation and the occurrence of trisomy 21 are facing major challenges. PMID:26017139

On the impact of fjord geometry on grounding line stability

NASA Astrophysics Data System (ADS)

Åkesson, H.; Nick, F. M.; Morlighem, M.; Nisancioglu, K. H.

2016-12-01

Observations and reconstructions of Antarctic and Greenland marine-terminating glaciers and their grounding lines show that their response to external forcings is highly dependent on the geometry of individual glaciers, such as fjord geometry. While recent retreat of these glaciers is broadly consistent with warmer atmospheric and oceanic conditions, we observe considerable spatial and temporal variability, with diverse glacier behavior within the same regions. The relatively short observational record of marine-terminating glaciers also needs to be placed in a long-term context. Reconstructions of marine-terminating glaciers, however, indicate highly asynchronous retreat histories despite being subject to similar climatic forcings. These lines of evidence suggest that regional climate forcing alone cannot explain marine-terminating glacier behavior, and that these glaciers cannot be used uncritically as indicators of past climates because of their heterogeneous response to climate change. Here we use a dynamic flowline model with a physical treatment of iceberg calving to assess the effect of fjord geometry on grounding line stability on decadal and longer time scales. The model includes driving and resistive stresses of ice flow and is applied to idealized fjord geometries representing different real-world glaciers. We find that the geometry can override the signal from the ambient forcing over multiple centuries, resulting in non-linear, rapid grounding line migration. In particular we highlight the importance of fjord width, which has received relatively little attention in terms of marine ice sheet instability. Our findings provide new insights into grounding line behavior and may explain some of the documented heterogeneous, asynchronous patterns of marine-terminating glaciers in Greenland, Antarctica, Alaska and elsewhere. Further, we investigate the geometric influence on the reversibility and hysteresis of grounding line migration, relevant for oscillatory glacier behavior, marine-terminating glacier retreat-advance cycles and Heinrich events. Finally, we present comparative, preliminary results using the 3-dimensional ice sheet model ISSM and discuss our findings in terms of ice shelf stability and buttressing.

C 90 temperature effects on relative stabilities of the IPR isomers

NASA Astrophysics Data System (ADS)

Slanina, Zdeněk; Zhao, Xiang; Lee, Shyi-Long; Ōsawa, Eiji

1997-07-01

The complete set of 46 isolated-pentagon-rule (IPR) isomers of C 90 is treated by the SAMI quantum-chemical method (Semi-Ab-Initio Model 1), and their energetics is also checked by ab initio SCF computations (HF/3-21G, HF/4-31G) and the AM1 and PM3 semiempirical methods. All the methods point out a C2 species as the system state (with an exception at the HF/3-21G level). However, the energetics itself is not able to produce a good agreement with recent observations (one C2 v, three C2, and one C1, separeted into three HPLC fractions). The symmetries of the five SAM1 lowest-energy structures are: C2, C2 v, Cs, D5 h, C1. In order to respect temperature effects on relative stabilities, entropy contributions are also computed and significant changes are found. The symmetries of the five structures most populated in a high-temperature region are according to the SAM1 computations: two times C2, Cs, C2 v, C1. One of the recently reported HPLC fractions shows 70 lines in the 13C NMR spectrum, assigned to a C2 species (45 lines) and C2 v species (25 lines, 5 weaker). There is however an alternative interpretation of the spectrum: a Cs (46 lines, 2 weaker) and a C2 v species (24 lines, 3 weaker). The last two structures are indeed present in the SAM1 high-temperature stability set so that agreement between observations and calculations can be achieved.

KELVIN–HELMHOLTZ INSTABILITY IN SOLAR CHROMOSPHERIC JETS: THEORY AND OBSERVATION

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

Kuridze, D.; Henriques, V.; Mathioudakis, M.

2016-10-20

Using data obtained by the high-resolution CRisp Imaging SpectroPolarimeter instrument on the Swedish 1 m Solar Telescope, we investigate the dynamics and stability of quiet-Sun chromospheric jets observed at the disk center. Small-scale features, such as rapid redshifted and blueshifted excursions, appearing as high-speed jets in the wings of the H α line, are characterized by short lifetimes and rapid fading without any descending behavior. To study the theoretical aspects of their stability without considering their formation mechanism, we model chromospheric jets as twisted magnetic flux tubes moving along their axis, and use the ideal linear incompressible magnetohydrodynamic approximation tomore » derive the governing dispersion equation. Analytical solutions of the dispersion equation indicate that this type of jet is unstable to Kelvin–Helmholtz instability (KHI), with a very short (few seconds) instability growth time at high upflow speeds. The generated vortices and unresolved turbulent flows associated with the KHI could be observed as a broadening of chromospheric spectral lines. Analysis of the H α line profiles shows that the detected structures have enhanced line widths with respect to the background. We also investigate the stability of a larger-scale H α jet that was ejected along the line of sight. Vortex-like features, rapidly developing around the jet’s boundary, are considered as evidence of the KHI. The analysis of the energy equation in the partially ionized plasma shows that ion–neutral collisions may lead to fast heating of the KH vortices over timescales comparable to the lifetime of chromospheric jets.« less

Architecture for Integrated Medical Model Dynamic Probabilistic Risk Assessment

NASA Technical Reports Server (NTRS)

Jaworske, D. A.; Myers, J. G.; Goodenow, D.; Young, M.; Arellano, J. D.

2016-01-01

Probabilistic Risk Assessment (PRA) is a modeling tool used to predict potential outcomes of a complex system based on a statistical understanding of many initiating events. Utilizing a Monte Carlo method, thousands of instances of the model are considered and outcomes are collected. PRA is considered static, utilizing probabilities alone to calculate outcomes. Dynamic Probabilistic Risk Assessment (dPRA) is an advanced concept where modeling predicts the outcomes of a complex system based not only on the probabilities of many initiating events, but also on a progression of dependencies brought about by progressing down a time line. Events are placed in a single time line, adding each event to a queue, as managed by a planner. Progression down the time line is guided by rules, as managed by a scheduler. The recently developed Integrated Medical Model (IMM) summarizes astronaut health as governed by the probabilities of medical events and mitigation strategies. Managing the software architecture process provides a systematic means of creating, documenting, and communicating a software design early in the development process. The software architecture process begins with establishing requirements and the design is then derived from the requirements.

Phase II trial of bevacizumab and erlotinib as a second-line therapy for advanced hepatocellular carcinoma.

PubMed

Kaseb, Ahmed O; Morris, Jeffrey S; Iwasaki, Michiko; Al-Shamsi, Humaid O; Raghav, Kanwal Pratap Singh; Girard, Lauren; Cheung, Sheree; Nguyen, Van; Elsayes, Khaled M; Xiao, Lianchun; Abdel-Wahab, Reham; Shalaby, Ahmed S; Hassan, Manal; Hassabo, Hesham M; Wolff, Robert A; Yao, James C

2016-01-01

Clinicaltrials.gov #NCT01180959. Early clinical studies of bevacizumab and erlotinib in advanced hepatocellular carcinoma (HCC) have a tolerable toxicity and a promising clinical outcome. We evaluated the efficacy and tolerability of this combination as a second-line therapy for HCC refractory to sorafenib. For this single-arm, Phase II study, we recruited patients with Child-Pugh class A or B liver disease, Eastern Cooperative Oncology Group performance status 0-2, and advanced HCC that was not amenable to surgical or regional therapies and treatment with sorafenib had failed (disease progressed or patient could not tolerate sorafenib). Patients received 10 mg/kg intravenous bevacizumab every 14 days and 150 mg oral erlotinib daily for 28-day cycles until progression. Tumor response was evaluated every two cycles using Response Evaluation Criteria in Solid Tumors. The primary end point was the 16-week progression-free survival rate. Secondary end points included time to progression and overall survival. A total of 44 patients were enrolled and had a median follow-up time of 33.8 months (95% confidence interval [CI]: 23.5 months - not defined). The 16-week progression-free survival rate was 43% (95% CI: 28%-59%), median time to progression was 3.9 months (95% CI: 2.0-8.3 months), and median overall survival duration was 9.9 months (95% CI: 8.3-15.5 months). Grade 3-4 adverse events included fatigue (13%), acne (11%), diarrhea (9%), anemia (7%), and upper gastrointestinal hemorrhage (7%). Bevacizumab plus erlotinib was tolerable and showed a signal of survival benefit in the second-line setting for patients with advanced HCC. Because standard-of-care options are lacking in this setting, further studies to identify predictors of response to this regimen are warranted.

Effects of early and late harvest on agronomic performance and stability of late blight resistant (R-gene free) potato genotypes

USDA-ARS?s Scientific Manuscript database

To assess the effectiveness of genotype resistance to potato late blight, foliar blight development, area under disease progress curves (AUDPC) and tuber blight were quantified. Late blight resistant potato genotypes (R-gene free) were assessed for yield performance and stability at early (90 days) ...

Academic Functioning and Mental Health in Adolescence: Patterns, Progressions, and Routes from Childhood.

ERIC Educational Resources Information Center

Roeser, Robert W.; Eccles, Jacquelynne S.; Freedman-Doan, Carol

1999-01-01

Examined patterns of academic functioning and mental health in middle school students and the relation of such patterns to their prior and subsequent functioning. Found variegated patterns of academic and emotional functioning at eighth grade and stability in these patterns across the high school transition. Found some long-term stability among…

Efficiency of low dosage apatinib in post-first-line treatment of advanced lung adenocarcinoma.

PubMed

Zeng, Da-Xiong; Wang, Chang-Guo; Lei, Wei; Huang, Jian-An; Jiang, Jun-Hong

2017-09-12

Chemotherapy is the standard treatment of in advanced lung adenocarcinoma patients without driver mutation. However, few drugs could be selected when diseases progressed after second-line treatment. As a small molecule inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2), apatinib was suggested mainly using in advanced gastric cancer. In this study, we showed the results of apatinib as second-line to fourth-line treatment in EGFR wild-type advanced lung adenocarcinoma patients. 16 EGFR wild-type advanced lung adenocarcinoma patients were administrated apatinib (250-500 mg/d) orally. 3 patients showed partial response and 8 patients showed stable diseases response to apatinib, with a medium progression-free survival (PFS) of 4.4 month (2-10 months). The objective remission rate (ORR) was 18.75%(3/16). The total disease control rate (DCR) was 68.75% (11/16). The main toxicities were hypertension, hand-foot syndrome, proteinuria and thrombocytopenia which were tolerable and manageable. So, apatinib might be an optional choice for post-first-line treatment of EGFR wild-type advanced lung adenocarcinoma patients.

Integration of High-Risk Human Papillomavirus into Cellular Cancer-Related Genes in Head and Neck Cancer Cell Lines

PubMed Central

Walline, Heather M; Komarck, Christine M; McHugh, Jonathan B; Tang, Alice L; Owen, John H; Teh, Bin T; McKean, Erin; Glover, Thomas; Graham, Martin P; Prince, Mark E; Chepeha, Douglas B; Chinn, Steven B; Ferris, Robert L; Gollin, Susanne M; Hoffmann, Thomas K; Bier, Henning; Brakenhoff, Ruud; Bradford, Carol R; Carey, Thomas E

2017-01-01

Background HPV-positive oropharyngeal cancer is generally associated with excellent response to therapy, but some HPV-positive tumors progress despite aggressive therapy. This study evaluates viral oncogene expression and viral integration sites in HPV16 and HPV18-positive squamous carcinoma cell lines. Methods E6-E7 alternate transcripts were assessed by RT-PCR. Detection of integrated papillomavirus sequences (DIPS-PCR) and sequencing identified viral insertion sites and affected host genes. Cellular gene expression was assessed across viral integration sites. Results All HPV-positive cell lines expressed alternate HPVE6/E7 splicing indicative of active viral oncogenesis. HPV integration occurred within cancer-related genes TP63, DCC, JAK1, TERT, ATR, ETV6, PGR, PTPRN2, and TMEM237 in 8 HNSCC lines but UM-SCC-105 and UM-GCC-1 had only intergenic integration. Conclusions HPV integration into cancer-related genes occurred in 7/9 HPV-positive cell lines and of these six were from tumors that progressed. HPV integration into cancer-related genes may be a secondary carcinogenic driver in HPV-driven tumors. PMID:28236344

Introduction to Software Product Line Adoption

DTIC Science & Technology

2005-09-01

plans • improvement suggestions • risks and mitigation strategies • progress reports • risks and mitigation strategies • adoption plan • funding ... model • organization chart • product line concept of operations (CONOPS) • marketing plan • product proposals • acquisition strategy • organization risk

Fotemustine as second-line treatment for recurrent or progressive glioblastoma after concomitant and/or adjuvant temozolomide: a phase II trial of Gruppo Italiano Cooperativo di Neuro-Oncologia (GICNO).

PubMed

Brandes, Alba A; Tosoni, A; Franceschi, E; Blatt, V; Santoro, A; Faedi, M; Amistà, P; Gardiman, M; Labianca, R; Bianchini, C; Ermani, M; Reni, M

2009-09-01

Standardized salvage treatment has not yet proved effective in glioblastoma multiforme (GBM) patients who receive prior standard radiotherapy plus concomitant and adjuvant temozolomide. Patients with progressive GBM after radiotherapy plus concomitant and/or adjuvant temozolomide received three-weekly doses (100-75 mg m(2)) of fotemustine followed, after a 5-week rest, by fotemustine (100 mg m(2)) every 3 weeks for < or =1 year. Forty-three patients (29 M, 14 F; median age 51 years, range 34-68; median KPS 90) were enrolled. Progression-free survival at 6 months (PFS-6) was 20.9% (95% CI: 9-33%); three patients (7.1%) had partial response (PR); 15 (34.9%), disease stabilization (SD). The median survival was 6 months (95% CI: 5-7). MGMT promoter status was methylated in 8 (18.6%) and unmethylated in 26 (60.5%) and not assessable in 9 (20.9%) patients, respectively. Disease control was 75% versus 34.6% in methylated and unmethylated MGMT patients (P = 0.044); no significant difference was found between groups for PFS-6 and survival. Grade 3 and 4 thrombocytopenia and neutropenia were observed in 20.9 and 16.3% of patients, during the induction phase, and in 0 and 9.5% patients during the maintenance phase, respectively. The findings of the present trial, that evaluate fotemustine in a homogeneous population, may represent a new benchmark for nitrosourea activity. Moreover, this is the first study to evaluate correlation between MGMT promoter status and outcome of fotemustine for relapsing GBM previously treated with radiotherapy and temozolomide.

Biweekly cetuximab and irinotecan in advanced colorectal cancer patients progressing after at least one previous line of chemotherapy: results of a phase II single institution trial

PubMed Central

Martín-Martorell, P; Roselló, S; Rodríguez-Braun, E; Chirivella, I; Bosch, A; Cervantes, A

2008-01-01

This is a phase II institutional exploratory trial of biweekly irinotecan and cetuximab administration regimen in metastatic colorectal cancer patients progressing to at least one previous chemotherapy line. A total of 40 patients were treated between November 2005 and November 2007 with irinotecan 180 mg m−2 and cetuximab 500 mg m−2 q2w (every 2 weeks), in every 21-day cycles, until unacceptable toxicity or progressive disease. An overall response rate of 22.5% was obtained (two complete and seven partial responses). The disease control rate was 60%. The time to progression was 3.4 months and the overall survival was 8 months. The toxicity compared very favourably to weekly cetuximab combination schedules. Grade 3/4 adverse effects were observed in 12 patients. Overall, our results turn up very similar both in terms of toxicity and efficacy to those obtained by weekly and biweekly administration regimens. PMID:18665167

Say hello to the DSO

NASA Astrophysics Data System (ADS)

Pate, G.; Roberts, T.

1981-05-01

In the 2-to-10 GHz frequency range, the dielectrically stabilized oscillators (DSOs) with their small size, simple construction, and modest bias requirements, have advantages over cavity-stabilized oscillators (CSOs) and crystal-controlled multiplier chains (XCOs). Commercially available DSOs consist of a transistor oscillator locked to some frequency by a resonant disk of dielectric material. The disk is coupled to a microstrip line at the output of the oscillator. The stability of a DSO lies between that of a crystal-controlled oscillator and that of a cavity-stabilized oscillator. Dielectrically stabilized oscillators, built with nine basic parts and few solder joints, can be expected to be much more reliable than a CSO or XCO.

First- and Second-Line Bevacizumab in Addition to Chemotherapy for Metastatic Colorectal Cancer: A United States–Based Cost-Effectiveness Analysis

PubMed Central

Goldstein, Daniel A.; Chen, Qiushi; Ayer, Turgay; Howard, David H.; Lipscomb, Joseph; El-Rayes, Bassel F.; Flowers, Christopher R.

2015-01-01

Purpose The addition of bevacizumab to fluorouracil-based chemotherapy is a standard of care for previously untreated metastatic colorectal cancer. Continuation of bevacizumab beyond progression is an accepted standard of care based on a 1.4-month increase in median overall survival observed in a randomized trial. No United States–based cost-effectiveness modeling analyses are currently available addressing the use of bevacizumab in metastatic colorectal cancer. Our objective was to determine the cost effectiveness of bevacizumab in the first-line setting and when continued beyond progression from the perspective of US payers. Methods We developed two Markov models to compare the cost and effectiveness of fluorouracil, leucovorin, and oxaliplatin with or without bevacizumab in the first-line treatment and subsequent fluorouracil, leucovorin, and irinotecan with or without bevacizumab in the second-line treatment of metastatic colorectal cancer. Model robustness was addressed by univariable and probabilistic sensitivity analyses. Health outcomes were measured in life-years and quality-adjusted life-years (QALYs). Results Using bevacizumab in first-line therapy provided an additional 0.10 QALYs (0.14 life-years) at a cost of $59,361. The incremental cost-effectiveness ratio was $571,240 per QALY. Continuing bevacizumab beyond progression provided an additional 0.11 QALYs (0.16 life-years) at a cost of $39,209. The incremental cost-effectiveness ratio was $364,083 per QALY. In univariable sensitivity analyses, the variables with the greatest influence on the incremental cost-effectiveness ratio were bevacizumab cost, overall survival, and utility. Conclusion Bevacizumab provides minimal incremental benefit at high incremental cost per QALY in both the first- and second-line settings of metastatic colorectal cancer treatment. PMID:25691669

Flight-Test Evaluation of the Longitudinal Stability and Control Characteristics of 0.5-Scale Models of the Fairchild Lark Pilotless-Aircraft Configuration: Standard Configuration with Wing Flaps Deflected 60 Degrees and Model having Tail in Line with Wings, TED No. NACA 2387

NASA Technical Reports Server (NTRS)

Stone, David G.

1947-01-01

Flight tests were conducted at the Flight Test Station of the Pilotless Aircraft Research Division at Wallop Island, Va., to determine the longitudinal control and stability characteristics of 0.5-scale models of the Fairchild Lark pilotless aircraft with the tail in line with the wings a d with the horizontal wing flaps deflected 60 deg. The data were obtained by the use of a telemeter and by radar tracking.

A Technique for Measuring Rotocraft Dynamic Stability in the 40 by 80 Foot Wind Tunnel

NASA Technical Reports Server (NTRS)

Gupta, N. K.; Bohn, J. G.

1977-01-01

An on-line technique is described for the measurement of tilt rotor aircraft dynamic stability in the Ames 40- by 80-Foot Wind Tunnel. The technique is based on advanced system identification methodology and uses the instrumental variables approach. It is particulary applicable to real time estimation problems with limited amounts of noise-contaminated data. Several simulations are used to evaluate the algorithm. Estimated natural frequencies and damping ratios are compared with simulation values. The algorithm is also applied to wind tunnel data in an off-line mode. The results are used to develop preliminary guidelines for effective use of the algorithm.

Computerized dynamic posturography: the influence of platform stability on postural control.

PubMed

Palm, Hans-Georg; Lang, Patricia; Strobel, Johannes; Riesner, Hans-Joachim; Friemert, Benedikt

2014-01-01

Postural stability can be quantified using posturography systems, which allow different foot platform stability settings to be selected. It is unclear, however, how platform stability and postural control are mathematically correlated. Twenty subjects performed tests on the Biodex Stability System at all 13 stability levels. Overall stability index, medial-lateral stability index, and anterior-posterior stability index scores were calculated, and data were analyzed using analysis of variance and linear regression analysis. A decrease in platform stability from the static level to the second least stable level was associated with a linear decrease in postural control. The overall stability index scores were 1.5 ± 0.8 degrees (static), 2.2 ± 0.9 degrees (level 8), and 3.6 ± 1.7 degrees (level 2). The slope of the regression lines was 0.17 for the men and 0.10 for the women. A linear correlation was demonstrated between platform stability and postural control. The influence of stability levels seems to be almost twice as high in men as in women.

Titin domains progressively unfolded by force are homogenously distributed along the molecule.

PubMed

Bianco, Pasquale; Mártonfalvi, Zsolt; Naftz, Katalin; Kőszegi, Dorina; Kellermayer, Miklós

2015-07-21

Titin is a giant filamentous protein of the muscle sarcomere in which stretch induces the unfolding of its globular domains. However, the mechanisms of how domains are progressively selected for unfolding and which domains eventually unfold have for long been elusive. Based on force-clamp optical tweezers experiments we report here that, in a paradoxical violation of mechanically driven activation kinetics, neither the global domain unfolding rate, nor the folded-state lifetime distributions of full-length titin are sensitive to force. This paradox is reconciled by a gradient of mechanical stability so that domains are gradually selected for unfolding as the magnitude of the force field increases. Atomic force microscopic screening of extended titin molecules revealed that the unfolded domains are distributed homogenously along the entire length of titin, and this homogeneity is maintained with increasing overstretch. Although the unfolding of domains with progressively increasing mechanical stability makes titin a variable viscosity damper, the spatially randomized variation of domain stability ensures that the induced structural changes are not localized but are distributed along the molecule's length. Titin may thereby provide complex safety mechanims for protecting the sarcomere against structural disintegration under excessive mechanical conditions. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Micromachined silicon acoustic delay line with 3D-printed micro linkers and tapered input for improved structural stability and acoustic directivity

NASA Astrophysics Data System (ADS)

Cho, Y.; Kumar, A.; Xu, S.; Zou, J.

2016-10-01

Recent studies have shown that micromachined silicon acoustic delay lines can provide a promising solution to achieve real-time photoacoustic tomography without the need for complex transducer arrays and data acquisition electronics. To achieve deeper imaging depth and wider field of view, a longer delay time and therefore delay length are required. However, as the length of the delay line increases, it becomes more vulnerable to structural instability due to reduced mechanical stiffness. In this paper, we report the design, fabrication, and testing of a new silicon acoustic delay line enhanced with 3D printed polymer micro linker structures. First, mechanical deformation of the silicon acoustic delay line (with and without linker structures) under gravity was simulated by using finite element method. Second, the acoustic crosstalk and acoustic attenuation caused by the polymer micro linker structures were evaluated with both numerical simulation and ultrasound transmission testing. The result shows that the use of the polymer micro linker structures significantly improves the structural stability of the silicon acoustic delay lines without creating additional acoustic attenuation and crosstalk. In addition, the improvement of the acoustic acceptance angle of the silicon acoustic delay lines was also investigated to better suppress the reception of unwanted ultrasound signals outside of the imaging plane. These two improvements are expected to provide an effective solution to eliminate current limitations on the achievable acoustic delay time and out-of-plane imaging resolution of micromachined silicon acoustic delay line arrays.

Osimertinib in Japanese patients with EGFR T790M mutation-positive advanced non-small cell lung cancer: AURA3 trial.

PubMed

Akamatsu, Hiroaki; Katakami, Nobuyuki; Okamoto, Isamu; Kato, Terufumi; Kim, Young Hak; Imamura, Fumio; Shinkai, Masaharu; Hodge, Rachel A; Uchida, Hirohiko; Hida, Toyoaki

2018-04-26

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are the first-line treatment for patients with EGFR mutant non-small cell lung cancer (NSCLC). However, most patients become resistant to these drugs, so their disease progresses. Osimertinib, a third-generation EGFR-TKI that can inhibit the kinase even when the common resistance-conferring Thr790Met (T790M) mutation is present, is a promising therapeutic option for patients whose disease has progressed after first-line EGFR-TKI treatment. AURA3 was a randomized (2:1), open-label, phase 3 study comparing the efficacy of osimertinib (80 mg/day) with platinum-based therapy plus pemetrexed (500 mg/m 2 ) in 419 patients with advanced NSCLC with the EGFR T790M mutation in whom disease had progressed after first-line EGFR-TKI treatment. This subanalysis evaluated the safety and efficacy of osimertinib specifically in 63 Japanese patients enrolled in AURA3. The primary endpoint was progression-free survival (PFS) based on investigator assessment. PFS improvement was clinically meaningful in the osimertinib group (n=41) versus the platinum-pemetrexed group (n=22; hazard ratio 0.27, 95% confidence interval 0.13-0.56). The median PFS was 12.5 and 4.3 months in the osimertinib and platinum-pemetrexed groups, respectively. Grade ≥3 adverse events determined to be related to treatment occurred in five patients (12.2%) treated with osimertinib and 12 patients (54.5%) treated with platinum-pemetrexed. The safety and efficacy results in this subanalysis are consistent with the results of the overall AURA3 study, and support the use of osimertinib in Japanese patients with EGFR mutant and T790M NSCLC whose disease has progressed following first-line EGFR-TKI treatment. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Linear Stability of Binary Alloy Solidification for Unsteady Growth Rates

NASA Technical Reports Server (NTRS)

Mazuruk, K.; Volz, M. P.

2010-01-01

An extension of the Mullins and Sekerka (MS) linear stability analysis to the unsteady growth rate case is considered for dilute binary alloys. In particular, the stability of the planar interface during the initial solidification transient is studied in detail numerically. The rapid solidification case, when the system is traversing through the unstable region defined by the MS criterion, has also been treated. It has been observed that the onset of instability is quite accurately defined by the "quasi-stationary MS criterion", when the growth rate and other process parameters are taken as constants at a particular time of the growth process. A singular behavior of the governing equations for the perturbed quantities at the constitutional supercooling demarcation line has been observed. However, when the solidification process, during its transient, crosses this demarcation line, a planar interface is stable according to the linear analysis performed.

Ultralow-frequency-noise stabilization of a laser by locking to an optical fiber-delay line.

PubMed

Kéfélian, Fabien; Jiang, Haifeng; Lemonde, Pierre; Santarelli, Giorgio

2009-04-01

We report the frequency stabilization of an erbium-doped fiber distributed-feedback laser using an all-fiber-based Michelson interferometer of large arm imbalance. The interferometer uses a 1 km SMF-28 optical fiber spool and an acousto-optic modulator allowing heterodyne detection. The frequency-noise power spectral density is reduced by more than 40 dB for Fourier frequencies ranging from 1 Hz to 10 kHz, corresponding to a level well below 1 Hz2/Hz over the entire range; it reaches 10(-2) Hz2/Hz at 1 kHz. Between 40 Hz and 30 kHz, the frequency noise is shown to be comparable to the one obtained by Pound-Drever-Hall locking to a high-finesse Fabry-Perot cavity. Locking to a fiber delay line could consequently represent a reliable, simple, and compact alternative to cavity stabilization for short-term linewidth reduction.

Effect of first-line endocrine therapy in patients with hormone-sensitive advanced breast cancer: a network meta-analysis.

PubMed

Zhang, Tingting; Feng, Fubin; Zhao, Wenge; Tian, Jinhui; Yao, Yan; Zhou, Chao; Dong, Shengjie; Wang, Congcong; Zang, Chuanxin; Lv, Qingliang; Sun, Changgang

2018-01-01

Endocrine therapy is the cornerstone treatment for patients with hormone receptor-positive advanced breast cancer. We aimed to assess the effectiveness of various first-line endocrine monotherapies or combinations to determine the optimal sequence in a network meta-analysis. We searched PubMed, EMBASE, and the Cochrane Library for randomized controlled trials (RCTs) from inception up to November 21, 2017. We included only RCTs that assessed the effectiveness of the following treatments as a monotherapy or in combination as the first-line treatment: tamoxifen, anastrozole, letrozole, exemestane, fulvestrant, palbociclib, and ribociclib. The results were presented with pooled odds ratio or hazard ratio (HR), and 95% credible interval (CrI). The primary outcomes were objective response rate (ORR) and progression-free survival/time to progression. A total of 16 eligible articles (14 RCTs) involving 6,602 patients treated with 10 different first-line endocrine therapies were assessed in our network meta-analysis. Palbociclib plus letrozole was superior to anastrozole, letrozole, exemestane, fulvestrant 500 mg, and anastrozole plus fulvestrant (loading dose) (HR=0.44, 95% CrI: 0.33-0.58; HR=0.56, 95% CrI: 0.45-0.68; HR=0.45, 95% CrI: 0.32-0.61; HR=0.58, 95% CrI: 0.42-0.81; HR=0.50, 95% CrI: 0.37-0.68; respectively). However, there is no significant advantage compared with ribociclib plus letrozole (HR=1.00, 95% CrI: 0.72-1.39). In terms of ORR, ribociclib plus letrozole is more effective than palbociclib plus letrozole (odds ratio=1.30, 95% CrI: 0.83-2.02). Palbociclib plus letrozole and ribociclib plus letrozole might be the optimal first-line endocrine therapeutic choices for hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer due to a longer progression-free survival/time to progression and a more efficacious ORR.

76 FR 49533 - Spyker Automobielen B.V.; Receipt of Application for Temporary Exemption from FMVSS No. 126

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-10

... Standard (FMVSS) No. 126, Electronic Stability Control Systems. SUMMARY: In accordance with the procedures... line of vehicles from the requirements of FMVSS No. 126, the standard for electronic stability control systems. The basis of the application is that compliance would cause substantial economic hardship to a...

Pinning Stabilizes Neighboring Surface Nanobubbles against Ostwald Ripening.

PubMed

Dollet, Benjamin; Lohse, Detlef

2016-11-01

Pinning of the contact line and gas oversaturation explain the stability of single surface nanobubbles. In this article, we theoretically show that the pinning also suppresses the Ostwald ripening process between neighboring surface nanobubbles, thus explaining why in a population of neighboring surface nanobubbles different radii of curvature of the nanobubbles can be observed.

Stability analysis of cylinders with circular cutouts

NASA Technical Reports Server (NTRS)

Almroth, B. O.; Brogan, F. A.; Marlowe, M. B.

1973-01-01

The stability of axially compressed cylinders with circular cutouts is analyzed numerically. An extension of the finite-difference method is used which removes the requirement that displacement components be defined in the directions of the grid lines. The results of this nonlinear analysis are found to be in good agreement with earlier experimental results.

Development of Transit Coach Bonded Brake Lining Test Equipment and Test Procedures--Progress Report

DOT National Transportation Integrated Search

1984-01-01

Bonded brake linings have been introduced in limited quantities at several urban and suburban transit properties. The in-service capabilities of current bonding processes and brake materials are undergoing assessment, and field data on the wear and f...

Optical frequency locked loop for long-term stabilization of broad-line DFB laser frequency difference

NASA Astrophysics Data System (ADS)

Lipka, Michał; Parniak, Michał; Wasilewski, Wojciech

2017-09-01

We present an experimental realization of the optical frequency locked loop applied to long-term frequency difference stabilization of broad-line DFB lasers along with a new independent method to characterize relative phase fluctuations of two lasers. The presented design is based on a fast photodiode matched with an integrated phase-frequency detector chip. The locking setup is digitally tunable in real time, insensitive to environmental perturbations and compatible with commercially available laser current control modules. We present a simple model and a quick method to optimize the loop for a given hardware relying exclusively on simple measurements in time domain. Step response of the system as well as phase characteristics closely agree with the theoretical model. Finally, frequency stabilization for offsets within 4-15 GHz working range achieving <0.1 Hz long-term stability of the beat note frequency for 500 s averaging time period is demonstrated. For these measurements we employ an I/Q mixer that allows us to precisely and independently measure the full phase trace of the beat note signal.

Ultrastructural and some functional changes in tumor cells treated with stabilized iron oxide nanoparticles.

PubMed

Yurchenko, O V; Todor, I N; Khayetsky, I K; Tregubova, N A; Lukianova, N Yu; Chekhun, V F

2010-12-01

To study the ultrastructure and some functional indexes of tumor cells treated with stabilized iron nanoparticles in vitro. 3-[4,5dimethylthiazol-2-1]-2,5-diphenyltetrazolium bromide (MTT)-test, electron microscopy, polarography with applying of closed Clark's electrode. It was shown that cultivation of cells with stabilized Fe(3)O(4) leads to intracellular accumulation of ferromagnetic nanoparticles. The most active ferromagnetic uptake by cells has been observed after 24 and 48 h of incubation. The presence of ferromagnetic in cells led to altered mitochondrial structure that caused the decrease of oxygen uptake rate in the cells of all studied lines. Ferromagnetic released from the majority of cells via exocytosis or clasmacytosis after a certain period of time. The number of dead cells or cells with severe damage was moderate, so cytotoxic action of stabilized iron oxide nanoparticles was minimal toward the studied cell lines. the presence of ferromagnetic nanoparticles in culture medium led to alterations in mitochondria ultrastructural organization and decrease of oxygen uptake by mitochondria in sensitive and anticancer-drugs resistant cells.

Genomic instability of osteosarcoma cell lines in culture: impact on the prediction of metastasis relevant genes.

PubMed

Muff, Roman; Rath, Prisni; Ram Kumar, Ram Mohan; Husmann, Knut; Born, Walter; Baudis, Michael; Fuchs, Bruno

2015-01-01

Osteosarcoma is a rare but highly malignant cancer of the bone. As a consequence, the number of established cell lines used for experimental in vitro and in vivo osteosarcoma research is limited and the value of these cell lines relies on their stability during culture. Here we investigated the stability in gene expression by microarray analysis and array genomic hybridization of three low metastatic cell lines and derivatives thereof with increased metastatic potential using cells of different passages. The osteosarcoma cell lines showed altered gene expression during in vitro culture, and it was more pronounced in two metastatic cell lines compared to the respective parental cells. Chromosomal instability contributed in part to the altered gene expression in SAOS and LM5 cells with low and high metastatic potential. To identify metastasis-relevant genes in a background of passage-dependent altered gene expression, genes involved in "Pathways in cancer" that were consistently regulated under all passage comparisons were evaluated. Genes belonging to "Hedgehog signaling pathway" and "Wnt signaling pathway" were significantly up-regulated, and IHH, WNT10B and TCF7 were found up-regulated in all three metastatic compared to the parental cell lines. Considerable instability during culture in terms of gene expression and chromosomal aberrations was observed in osteosarcoma cell lines. The use of cells from different passages and a search for genes consistently regulated in early and late passages allows the analysis of metastasis-relevant genes despite the observed instability in gene expression in osteosarcoma cell lines during culture.

A compact frequency stabilized telecom laser diode for space applications

NASA Astrophysics Data System (ADS)

Philippe, C.; Holleville, D.; Le Targat, R.; Wolf, P.; Leveque, T.; Le Goff, R.; Martaud, E.; Acef, O.

2017-09-01

We report on a Telecom laser diode (LD) frequency stabilization to a narrow iodine hyperfine line in the green range, after frequency tripling process using fibered nonlinear waveguide PPLN crystals. We have generated up to 300 mW optical power in the green range ( 514 nm) from 800 mW of infrared power ( 1542 nm), corresponding to a nonlinear conversion efficiency h = P3?/P? 36%. Less than 10 mW of the generated green power are used for Doppler-free spectroscopy of 127I2 molecular iodine, and -therefore- for the frequency stabilization purpose. The frequency tripling optical setup is very compact (< 5 l), fully fibered, and could operate over the full C-band of the Telecom range (1530 nm - 1565 nm). Several thousands of hyperfine iodine lines may thus be interrogated in the 510 nm - 521 nm range. We build up an optical bench used at first in free space configuration, using the well-known modulation transfer spectroscopy technique (MTS), in order to test the potential of this new frequency standard based on the couple "1.5 ?m laser / iodine molecule". We have already demonstrated a preliminary frequency stability of 4.8 x 10-14 ? -1/2 with a minimum value of 6 x 10-15 reached after 50 s of integration time, conferred to a laser diode operating at 1542.1 nm. We focus now our efforts to expand the frequency stability to a longer integration time in order to meet requirements of many space experiments, such earth gravity missions, inters satellites links or space to ground communications. Furthermore, we investigate the potential of a new approach based on frequency modulation technique (FM), associated to a 3rd harmonic detection of iodine lines to increase the compactness of the optical setup.

One-dimensional terahertz imaging of surfactant-stabilized dodecane-brine emulsion

NASA Astrophysics Data System (ADS)

Nickel, Daniel Vincent

Terahertz line-images of surfactant-stabilized dodecane(C12H 26)-brine emulsions are obtained by translating the emulsified region through the focus of a terahertz time-domain spectrometer, capturing a time-domain waveform at each vertical position. From these images, relative dodecane content, emulsion size, and stability can be extracted to evaluate the efficacy of the surfactant in solvating the dodecane. In addition, the images provide insight into the dynamics of concentrated emulsions after mixing.

Disease management patterns for postmenopausal women in Europe with hormone-receptor-positive, human epidermal growth factor receptor-2 negative advanced breast cancer.

PubMed

André, Fabrice; Neven, Patrick; Marinsek, Nina; Zhang, Jie; Baladi, Jean-Francois; Degun, Ravi; Benelli, Giancarlo; Saletan, Stephen; Jerusalem, Guy

2014-06-01

International guidelines for hormone-receptor-positive (HR(+)), human epidermal growth factor receptor-2 negative (HER2(-)) advanced breast cancer (BC) recommend sequential lines of hormonal therapy (HT), and only recommend chemotherapy for patients with extensive visceral involvement or rapidly progressive disease. This study evaluated actual physician-reported treatments for advanced BC in Europe. We conducted a retrospective chart review of 355 postmenopausal women with HR(+), HER2(-) advanced BC who progressed on ≥1 line of HT (adjuvant or advanced) and completed ≥1 line of chemotherapy (advanced). Treatment choice was evaluated for each line of therapy. Of 355 patients, 111 (31%) received first-line chemotherapy, whereas 218 (61%) and 26 (7%) switched from HT to chemotherapy in second and third line, respectively. More patients receiving first-line HT had bone metastases (73% vs 27% chemotherapy). Patients treated with first-line chemotherapy had more brain (12% vs 3% HT) or extensive liver (13% vs 6% HT) metastases. Subgroup analysis of 188 patients who received first-line HT and had de novo advanced BC or relapsed/recurrent disease more than 1 year after adjuvant therapy found that the majority (89%; n = 167) of these patients switched to chemotherapy in second line. However, among these 167 patients, 27% had no significant changes in metastases between first and second line. Among the 73% of patients who had significant changes in metastases, 20% had no brain metastases or extensive visceral disease. Our study suggests that the guideline-recommended use of multiple HT lines is open to interpretation and that optimal treatment for European postmenopausal women with HR(+), HER2(-) advanced BC who responded to HT may not be achieved.

A decision tree-based on-line preventive control strategy for power system transient instability prevention

NASA Astrophysics Data System (ADS)

Xu, Yan; Dong, Zhao Yang; Zhang, Rui; Wong, Kit Po

2014-02-01

Maintaining transient stability is a basic requirement for secure power system operations. Preventive control deals with modifying the system operating point to withstand probable contingencies. In this article, a decision tree (DT)-based on-line preventive control strategy is proposed for transient instability prevention of power systems. Given a stability database, a distance-based feature estimation algorithm is first applied to identify the critical generators, which are then used as features to develop a DT. By interpreting the splitting rules of DT, preventive control is realised by formulating the rules in a standard optimal power flow model and solving it. The proposed method is transparent in control mechanism, on-line computation compatible and convenient to deal with multi-contingency. The effectiveness and efficiency of the method has been verified on New England 10-machine 39-bus test system.

Constrained off-line synthesis approach of model predictive control for networked control systems with network-induced delays.

PubMed

Tang, Xiaoming; Qu, Hongchun; Wang, Ping; Zhao, Meng

2015-03-01

This paper investigates the off-line synthesis approach of model predictive control (MPC) for a class of networked control systems (NCSs) with network-induced delays. A new augmented model which can be readily applied to time-varying control law, is proposed to describe the NCS where bounded deterministic network-induced delays may occur in both sensor to controller (S-A) and controller to actuator (C-A) links. Based on this augmented model, a sufficient condition of the closed-loop stability is derived by applying the Lyapunov method. The off-line synthesis approach of model predictive control is addressed using the stability results of the system, which explicitly considers the satisfaction of input and state constraints. Numerical example is given to illustrate the effectiveness of the proposed method. Copyright © 2014 ISA. Published by Elsevier Ltd. All rights reserved.

Wide band continuous all-fiber comb generator at 1.5 micron

NASA Astrophysics Data System (ADS)

Lemaître, François; Mondin, Linda; Orlik, X.

2017-11-01

We present an all-fiber continuous optical frequency comb-generator (OFCG) able to generate over 6 nm (750 GHz) at 1560 nm using a combination of electro-optic and acousto-optic modulations. As opposed to numerous experimental setups that use the longitudinal modes of an optical cavity to generate continuous optical frequency combs, our setup doesn't need any active stabilization of the cavity length since we use the intrinsically high stability of radiofrequency sources to generate the multiple lines of the comb laser. Moreover, compared to the work of ref [1], the hybrid optical modulation we use allows to suppress the problem of instability due interferences between the generated lines. We notice that these lines benefit from the spectral quality of the seed laser because the spectral width of the synthesized hyperfrequency and radiofrequency signals are generally narrower than laser sources.

Far infrared maser communications technology

NASA Technical Reports Server (NTRS)

Claspy, P. C.; Pao, Y. H.

1975-01-01

An optically pumped FIR laser was constructed and tested. Optimum operating conditions were determined with CH3OH as the lasing medium. The laser was found to operate equally well with flowing gas or in a sealed off configuration. The FIR cavity stability and pump laser stability were found to have significant problems. The absorption coefficient per unit pressure of 1-1 difluoroethylene at the P(22) and P(24) lines of the 10.4 micron CO2 band was measured. The FIR line pumped by P(22) occurs at approximately 890 microns, which may be in an atmospheric transmission window. It was found that significant Stark tuning of absorption lines of methanol and 1-1 difluoroethylene can be accomplished, even at the usual 100 to 300 mTorr operating pressures of FIR lasers. This means that the use of Stark tuning may enable more effective use of pump laser output.

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

Kahl, S.B.

Although significant progress toward the application of boronated LDL for site selective boron drug delivery has been made during the past year, the loss of our animal and cell culture testing site at WSU has seriously hampered progress on this project. Results are reported of one in vivo biodistribution study in B16BL6-bearing mice and a series of in vitro studies that demonstrate very substantial uptake of boronated LDL in certain cell lines. The influence of 17{alpha}-ethinyl estradiol (EE) on cellular uptake has also been probed. Most significantly LDL loaded with HC was demonstrated to be taken up with exceptional ariditymore » in several lines. Significant progress has also been made in the development of a rapid infrared analysis of boron in boronated LDL solution, which may be useful for clinical BNCT studies in Finland.« less

Atherosclerosis. Potential targets for stabilization and regression.

PubMed

Schwartz, C J; Valente, A J; Sprague, E A; Kelley, J L; Cayatte, A J; Mowery, J

1992-12-01

Reviewed are various aspects of atherosclerotic plaque stabilization and regression in humans and experimental animals. Plaque regression is a function of the dynamic balance among initiation, progression, stabilization, and removal of plaque constituents. Pseudoregression, the result of the triad thrombolysis, age- or lesion-dependent arterial dilatation, and relaxation of vasospasm, may readily give rise to angiographic misinterpretation. Although lowering of plasma cholesterol and low density lipoprotein-cholesterol has demonstrated significant clinical benefits in a number of clinical trials, the magnitude of angiographic regressive changes is relatively small despite aggressive lipid-lowering regimens. The emerging need for alternative or complementary therapeutic interventions has been emphasized. In particular, they should be targeted to pivotal cellular or molecular mechanisms in initiation, progression, or stabilization. Potentially important therapeutic targets include the use of antioxidants or free radical scavengers such as Probucol or its analogues, butylated hydroxytoluene, tocopherols, and possibly the tocotrienols. Other therapeutic targets include intimal monocyte-macrophage recruitment, macrophage cholesterol acyltransferase inhibition, stimulation of the high density lipoprotein-mediated reverse cholesterol transport system, smooth muscle cell migration to and proliferation in the arterial intima, and intimal connective tissue synthesis. Whether the isoprenylated proteins associated with the cholesterol biosynthetic pathway will give rise to compounds regulating smooth muscle cell growth has yet to be determined. Because of the importance of thrombosis in the pathogenesis and progression of lesions, the need to develop interventional strategies targeted at endothelial cell thromboresistance and thromboregulation must assume a high priority in future research and development. Other areas of therapeutic promise include the calcium channel blockers and angiotensin converting enzyme inhibitors.(ABSTRACT TRUNCATED AT 250 WORDS)

Sulforaphane reduces molecular response to hypoxia in ovarian tumor cells independently of their resistance to chemotherapy.

PubMed

Pastorek, Michal; Simko, Veronika; Takacova, Martina; Barathova, Monika; Bartosova, Maria; Hunakova, Luba; Sedlakova, Olga; Hudecova, Sona; Krizanova, Olga; Dequiedt, Franck; Pastorekova, Silvia; Sedlak, Jan

2015-07-01

One of the recently emerging anticancer strategies is the use of natural dietary compounds, such as sulforaphane, a cancer-chemopreventive isothiocyanate found in broccoli. Based on the growing evidence, sulforaphane acts through molecular mechanisms that interfere with multiple oncogenic pathways in diverse tumor cell types. Herein, we investigated the anticancer effects of bioavailable concentrations of sulforaphane in ovarian carcinoma cell line A2780 and its two derivatives, adriamycin-resistant A2780/ADR and cisplatin-resistant A2780/CP cell lines. Since tumor microenvironment is characterized by reduced oxygenation that induces aggressive tumor phenotype (such as increased invasiveness and resistance to chemotherapy), we evaluated the effects of sulforaphane in ovarian cancer cells exposed to hypoxia (2% O2). Using the cell-based reporter assay, we identified several oncogenic pathways modulated by sulforaphane in hypoxia by activating anticancer responses (p53, ARE, IRF-1, Pax-6 and XRE) and suppressing responses supporting tumor progression (AP-1 and HIF-1). We further showed that sulforaphane decreases the level of HIF-1α protein without affecting its transcription and stability. It can also diminish transcription and protein level of the HIF-1 target, CA IX, which protects tumor cells from hypoxia-induced pH imbalance and facilitates their migration/invasion. Accordingly, sulforaphane treatment leads to diminished pH regulation and reduced migration of ovarian carcinoma cells. These effects occur in all three ovarian cell lines suggesting that sulforaphane can overcome the chemoresistance of cancer cells. This offers a path potentially exploitable in sensitizing resistant cancer cells to therapy, and opens a window for the combined treatments of sulforaphane either with conventional chemotherapy, natural compounds, or with other small molecules.

Insulin-Like Growth Factor 2 Silencing Restores Taxol Sensitivity in Drug Resistant Ovarian Cancer

PubMed Central

Brouwer-Visser, Jurriaan; Lee, Jiyeon; McCullagh, KellyAnne; Cossio, Maria J.; Wang, Yanhua; Huang, Gloria S.

2014-01-01

Drug resistance is an obstacle to the effective treatment of ovarian cancer. We and others have shown that the insulin-like growth factor (IGF) signaling pathway is a novel potential target to overcome drug resistance. The purpose of this study was to validate IGF2 as a potential therapeutic target in drug resistant ovarian cancer and to determine the efficacy of targeting IGF2 in vivo. An analysis of The Cancer Genome Atlas (TCGA) data in the serous ovarian cancer cohort showed that high IGF2 mRNA expression is significantly associated with shortened interval to disease progression and death, clinical indicators of drug resistance. In a genetically diverse panel of ovarian cancer cell lines, the IGF2 mRNA levels measured in cell lines resistant to various microtubule-stabilizing agents including Taxol were found to be significantly elevated compared to the drug sensitive cell lines. The effect of IGF2 knockdown on Taxol resistance was investigated in vitro and in vivo. Transient IGF2 knockdown significantly sensitized drug resistant cells to Taxol treatment. A Taxol-resistant ovarian cancer xenograft model, developed from HEY-T30 cells, exhibited extreme drug resistance, wherein the maximal tolerated dose of Taxol did not delay tumor growth in mice. Blocking the IGF1R (a transmembrane receptor that transmits signals from IGF1 and IGF2) using a monoclonal antibody did not alter the response to Taxol. However, stable IGF2 knockdown using short-hairpin RNA in HEY-T30 effectively restored Taxol sensitivity. These findings validate IGF2 as a potential therapeutic target in drug resistant ovarian cancer and show that directly targeting IGF2 may be a preferable strategy compared with targeting IGF1R alone. PMID:24932685

Scoliosis-Specific exercises can reduce the progression of severe curves in adult idiopathic scoliosis: a long-term cohort study.

PubMed

Negrini, Alessandra; Negrini, Maria Gabriella; Donzelli, Sabrina; Romano, Michele; Zaina, Fabio; Negrini, Stefano

2015-01-01

Scoliosis fusion surgery is generally considered the only means to stop the progression of adult idiopathic scoliosis (ADIS), but for patients refusing surgery there is lack of evidence in favour of conservative treatment. The aim of the present study was to verify the possible effectiveness of scoliosis-specific exercises when facing ADIS progression. We designed a retrospective cohort study. We included 34 ADIS patients in treatment at our Institute (5 males and 29 females, mean age was 38.0 ± 11.0), exclusively treated with specific Scoliosis Specific SEAS exercises. SEAS exercises are scoliosis-specific exercises. In adult patients they are aimed to recover postural collapse, postural control and vertebral stability through an active self-correction. Postural integration is a key element, including the neuromotor integration of correct postures and an ergonomic education program. Therapy includes at least two weekly exercise sessions each lasting 45 min. Radiographic progression was the main outcome and it was analysed as a continuous variable. One way ANOVA and paired t-test were applied for continuous data, while chi-square test was applied for categorical data. Alpha was set at 0.05. The mean Cobb angle of the patients included into the present study, was 55.8 ± 13.2 °. Fifteen patients had previous x-rays testifying scoliosis progression: the average curve progression (worsening) was 9.8 ± 6.6 ° at a median of 25 (range 17-48) years. The remaining were characterized by more severe curves, exceeding 40 ° Cobb (mean curvature 50.9 ± 13.6) but it was not possible to prove that the curves had progressed in these cases. After an average period of 2 years of treatment (range 1-18y), 68 % of the patients experienced an improvement in their scoliosis. However in one patient (3 %) the scoliosis worsened by 5 ° in 18 years (progression rate reduced from 0.5 ° to 0.27 ° per year). Patients improved 4.6 ± 5.0 ° Cobb (P < 0.05), with no differences based on the localization of the curve, gender, age, length of treatment, Cobb degrees at the start of observation or treatment. Scoliosis Specific SEAS Exercises proved to be superior to natural history in ADIS, at least in individual cases and should be considered as a first line treatment especially in patients refusing scoliosis surgery.

[Fundus autofluorescence in dry AMD - impact on disease progression].

PubMed

Vidinova, C N; Gouguchkova, P T; Vidinov, K N

2013-11-01

Fundus autofluorescence is a novel technique that gives us information about the RPE cells by evaluating the distribution of lipofuscin in the retina. The purpose of our study was to evaluate the diagnostic abilities of OCT, RTVue and fundus autofluorescence in predicting the progression of dry AMD. In our study 37 dry AMD patients were enrolled: 22 of them with druses and 15 with developed geographic atrophy. They all underwent complete ophthalmological examinations including OCT and autofluorescence. We used the RTVue OCT programmes HD line, Cross line, EMM5 and EMM5 progression in all cases. The autofluorescence was recorded with the help of the Canon CX1 fundus camera. OCT images in the AMD patients with dry AMD and large druses showed typical undulations in the RPE/choroid line and occasionally drusenoid detachment of the RPE. Autofluorescence showed different patterns. The confluent reticular autofluorescence was associated with the development of neovascular membranes. In geographic atrophy patient OCTs showed diminished retinal thickness measured with EMM5. On autofluorescence the findings at the border zone atrophic/normal retina were of particular importance. The diffuse increased autofluorescence in that area was considered to be a sign for further atrophy progression. Our results point out that OCT in combination with autofluorescence is important in following the progression of dry AMD. Pathological autofluorescence at the border of atrophic lesions is an important sign for disease activity. Although both OCT and autofluorescence visualise the changes in RPE, autofluorescence is of key importance in predicting the development of the disease. Georg Thieme Verlag KG Stuttgart · New York.

Fabrication and Characterization of Quinoa Protein Nanoparticle-Stabilized Food-Grade Pickering Emulsions with Ultrasound Treatment: Interfacial Adsorption/Arrangement Properties.

PubMed

Qin, Xin-Sheng; Luo, Zhi-Gang; Peng, Xi-Chun

2018-05-02

The natural quinoa protein isolate (QPI) was largely reflected in the nanoparticle form at pH 7.0 (∼401 nm), and the ultrasound at 20 min progressively improved the contact angle (wettability) and surface hydrophobicity of the nanoparticles. Ultrasound process also modified the type of intraparticle interaction, and the internal forces of sonicated particles were largely maintained by both disulfide bonds and hydrophobic interaction forces. In emulsion system, the ultrasound progressively increased the emulsification efficiency of the QPI nanoparticles, particularly at high protein concentration ( c > 1%, w/ v) and higher emulsion stability against coalescence. As compared with the natural QPI-stabilized emulsions, the 20 min sonicated emulsions exhibited higher packing and adsorption at the protein interface. The microstructure of emulsions that occurs is bridging flocculation of droplets at low c (≤1%, w/ v), while the amount of protein particles could be high enough to cover the droplet surface at high c ( >1%, w/ v) with hexagonal array model arrangement. Thus these results illustrated that both natural and sonicated QPI nanoparticles could be performed as effective food-grade stabilizer for Pickering emulsion; however, the sonicated QPI nanoparticles exhibited much better emulsifying and interfacial properties.

[Development and current situation of reconstruction methods following total sacrectomy].

PubMed

Huang, Siyi; Ji, Tao; Guo, Wei

2018-05-01

To review the development of the reconstruction methods following total sacrectomy, and to provide reference for finding a better reconstruction method following total sacrectomy. The case reports and biomechanical and finite element studies of reconstruction following total sacrectomy at home and abroad were searched. Development and current situation were summarized. After developing for nearly 30 years, great progress has been made in the reconstruction concept and fixation techniques. The fixation methods can be summarized as the following three strategies: spinopelvic fixation (SPF), posterior pelvic ring fixation (PPRF), and anterior spinal column fixation (ASCF). SPF has undergone technical progress from intrapelvic rod and hook constructs to pedicle and iliac screw-rod systems. PPRF and ASCF could improve the stability of the reconstruction system. Reconstruction following total sacrectomy remains a challenge. Reconstruction combining SPF, PPRF, and ASCF is the developmental direction to achieve mechanical stability. How to gain biological fixation to improve the long-term stability is an urgent problem to be solved.

The long non-coding RNA LSINCT5 promotes malignancy in non-small cell lung cancer by stabilizing HMGA2.

PubMed

Tian, Yuheng; Zhang, Lina; Chen, Shuwen; Ma, Yuan; Liu, Yanyan

2018-06-08

Long non-coding RNAs (lncRNAs) can actively participate in tumorigenesis in various cancers. However, the involvement of lncRNA long stress induced non-coding transcripts 5 (LSINCT5) in non-small cell lung cancer (NSCLC) remains largely unknown. Here we showed a novel lncRNA signature in NSCLC through lncRNA profiling. Increased LSINCT5 expression positively correlates with malignant clinicopathological features and poor survival. LSINCT5 can promote migration and viability of various NSCLC cells in vitro and also enhance lung cancer progression in vivo. RNA immunoprecipitation followed by mass spectrometry has identified that LSINCT5 interacts with HMGA2. This physical interaction can increase the stability of HMGA2 by inhibiting proteasome-mediated degradation. Therefore, LSINCT5 may possibly contribute to NSCLC tumorigenesis by stabilizing the oncogenic factor of HMGA2. This novel LSINCT5/HMGA2 axis can modulate lung cancer progression and might be a promising target for pharmacological intervention.

Progress in Payload Separation Risk Mitigation for a Deployable Venus Heat Shield

NASA Technical Reports Server (NTRS)

Smith, Brandon P.; Yount, Bryan C.; Venkatapathy, Ethiraj; Stern, Eric C.; Prabhu, Dinesh K.; Litton, Daniel K.

2013-01-01

A deployable decelerator known as the Adaptive Deployable Entry and Placement Technology (ADEPT) offers substantial science and mass savings for the Venus In Situ Explorer (VISE) mission. The lander and science payload must be separated from ADEPT during atmospheric entry. This paper presents a trade study of the separation system concept of operations and provides a conceptual design of the baseline: aft-separation with a subsonic parachute. Viability of the separation system depends on the vehicle's dynamic stability characteristics during deceleration from supersonic to subsonic speeds. A trajectory sensitivity study presented shows that pitch damping and Venusian winds drive stability prior to parachute deployment, while entry spin rate is not a driver of stability below Mach 5. Additionally, progress in free-flight CFD techniques capable of computing aerodynamic damping parameters is presented. Exploratory simulations of ADEPT at a constant speed of Mach number of 0.8 suggest the vehicle may have an oscillation limit cycle near 5 angle-of-attack. The proposed separation system conceptual design is thought to be viable.

Treatment of a patient with posterior cortical atrophy (PCA) with chiropractic manipulation and Dynamic Neuromuscular Stabilization (DNS): A case report

PubMed Central

Francio, Vinicius T.; Boesch, Ron; Tunning, Michael

2015-01-01

Objective: Posterior cortical atrophy (PCA) is a rare progressive neurodegenerative syndrome which unusual symptoms include deficits of balance, bodily orientation, chronic pain syndrome and dysfunctional motor patterns. Current research provides minimal guidance on support, education and recommended evidence-based patient care. This case reports the utilization of chiropractic spinal manipulation, dynamic neuromuscular stabilization (DNS), and other adjunctive procedures along with medical treatment of PCA. Clinical features: A 54-year-old male presented to a chiropractic clinic with non-specific back pain associated with visual disturbances, slight memory loss, and inappropriate cognitive motor control. After physical examination, brain MRI and PET scan, the diagnosis of PCA was recognized. Intervention and Outcome: Chiropractic spinal manipulation and dynamic neuromuscular stabilization were utilized as adjunctive care to conservative pharmacological treatment of PCA. Outcome measurements showed a 60% improvement in the patient’s perception of health with restored functional neuromuscular pattern, improvements in locomotion, posture, pain control, mood, tolerance to activities of daily living (ADLs) and overall satisfactory progress in quality of life. Yet, no changes on memory loss progression, visual space orientation, and speech were observed. Conclusion: PCA is a progressive and debilitating condition. Because of poor awareness of PCA by physicians, patients usually receive incomplete care. Additional efforts must be centered on the musculoskeletal features of PCA, aiming enhancement in quality of life and functional improvements (FI). Adjunctive rehabilitative treatment is considered essential for individuals with cognitive and motor disturbances, and manual medicine procedures may be consider a viable option. PMID:25729084

Geomorphic and vegetative recovery processes along modified stream channels of West Tennessee

USGS Publications Warehouse

Simon, Andrew; Hupp, C.R. Tennessee

1992-01-01

Hundreds of miles of streams in West Tennessee have been channelized or otherwise modt@ed since the turn of century. After all or parts of a stream are straightened, dredged, or cleared, systematic hydrologic, geomorphic, and ecologic processes collectively begin to reduce energy conditions towards the premodified state. One hundred and five sites along 15 streams were studied in the Obion, Forked Deer, Hatchie, and Wolf River basins. All studied streams, except the Hatchie River, have had major channel modi@cation along all or parts of their courses. Bank material shear-strength properties were determined through drained borehole-shear testing (168 tests) and used to interpret present critical bank conditions and factors of safety, and to estimate future channel-bank stability. Mean values of cohesive strength and angle of internal friction were 1.26 pounds per square inch and 30.1 degrees, respectively. Dendrogeomorphic analyses were made using botanical evidence of channel-bank failures to determine rates of channel widening; buried riparian stems were analyzed to determine rates of bank accretion. Channel bed-level changes through time and space were represented by a power equation. Plant ecological analyses were ma& to infer relative bank stability, to identify indicator species of the stage of bank recovery, and to determine patterns of vegetation development through the course of channel evolution. Quantitative data on morphologic changes were used with previously developed six-stage models of channel evolution and bank-slope development to estimate trends of geomorphic and ecologic processes and forms through time. Immediately after channel modr@cations, a 10- to 1%yearperiod of channel-bed degradation ensues at and upstream from the most recent modifications (area of maximum disturbance). Channel-bed lowering by &gradation was as much as 20 feet along some stream reaches. Downstream from the area of maximum disturbance, the bed was aggraded by the deposition of sediment supplied by knickpoint migration upstream; aggradation also occurred in initially degraded sites with time. Additionally, if degradation caused an increase in bank height beyond the critical limits of the bank material, a period of channel widening by mass wasting followed. Degradation knickpoints migrated upstream at rates greater than 1 mile per year; the rates attenuated with distance above the area of maximum disturbance. Channel widening rates of up to 16 feet per year were documented along some severely degraded reaches. Planar failures were generally more frequent but rotational failures dominated the most rapidly widening reaches. Total volumes of bank erosion may represent 75percent or more of the total material eroded from the channel, but this material generally exits the drainage basin. Mean factors of safety vary with the stage of channel evolution with the lowest values for planar and rotational failures occurring during the threshold stage (stage IV) 1.00 and 1.15, respectively. As channel gradients decrease, degradation ceases and then a period of ?secondary aggradation ? (at lesser rates than degradation) and bank accretion begins that may fill the channel to near floodplain level. This shift@ in process represents an oscillation in channel bed-level adjustment. Streams in basins underlain by loess may require an order of magnitude more time than sand-bed streams to stabilize due to a lack of coarse-grained material (sand) for aggradation. A systematic progression of riparian species that reflects the six-stage model of channel evolution has been identified. This progression can be used to infer ambient channel stability and hydrogeomorphic conditions. Woody vegetation establishes on low- and mid-bank surfaces (the slough line, initially) at about the same time that bank accretion begins. This slough line forms at a mean temporary stability angle of 24 degrees and expands upslope with time by the accretion of sediments. Species involve

The effects of estradiol and selective estrogen receptor modulators on gene expression and messenger RNA stability in immortalized sheep endometrial stromal cells and human endometrial adenocarcinoma cells.

PubMed

Farnell, Yuhua Z; Ing, Nancy H

2003-03-01

The purpose of this study was to identify an endometrial cell line that maintained the E2 up-regulation of estrogen receptor (ER) mRNA by enhanced message stability and to assess its dependence on ER protein. Estradiol (E2) effects on gene expression were measured in three cell lines: one immortalized from sheep endometrial stroma (ST) and two from human endometrial adenocarcinomas (Ishikawa and ECC-1). E2 up-regulated ER mRNA levels in ST and Ishikawa cells, but down-regulated ER mRNA levels in ECC-1 cells. E2 up-regulated progesterone receptor (PR), glyceraldehyde 3-phosphate dehydrogenase (GAPDH), and transforming growth factor-alpha (TGF-alpha) in both Ishikawa and ECC-1 cells. The selective estrogen receptor modulator ICI 182,780 antagonized the E2-induced up-regulation of ER and/or PR mRNA levels in all three cells, while another, GW 5638, antagonized the up-regulation of PR mRNA in Ishikawa and ECC-1 cells. In mechanistic studies, E2 had no effect on ER mRNA stability in ST cells and it destabilized ER mRNA in ECC-1 cells. Thus, Ishikawa cells appear to be the most physiologically relevant cell line in which to study the up-regulation of ER mRNA levels by enhanced mRNA stability. Its antagonism by ICI 182,780 reveals that ER protein is involved in this E2 response.

Recent advances in collisional effects on spectra of molecular gases and their practical consequences

NASA Astrophysics Data System (ADS)

Hartmann, Jean-Michel; Tran, Ha; Armante, Raymond; Boulet, Christian; Campargue, Alain; Forget, François; Gianfrani, Livio; Gordon, Iouli; Guerlet, Sandrine; Gustafsson, Magnus; Hodges, Joseph T.; Kassi, Samir; Lisak, Daniel; Thibault, Franck; Toon, Geoffrey C.

2018-07-01

We review progress, since publication of the book ``Collisional effects on molecular spectra: Laboratory experiments and models, consequences for applications" (Elsevier, Amsterdam, 2008), on measuring, modeling and predicting the influence of pressure (ie of intermolecular collisions) on the spectra of gas molecules. We first introduce recently developed experimental techniques of high accuracy and sensitivity. We then complement the aforementioned book by presenting the theoretical approaches, results and data proposed (mostly) in the last decade on the topics of isolated line shapes, line-broadening and -shifting, line-mixing, the far wings and associated continua, and collision-induced absorption. Examples of recently demonstrated consequences of the progress in the description of spectral shapes for some practical applications (metrology, probing of gas media, climate predictions) are then given. Remaining issues and directions for future research are finally discussed.

GPRC6A regulates prostate cancer progression

PubMed Central

Pi, Min; Quarles, L. Darryl

2011-01-01

BACKGROUND GPRC6A is a nutrient sensing GPCR that is activated in vitro by a variety of ligands, including amino acids, calcium, zinc, osteocalcin (OC) and testosterone. The association between nutritional factors and risk of prostate cancer, the finding of increased expression of OC in prostate cancer cells and the association between GPRC6A and risk of prostate cancer in Japanese men implicates a role of GPRC6A in prostate cancer. METHODS We examined if GPRC6A is expressed in human prostate cancer cell lines and used siRNA-mediated knockdown GPRC6A expression in prostate cancer cells to explore the function of GPRC6A in vitro. To assess the role GPRC6A in prostate cancer progression in vivo we intercrossed Gprc6a−/− mice onto the TRAMP mouse prostate cancer model. RESULTS GPRC6A transcripts were markedly increased in prostate cancer cell lines 22Rv1, PC-3 and LNCaP, compared to the normal prostate RWPE-1 cell line. In addition, a panel of GPRC6A ligands, including calcium, OC, and arginine, exhibited in prostate cancer cell lines a dose-dependent stimulation of ERK activity, cell proliferation, chemotaxis, and prostate specific antigen and Runx 2 gene expression. These responses were inhibited by siRNA-mediated knockdown of GPRC6A. Finally, transfer of Gprc6a deficiency onto a TRAMP mouse model of prostate cancer significantly retarded prostate cancer progression and improved survival of compound Gprc6a−/−/TRAMP mice. CONCLUSIONS GPRC6A is a novel molecular target for regulating prostate growth and cancer progression. Increments in GPRC6A may augment the ability of prostate cancer cells to proliferate in response to dietary and bone derived ligands. PMID:21681779

An AKT activity threshold regulates androgen-dependent and androgen-independent PSA expression in prostate cancer cell lines.

PubMed

Paliouras, Miltiadis; Diamandis, Eleftherios P

2008-06-01

The androgen receptor (AR) plays an important role in early prostate cancer by activating transcription of a number of genes participating in cell proliferation and growth and cancer progression. However, as the cancer progresses, prostate cancer cells transform from an androgen-dependent to an androgen-independent state. Androgen-independent prostate cancer can manifest itself in several forms, including a percentage of cancers that show reduced levels of prostate-specific antigen (PSA) and can progress without the need for the ligand or active receptor. Therefore, our goal was to examine the role of intracellular signaling pathways in an androgen-independent prostate cancer in vitro model. Using the cell line PC3(AR)(2), we stimulated cells with 5-alpha-dihydrotestosterone (DHT) and epidermal growth factor (EGF) and then analyzed PSA expression. We observed lower PSA expression when cells were jointly stimulated with DHT and EGF, and this was associated with an increase in AKT activity. We examined the role of AKT in AR activity and PSA expression by creating stable PC3(AR)(2) cell lines transfected with a PI3K-Ras-effector loop mutant. These cell lines showed lower DHT-stimulated PSA expression that correlated to changes in the phosphorylated state of AR. Therefore, we propose an in vitro androgen-independent model in which a PI3K/AKT activity threshold and subsequent AR transactivation regulate PSA expression.

Genome-wide Control of Heterochromatin Replication by the Telomere Capping Protein TRF2.

PubMed

Mendez-Bermudez, Aaron; Lototska, Liudmyla; Bauwens, Serge; Giraud-Panis, Marie-Josèphe; Croce, Olivier; Jamet, Karine; Irizar, Agurtzane; Mowinckel, Macarena; Koundrioukoff, Stephane; Nottet, Nicolas; Almouzni, Genevieve; Teulade-Fichou, Mare-Paule; Schertzer, Michael; Perderiset, Mylène; Londoño-Vallejo, Arturo; Debatisse, Michelle; Gilson, Eric; Ye, Jing

2018-05-03

Hard-to-replicate regions of chromosomes (e.g., pericentromeres, centromeres, and telomeres) impede replication fork progression, eventually leading, in the event of replication stress, to chromosome fragility, aging, and cancer. Our knowledge of the mechanisms controlling the stability of these regions is essentially limited to telomeres, where fragility is counteracted by the shelterin proteins. Here we show that the shelterin subunit TRF2 ensures progression of the replication fork through pericentromeric heterochromatin, but not centromeric chromatin. In a process involving its N-terminal basic domain, TRF2 binds to pericentromeric Satellite III sequences during S phase, allowing the recruitment of the G-quadruplex-resolving helicase RTEL1 to facilitate fork progression. We also show that TRF2 is required for the stability of other heterochromatic regions localized throughout the genome, paving the way for future research on heterochromatic replication and its relationship with aging and cancer. Copyright © 2018 Elsevier Inc. All rights reserved.

BRCA1 interaction of centrosomal protein Nlp is required for successful mitotic progression.

PubMed

Jin, Shunqian; Gao, Hua; Mazzacurati, Lucia; Wang, Yang; Fan, Wenhong; Chen, Qiang; Yu, Wei; Wang, Mingrong; Zhu, Xueliang; Zhang, Chuanmao; Zhan, Qimin

2009-08-21

Breast cancer susceptibility gene BRCA1 is implicated in the control of mitotic progression, although the underlying mechanism(s) remains to be further defined. Deficiency of BRCA1 function leads to disrupted mitotic machinery and genomic instability. Here, we show that BRCA1 physically interacts and colocalizes with Nlp, an important molecule involved in centrosome maturation and spindle formation. Interestingly, Nlp centrosomal localization and its protein stability are regulated by normal cellular BRCA1 function because cells containing BRCA1 mutations or silenced for endogenous BRCA1 exhibit disrupted Nlp colocalization to centrosomes and enhanced Nlp degradation. Its is likely that the BRCA1 regulation of Nlp stability involves Plk1 suppression. Inhibition of endogenous Nlp via the small interfering RNA approach results in aberrant spindle formation, aborted chromosomal segregation, and aneuploidy, which mimic the phenotypes of disrupted BRCA1. Thus, BRCA1 interaction of Nlp might be required for the successful mitotic progression, and abnormalities of Nlp lead to genomic instability.

BRCA1 Interaction of Centrosomal Protein Nlp Is Required for Successful Mitotic Progression*♦

PubMed Central

Jin, Shunqian; Gao, Hua; Mazzacurati, Lucia; Wang, Yang; Fan, Wenhong; Chen, Qiang; Yu, Wei; Wang, Mingrong; Zhu, Xueliang; Zhang, Chuanmao; Zhan, Qimin

2009-01-01

Breast cancer susceptibility gene BRCA1 is implicated in the control of mitotic progression, although the underlying mechanism(s) remains to be further defined. Deficiency of BRCA1 function leads to disrupted mitotic machinery and genomic instability. Here, we show that BRCA1 physically interacts and colocalizes with Nlp, an important molecule involved in centrosome maturation and spindle formation. Interestingly, Nlp centrosomal localization and its protein stability are regulated by normal cellular BRCA1 function because cells containing BRCA1 mutations or silenced for endogenous BRCA1 exhibit disrupted Nlp colocalization to centrosomes and enhanced Nlp degradation. Its is likely that the BRCA1 regulation of Nlp stability involves Plk1 suppression. Inhibition of endogenous Nlp via the small interfering RNA approach results in aberrant spindle formation, aborted chromosomal segregation, and aneuploidy, which mimic the phenotypes of disrupted BRCA1. Thus, BRCA1 interaction of Nlp might be required for the successful mitotic progression, and abnormalities of Nlp lead to genomic instability. PMID:19509300

Progress on 10 Kelvin cryo-cooled sapphire oscillator

NASA Technical Reports Server (NTRS)

Wang, Rabi T.; Dick, G. John; Diener, William A.

2004-01-01

We present recent progress on the 10 Kelvin Cryocooled Sapphire Oscillator (10K CSO). Included are incorporation of a new pulse tube cryocooler, cryocooler vibration comparisons between G-M and pulse-tube types, phase noise, and frequency stability tests. For the advantage of a single stage pulse tube cryocooler, we also present results for a 40K Compensated Sapphire Oscillator (40K CSO).

Progress in biocatalysis with immobilized viable whole cells: systems development, reaction engineering and applications.

PubMed

Polakovič, Milan; Švitel, Juraj; Bučko, Marek; Filip, Jaroslav; Neděla, Vilém; Ansorge-Schumacher, Marion B; Gemeiner, Peter

2017-05-01

Viable microbial cells are important biocatalysts in the production of fine chemicals and biofuels, in environmental applications and also in emerging applications such as biosensors or medicine. Their increasing significance is driven mainly by the intensive development of high performance recombinant strains supplying multienzyme cascade reaction pathways, and by advances in preservation of the native state and stability of whole-cell biocatalysts throughout their application. In many cases, the stability and performance of whole-cell biocatalysts can be highly improved by controlled immobilization techniques. This review summarizes the current progress in the development of immobilized whole-cell biocatalysts, the immobilization methods as well as in the bioreaction engineering aspects and economical aspects of their biocatalytic applications.

77 FR 43657 - Progressive Rail, Incorporated-Discontinuance of Service Exemption-in Barron County, WI

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-25

....05 at or near Rice Lake. The Lines are owned by WCL and have been operated by PGR since 2004 under...), Poskin (MP 85.4), Barron (MP 91.10), Cameron (MP 96.1), and Rice Lake (MP 56.05). \\1\\ See Progressive...

48 CFR 252.232-7002 - Progress payments for foreign military sales acquisitions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Progress payments for... System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE CLAUSES AND FORMS SOLICITATION... distributed to each country's requirements; and (2) Total price per contract line item applicable to each...

Puroindoline genes introduced into durum wheat reduce milling energy and change milling behavior similar to soft common wheats

USDA-ARS?s Scientific Manuscript database

Grain physical characteristics and milling behavior of a durum wheat line in which both wild-type puroindoline alleles were translocated and stabilized after backcrossing (Svevo-Pin) were compared with the parent line (Svevo). The only observed differences between grain characteristics were the mech...

Characterization of a highly efficient chevron-shaped anti-contamination device

NASA Astrophysics Data System (ADS)

Fiore, M.; Vermeersch, O.; Forte, M.; Casalis, G.; François, C.

2016-04-01

This paper is devoted to the characterization of an optimized chevron-shaped anti-contamination device (ACD). This device can prevent efficiently the propagation of turbulence from the fuselage along the attachment line (hypothetical streamline that spreads the flow going to suction side and the one going to pressure side) of swept wings and enables the development of a new laminar boundary layer downstream. More specifically, the aim is to prevent boundary-layer transition along the attachment line by a contamination process. This process is characterized by the typical Reynolds number overline{R} and the associated Poll's criterion. Thus, ACD efficiency will be expressed in terms of overline{R} values. Some experiments performed on a new numerically optimized ACD have shown its ability to prevent leading-edge contamination up to overline{R} values close to the natural transition process of the laminar boundary layer along the attachment line. The corresponding stability analysis of the laminar boundary layer is made using the Görtler-Hämmerlin stability approach. The study is completed with the different transition processes that can occur downstream the attachment line, around the airfoil, especially with crossflow analysis.

Project SQUID. Quarterly Progress Report

DTIC Science & Technology

1949-07-01

the sodium line reversal method for flame temperature determination ., Determination of Point Temperatures in Turbulent Flames Using the Sodium Line...taken to determine the approximate position of the line. Then, with the G-M tube in position and using the photo­ graph as an indicator, the region... beams are wide, the latter yielding a greater source of X-rays. Hence, by using that window yielding the broadest beam greater intensity of X-rays

Cognitive impairment, dementia, and personality stability among older adults

PubMed Central

Terracciano, Antonio; Stephan, Yannick; Luchetti, Martina; Sutin, Angelina R.

2017-01-01

There is contrasting evidence on personality stability in advanced age, and limited knowledge on the impact of cognitive impairment and dementia on trait stability. Group- and individual-level longitudinal analyses of the five major dimensions of personality assessed twice over 4-years (N = 9,935) suggest that rank-order stability was progressively lower with advancing age (from rtt = 0.68 for age 50–60 to rtt = 0.58 for age >80 years). Stability was low in the dementia group (rtt = 0.43), and this was not simply due to lower reliability given that internal consistency remained adequate in the dementia group. Among individuals with no cognitive impairment or dementia, there was no association between stability and age (rtt = 0.70 even for age >80). These results suggest that the lower personality stability in older adults is not due to age but cognitive impairment and dementia. PMID:29214858

Atlantis OMS Pods and Vertical Stabilizer

NASA Image and Video Library

2011-07-09

S135-E-006375 (9 July 2011) --- Without the sun's being temporarily available to highlight space shuttle Atlantis' cargo bay and vertical stabilizer, the spacecraft barely shows through as a silhouette in this image photographed from the aft flight deck. The thin blue line of Earth?s atmosphere is the dominant feature in the photo. Photo credit: NASA

Progress in development of male sterile germplasm for hybrid rice breeding

USDA-ARS?s Scientific Manuscript database

Currently, there are two types of male sterility mainly commercialized in hybrid rice production, three-line type or cytoplasmic male sterility (CMS) and two-line type or environmental male sterility (EMS). The great majority belongs to the CMS and there are four strategies that have been proven suc...

33 CFR 207.610 - St. Lawrence River, Cape Vincent Harbor, N.Y.; use, administration, and navigation of the harbor...

Code of Federal Regulations, 2012 CFR

2012-07-01

... in progress at the time. (e) The use of chains in making fast to the breakwater is prohibited. Lines...) Each and every vessel made fast to the breakwater, or anchored in the harbor without a line made fast...

33 CFR 207.610 - St. Lawrence River, Cape Vincent Harbor, N.Y.; use, administration, and navigation of the harbor...

Code of Federal Regulations, 2011 CFR

2011-07-01

... in progress at the time. (e) The use of chains in making fast to the breakwater is prohibited. Lines...) Each and every vessel made fast to the breakwater, or anchored in the harbor without a line made fast...

33 CFR 207.610 - St. Lawrence River, Cape Vincent Harbor, N.Y.; use, administration, and navigation of the harbor...

Code of Federal Regulations, 2013 CFR

2013-07-01

... in progress at the time. (e) The use of chains in making fast to the breakwater is prohibited. Lines...) Each and every vessel made fast to the breakwater, or anchored in the harbor without a line made fast...

33 CFR 207.610 - St. Lawrence River, Cape Vincent Harbor, N.Y.; use, administration, and navigation of the harbor...

Code of Federal Regulations, 2014 CFR

2014-07-01

... in progress at the time. (e) The use of chains in making fast to the breakwater is prohibited. Lines...) Each and every vessel made fast to the breakwater, or anchored in the harbor without a line made fast...

Careful Selection of Reference Genes Is Required for Reliable Performance of RT-qPCR in Human Normal and Cancer Cell Lines

PubMed Central

Jacob, Francis; Guertler, Rea; Naim, Stephanie; Nixdorf, Sheri; Fedier, André; Hacker, Neville F.; Heinzelmann-Schwarz, Viola

2013-01-01

Reverse Transcription - quantitative Polymerase Chain Reaction (RT-qPCR) is a standard technique in most laboratories. The selection of reference genes is essential for data normalization and the selection of suitable reference genes remains critical. Our aim was to 1) review the literature since implementation of the MIQE guidelines in order to identify the degree of acceptance; 2) compare various algorithms in their expression stability; 3) identify a set of suitable and most reliable reference genes for a variety of human cancer cell lines. A PubMed database review was performed and publications since 2009 were selected. Twelve putative reference genes were profiled in normal and various cancer cell lines (n = 25) using 2-step RT-qPCR. Investigated reference genes were ranked according to their expression stability by five algorithms (geNorm, Normfinder, BestKeeper, comparative ΔCt, and RefFinder). Our review revealed 37 publications, with two thirds patient samples and one third cell lines. qPCR efficiency was given in 68.4% of all publications, but only 28.9% of all studies provided RNA/cDNA amount and standard curves. GeNorm and Normfinder algorithms were used in 60.5% in combination. In our selection of 25 cancer cell lines, we identified HSPCB, RRN18S, and RPS13 as the most stable expressed reference genes. In the subset of ovarian cancer cell lines, the reference genes were PPIA, RPS13 and SDHA, clearly demonstrating the necessity to select genes depending on the research focus. Moreover, a cohort of at least three suitable reference genes needs to be established in advance to the experiments, according to the guidelines. For establishing a set of reference genes for gene normalization we recommend the use of ideally three reference genes selected by at least three stability algorithms. The unfortunate lack of compliance to the MIQE guidelines reflects that these need to be further established in the research community. PMID:23554992

The transcriptional diversity of 25 Drosophila cell lines

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

Cherbas, Lucy; Willingham, Aarron; Zhang, Dayu

2010-12-22

Drosophila melanogaster cell lines are important resources for cell biologists. In this article, we catalog the expression of exons, genes, and unannotated transcriptional signals for 25 lines. Unannotated transcription is substantial (typically 19% of euchromatic signal). Conservatively, we identify 1405 novel transcribed regions; 684 of these appear to be new exons of neighboring, often distant, genes. Sixty-four percent of genes are expressed detectably in at least one line, but only 21% are detected in all lines. Each cell line expresses, on average, 5885 genes, including a common set of 3109. Expression levels vary over several orders of magnitude. Major signalingmore » pathways are well represented: most differentiation pathways are ‘‘off’’ and survival/growth pathways ‘‘on.’’ Roughly 50% of the genes expressed by each line are not part of the common set, and these show considerable individuality. Thirty-one percent are expressed at a higher level in at least one cell line than in any single developmental stage, suggesting that each line is enriched for genes characteristic of small sets of cells. Most remarkable is that imaginal disc-derived lines can generally be assigned, on the basis of expression, to small territories within developing discs. These mappings reveal unexpected stability of even fine-grained spatial determination. No two cell lines show identical transcription factor expression. We conclude that each line has retained features of an individual founder cell superimposed on a common ‘‘cell line‘‘ gene expression pattern. We report the transcriptional profiles of 25 Drosophila melanogaster cell lines, principally by whole-genome tiling microarray analysis of total RNA, carried out as part of the modENCODE project. The data produced in this study add to our knowledge of the cell lines and of the Drosophila transcriptome in several ways. We summarize the expression of previously annotated genes in each of the 25 lines with emphasis on what those patterns reveal about the origins of the lines and the stability of spatial expression patterns. In addition, we offer an initial analysis of previously unannotated transcripts in the cell lines.« less

Design and synthesis of dimethylaminomethyl-substituted curcumin derivatives/analogues: potent antitumor and antioxidant activity, improved stability and aqueous solubility compared with curcumin.

PubMed

Fang, Xubin; Fang, Lei; Gou, Shaohua; Cheng, Lin

2013-03-01

A series of dimethylaminomethyl-substituted curcumin derivatives/analogues were designed and synthesized. All compounds effectively inhibited HepG2, SGC-7901, A549 and HCT-116 tumor cell lines proliferation in MTT assay. Particularly, compounds 2a and 3d showed much better activity than curcumin against all of the four tumor cell lines. Antioxidant test revealed that these compounds had higher free radical scavenging activity than curcumin towards both DPPH and galvinoxyl radicals. Furthermore, the aqueous solubility and stability of the target compounds were also significantly improved compared with curcumin. Copyright © 2013 Elsevier Ltd. All rights reserved.

A widely tunable 10-μm quantum cascade laser phase-locked to a state-of-the-art mid-infrared reference for precision molecular spectroscopy

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

Sow, P. L. T.; Mejri, S.; Tokunaga, S. K.

2014-06-30

We report the coherent phase-locking of a quantum cascade laser (QCL) at 10-μm to the secondary frequency standard of this spectral region, a CO{sub 2} laser stabilized on a saturated absorption line of OsO{sub 4}. The stability and accuracy of the standard are transferred to the QCL resulting in a line width of the order of 10 Hz, and leading to the narrowest QCL to date. The locked QCL is then used to perform absorption spectroscopy spanning 6 GHz of NH{sub 3} and methyltrioxorhenium, two species of interest for applications in precision measurements.

Microchannel plate life testing for UV spectroscopy instruments

NASA Astrophysics Data System (ADS)

Darling, N. T.; Siegmund, O. H. W.; Curtis, T.; McPhate, J.; Tedesco, J.; Courtade, S.; Holsclaw, G.; Hoskins, A.; Al Dhafri, S.

2017-08-01

The Emirates Mars Mission (EMM) UV Spectrograph (EMUS) is a far ultraviolet (102 nm to 170 nm) imaging spectrograph for characterization of the Martian exosphere and thermosphere. Imaging is accomplished by a photon counting open-face microchannel plate (MCP) detector using a cross delay line (XDL) readout. An MCP gain stabilization ("scrub") followed by lifetime spectral line burn-in simulation has been completed on a bare MCP detector at SSL. Gain and sensitivity stability of better than 7% has been demonstrated for total dose of 2.5 × 1012 photons cm-2 (2 C · cm-2 ) at 5.5 kHz mm-2 counting rates, validating the efficacy of an initial low gain full-field scrub.

Realization of LOS (Line of Sight) stabilization based on reflector using carrier attitude compensation method

NASA Astrophysics Data System (ADS)

Mao, Yao; Tian, Jing; Ma, Jia-guang

2015-02-01

The techonology of LOS stabilization is widely applicated in moving carrier photoelectric systems such as shipborne, airborne and so on. In application situations with compact structure, such as LOS stabilization system of unmanned aerial vehicle, LOS stabilization based on reflector is adopted, and the detector is installed on the carrier to reduce the volume of stabilized platform and loading weight. However, the LOS deflection angle through reflector and the rotation angle of the reflector has a ratio relation of 2:1, simple reflector of stable inertial space can not make the optical axis stable. To eliminate the limitation of mirror stabilizing method, this article puts forward the carrier attitude compensation method, which uses the inertial sensor installed on the carrier to measure the attitude change of the carrier, and the stabilized platform rotating half of the carrier turbulence angle to realize the LOS stabilization.

Astaxanthin Inhibits Proliferation of Human Gastric Cancer Cell Lines by Interrupting Cell Cycle Progression.

PubMed

Kim, Jung Ha; Park, Jong-Jae; Lee, Beom Jae; Joo, Moon Kyung; Chun, Hoon Jai; Lee, Sang Woo; Bak, Young-Tae

2016-05-23

Astaxanthin is a carotenoid pigment that has antioxidant, antitumoral, and anti-inflammatory properties. In this in vitro study, we investigated the mechanism of anticancer effects of astaxanthin in gastric carcinoma cell lines. The human gastric adenocarcinoma cell lines AGS, KATO-III, MKN-45, and SNU-1 were treated with various concentrations of astaxanthin. A cell viability test, cell cycle analysis, and immunoblotting were performed. The viability of each cancer cell line was suppressed by astaxanthin in a dose-dependent manner with significantly decreased proliferation in KATO-III and SNU-1 cells. Astaxanthin increased the number of cells in the G0/G1 phase but reduced the proportion of S phase KATO-III and SNU-1 cells. Phosphorylated extracellular signal-regulated kinase (ERK) was decreased in an inverse dose-dependent correlation with astaxanthin concentration, and the expression of p27(kip-1) increased the KATO-III and SNU-1 cell lines in an astaxanthin dose-dependent manner. Astaxanthin inhibits proliferation by interrupting cell cycle progression in KATO-III and SNU-1 gastric cancer cells. This may be caused by the inhibition of the phosphorylation of ERK and the enhanced expression of p27(kip-1).

Apparatus for simultaneously disreefing a centrally reefed clustered parachute system

DOEpatents

Johnson, Donald W.

1988-01-01

A single multi-line cutter is connected to each of a cluster of parachutes by a separate short tether line that holds the parachutes, initially reefed by closed loop reefing lines, close to one another. The closed loop reefing lines and tether lines, one from each parachute, are disposed within the cutter to be simultaneously cut by its actuation when a central line attached between the payload and the cutter is stretched upon deployment of the cluster. A pyrotechnic or electronic time delay may be included in the cutter to delay the actual simultaneous cutting of all lines until the clustered parachutes attain a measure of stability prior to being disreefed. A second set of reefing lines and second tether lines may be provided for each parachute, to enable a two-stage, separately timed, step-by-step disreefing.

Apparatus for simultaneously disreefing a centrally reefed clustered parachute system

DOEpatents

Johnson, D.W.

1988-06-21

A single multi-line cutter is connected to each of a cluster of parachutes by a separate short tether line that holds the parachutes, initially reefed by closed loop reefing lines, close to one another. The closed loop reefing lines and tether lines, one from each parachute, are disposed within the cutter to be simultaneously cut by its actuation when a central line attached between the payload and the cutter is stretched upon deployment of the cluster. A pyrotechnic or electronic time delay may be included in the cutter to delay the actual simultaneous cutting of all lines until the clustered parachutes attain a measure of stability prior to being disreefed. A second set of reefing lines and second tether lines may be provided for each parachute, to enable a two-stage, separately timed, step-by-step disreefing. 13 figs.

Rare presentation of intractable tuberculous panophthalmitis with intraocular and intraorbital abscesses: a case report.

PubMed

Boonsopon, Sutasinee; Tesavibul, Nattaporn; Uiprasertkul, Mongkol; Leeamornsiri, Supinda; Choopong, Pitipol

2017-07-04

We report a rare presentation of extrapulmonary tuberculosis. A 29-year-old Burmese woman with human immunodeficiency virus infection and known pulmonary tuberculosis who had been treated for 5 months presented to our hospital with unilateral progressive painful visual loss of 1 month's duration. She was diagnosed with tuberculous panophthalmitis with subretinal and intraorbital abscesses, conjunctival abscess, and extraocular muscle tuberculoma. The diagnosis was confirmed by a conjunctival pus swab with a positive result for acid-fast bacilli and a positive result for a mycobacterial culture. There was high suspicion of multidrug-resistant tuberculosis. Despite receiving ongoing aggressive treatment with conventional antituberculous medications, this patient required subtotal orbital exenteration to control her infection and prevent further progression. Second-line antituberculous medications were added to the first-line therapy, with satisfactory results achieved. Tuberculous panophthalmitis with intraocular and intraorbital abscesses is a rare presentation of extrapulmonary tuberculosis. Patients who do not respond to first-line antituberculous therapy might be infected with either single-drug or multidrug-resistant Mycobacterium tuberculosis. Patient compliance is one of the key factors that can alter the course of treatment. Careful patient monitoring can improve disease progression, outcome, and prognosis.

Cost-effectiveness analysis in the Spanish setting of the PEAK trial of panitumumab plus mFOLFOX6 compared with bevacizumab plus mFOLFOX6 for first-line treatment of patients with wild-type RAS metastatic colorectal cancer.

PubMed

Rivera, Fernando; Valladares, Manuel; Gea, Salvador; López-Martínez, Noemí

2017-06-01

To assess the cost-effectiveness of panitumumab in combination with mFOLFOX6 (oxaliplatin, 5-fluorouracil, and leucovorin) vs bevacizumab in combination with mFOLFOX6 as first-line treatment of patients with wild-type RAS metastatic colorectal cancer (mCRC) in Spain. A semi-Markov model was developed including the following health states: Progression free; Progressive disease: Treat with best supportive care; Progressive disease: Treat with subsequent active therapy; Attempted resection of metastases; Disease free after metastases resection; Progressive disease: after resection and relapse; and Death. Parametric survival analyses of patient-level progression free survival and overall survival data from the PEAK Phase II clinical trial were used to estimate health state transitions. Additional data from the PEAK trial were considered for the dose and duration of therapy, the use of subsequent therapy, the occurrence of adverse events, and the incidence and probability of time to metastasis resection. Utility weightings were calculated from patient-level data from panitumumab trials evaluating first-, second-, and third-line treatments. The study was performed from the Spanish National Health System (NHS) perspective including only direct costs. A life-time horizon was applied. Probabilistic sensitivity analyses and scenario sensitivity analyses were performed to assess the robustness of the model. Based on the PEAK trial, which demonstrated greater efficacy of panitumumab vs bevacizumab, both in combination with mFOLFOX6 first-line in wild-type RAS mCRC patients, the estimated incremental cost per life-year gained was €16,567 and the estimated incremental cost per quality-adjusted life year gained was €22,794. The sensitivity analyses showed the model was robust to alternative parameters and assumptions. The analysis was based on a simulation model and, therefore, the results should be interpreted cautiously. Based on the PEAK Phase II clinical trial and taking into account Spanish costs, the results of the analysis showed that first-line treatment of mCRC with panitumumab + mFOLFOX6 could be considered a cost-effective option compared with bevacizumab + mFOLFOX6 for the Spanish NHS.

Ice shelf structure and stability: Larsen C Ice Shelf, Antarctica

NASA Astrophysics Data System (ADS)

Hubbard, B. P.; Ashmore, D.; Bevan, S. L.; Booth, A. D.; Holland, P.; Jansen, D.; Kuipers Munneke, P.; Kulessa, B.; Luckman, A. J.; Sevestre, H.; O'Leary, M.

2017-12-01

We report on recent empirical investigations of the internal structure and stability (or otherwise) of Larsen C Ice Shelf (LCIS), Antarctica, focusing on research carried out for the MIDAS research project between 2014 and 2017. Borehole- and surface geophysics-based fieldwork carried out in austral springs 2014 and 2015 revealed that ephemeral surface ponds, preferentially located within the major inlets within the northern sector of the ice shelf, result in the formation of several tens of metres of (relatively dense) subsurface ice within what would otherwise have been a progressively densifying snow and firn column. Five boreholes were drilled throughout the sector and logged by optical televiewer, showing this refrozen ice to be extensive and of variable composition depending on its process of formation. Mapping the depth-distribution of the resulting ice types and associating each with a simple flow-line model of ice motion and accumulation indicates that this area of LCIS has experienced substantial melting for some centuries but that surface ponding has only occurred in recent decades, possibly restricted to the past 20 years. We also present near-surface temperature data that reveal surprising temporal patterns in foehn wind activity and intensity. Finally, we report on the geometrical extension and widening of a rift that was responsible for calving a 5,800 km^2 iceberg from the LCIS in July 2017. The nature of rift propagation through `suture' ice bands, widely considered to be composed of marine ice, is contrasted with that of its propagation through meteoric ice.

HTLV-1 Tax upregulates early growth response protein 1 through nuclear factor-κB signaling

PubMed Central

Han, Jingxian; Liu, Xihong; Lv, Zhuangwei; Li, Huanhuan; Yuan, Lixiang; Li, Xiangping; Sun, Shuming; Wang, Hui; Huang, Xinxiang

2017-01-01

Human T cell leukemia virus type 1 (HTLV-1) is a complex retrovirus that causes adult T cell leukemia (ATL) in susceptible individuals. The HTLV-1-encoded oncoprotein Tax induces persistent activation of the nuclear factor-κB (NF-κB) pathway. Early growth response protein 1 (EGR1) is overexpressed in HTLV-1-infected T cell lines and ATL cells. Here, we showed that both Tax expression and HTLV-1 infection promoted EGR1 overexpression. Loss of the NF-κB binding site in the EGR1 promotor or inhibition of NF-κB activation reduced Tax-induced EGR1 upregulation. Tax mutants unable to activate NF-κB induced only slight EGR1 upregulation as compared with wild-type Tax, confirming NF-κB pathway involvement in EGR1 regulation. Tax also directly interacted with the EGR1 protein and increased endogenous EGR1 stability. Elevated EGR1 in turn promoted p65 nuclear translocation and increased NF-κB activation. These results demonstrate a positive feedback loop between EGR1 expression and NF-κB activation in HTLV-1-infected and Tax-expressing cells. Both NF-κB activation and Tax-induced EGR1 stability upregulated EGR1, which in turn enhanced constitutive NF-κB activation and facilitated ATL progression in HTLV-1-infected cells. These findings suggest EGR1 may be an effective anti-ATL therapeutic target. PMID:28881635

Msc1 acts through histone H2A.Z to promote chromosome stability in Schizosaccharomyces pombe.

PubMed

Ahmed, Shakil; Dul, Barbara; Qiu, Xinxing; Walworth, Nancy C

2007-11-01

As a central component of the DNA damage checkpoint pathway, the conserved protein kinase Chk1 mediates cell cycle progression when DNA damage is generated. Msc1 was identified as a multicopy suppressor capable of facilitating survival in response to DNA damage of cells mutant for chk1. We demonstrate that loss of msc1 function results in an increased rate of chromosome loss and that an msc1 null allele exhibits genetic interactions with mutants in key kinetochore components. Multicopy expression of msc1 robustly suppresses a temperature-sensitive mutant (cnp1-1) in the centromere-specific histone H3 variant CENP-A, and localization of CENP-A to the centromere is compromised in msc1 null cells. We present several lines of evidence to suggest that Msc1 carries out its function through the histone H2A variant H2A.Z, encoded by pht1 in fission yeast. Like an msc1 mutant, a pht1 mutant also exhibits chromosome instability and genetic interactions with kinetochore mutants. Suppression of cnp1-1 by multicopy msc1 requires pht1. Likewise, suppression of the DNA damage sensitivity of a chk1 mutant by multicopy msc1 also requires pht1. We present the first genetic evidence that histone H2A.Z may participate in centromere function in fission yeast and propose that Msc1 acts through H2A.Z to promote chromosome stability and cell survival following DNA damage.

Msc1 Acts Through Histone H2A.Z to Promote Chromosome Stability in Schizosaccharomyces pombe

PubMed Central

Ahmed, Shakil; Dul, Barbara; Qiu, Xinxing; Walworth, Nancy C.

2007-01-01

As a central component of the DNA damage checkpoint pathway, the conserved protein kinase Chk1 mediates cell cycle progression when DNA damage is generated. Msc1 was identified as a multicopy suppressor capable of facilitating survival in response to DNA damage of cells mutant for chk1. We demonstrate that loss of msc1 function results in an increased rate of chromosome loss and that an msc1 null allele exhibits genetic interactions with mutants in key kinetochore components. Multicopy expression of msc1 robustly suppresses a temperature-sensitive mutant (cnp1-1) in the centromere-specific histone H3 variant CENP-A, and localization of CENP-A to the centromere is compromised in msc1 null cells. We present several lines of evidence to suggest that Msc1 carries out its function through the histone H2A variant H2A.Z, encoded by pht1 in fission yeast. Like an msc1 mutant, a pht1 mutant also exhibits chromosome instability and genetic interactions with kinetochore mutants. Suppression of cnp1-1 by multicopy msc1 requires pht1. Likewise, suppression of the DNA damage sensitivity of a chk1 mutant by multicopy msc1 also requires pht1. We present the first genetic evidence that histone H2A.Z may participate in centromere function in fission yeast and propose that Msc1 acts through H2A.Z to promote chromosome stability and cell survival following DNA damage. PMID:17947424

A semi-active control suspension system for railway vehicles with magnetorheological fluid dampers

NASA Astrophysics Data System (ADS)

Wei, Xiukun; Zhu, Ming; Jia, Limin

2016-07-01

The high-speed train has achieved great progress in the last decades. It is one of the most important modes of transportation between cities. With the rapid development of the high-speed train, its safety issue is paid much more attention than ever before. To improve the stability of the vehicle with high speed, extra dampers (i.e. anti-hunting damper) are used in the traditional bogies with passive suspension system. However, the curving performance of the vehicle is undermined due to the extra lateral force generated by the dampers. The active suspension systems proposed in the last decades attempt to solve the vehicle steering issue. However, the active suspension systems need extra actuators driven by electrical power or hydraulic power. There are some implementation and even safety issues which are not easy to be overcome. In this paper, an innovative semi-active controlled lateral suspension system for railway vehicles is proposed. Four magnetorheological fluid dampers are fixed to the primary suspension system of each bogie. They are controlled by online controllers for enhancing the running stability on the straight track line on the one hand and further improving the curving performance by controlling the damper force on the other hand. Two control strategies are proposed in the light of the pure rolling concept. The effectiveness of the proposed strategies is demonstrated by SIMPACK and Matlab co-simulation for a full railway vehicle with two conventional bogies.

A Study on Multi-Swing Stability Analysis of Power System using Damping Rate Inversion

NASA Astrophysics Data System (ADS)

Tsuji, Takao; Morii, Yuki; Oyama, Tsutomu; Hashiguchi, Takuhei; Goda, Tadahiro; Nomiyama, Fumitoshi; Kosugi, Narifumi

In recent years, much attention is paid to the nonlinear analysis method in the field of stability analysis of power systems. Especially for the multi-swing stability analysis, the unstable limit cycle has an important meaning as a stability margin. It is required to develop a high speed calculation method of stability boundary regarding multi-swing stability because the real-time calculation of ATC is necessary to realize the flexible wheeling trades. Therefore, the authors have developed a new method which can calculate the unstable limit cycle based on damping rate inversion method. Using the unstable limit cycle, it is possible to predict the multi-swing stability at the time when the fault transmission line is reclosed. The proposed method is tested in Lorenz equation, single-machine infinite-bus system model and IEEJ WEST10 system model.

Stability of organic solar cells: challenges and strategies.

PubMed

Cheng, Pei; Zhan, Xiaowei

2016-05-03

Organic solar cells (OSCs) present some advantages, such as simple preparation, light weight, low cost and large-area flexible fabrication, and have attracted much attention in recent years. Although the power conversion efficiencies have exceeded 10%, the inferior device stability still remains a great challenge. In this review, we summarize the factors limiting the stability of OSCs, such as metastable morphology, diffusion of electrodes and buffer layers, oxygen and water, irradiation, heating and mechanical stress, and survey recent progress in strategies to increase the stability of OSCs, such as material design, device engineering of active layers, employing inverted geometry, optimizing buffer layers, using stable electrodes and encapsulation. Some research areas of device stability that may deserve further attention are also discussed to help readers understand the challenges and opportunities in achieving high efficiency and high stability of OSCs towards future industrial manufacture.

Nuclear-coupled thermal-hydraulic stability analysis of boiling water reactors

NASA Astrophysics Data System (ADS)

Karve, Atul A.

We have studied the nuclear-coupled thermal-hydraulic stability of boiling water reactors (BWRs) using a model we developed from: the space-time modal neutron kinetics equations based on spatial omega-modes, the equations for two-phase flow in parallel boiling channels, the fuel rod heat conduction equations, and a simple model for the recirculation loop. The model is represented as a dynamical system comprised of time-dependent nonlinear ordinary differential equations, and it is studied using stability analysis, modern bifurcation theory, and numerical simulations. We first determine the stability boundary (SB) in the most relevant parameter plane, the inlet-subcooling-number/external-pressure-drop plane, for a fixed control rod induced external reactivity equal to the 100% rod line value and then transform the SB to the practical power-flow map. Using this SB, we show that the normal operating point at 100% power is very stable, stability of points on the 100% rod line decreases as the flow rate is reduced, and that points are least stable in the low-flow/high-power region. We also determine the SB when the modal kinetics is replaced by simple point reactor kinetics and show that the first harmonic mode has no significant effect on the SB. Later we carry out the relevant numerical simulations where we first show that the Hopf bifurcation, that occurs as a parameter is varied across the SB is subcritical, and that, in the important low-flow/high-power region, growing oscillations can result following small finite perturbations of stable steady-states on the 100% rod line. Hence, a point on the 100% rod line in the low-flow/high-power region, although stable, may nevertheless be a point at which a BWR should not be operated. Numerical simulations are then done to calculate the decay ratios (DRs) and frequencies of oscillations for various points on the 100% rod line. It is determined that the NRC requirement of DR < 0.75-0.8 is not rigorously satisfied in the low-flow/high-power region and hence these points should be avoided during normal startup and shutdown operations. The frequency of oscillation is shown to decrease as the flow rate is reduced and the frequency of 0.5Hz observed in the low-flow/high-power region is consistent with those observed during actual instability incidents. Additional numerical simulations show that in the low-flow/high-power region, for the same initial conditions, the use of point kinetics leads to damped oscillations, whereas the model that includes the modal kinetics equations results in growing nonlinear oscillations. Thus, we show that side-by-side out-of-phase growing power oscillations result due to the very important first harmonic mode effect and that the use of point kinetics, which fails to predict these growing oscillations, leads to dramatically nonconservative results. Finally, the effect of a simple recirculation loop model that we develop is studied by carrying out additional stability analyses and additional numerical simulations. It is shown that the loop has a stabilizing effect on certain points on the 100% rod line for time delays equal to integer multiples of the natural period of oscillation, whereas it has a destabilizing effect for half-integer multiples. However, for more practical time delays, it is determined that the overall effect generally is destabilizing.

Statistical evaluation of stability data: criteria for change-over-time and data variability.

PubMed

Bar, Raphael

2003-01-01

In a recently issued ICH Q1E guidance on evaluation of stability data of drug substances and products, the need to perform a statistical extrapolation of a shelf-life of a drug product or a retest period for a drug substance is based heavily on whether data exhibit a change-over-time and/or variability. However, this document suggests neither measures nor acceptance criteria of these two parameters. This paper demonstrates a useful application of simple statistical parameters for determining whether sets of stability data from either accelerated or long-term storage programs exhibit a change-over-time and/or variability. These parameters are all derived from a simple linear regression analysis first performed on the stability data. The p-value of the slope of the regression line is taken as a measure for change-over-time, and a value of 0.25 is suggested as a limit to insignificant change of the quantitative stability attributes monitored. The minimal process capability index, Cpk, calculated from the standard deviation of the regression line, is suggested as a measure for variability with a value of 2.5 as a limit for an insignificant variability. The usefulness of the above two parameters, p-value and Cpk, was demonstrated on stability data of a refrigerated drug product and on pooled data of three batches of a drug substance. In both cases, the determined parameters allowed characterization of the data in terms of change-over-time and variability. Consequently, complete evaluation of the stability data could be pursued according to the ICH guidance. It is believed that the application of the above two parameters with their acceptance criteria will allow a more unified evaluation of stability data.

Indoleamine-2,3-dioxygenase, an immunosuppressive enzyme that inhibits natural killer cell function, as a useful target for ovarian cancer therapy

PubMed Central

WANG, DONGDONG; SAGA, YASUSHI; MIZUKAMI, HIROAKI; SATO, NAOTO; NONAKA, HIROAKI; FUJIWARA, HIROYUKI; TAKEI, YUJI; MACHIDA, SHIZUO; TAKIKAWA, OSAMU; OZAWA, KEIYA; SUZUKI, MITSUAKI

2012-01-01

This study examined the role of the immunosuppressive enzyme indoleamine-2,3-dioxygenase (IDO) in ovarian cancer progression, and the possible application of this enzyme as a target for ovarian cancer therapy. We transfected a short hairpin RNA vector targeting IDO into the human ovarian cancer cell line SKOV-3, that constitutively expresses IDO and established an IDO downregulated cell line (SKOV-3/shIDO) to determine whether inhibition of IDO mediates the progression of ovarian cancer. IDO downregulation suppressed tumor growth and peritoneal dissemination in vivo, without influencing cancer cell growth. Moreover, IDO downregulation enhanced the sensitivity of cancer cells to natural killer (NK) cells in vitro, and promoted NK cell accumulation in the tumor stroma in vivo. These findings indicate that downregulation of IDO controls ovarian cancer progression by activating NK cells, suggesting IDO targeting as a potential therapy for ovarian cancer. PMID:22179492

The p90 ribosomal S6 kinase 2 specifically affects mitotic progression by regulating the basal level, distribution and stability of mitotic spindles

PubMed Central

Park, Yun Yeon; Nam, Hyun-Ja; Do, Mihyang; Lee, Jae-Ho

2016-01-01

RSK2, also known as RPS6KA3 (ribosomal protein S6 kinase, 90 kDa, polypeptide 3), is a downstream kinase of the mitogen-activated protein kinase (MAPK) pathway, which is important in regulating survival, transcription, growth and proliferation. However, its biological role in mitotic progression is not well understood. In this study, we examined the potential involvement of RSK2 in the regulation of mitotic progression. Interestingly, depletion of RSK2, but not RSK1, caused the accumulation of mitotic cells. Time-lapse analysis revealed that mitotic duration, particularly the duration for metaphase-to-anaphase transition was prolonged in RSK2-depleted cells, suggesting activation of spindle assembly checkpoint (SAC). Indeed, more BubR1 (Bub1-related kinase) was present on metaphase plate kinetochores in RSK2-depleted cells, and depletion of BubR1 abolished the mitotic accumulation caused by RSK2 depletion, confirming BubR1-dependent SAC activation. Along with the shortening of inter-kinetochore distance, these data suggested that weakening of the tension across sister kinetochores by RSK2 depletion led to the activation of SAC. To test this, we analyzed the RSK2 effects on the stability of kinetochore–microtubule interactions, and found that RSK2-depleted cells formed less kinetochore–microtubule fibers. Moreover, RSK2 depletion resulted in the decrease of basal level of microtubule as well as an irregular distribution of mitotic spindles, which might lead to observed several mitotic progression defects such as increase in unaligned chromosomes, defects in chromosome congression and a decrease in pole-to-pole distance in these cells. Taken together, our data reveal that RSK2 affects mitotic progression by regulating the distribution, basal level and the stability of mitotic spindles. PMID:27491410

βTrCP controls the lysosome-mediated degradation of CDK1, whose accumulation correlates with tumor malignancy

PubMed Central

Herrero-Ruiz, Joaquín; Mora-Santos, Mar; Giráldez, Servando; Sáez, Carmen; Japón, Miguel Á.; Tortolero, Maria; Romero, Francisco

2014-01-01

In mammals, cell cycle progression is controlled by cyclin-dependent kinases, among which CDK1 plays important roles in the regulation of the G2/M transition, G1 progression and G1/S transition. CDK1 is highly regulated by its association to cyclins, phosphorylation and dephosphorylation, changes in subcellular localization, and by direct binding of CDK inhibitor proteins. CDK1 steady-state protein levels are held constant throughout the cell cycle by a coordinated regulation of protein synthesis and degradation. We show that CDK1 is ubiquitinated by the E3 ubiquitin ligase SCFβTrCP and degraded by the lysosome. Furthermore, we found that DNA damage not only triggers the stabilization of inhibitory phosphorylation sites on CDK1 and repression of CDK1 gene expression, but also regulates βTrCP-induced CDK1 degradation in a cell type-dependent manner. Specifically, treatment with the chemotherapeutic agent doxorubicin in certain cell lines provokes CDK1 degradation and induces apoptosis, whereas in others it inhibits destruction of the protein. These observations raise the possibility that different tumor types, depending on their pathogenic spectrum mutations, may display different sensitivity to βTrCP-induced CDK1 degradation after DNA damage. Finally, we found that CDK1 accumulation in patients’ tumors shows a negative correlation with βTrCP and a positive correlation with the degree of tumor malignancy. PMID:25149538

Nanomedicine for prostate cancer using nanoemulsion: A review.

PubMed

Sasikumar, Aravindsiva; Kamalasanan, Kaladhar

2017-08-28

Prostate cancer (PCa) is a worldwide issue, with burgeoning rise in prevalence, morbidity and mortality. Targeted drug delivery, a long sort solution in this regard using controlled release (CR) - nanocarriers, is still a challenge. There is an emerging criticism that, the challenges are due to less appreciation for the biological barriers and lack of corresponding newer technologies. Over the years, more understanding about the biological barriers has come with the progress in characterization techniques. Correspondingly, there is a change in opinion about approaches in clinical trial that; focus of the end point need to be shifted towards disease stabilization for these explorative technologies. Currently, there is a requirement to overcome these newly identified challenges to develop newer affordable therapeutics. The ongoing clinical protocol for therapy using CR-nanocarriers is intravenous injection followed by local targeting to cancer site. This is the most accepted protocol and new CR-nanocarriers are being developed to suit this protocol. In this review, recent progress in treatment of PCa using CR-nanocarriers is analyzed with respect to newly identified biological barriers and design challenges. Possibilities of exploring nanoemulsion (NE) platform for targeted drug delivery to PCa are examined. Repurposing of drugs and combination therapy using NE platform targeted to PCa can be explored for design and development of affordable nanomedicine. In 20yrs. from now there expected to be numerous affordable nanomedicine technologies available in market exploring these lines. Copyright © 2017 Elsevier B.V. All rights reserved.

Meiotic behavior as a selection tool in silage corn breeding.

PubMed

Souza, V F; Pagliarini, M S; Scapim, C A; Rodovalho, M; Faria, M V

2010-10-19

In breeding programs, commercial hybrids are frequently used as a source of inbred lines to obtain new hybrids. Considering that maize production is dependent on viable gametes, the selection of populations to obtain inbred lines with high meiotic stability could contribute to the formation of new silage corn hybrids adapted to specific region. We evaluated the meiotic stability of five commercial hybrids of silage corn used in southern Brazil with conventional squashing methods. All of them showed meiotic abnormalities. Some abnormalities, such as abnormal chromosome segregation and absence of cytokinesis, occurred in all the genotypes, while others, including cytomixis and abnormal spindle orientation, were found only in some genotypes. The hybrid SG6010 had the lowest mean frequency of abnormal cells (21.27%); the highest frequency was found in the hybrid P30K64 (44.43%). However, the frequency of abnormal meiotic products was much lower in most genotypes, ranging from 7.63% in the hybrid CD304 to 43.86% in Garra. Taking into account the percentage of abnormal meiotic products and, hence, meiotic stability, only the hybrids CD304, P30K64, SG6010, and P30F53 are recommended to be retained in the breeding program to obtain inbred lines to create new hybrids.

Post-translational modification and stability of low molecular weight cyclin E.

PubMed

Mull, B B; Cox, J; Bui, T; Keyomarsi, K

2009-09-03

Our laboratory has previously described the presence of five tumor-specific low molecular weight isoforms of cyclin E in both tumor cell lines and breast cancer patient biopsies. We have also shown that one of these low forms arises from an alternate start site, whereas the other four appear as two sets of doublets following cleavage through an elastase-like enzyme. However, the origin of both sets of doublets was unknown. Here, we demonstrate that the larger isoform of each doublet is the result of phosphorylation at a key degradation site. Through site-directed mutagenesis of different phosphorylation sites within the cyclin E protein, we discovered that phosphorylation of threonine 395 is responsible for generating the larger isoform of each doublet. Because phosphorylation of threonine 395 has been linked to the proteasome-mediated degradation of full length cyclin E, we examined the stability of T395A phospho-mutants in both non-tumorigenic mammary epithelial cells and tumor cells. The results revealed that the low molecular weight isoforms appear to be stable in both a tumor cell line and a non-tumor forming cell line regardless of the presence of this critical phosphorylation site. The stability of low molecular weight cyclin E may have implications for both tumorigenesis and treatment of tumors expressing them.

Report on Progress Toward Security and Stability in Afghanistan

DTIC Science & Technology

2012-12-01

availability becomes more difficult further away from the cities. A lack of sufficient progress in governance and sustainable economic ...their confinement to areas away from major population centers. A small number of high-profile attacks (HPAs) occurred during the reporting period...activities were related to criminal networks. A small number of high-profiles attacks (HPAs) occurred during the reporting period. Contrary to insurgents

Prediction of the Long Term Stability of Polyester-Based Recording Media. First Annual Report, June 1982; Second Annual Report, August 1983; Progress Report, December 1984.

ERIC Educational Resources Information Center

Brown, Daniel W.; And Others

This document comprises three progress reports for a 5-year environmental aging study aimed at establishing the lifetimes of magnetic tapes and the poly(ethylene terephthalate) (PET) base of photographic and electronic film under archival storage conditions. The first annual report (1982) introduces the rationale for the project, provides…

Rapid Progressive Disease After Nivolumab Therapy in Three Patients with Metastatic Renal Cell Carcinoma

PubMed Central

KOBARI, YUKI; KONDO, TSUNENORI; TAKAGI, TOSHIO; OMAE, KENJI; NAKAZAWA, HAYAKAZU; TANABE, KAZUNARI

2017-01-01

Background/Aim: Rapid progressive disease (RPD), accelerated tumour growth immediate after the initiation of immune checkpoint inhibitor therapy, has been reported in melanoma and lung cancer. Herein, we describe 3 cases of RPD during the initial phase of nivolumab treatment for metastatic renal cell carcinoma. Patients and Methods: The first and second patients received nivolumab in the fourth-line setting. The third patient received nivolumab therapy as third-line treatment. Results: The first patient developed severe respiratory failure due to carcinomatous lymphangiosis 14 days after initiation of nivolumab therapy. The second patient developed leg paraplegia due to rapid growth of the metastatic tumour at the sixth thoracic vertebrae 5 days later. The third patient developed grade 4 hypercalcemia due to RPD on day 3. Conclusion: Clinicians should be aware of RPD during the initial phase of nivolumab therapy, especially in patients with critical lesions in the late-line setting. PMID:28652455

Recent progress on the genetics and molecular breeding of brown planthopper resistance in rice.

PubMed

Hu, Jie; Xiao, Cong; He, Yuqing

2016-12-01

Brown planthopper (BPH) is the most devastating pest of rice. Host-plant resistance is the most desirable and economic strategy in the management of BPH. To date, 29 major BPH resistance genes have been identified from indica cultivars and wild rice species, and more than ten genes have been fine mapped to chromosome regions of less than 200 kb. Four genes (Bph14, Bph26, Bph17 and bph29) have been cloned. The increasing number of fine-mapped and cloned genes provide a solid foundation for development of functional markers for use in breeding. Several BPH resistant introgression lines (ILs), near-isogenic lines (NILs) and pyramided lines (PLs) carrying single or multiple resistance genes were developed by marker assisted backcross breeding (MABC). Here we review recent progress on the genetics and molecular breeding of BPH resistance in rice. Prospect for developing cultivars with durable, broad-spectrum BPH resistance are discussed.

Straight A's: Public Education Policy and Progress. Volume 12, Number 5

ERIC Educational Resources Information Center

Amos, Jason, Ed.

2012-01-01

"Straight A's: Public Education Policy and Progress" is a biweekly newsletter that focuses on education news and events both in Washington, DC and around the country. The following articles are included in this issue: (1) House Committee Passes Education Reform Legislation: On Party-Line Votes, Committee Passes Accountability and Teacher…

Solid State Mini-RPV Color Imaging System

DTIC Science & Technology

1975-09-12

completed in the design and construction phase . Con- siderations are now in progress for conducting field tests of the equipment against "real world...Simplified Parallel Injection Configuration 2-21 CID Parallel Injection Configuration 2-23 Element Rate Timing 2-25 Horizontal Input and Phase Line...Timing 2-26 Line Reset /Injection Timing 2-27 Line Rate Timing (Start of Readout) 2-28 Driver A4 Block Diagram 2-31 Element Scan Time Base

76 FR 22928 - Nextera Energy Point Beach, LLC; Point Beach Nuclear Plant, Units 1 and 2; Environmental...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-25

... implementation. There would be no land use changes along transmission lines (no new lines would be required for...-term grid reliability and stability. Land use conditions would not change significantly PBNP, and there... result from the proposed EPU. Non-Radiological Impacts Land Use and Aesthetic Impacts Potential land use...

A general solution to the hidden-line problem. [to graphically represent aerodynamic stability derivatives

NASA Technical Reports Server (NTRS)

Hedgley, D. R., Jr.

1982-01-01

The requirements for computer-generated perspective projections of three dimensional objects has escalated. A general solution was developed. The theoretical solution to this problem is presented. The method is very efficient as it minimizes the selection of points and comparison of line segments and hence avoids the devastation of square-law growth.

Dihydroartemisinin inhibits indoxyl sulfate (IS)-promoted cell cycle progression in mesangial cells by targeting COX-2/mPGES-1/PGE2 cascade.

PubMed

Mungun, Harr-Keshauve; Li, Shuzhen; Zhang, Yue; Huang, Songming; Jia, Zhanjun; Ding, Guixia; Zhang, Aihua

2018-01-01

Dihydroartemisinin (DHA) is a semisynthetic derivative of artemisinin and has been used as an antimalarial drug. Recently, roles of artemisinin and its derivatives in treating diseases besides antimalarial effect were documented. Thus, this study was undertaken to investigate the role of DHA in indoxyl sulfate (IS)-promoted cell cycle progression in glomerular mesangial cells, as well as the potential mechanisms. Under the basal condition, DHA significantly retarded the cell cycle progression as shown by decreased cell percentage in S phase and increased cell percentage in G1/G0 phases in line with reduced cell cycle proteins cyclin A2 and cyclin D1. Interestingly, DHA also inactivated the COX-2/mPGES-1/PGE 2 cascade which has been shown to play a critical role in promoting the mesangial cell cycle progression by our previous studies. Next, we investigated the role of DHA in IS-triggered cell cycle progression in this mesangial cell line. As expected, DHA treatment significantly retarded IS-induced cell cycle progression and inhibited the activation of COX-2/mPGES-1/PGE 2 cascade induced by IS. In summary, these data indicated that DHA inhibited the cell cycle progression in glomerular mesangial cells under normal condition or IS challenge possibly through the inhibition of COX-2/mPGES-1/PGE 2 cascade, suggesting a potential of DHA in treating glomerular diseases with mesangial cell proliferation.

Recent progress in stabilizing hybrid perovskites for solar cell applications

NASA Astrophysics Data System (ADS)

Chen, Jianqing; Cai, Xin; Yang, Donghui; Song, Dan; Wang, Jiajia; Jiang, Jinghua; Ma, Aibin; Lv, Shiquan; Hu, Michael Z.; Ni, Chaoying

2017-07-01

Hybrid inorganic-organic perovskites have quickly evolved as a promising group of materials for solar cells and optoelectronic applications mainly owing to the inexpensive materials, relatively simple and versatile fabrication and high power conversion efficiency (PCE). The certified energy conversion efficiency for perovskite solar cell (PSC) has reached above 20%, which is compatible to the current best for commercial applications. However, long-term stabilities of the materials and devices remain to be the biggest challenging issue for realistic implementation of the PSCs. This article discusses the key issues related to the stability of perovskite absorbing layer including crystal structural stability, chemical stability under moisture, oxygen, illumination and interface reaction, effects of electron-transporting materials (ETM), hole-transporting materials (HTM), contact electrodes, ion migration and preparation conditions. Towards the end, prospective strategies for improving the stability of PSCs are also briefly discussed and summarized. We focus on recent understanding of the stability of materials and devices and our perspectives about the strategies for the stability improvement.

Kinetics and mechanical stability of the fibril state control fibril formation time of polypeptide chains: A computational study

NASA Astrophysics Data System (ADS)

Kouza, Maksim; Co, Nguyen Truong; Li, Mai Suan; Kmiecik, Sebastian; Kolinski, Andrzej; Kloczkowski, Andrzej; Buhimschi, Irina Alexandra

2018-06-01

Fibril formation resulting from protein misfolding and aggregation is a hallmark of several neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. Despite much progress in the understanding of the protein aggregation process, the factors governing fibril formation rates and fibril stability have not been fully understood. Using lattice models, we have shown that the fibril formation time is controlled by the kinetic stability of the fibril state but not by its energy. Having performed all-atom explicit solvent molecular dynamics simulations with the GROMOS43a1 force field for full-length amyloid beta peptides Aβ40 and Aβ42 and truncated peptides, we demonstrated that kinetic stability can be accessed via mechanical stability in such a way that the higher the mechanical stability or the kinetic stability, the faster the fibril formation. This result opens up a new way for predicting fibril formation rates based on mechanical stability that may be easily estimated by steered molecular dynamics.

Optical frequency stabilization in infrared region using improved dual feed-back loop

NASA Astrophysics Data System (ADS)

Ružička, B.; Číp, O.; Lazar, J.

2007-03-01

Modern technologies such as DWDM (Dense Wavelength Division Multiplex) need precise stability of laser frequencies. According to this fact, requirements of new etalons of optical frequencies in the telecommunication band is rapidly growing. Lasers working in near infrared telecommunication band (1500-1600 nm) can be stabilized to 12C IIH II or 13C IIH II (acetylene) gas absorption lines. The acetylene gas absorption has been widely studied and accepted by international bodies of standardization as a primary wavelength reference in the near infrared band around 1550 nm. Our aim was to design and develop a compact fibre optics laser system generating coherent light in near-IR band with high frequency stability (at least 1.10 -8). This system should become a base for realization of a primary frequency standard for optical communications in the Czech Republic. Such an etalon will be needed for calibration of wavelengthmeters and spectral analysers for DWDM communication systems. We are co-operating with CMI (Czech Metrology Institute) on this project. We present stabilized laser system based on a single frequency DFB (Distributed Feedback) laser diode with a narrow spectral profile. The laser is pre-stabilized by means of the FM-spectroscopy on a passive resonator. Thanks to a fast feed-back loop we are able to improve spectral characteristics of the laser. The laser frequency is locked by a relatively slow second feed-back loop on an absorption line of acetylene vapour which is sealed in a cell under the optimised pressure.

Comparison of Quasi-Conservative Pressure-Based and Fully-Conservative Formulations for the Simulation of Transcritical Flows

NASA Astrophysics Data System (ADS)

Lacaze, Guilhem; Oefelein, Joseph

2016-11-01

High-pressure flows are known to be challenging to simulate due to thermodynamic non-linearities occurring in the vicinity of the pseudo-boiling line. This study investigates the origin of this issue by analyzing the behavior of thermodynamic processes at elevated pressure and low temperature. We show that under transcritical conditions, non-linearities significantly amplify numerical errors associated with construction of fluxes. These errors affect the local density and energy balances, which in turn creates pressure oscillations. For that reason, solvers based on a conservative system of equations that transport density and total energy are subject to unphysical pressure variations in gradient regions. These perturbations hinder numerical stability and degrade the accuracy of predictions. To circumvent this problem, the governing system can be reformulated to a pressure-based treatment of energy. We present comparisons between the pressure-based and fully conservative formulations using a progressive set of canonical cases, including a cryogenic turbulent mixing layer at rocket engine conditions. Department of Energy, Office of Science, Basic Energy Sciences Program.

[Artificial control of blood-nerve barrier: a novel therapeutic approach to peripheral neuropathies].

PubMed

Kanda, Takashi

2011-11-01

Blood-nerve barrier (BNB) is a "Janus-faced" structure for the peripheral nerve parenchyma. Healthy BNB may contribute to stabilize the internal milleu of peripheral nervous system (PNS) and to stop the entrance of toxic substances and harmful leukocytes into nerve parenchyma. On the other hand, healthy BNB may sometimes be a drawback because the peripheral nerve parenchyma cannot receive enough amount of nutrients and growth factors and cannot excrete toxic substances into systemic circulation because of its presence. Here we present a future therapeutic strategy to control BNB function, based on the basic knowledge acquired from recently developed human immortalized cell lines of BNB origin. If we can artificially regulate the BNB permeability and the expression of adhesion molecules on the surface of BNB-forming endothelial cells, and stop the entrance of toxic substances as well as pathogenic leukocytes into PNS parenchyma, the treatment of inflammatory neuropathies may make great progresses. For hereditary, metabolic and ischemic neuropathies, the promotion of the entrance of growth factors into PNS parenchyma and of the excretion of toxic substances should powerfully encourage the regeneration of axons.

NDRG1, a growth and cancer related gene: regulation of gene expression and function in normal and disease states.

PubMed

Ellen, Thomas P; Ke, Qingdong; Zhang, Ping; Costa, Max

2008-01-01

N-myc downstream-regulated gene 1 (NDRG1) is an intracellular protein that is induced under a wide variety of stress and cell growth-regulatory conditions. NDRG1 is up-regulated by cell differentiation signals in various cancer cell lines and suppresses tumor metastasis. Despite its specific role in the molecular cause of Charcot-Marie-Tooth type 4D disease, there has been more interest in the gene as a marker of tumor progression and enhancer of cellular differentiation. Because it is strongly up-regulated under hypoxic conditions, and this condition is prevalent in solid tumors, its regulation is somewhat complex, governed by hypoxia-inducible factor 1 alpha (HIF-1alpha)- and p53-dependent pathways, as well as its namesake, neuroblastoma-derived myelocytomatosis, and probably many other factors, at the transcriptional and translational levels, and through mRNA stability. We survey the data for clues to the NDRG1 gene's mechanism and for indications that the NDRG1 gene may be an efficient diagnostic tool and therapy in many types of cancers.

Improvement of the antiproliferative effect of rapamycin on tumor cell lines by poly (monomethylitaconate)-based pH-sensitive, plasma stable liposomes.

PubMed

Ghanbarzadeh, Saeed; Arami, Sanam; Pourmoazzen, Zhaleh; Khorrami, Arash

2014-03-01

pH-responsive polymers produce liposomes with pH-sensitive property which can release their encapsulated drug under mild acidic conditions found inside the cellular endosomes, inflammatory tissues and cancerous cells. The aim of this study was preparing pH-sensitive and plasma stable liposomes in order to enhance the selectivity and antiproliferative effect of Rapamycin. In the present study we used PEG-poly (monomethylitaconate)-CholC6 (PEG-PMMI-CholC6) copolymer and Oleic acid (OA) to induce pH-sensitive property in Rapamycin liposomes. pH-sensitive liposomal formulations bearing copolymer PEG-PMMI-CholC6 and OA were characterized in regard to physicochemical stability, pH-responsiveness and stability in human plasma. The ability of pH-sensitive liposomes in enhancing the cytotoxicity of Rapamycin was evaluated in vitro by using colon cancer cell line (HT-29) and compared with its cytotoxicity on human umbilical vein endothelial cell (HUVEC) line. Both formulations were found to release their contents under mild acidic conditions rapidly. However, unlike OA-based liposomes, the PEG-PMMI-CholC6 bearing liposomes preserved their pH-sensitivity in plasma. Both types of pH-sensitive Rapamycin-loaded liposomes exhibited high physicochemical stability and could deliver antiproliferative agent into HT-29 cells much more efficiently in comparison with conventional liposomes. Conversely, the antiproliferative effect of pH-sensitive liposomes on HUVEC cell line was less than conventional liposomes. This study showed that both OA and PEG-PMMI-CholC6-based vesicles could submit pH-sensitive property, however, only PEG-PMMI-CholC6-based liposomes could preserve pH-sensitive property after incubation in plasma. As a result pH-sensitive PEG-PMMI-CholC6-based liposomal formulation can improve the selectivity, stability and antiproliferative effect of Rapamycin. Copyright © 2014 Elsevier B.V. All rights reserved.

Office of Inspector General audit report on Project Hanford management contract costs and performance

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

NONE

1998-11-01

On August 6, 1996, the Richland Operations Office (Richland) awarded the Project Hanford Management Contract (Management Contract) to Fluor Daniel Hanford, Inc. (Fluor Daniel). This performance-based, 5-year contract to support cleanup of the Department of Energy`s (DOE) Hanford Site (Hanford) contained performance goals or expectations related to the stabilization, transition, and diversification of the Tri-Cities` economy near Hanford in southeastern Washington. One of these economic goals was that Fluor Daniel and its major subcontractors would help generate 3,000 new, non-Hanford, private sector jobs that would help stabilize and diversify the Tri-Cities` economy. The contract specifically called for Fluor Daniel tomore » help generate 200 jobs, establish an investment fund, and bring 6 new growth-oriented enterprise companies to the Tri-Cities by the end of Fiscal Year (FY) 1997. The objective of the audit was to determine whether Richland was making adequate progress in stabilizing and diversifying the economy of the Tri-Cities by creating 3,000 new, non-Hanford jobs within 5 years. Accordingly, the author examined the progress made in FY 1997, which was the first year of the Management Contract. Richland and Fluor Daniel are at risk of not meeting the Management Contract`s goals of stabilizing and diversifying the economy of the Tri-Cities because most of the new jobs created during FY 1997 were not comparable to Hanford jobs and, thus, may not sustain long-term economic goals. Therefore, Fluor Daniel has not met its expectations in the first year and is not making adequate progress toward meeting the Management Contract`s overall economic goals.« less

The effects of certain glycols, substituted glycols and related organic solvents on the thermal stability of soluble collagen

PubMed Central

Hart, G. J.; Russell, A. E.; Cooper, D. R.

1971-01-01

The effects of a number of related diols, substituted diols and glycerol on the thermal stability of acid-soluble calf skin collagen were investigated. Thermal transition temperatures were determined by optical rotation measurement. Short-chain diols with terminal hydroxyl groups, i.e. ethylene glycol and propane-1,3-diol, stabilized the protein at all accessible concentrations. Stabilization was also observed with glycerol and diethylene glycol. Higher homologues in the diol series produced various effects, as did hydroxyl-group positional isomerism. Monoalkyl substitution of diols progressively lowered the denaturation temperature of collagen. Results are discussed in relation to possible mechanisms of perturbant action. PMID:5169191

Dynamic Control of Topological Defects in Artificial Colloidal Ice

DOE PAGES

Libál, A.; Nisoli, C.; Reichhardt, C.; ...

2017-04-05

We demonstrate the use of an external field to stabilize and control defect lines connecting topological monopoles in spin ice. For definiteness we perform Brownian dynamics simulations with realistic units mimicking experimentally realized artificial colloidal spin ice systems, and show how defect lines can grow, shrink or move under the action of direct and alternating fields. Asymmetric alternating biasing forces can cause the defect line to ratchet in either direction, making it possible to precisely position the line at a desired location. Such manipulation could be employed to achieve mobile information storage in these metamaterials.

Dynamic Control of Topological Defects in Artificial Colloidal Ice

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

Libál, A.; Nisoli, C.; Reichhardt, C.

We demonstrate the use of an external field to stabilize and control defect lines connecting topological monopoles in spin ice. For definiteness we perform Brownian dynamics simulations with realistic units mimicking experimentally realized artificial colloidal spin ice systems, and show how defect lines can grow, shrink or move under the action of direct and alternating fields. Asymmetric alternating biasing forces can cause the defect line to ratchet in either direction, making it possible to precisely position the line at a desired location. Such manipulation could be employed to achieve mobile information storage in these metamaterials.

[About the infection of Drosophila female germ line cells by sigma virus (author's transl)].

PubMed

Brun, G

1977-01-01

The results which have been presented by Bregliano (1973) and Bregliano et Fleuriet (1975) in this "Annales" are discussed. The author's conclusion is that there are two distinct mechanisms for contamination of the cysts of non-stabilized females (in stabilized females, all cells, including oogonial cells, are infected in carrier state by sigma). Hypotheses are discussed.

Small satellite generic bus structure

NASA Astrophysics Data System (ADS)

Fiore, John N.; Summers, George D.

1993-02-01

A 'Smallsat' generic structure has been developed for LEO and expendable launch vehicles. The structure makes extensive use of Al-alloy honeycomb-stabilized panels in order to satisfy stiffness, weight, strength and thermal stability requirements in the LEO environment, in conjunction with discrete applications of multilayered insulation blankets and silverized Teflon radiators. The Smallsat structure is ideally suited for assembly-line manufacturing and storage until required.

The role of non-ionizing radiation pressure in star formation: the stability of cores and filaments

NASA Astrophysics Data System (ADS)

Seo, Young Min; Youdin, Andrew N.

2016-09-01

Stars form when filaments and dense cores in molecular clouds fragment and collapse due to self-gravity. In the most basic analyses of gravitational stability, the competition between self-gravity and thermal pressure sets the critical (I.e. maximum stable) mass of spheres and the critical line density of cylinders. Previous work has considered additional support from magnetic fields and turbulence. Here, we consider the effects of non-ionizing radiation, specifically the inward radiation pressure force that acts on dense structures embedded in an isotropic radiation field. Using hydrostatic, isothermal models, we find that irradiation lowers the critical mass and line density for gravitational collapse, and can thus act as a trigger for star formation. For structures with moderate central densities, ˜103 cm-3, the interstellar radiation field in the Solar vicinity has an order unity effect on stability thresholds. For more evolved objects with higher central densities, a significant lowering of stability thresholds requires stronger irradiation, as can be found closer to the Galactic centre or near stellar associations. Even when strong sources of ionizing radiation are absent or extincted, our study shows that interstellar irradiation can significantly influence the star formation process.

The amino-terminal matrix assembly domain of fibronectin stabilizes cell shape and prevents cell cycle progression.

PubMed

Christopher, R A; Judge, S R; Vincent, P A; Higgins, P J; McKeown-Longo, P J

1999-10-01

Adhesion to the extracellular matrix modulates the cellular response to growth factors and is critical for cell cycle progression. The present study was designed to address the relationship between fibronectin matrix assembly and cell shape or shape dependent cellular processes. The binding of fibronectin's amino-terminal matrix assembly domain to adherent cells represents the initial step in the assembly of exogenous fibronectin into the extracellular matrix. When added to monolayers of pulmonary artery endothelial cells, the 70 kDa fragment of fibronectin (which contains the matrix assembly domain) stabilized both the extracellular fibronectin matrix as well as the actin cytoskeleton against cytochalasin D-mediated structural reorganization. This activity appeared to require specific fibronectin sequences as fibronectin fragments containing the cell adhesion domain as well as purified vitronectin were ineffective inhibitors of cytochalasin D-induced cytoarchitectural restructuring. Such pronounced morphologic consequences associated with exposure to the 70 kDa fragment suggested that this region of the fibronectin molecule may affect specific growth traits known to be influenced by cell shape. To assess this possibility, the 70 kDa fragment was added to scrape-wounded monolayers of bovine microvessel endothelium and the effects on two shape-dependent processes (i.e. migration and proliferation) were measured as a function of time after injury and location from the wound. The addition of amino-terminal fragments of fibronectin to the monolayer significantly inhibited (by >50%) wound closure. Staining of wounded monolayers with BrdU, moreover, indicated that either the 70 kDa or 25 kDa amino-terminal fragments of fibronectin, but not the 40 kDa collagen binding fragment, also inhibited cell cycle progression. These results suggest that the binding of fibronectin's amino-terminal region to endothelial cell layers inhibits cell cycle progression by stabilizing cell shape.

Impact of the use of autologous stem cell transplantation at first relapse both in naïve and previously rituximab exposed follicular lymphoma patients treated in the GELA/GOELAMS FL2000 study

PubMed Central

Le Gouill, Steven; De Guibert, Sophie; Planche, Lucie; Brice, Pauline; Dupuis, Jehan; Cartron, Guillaume; Van Hoof, Achiel; Casasnovas, Olivier; Gyan, Emmanuel; Tilly, Hervé; Fruchart, Christophe; Deconinck, Eric; Fitoussi, Olivier; Gastaud, Lauris; Delwail, Vincent; Gabarre, Jean; Gressin, Rémy; Blanc, Michel; Foussard, Charles; Salles, Gilles

2011-01-01

Background We analyzed detailed characteristics and salvage treatment in 175 follicular lymphoma patients from the FL2000 study who were in progression after first-line therapy with or without addition of rituximab to chemotherapy and interferon. Design and Methods The impact of using autologous stem cell transplantation and/or rituximab administration at first progression was investigated, taking into account initial therapy. With a median follow up of 31 months, 3-year event free and overall survival rates after progression were 50% (95%CI 42–58%) and 72% (95%CI 64–78%), respectively. Results The 3-year event free rate of rituximab re-treated patients (n=112) was 52% (95%CI 41–62%) versus 40% (95%CI 24–55%) for those not receiving rituximab second line (n=53) (P=0.075). There was a significant difference in 3-year overall survival between patients receiving autologous stem cell transplantation and those not: 92% (95%CI 78–97%) versus 63% (95%CI 51–72%) (P=0.0003), respectively. In multivariate analysis, both autologous stem cell transplantation and period of progression/relapse affected event free and overall survival. Conclusions Regardless of front-line rituximab exposure, this study supports incorporating autologous stem cell transplantation in the therapeutic approach at first relapse for follicular lymphoma patients. PMID:21486862

The effect of point-of-care personal digital assistant use on resident documentation discrepancies.

PubMed

Carroll, Aaron E; Tarczy-Hornoch, Peter; O'Reilly, Eamon; Christakis, Dimitri A

2004-03-01

We recently found documentation discrepancies in 60% of resident daily-progress notes with respect to patient weight, medications, or vascular lines. To what extent information systems can decrease such discrepancies is unknown. To determine whether a point-of-care personal digital assistant (PDA)-based patient record and charting system could reduce the number of resident progress-note documentation discrepancies in a neonatal intensive care unit (NICU). We conducted a before-and-after trial in an academic NICU. Our intervention was a PDA-based patient record and charting system used by all NICU resident physicians over the study period. We analyzed all resident daily-progress notes from 40 randomly selected days over 4 months in both the baseline and intervention periods. Using predefined reference standards, we determined the accuracy of recorded information for patient weights, medications, and vascular lines. Logistic and Poisson regression were used in analyses to control for potential confounding factors. A total of 339 progress notes in the baseline period and 432 progress notes in the intervention period were reviewed. When controlling for covariates in the regression, there were significantly fewer documentation discrepancies of patient weights in notes written by using the PDA system (14.4%-4.4% of notes; odds ratio [OR]: 0.29; 95% confidence interval [CI]: 0.15-0.56). When using the PDA system, there were no significant changes in the numbers of notes with documentation discrepancies of medications (27.7%-17.1% of notes; OR: 0.63; 95% CI: 0.35-1.13) or vascular lines (33.6%-36.1% of notes; OR: 1.11; 95% CI: 0.66-1.87). The use of our PDA-based point-of-care patient record and charting system showed a modest benefit in reducing the number of documentation discrepancies in resident daily-progress notes. Further study of PDAs in information systems is warranted before they are widely adopted.

The life and miracles of kinetochores

PubMed Central

Santaguida, Stefano; Musacchio, Andrea

2009-01-01

Kinetochores are large protein assemblies built on chromosomal loci named centromeres. The main functions of kinetochores can be grouped under four modules. The first module, in the inner kinetochore, contributes a sturdy interface with centromeric chromatin. The second module, the outer kinetochore, contributes a microtubule-binding interface. The third module, the spindle assembly checkpoint, is a feedback control mechanism that monitors the state of kinetochore–microtubule attachment to control the progression of the cell cycle. The fourth module discerns correct from improper attachments, preventing the stabilization of the latter and allowing the selective stabilization of the former. In this review, we discuss how the molecular organization of the four modules allows a dynamic integration of kinetochore–microtubule attachment with the prevention of chromosome segregation errors and cell-cycle progression. PMID:19629042

DISTRIBUTED AMPLIFIER INCORPORATING FEEDBACK

DOEpatents

Bell, P.R. Jr.

1958-10-21

An improved distributed amplifier system employing feedback for stabilization is presented. In accordance with the disclosed invention, a signal to be amplified is applled to one end of a suitable terminated grid transmission line. At intervals along the transmission line, the signal is fed to stable, resistance-capacitance coupled amplifiers incorporating feedback loops therein. The output current from each amplifier is passed through an additional tube to minimize the electrostatic capacitance between the tube elements of the last stage of the amplifier, and fed to appropriate points on an output transmission line, similar to the grid line, but terminated at the opposite (input) end. The output taken from the unterminated end of the plate transmission line is proportional to the input voltage impressed upon the grid line.

Protein B61 as a new growth factor: expression of B61 and up-regulation of its receptor epithelial cell kinase during melanoma progression.

PubMed

Easty, D J; Guthrie, B A; Maung, K; Farr, C J; Lindberg, R A; Toso, R J; Herlyn, M; Bennett, D C

1995-06-15

Epithelial cell kinase (ECK) is a receptor protein tyrosine kinase, the role of which in melanoma biology is unclear. Here we studied the role of ECK during melanoma progression. ECK mRNA was overexpressed in virtually all melanoma lines tested, and levels were significantly higher in cell lines from distant metastases than primary melanomas; melanocytes were negative. Gene amplification was not detected in melanomas. Levels of ECK protein corresponded well with mRNA levels. B61 or LERK-1, recently identified as an ECK ligand, stimulated the growth of ECK-expressing melanoma cell lines, its first identified biological activity. Melanoma chemotaxis and chemoinvasion were not affected by B61. Growth of normal melanocytes was not affected. mRNA for B61 was detected in both melanoma cell lines and normal melanocytes. B61 was also identified by Western blotting and ECK binding activity with the use of a BIAcore binding assay in melanoma cell-conditioned media. These results suggest that B61 is an autocrine growth factor for melanomas but not normal melanocytes.

Long-term follow-up analysis of 100 patients with splenic marginal zone lymphoma treated with splenectomy as first-line treatment.

PubMed

Lenglet, Julien; Traullé, Catherine; Mounier, Nicolas; Benet, Claire; Munoz-Bongrand, Nicolas; Amorin, Sandy; Noguera, Maria-Elena; Traverse-Glehen, Alexandra; Ffrench, Martine; Baseggio, Lucile; Felman, Pascale; Callet-Bauchu, Evelyne; Brice, Pauline; Berger, Françoise; Salles, Gilles; Brière, Josette; Coiffier, Bertrand; Thieblemont, Catherine

2014-08-01

Splenectomy is considered as one of the first-line treatments for symptomatic patients with splenic marginal zone lymphoma (SMZL). Between 1997 and 2012, 100 hepatitis C virus-negative patients with SMZL were treated by splenectomy as first-line treatment. At 6 months, all patients but three recovered from all cytopenias. The median lymphocyte count at 6 months and 1 year was 11.51 × 10(9)/L and 6.9 × 10(9)/L, respectively. Median progression-free survival (PFS) was 8.25 years. The 5-year and 10-year overall survival (OS) rates were 84% and 67%, respectively. Histological transformation occurred in 11% of patients, and was the only parameter significantly associated with a shorter time to progression (p = 0.0001). Significant prognostic factors for OS were age (p = 0.0356) and histological transformation (p = 0.0312). In this large retrospective cohort, we confirmed that splenectomy as first-line treatment in patients with SMZL corrected cytopenias and lymphocytosis within the first year and was associated with a good PFS.

Real-life effectiveness of erlotinib as second-line treatment of stage IIIB/IV squamous non-small cell lung cancer: Results of the PEPiTA observational study.

PubMed

Monnet, Isabelle; Audigier-Valette, Clarisse; Girard, Nicolas; Vergnenègre, Alain; Molinier, Olivier; Souquet, Pierre Jean; Blanchon, François; Bonnetain, Franck; Taguieva-Pioger, Naila; Lamour, Corinne; Wislez, Marie

2016-08-01

Erlotinib, an inhibitor of tyrosine kinase activity of the epidermal growth factor receptor, is effective in non-small cell lung cancer (NSCLC). Data on erlotinib use in squamous NSCLC are limited. This observational study aimed at evaluating the efficacy and safety of second-line erlotinib in patients with stage IIIB/IV squamous NSCLC in a real-life setting. Patients with predominantly squamous stage IIIB/IV NSCLC, who failed first-line platinum-based therapy, were recruited and followed-up for 12 months. Patients underwent visits each trimester. Data were derived from case report forms, and functional assessment of cancer therapy-lung (FACT-L) questionnaires. A total of 152 patients were enrolled; the majority were males (90%) and mean age was 67.7 years. All patients had squamous (97%) or predominantly squamous (3%) NSCLC, of stage IIIB (21%) or IV (79%). Median progression free survival (PFS) and overall survival were 3 and 5.8 months, respectively. Disease progression was observed in the majority of the patients, mostly due to progression of primary tumour and/or metastatic sites, and led to death in 91/107 of patients. Of the 107 deaths reported, none were due to erlotinib. FACT-L questionnaires were interpretable up to the first visit and were in line with PFS data, showing a relatively good quality of life up to Month 3 (mean total score=78.8). No new or unexpected safety issues were reported. The results of this real-life cohort study like those of previous phase III/IV subgroups study analyses indicate that erlotinib is a valuable option for second-line treatment of stage IIIB/IV squamous NSCLC. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Effects of antioxidants on the quality and genomic stability of induced pluripotent stem cells

PubMed Central

Luo, Lan; Kawakatsu, Miho; Guo, Chao-Wan; Urata, Yoshishige; Huang, Wen-Jing; Ali, Haytham; Doi, Hanako; Kitajima, Yuriko; Tanaka, Takayuki; Goto, Shinji; Ono, Yusuke; Xin, Hong-Bo; Hamano, Kimikazu; Li, Tao-Sheng

2014-01-01

Effects of antioxidants on the quality and genomic stability of induced pluripotent stem (iPS) cells were investigated with two human iPS cell lines (201B7 and 253G1). Cells used in this study were expanded from a single colony of each cell line with the addition of proprietary antioxidant supplement or homemade antioxidant cocktail in medium, and maintained in parallel for 2 months. The cells grew well in all culture conditions and kept “stemness”. Although antioxidants modestly decreased the levels of intracellular reactive oxygen species, there were no differences in the expression of 53BP1 and pATM, two critical molecules related with DNA damage and repair, under various culture conditions. CGH analysis showed that the events of genetic aberrations were decreased only in the 253G1 iPS cells with the addition of homemade antioxidant cocktail. Long-term culture will be necessary to confirm whether low dose antioxidants improve the quality and genomic stability of iPS cells. PMID:24445363

Mode stabilization in quantum cascade lasers via an intra-cavity cascaded nonlinearity.

PubMed

St-Jean, M Renaudat; Amanti, M I; Bismuto, A; Beck, M; Faist, J; Sirtori, C

2017-02-06

We present self-stabilization of the inter-mode separation of a quantum cascade laser (QCL) emitting at 9 μm via cascaded second order nonlinearity. This effect has been observed in lasers that have the optical cavity embedded into a microwave strip-line. The intermodal beat note spectra narrow with increasing laser output power, up to less than 100 kHz. A flat frequency response to direct modulation up to 14 GHz is reported for these microstrip QCLs. The laser inter-mode spacing can be locked to an external RF signal and tuned by more than 1 MHz from the free-running spacing. A parallel study on the same laser material in a non-microstrip line waveguide shows superior performances of the microstrip QCL in terms of the intermodal spectral locking and stability. Finally by analyzing our results with the theory of the injection locking of coupled oscillators, we deduce that the microwave power injected in the microstrip QCL is 2 orders of magnitude higher than in the reference laser.

Magneto-hydrodynamically stable axisymmetric mirrorsa)

NASA Astrophysics Data System (ADS)

Ryutov, D. D.; Berk, H. L.; Cohen, B. I.; Molvik, A. W.; Simonen, T. C.

2011-09-01

Making axisymmetric mirrors magnetohydrodynamically (MHD) stable opens up exciting opportunities for using mirror devices as neutron sources, fusion-fission hybrids, and pure-fusion reactors. This is also of interest from a general physics standpoint (as it seemingly contradicts well-established criteria of curvature-driven instabilities). The axial symmetry allows for much simpler and more reliable designs of mirror-based fusion facilities than the well-known quadrupole mirror configurations. In this tutorial, after a summary of classical results, several techniques for achieving MHD stabilization of the axisymmetric mirrors are considered, in particular: (1) employing the favorable field-line curvature in the end tanks; (2) using the line-tying effect; (3) controlling the radial potential distribution; (4) imposing a divertor configuration on the solenoidal magnetic field; and (5) affecting the plasma dynamics by the ponderomotive force. Some illuminative theoretical approaches for understanding axisymmetric mirror stability are described. The applicability of the various stabilization techniques to axisymmetric mirrors as neutron sources, hybrids, and pure-fusion reactors are discussed; and the constraints on the plasma parameters are formulated.

Management of pediatric mandibular fractures using bioresorbable plating system - Efficacy, stability, and clinical outcomes: Our experiences and literature review.

PubMed

Singh, Mahinder; Singh, R K; Passi, Deepak; Aggarwal, Mohit; Kaur, Guneet

2016-01-01

The purpose of this study was to determine the efficacy and stability of the biodegradable fixation system for treatment of mandible fractures in pediatric patients by measuring the bite force. Sixty pediatric patients with mandibular fractures (36 males, 24 females) were included in this study. The 2.5-mm resorbable plates were adapted along Champy's line of ideal osteosynthesis and secured with four 2.5 mm diameter monocortical resorbable screws, 8 mm in length. All patients were followed for 10 months. Clinical parameters, such as soft tissue infection, nonunion, malunion, implant exposure, malocclusion, nerve injury, and bite force for stability, were prospectively assessed. Adequate fixation and primary bone healing was achieved in 100% of the cases. Six minor complications (10%) were observed: 2 soft tissue infections (3%), 1 plate dehiscence (2%), 1 malocclusion (2%), and 2 paresthesia (3%). 2.5-mm resorbable plating system along Champy's line of ideal osteosynthesis is a good treatment modality for mandible fractures in pediatric patients.

Calibration of high voltages at the ppm level by the difference of ^{83{m}}Kr conversion electron lines at the KATRIN experiment

NASA Astrophysics Data System (ADS)

Arenz, M.; Baek, W.-J.; Beck, M.; Beglarian, A.; Behrens, J.; Bergmann, T.; Berlev, A.; Besserer, U.; Blaum, K.; Bode, T.; Bornschein, B.; Bornschein, L.; Brunst, T.; Buzinsky, N.; Chilingaryan, S.; Choi, W. Q.; Deffert, M.; Doe, P. J.; Dragoun, O.; Drexlin, G.; Dyba, S.; Edzards, F.; Eitel, K.; Ellinger, E.; Engel, R.; Enomoto, S.; Erhard, M.; Eversheim, D.; Fedkevych, M.; Fischer, S.; Formaggio, J. A.; Fränkle, F. M.; Franklin, G. B.; Friedel, F.; Fulst, A.; Gil, W.; Glück, F.; Ureña, A. Gonzalez; Grohmann, S.; Grössle, R.; Gumbsheimer, R.; Hackenjos, M.; Hannen, V.; Harms, F.; Haußmann, N.; Heizmann, F.; Helbing, K.; Herz, W.; Hickford, S.; Hilk, D.; Hillesheimer, D.; Howe, M. A.; Huber, A.; Jansen, A.; Kellerer, J.; Kernert, N.; Kippenbrock, L.; Kleesiek, M.; Klein, M.; Kopmann, A.; Korzeczek, M.; Kovalík, A.; Krasch, B.; Kraus, M.; Kuckert, L.; Lasserre, T.; Lebeda, O.; Letnev, J.; Lokhov, A.; Machatschek, M.; Marsteller, A.; Martin, E. L.; Mertens, S.; Mirz, S.; Monreal, B.; Neumann, H.; Niemes, S.; Off, A.; Osipowicz, A.; Otten, E.; Parno, D. S.; Pollithy, A.; Poon, A. W. P.; Priester, F.; Ranitzsch, P. C.-O.; Rest, O.; Robertson, R. G. H.; Roccati, F.; Rodenbeck, C.; Röllig, M.; Röttele, C.; Ryšavý, M.; Sack, R.; Saenz, A.; Schimpf, L.; Schlösser, K.; Schlösser, M.; Schönung, K.; Schrank, M.; Seitz-Moskaliuk, H.; Sentkerestiová, J.; Sibille, V.; Slezák, M.; Steidl, M.; Steinbrink, N.; Sturm, M.; Suchopar, M.; Suesser, M.; Telle, H. H.; Thorne, L. A.; Thümmler, T.; Titov, N.; Tkachev, I.; Trost, N.; Valerius, K.; Vénos, D.; Vianden, R.; Hernández, A. P. Vizcaya; Weber, M.; Weinheimer, C.; Weiss, C.; Welte, S.; Wendel, J.; Wilkerson, J. F.; Wolf, J.; Wüstling, S.; Zadoroghny, S.

2018-05-01

The neutrino mass experiment KATRIN requires a stability of 3 ppm for the retarding potential at - 18.6 kV of the main spectrometer. To monitor the stability, two custom-made ultra-precise high-voltage dividers were developed and built in cooperation with the German national metrology institute Physikalisch-Technische Bundesanstalt (PTB). Until now, regular absolute calibration of the voltage dividers required bringing the equipment to the specialised metrology laboratory. Here we present a new method based on measuring the energy difference of two ^{83{m}}Kr conversion electron lines with the KATRIN setup, which was demonstrated during KATRIN's commissioning measurements in July 2017. The measured scale factor M=1972.449(10) of the high-voltage divider K35 is in agreement with the last PTB calibration 4 years ago. This result demonstrates the utility of the calibration method, as well as the long-term stability of the voltage divider.

[Atezolizumab (Tecentriq®): Activity, indication and modality of use in advanced or metastatic urinary bladder carcinoma].

PubMed

Bernard-Tessier, Alice; Bonnet, Clément; Lavaud, Pernelle; Gizzi, Marco; Loriot, Yohann; Massard, Christophe

2018-02-01

Treatments for patients with metastatic or advanced urothelial carcinomas on progression after first line chemotherapy or unfit for cisplatin are currently limited. Atezolizumab (Tecentriq ® ) is a monoclonal antibody targeting PD-L1. The first of IMVIGOR 210 phase II trial (NCT02951767) investigated atezolizumab as front line treatment among 119 patients with metastatic urothelial cancer unfit for cisplatin. Response rate was 23% and median overall survival 15.9 months. The second cohort (NCT02108652) included 310 patients whose tumors were progressing after first line platinum-based chemotherapy. Response rate was 15% and median overall survival 7.9 months. Among patients with high PD-L1 expression on infiltrating immune cells (ICs), response rate was 26% and median overall survival 11 months. Atezolizumab was well-tolerated in both cohorts with 66% of treatment-related toxicities including 12% (cohort 1) and 7% (cohort 2) of grade 3-4 adverse events. These results led to an approval by the FDA in United States and the EMA in Europe. In France, atezolizumab was available through an early access agreement by the French National Agency for Medicines and Health Products (ANSM) for patients with metastatic or advanced urothelial carcinomas on progression after first line chemotherapy or unfit for cisplatin. So far, its avaibility in France within the EMA approval is pending its pricing. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Development of optical fiber frequency and time distribution systems

NASA Technical Reports Server (NTRS)

Lutes, G.

1982-01-01

The development of ultra stable optical fiber distribution systems for the dissemination of frequency and timing references is reported. The ultimate design goals for these systems are a frequency stability of 10 to the -17 power for tau or = 100 sec and time stability of + or - 0.1 ns for 1 year and operation over distances or = 30 km. A prototype system is reviewed and progress is discussed.

JPRS Report, China

DTIC Science & Technology

1989-12-13

89-116 13 December 1989 SOCIAL 55 A few in the mass media even lopsidedly played up the "patriotic enthusiasm" of university students, causing the...the news media has a higher level of socialist responsibility for safeguarding social stability and progress. Under the present situation, stability...and unity are in the fundamental interests of the Chinese people as well as China’s social development. The news media must consciously undertake

Large Eddy Simulations of the Vortex-Flame Interaction in a Turbulent Swirl Burner

NASA Astrophysics Data System (ADS)

Lu, Zhen; Elbaz, Ayman M.; Hernandez Perez, Francisco E.; Roberts, William L.; Im, Hong G.

2017-11-01

A series of swirl-stabilized partially premixed flames are simulated using large eddy simulation (LES) along with the flamelet/progress variable (FPV) model for combustion. The target burner has separate and concentric methane and air streams, with methane in the center and the air flow swirled through the tangential inlets. The flame is lifted in a straight quarl, leading to a partially premixed state. By fixing the swirl number and air flow rate, the fuel jet velocity is reduced to study flame stability as the flame approaches the lean blow-off limit. Simulation results are compared against measured data, yielding a generally good agreement on the velocity, temperature, and species mass fraction distributions. The proper orthogonal decomposition (POD) method is applied on the velocity and progress variable fields to analyze the dominant unsteady flow structure, indicating a coupling between the precessing vortex core (PVC) and the flame. The effects of vortex-flame interactions on the stabilization of the lifted swirling flame are also investigated. For the stabilization of the lifted swirling flame, the effects of convection, enhanced mixing, and flame stretching introduced by the PVC are assessed based on the numerical results. This research work was sponsored by King Abdullah University of Science and Technology (KAUST) and used computational resources at KAUST Supercomputing Laboratory.

TP53-dependent chromosome instability is associated with transient reductions in telomere length in immortal telomerase-positive cell lines

NASA Technical Reports Server (NTRS)

Schwartz, J. L.; Jordan, R.; Liber, H.; Murnane, J. P.; Evans, H. H.

2001-01-01

Telomere shortening in telomerase-negative somatic cells leads to the activation of the TP53 protein and the elimination of potentially unstable cells. We examined the effect of TP53 gene expression on both telomere metabolism and chromosome stability in immortal, telomerase-positive cell lines. Telomere length, telomerase activity, and chromosome instability were measured in multiple clones isolated from three related human B-lymphoblast cell lines that vary in TP53 expression; TK6 cells express wild-type TP53, WTK1 cells overexpress a mutant form of TP53, and NH32 cells express no TP53 protein. Clonal variations in both telomere length and chromosome stability were observed, and shorter telomeres were associated with higher levels of chromosome instability. The shortest telomeres were found in WTK1- and NH32-derived cells, and these cells had 5- to 10-fold higher levels of chromosome instability. The primary marker of instability was the presence of dicentric chromosomes. Aneuploidy and other stable chromosome alterations were also found in clones showing high levels of dicentrics. Polyploidy was found only in WTK1-derived cells. Both telomere length and chromosome instability fluctuated in the different cell populations with time in culture, presumably as unstable cells and cells with short telomeres were eliminated from the growing population. Our results suggest that transient reductions in telomere lengths may be common in immortal cell lines and that these alterations in telomere metabolism can have a profound effect on chromosome stability. Copyright 2000 Wiley-Liss, Inc.

Transient Fe Emission features in AGN: A new diagnostic of Accreting Systems

NASA Astrophysics Data System (ADS)

Turner, T. J.; Reeves, J. R.; George, I. M.; Kraemer, S. B.

2004-08-01

Chandra and XMM data have revealed narrow and highly redshifted Fe K emission lines in a handful of AGN. Rapid flux variability and energy shifts of the lines have lead to speculations for their origin ranging from hotspots on the accretion disk to emission from decelerating ejected blobs of gas traveling close to the escape velocity. Whichever scenario proves true, these lines are invaluable in tracing gas close to the black hole, and arguably less subject to the ambiguities which have plagued interpretation of broad `disk lines'. I review observations of such lines to date and discuss progress possible with current and future instrumentation.

Real-world Outcomes of Multiple Myeloma: Retrospective Analysis of the Czech Registry of Monoclonal Gammopathies.

PubMed

Hájek, Roman; Jarkovsky, Jiri; Maisnar, Vladimír; Pour, Ludek; Špička, Ivan; Minařík, Jiri; Gregora, Evžen; Kessler, Petr; Sýkora, Michal; Fraňková, Hana; Campioni, Marco; DeCosta, Lucy; Treur, Maarten; Gonzalez-McQuire, Sebastian; Bouwmeester, Walter

2018-06-01

Real-world data on patient outcomes and treatment patterns in multiple myeloma (MM) are limited. The present noninterventional, observational, retrospective analysis of prospectively collected Czech patient medical record data from the Registry of Monoclonal Gammopathies estimated real-world outcomes in adults with a diagnosis of symptomatic MM made between May 2007 and June 2014. In total, 2446 patients had initiated first-line treatment. The median overall survival since the diagnosis (primary endpoint) was 50.3 months (95% confidence interval, 46.1-54.5 months) and decreased with each successive treatment line. A similar trend was observed for progression-free survival and the depth of response. In line with European guidelines and clinical practice, bortezomib-, thalidomide-, and lenalidomide-based regimens were most commonly used across all treatment lines (42.3%, 28.9%, and 18.4%, respectively). In the first line, bortezomib and thalidomide were used most often, with lenalidomide the most commonly used agent in the relapse setting (second to fourth lines). Exploratory analyses revealed that younger age (≤ 65 years), lower international staging system stage, and previous stem cell transplantation were associated with significant improvements in overall and progression-free survival, especially in the early treatment lines. The present study is the first analysis of Czech data from the Registry of Monoclonal Gammopathies, and it provides important insights into the real-world management of MM for physicians and healthcare providers. Copyright © 2018 Elsevier Inc. All rights reserved.

Outcome and prognostic factors in metastatic urothelial carcinoma patients receiving second-line chemotherapy: an analysis of real-world clinical practice data in Japan.

PubMed

Matsumoto, Ryuji; Abe, Takashige; Ishizaki, Junji; Kikuchi, Hiroshi; Harabayashi, Toru; Minami, Keita; Sazawa, Ataru; Mochizuki, Tango; Akino, Tomoshige; Murakumo, Masashi; Osawa, Takahiro; Maruyama, Satoru; Murai, Sachiyo; Shinohara, Nobuo

2018-06-25

The objective of the present study was to investigate the survival outcome and prognostic factors of metastatic urothelial carcinoma patients treated with second-line systemic chemotherapy in real-world clinical practice. Overall, 114 patients with metastatic urothelial carcinoma undergoing second-line systemic chemotherapy were included in this retrospective analysis. The dominant second-line chemotherapy was a paclitaxel-based combination regimen (60%, 68/114). We assessed the progression-free survival and overall survival times using the Kaplan-Meier method. The Cox proportional hazards model was applied to identify the factors affecting overall survival. The median progression-free survival and overall survival times were 4 and 9 months, respectively. In the multivariate analysis, an Eastern Cooperative Oncology Group performance status score greater than 0 at presentation, C-reactive protein level ≧1 mg/dl and poor response to prior chemotherapy were adverse prognostic indicators. Patients with 0, 1, 2 and 3 of those risk factors had a median overall survival of 17, 12, 7 and 3 months, respectively. The Eastern Cooperative Oncology Group performance status at presentation, C-reactive protein level and response to prior chemotherapy were prognostic factors for metastatic urothelial carcinoma patients undergoing second-line chemotherapy. In the future, this information might help guide the choice of salvage treatment, such as second-line chemotherapy or immune checkpoint inhibitors, after the failure of first-line chemotherapy.

Axitinib treatment in advanced RAI-resistant differentiated thyroid cancer (DTC) and refractory medullary thyroid cancer (MTC).

PubMed

Capdevila, Jaume; Trigo, José Manuel; Aller, Javier; Manzano, José Luís; Adrián, Silvia García; Llopis, Carles Zafón; Reig, Òscar; Bohn, Uriel; Cajal, Teresa Ramón Y; Duran-Poveda, Manuel; Astorga, Beatriz González; López-Alfonso, Ana; Martínez, Javier Medina; Porras, Ignacio; Reina, Juan Jose; Palacios, Nuria; Grande, Enrique; Cillán, Elena; Matos, Ignacio; Grau, Juan Jose

2017-10-01

Axitinib, an antiangiogenic multikinase inhibitor (MKI), was evaluated in the compassionate use programme (CUP) in Spain (October 2012-November 2014). 47 patients with advanced radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC, n  = 34) or medullary thyroid cancer (MTC, n  = 13) with documented disease progression were treated with axitinib 5 mg b.i.d. The primary efficacy endpoint was objective response rate (ORR) by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. Progression-free survival (PFS) and adverse events (AEs) were secondary objectives. Regulatory authorities validated the CUP, and all patients signed informed consent form. Axitinib was administered as first-line therapy in 17 patients (36.2%), as second-line in 18 patients (38.3%) and as third/fourth-line in 12 patients (25.5%). With a median follow-up of 11.5 months (0-24.3), ORR was 27.7% (DTC: 29.4% and MTC: 23.1%) and median PFS was 8.1 months (95% CI: 4.1-12.2) (DTC: 7.4 months (95% CI: 3.1-11.8) and MTC: 9.4 months (95% CI: 4.8-13.9)). Better outcomes were reported with first-line axitinib, with an ORR of 53% and a median PFS of 13.6 months compared with 16.7% and 10.6 months as second-line treatment. Twelve (25.5%) patients required dose reduction to 3 mg b.i.d. All-grade AEs included asthenia (53.2%), diarrhoea (36.2%), hypertension (31.9%) and mucositis (29.8%); grade 3/4 AEs included anorexia (6.4%), diarrhoea (4.3%) and cardiac toxicity (4.3%). Axitinib had a tolerable safety profile and clinically meaningful activity in refractory and progressive thyroid cancer regardless of histology as first-line therapy. To our knowledge, this is the first time that cross-resistance between MKIs is suggested in thyroid cancer, highlighting the importance of prospective sequential clinical studies. © 2017 European Society of Endocrinology.

Cost-effectiveness analysis of panitumumab plus mFOLFOX6 compared with bevacizumab plus mFOLFOX6 for first-line treatment of patients with wild-type RAS metastatic colorectal cancer.

PubMed

Graham, Christopher N; Hechmati, Guy; Hjelmgren, Jonas; de Liège, Frédérique; Lanier, Julie; Knox, Hediyyih; Barber, Beth

2014-11-01

To investigate the cost-effectiveness of panitumumab plus mFOLFOX6 (oxaliplatin, 5-fluorouracil and leucovorin) compared with bevacizumab plus mFOLFOX6 in first-line treatment of patients with wild-type RAS metastatic colorectal cancer (mCRC). A semi-Markov model was constructed from a French health collective perspective, with health states related to first-line treatment (progression-free), disease progression with and without subsequent active treatment, resection of metastases, disease-free after successful resection and death. Parametric survival analyses of patient-level progression-free and overall survival data from the only head-to-head clinical trial of panitumumab and bevacizumab (PEAK) were performed to estimate transitions to disease progression and death. Additional data from PEAK informed the amount of each drug consumed, duration of therapy, subsequent therapy use, and toxicities related to mCRC treatment. Literature and French public data sources were used to estimate unit costs associated with treatment and duration of subsequent active therapies. Utility weights were calculated from patient-level data from panitumumab trials in the first-, second- and third-line settings. A life-time perspective was applied. Scenario, one-way, and probabilistic sensitivity analyses were performed. Based on a head-to-head clinical trial that demonstrates better efficacy outcomes for patients with wild-type RAS mCRC who receive panitumumab plus mFOLFOX6 versus bevacizumab plus mFOLFOX6, the incremental cost per life-year gained was estimated to be €26,918, and the incremental cost per quality-adjusted life year (QALY) gained was estimated to be €36,577. Sensitivity analyses indicate the model is robust to alternative parameters and assumptions. The incremental cost per QALY gained indicates that panitumumab plus mFOLFOX6 represents good value for money in comparison to bevacizumab plus mFOLFOX6 and, with a willingness-to-pay ranging from €40,000 to €60,000, can be considered cost-effective in first-line treatment of patients with wild-type RAS mCRC. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Spectrophone stabilized laser with line center offset frequency control

NASA Technical Reports Server (NTRS)

Kavaya, M. J.; Menzies, R. T. (Inventor)

1984-01-01

Continuous offset tuning of a frequency stabilized CW gas laser is achieved by using a spectrophone filled with the same gas as the laser for sensing a dither modulation, detecting a first or second derivative of the spectrophone output with a lock-in amplifier, the detected output of which is integrated, and applying the integrator output as a correction signal through a circuit which adds to the dither signal from an oscillator a dc offset that is adjusted with a potentiometer to a frequency offset from the absorption line center of the gas, but within the spectral linewidth of the gas. Tuning about that offset frequency is achieved by adding a dc value to the detected output of the dither modulation before integration using a potentiometer.

A high-performance Hg(+) trapped ion frequency standard

NASA Technical Reports Server (NTRS)

Prestage, J. D.; Tjoelker, R. L.; Dick, G. J.; Maleki, L.

1992-01-01

A high-performance frequency standard based on (199)Hg(+) ions confined in a hybrid radio frequency (RF)/dc linear ion trap is demonstrated. This trap permits storage of large numbers of ions with reduced susceptibility to the second-order Doppler effect caused by the RF confining fields. A 160-mHz-wide atomic resonance line for the 40.5-GHz clock transition is used to steer the output of a 5-mHz crystal oscillator to obtain a stability of 2 x 10(exp -15) for 24,000-second averaging times. Measurements with a 37-mHz line width for the Hg(+) clock transition demonstrate that the inherent stability for this frequency standard is better than 1 x 10(exp -15) at 10,000-second averaging times.

Environmental Stability of Seed Carbohydrate Profiles in Soybeans Containing Different Alleles of the Raffinose Synthase 2 (RS2) Gene.

PubMed

Bilyeu, Kristin D; Wiebold, William J

2016-02-10

Soybean [Glycine max (L.) Merr.] is important for the high protein meal used for livestock feed formulations. Carbohydrates contribute positively or negatively to the potential metabolizable energy in soybean meal. The positive carbohydrate present in soybean meal consists primarily of sucrose, whereas the negative carbohydrate components are the raffinose family of oligosaccharides (RFOs), raffinose and stachyose. Increasing sucrose and decreasing raffinose and stachyose are critical targets to improve soybean. In three recently characterized lines, variant alleles of the soybean raffinose synthase 2 (RS2) gene were associated with increased sucrose and decreased RFOs. The objective of this research was to compare the environmental stability of seed carbohydrates in soybean lines containing wild-type or variant alleles of RS2 utilizing a field location study and a date of planting study. The results define the carbohydrate variation in distinct regional and temporal environments using soybean lines with different alleles of the RS2 gene.

The balance between keystone clustering and bed roughness in experimental step-pool stabilization

NASA Astrophysics Data System (ADS)

Johnson, J. P.

2016-12-01

Predicting how mountain channels will respond to environmental perturbations such as floods requires an improved quantitative understanding of morphodynamic feedbacks among bed topography, surface grain size and sediment sorting. In boulder-rich gravel streams, transport and sorting often lead to the development of step pool morphologies, which are expressed both in bed topography and coarse grain clustering. Bed stability is difficult to measure, and is sometimes inferred from the presence of step pools. I use scaled flume experiments to explore feedbacks among surface grain sizes, coarse grain clustering, bed roughness and hydraulic roughness during progressive bed stabilization and over a range of sediment transport rates. While grain clusters are sometimes identified by subjective interpretation, I quantify the degree of coarse surface grain clustering using spatial statistics, including a novel normalization of Ripley's K function. This approach is objective and provides information on the strength of clustering over a range of length scales. Flume experiments start with an initial bed surface with a broad grain size distribution and spatially random positions. Flow causes the bed surface to progressively stabilize in response to erosion, surface coarsening, roughening and grain reorganization. At 95% confidence, many but not all beds stabilized with coarse grains becoming more clustered than complete spatial randomness (CSR). I observe a tradeoff between topographic roughness and clustering. Beds that stabilized with higher degrees of coarse-grain clustering were topographically smoother, and vice-versa. Initial conditions influenced the degree of clustering at stability: Beds that happened to have fewer initial coarse grains had more coarse grain reorganization during stabilization, leading to more clustering. Finally, regressions demonstrate that clustering statistics actually predict hydraulic roughness significantly better than does D84 (the size at which 84% of grains are smaller). In the experimental data, the spatial organization of surface grains is a stronger control on flow characteristics than the size of surface grains.

On the Progression and Stability of Adolescent Identity Formation: A Five-Wave Longitudinal Study in Early-to-Middle and Middle-to-Late Adolescence

ERIC Educational Resources Information Center

Meeus, Wim; Van De Schoot, Rens; Keijsers, Loes; Schwartz, Seth J.; Branje, Susan

2010-01-01

This study examined identity development in a 5-wave study of 923 early-to-middle and 390 middle-to-late adolescents thereby covering the ages of 12-20. Systematic evidence for identity progression was found: The number of diffusions, moratoriums, and searching moratoriums (a newly obtained status) decreased, whereas the representation of the…

Report on Progress Toward Security and Stability in Afghanistan

DTIC Science & Technology

2010-11-01

National Governance Policy The Sub National Governance ( SNG ) Policy establishes a framework for instituting government reforms over the next 15 years.34...governance and development initiatives, such as the National Solidarity Program and the Afghan Social Outreach Program, align with the new SNG policy...review implementation progress from a financing perspective. 4. Municipal governance - A key component of the SNG policy reform will be to draft a

Postmortem stability of lung surfactant phospholipids.

PubMed

Lorente, J A; Lorente, M; Villanueva, E

1992-09-01

The postmortem stability of the main phospholipids of lung surfactant-phosphatidyl choline (PC), phosphatidyl ethanolamine (PE), phosphatidyl inositol (PI), phosphatidyl serine (PS) and sphingomyelin (S) in three different deaths; one caused by fresh-water drowning, one by salt-water drowning, and one from a sodium-pentobarbital overdose has been studied. The drug overdose was considered the control because there was no surfactant involvement. The results show the stability of these kinds of lipids in the first 24 h, with a progressive decrease from 48 h on until 96 h, with a significant correlation to the time of P less than 0.01 in most cases.

Effect of antibodies on pathogen dynamics with delays and two routes of infection

NASA Astrophysics Data System (ADS)

Elaiw, A. M.; Almatrafi, A. A.; Hobiny, A. D.

2018-06-01

We study the global stability of pathogen dynamics models with saturated pathogen-susceptible and infected-susceptible incidence. The models incorporate antibody immune response and three types of discrete or distributed time delays. We first show that the solutions of the model are nonnegative and ultimately bounded. We determine two threshold parameters, the basic reproduction number and antibody response activation number. We establish the existence and stability of the steady states. We study the global stability analysis of models using Lyapunov method. The numerical simulations have shown that antibodies can reduce the pathogen progression.

Martensite Formation in Partially and Fully Austenitic Plain Carbon Steels

NASA Astrophysics Data System (ADS)

van Bohemen, S. M. C.; Sietsma, J.

2009-05-01

The progress of martensite formation in plain carbon steels Fe-0.46C, Fe-0.66C, and Fe-0.80C has been investigated by dilatometry. It is demonstrated that carbon enrichment of the remaining austenite due to intercritical annealing of Fe-0.46C and Fe-0.66C does not only depress the start temperature for martensite, but also slows the progress of the transformation with temperature compared to full austenitization. In contrast, such a change of kinetics is not observed when the remaining austenite of lean-Si steel Fe-0.80C is stabilized due to a partial transformation to bainite, which suggests that the stabilization is not of a chemical but of a mechanical nature. The growth of bainite and martensite is accompanied by a shape change at the microstructural scale, which leads to plastic deformation and thus strengthening of the surrounding austenite. Based on this stabilizing mechanism, the athermal transformation kinetics is rationalized by balancing the increase in driving force corresponding to a temperature decrease with the increase in strain energy required for the formation of martensite in the strengthened remaining austenite.

Flexible Wing Base Micro Aerial Vehicles: Vision-Guided Flight Stability and Autonomy for Micro Air Vehicles

NASA Technical Reports Server (NTRS)

Ettinger, Scott M.; Nechyba, Michael C.; Ifju, Peter G.; Wazak, Martin

2002-01-01

Substantial progress has been made recently towards design building and test-flying remotely piloted Micro Air Vehicle's (MAVs). We seek to complement this progress in overcoming the aerodynamic obstacles to.flight at very small scales with a vision stability and autonomy system. The developed system based on a robust horizon detection algorithm which we discuss in greater detail in a companion paper. In this paper, we first motivate the use of computer vision for MAV autonomy arguing that given current sensor technology, vision may he the only practical approach to the problem. We then briefly review our statistical vision-based horizon detection algorithm, which has been demonstrated at 30Hz with over 99.9% correct horizon identification. Next we develop robust schemes for the detection of extreme MAV attitudes, where no horizon is visible, and for the detection of horizon estimation errors, due to external factors such as video transmission noise. Finally, we discuss our feed-back controller for self-stabilized flight, and report results on vision autonomous flights of duration exceeding ten minutes.

Talking about German Verb Particles Identified in Concordance Lines--From Spontaneous to Expert-Like Metatalk

ERIC Educational Resources Information Center

Schaeffer-Lacroix, Eva

2016-01-01

Johns reports in his text "Kibbitzing one-to-ones" (1997) that corpus-informed metatalk with a foreign language expert helps apprentice writers to make progress in independent text revision. Expecting this progress to be based on the development of expert-like ways to observe language features, I integrated Johns' so-called kibbitzing…

Fundamental Research in Engineering Education. Identifying and Repairing Student Misconceptions in Thermal and Transport Science: Concept Inventories and Schema Training Studies

ERIC Educational Resources Information Center

Miller, Ronald L.; Streveler, Ruth A.; Yang, Dazhi; Roman, Aidsa I. Santiago

2011-01-01

This paper summarizes progress on two related lines of chemical engineering education research: 1) identifying persistent student misconceptions in thermal and transport science (fluid mechanics, heat transfer, and thermodynamics); and, 2) developing a method to help students repair these misconceptions. Progress on developing the Thermal and…

Investigations on effects of the hole size to fix electrodes and interconnection lines in polydimethylsiloxane

NASA Astrophysics Data System (ADS)

Behkami, Saber; Frounchi, Javad; Ghaderi Pakdel, Firouz; Stieglitz, Thomas

2017-11-01

Translational research in bioelectronics medicine and neural implants often relies on established material assemblies made of silicone rubber (polydimethylsiloxane-PDMS) and precious metals. Longevity of the compound is of utmost importance for implantable devices in therapeutic and rehabilitation applications. Therefore, secure mechanical fixation can be used in addition to chemical bonding mechanisms to interlock PDMS substrate and insulation layers with metal sheets for interconnection lines and electrodes. One of the best ways to fix metal lines and electrodes in PDMS is to design holes in electrode rims to allow for direct interconnection between top to bottom layer silicone. Hence, the best layouts and sizes of holes (up to 6) which provide sufficient stability against lateral and vertical forces have been investigated with a variety of numbers of hole in line electrodes, which are simulated and fabricated with different layouts, sizes and materials. Best stability was obtained with radii of 100, 72 and 62 µm, respectively, and a single central hole in aluminum, platinum and MP35N foil line electrodes of 400  ×  500 µm2 size and of thickness 20 µm. The study showed that the best hole size which provides line electrode immobility (of thickness less than 30 µm) within a central hole is proportional to reverse value of Young’s Modulus of the material used. Thus, an array of line electrodes was designed and fabricated to study this effect. Experimental results were compared with simulation data. Subsequently, an approximation curve was generated as design rule to propose the best radius to fix line electrodes according to the material thickness between 10 and 200 µm using PDMS as substrate material.

Shotcrete for Expedient Structural Repair

DTIC Science & Technology

1991-12-01

pp. 29-44. Selmer - Olsen , R., "Examples of the Behavior of Shotcrete Linings Underground," Proceedings, Shotcrete for Ground Support, The Engineering... Selmer - Olsen , R. PAPER TITLE: Examples of the Behavior of Shotcrete Linings Underground DESCRIPTIVE TITLE NOTE: -0- BOOK/REPORT TITLE: Proceedings...prestressed tanks, thin overlays over structural materials, repair of concrete deteriorated by fire or earthquake, rock slope stabilization, and

Safety and Efficacy of Fingolimod and Natalizumab in Multiple Sclerosis After the Failure of First-Line Therapy: Single Center Experience Based on the Treatment of Forty-Four Patients.

PubMed

Puz, Przemysław; Lasek-Bal, Anetta

2016-11-10

BACKGROUND In Poland, natalizumab or fingolimod treatment can be delivered as a second-line therapy to those patients with relapsing-remitting multiple sclerosis (RRMS) who demonstrated no response to interferon or glatiramer acetate treatment for a minimum of one year. MATERIAL AND METHODS Analysis covered 44 RRMS patients switched from first- to second-line therapy. The annualized relapse rate, disability progression (assessed with Expanded Disability Status Scale, EDSS) and MRI results (new or enlarged T2 lesions and new Gd-positive lesions) before and after switching were compared. The occurrence of adverse events was also assessed. RESULTS The annualized relapse rate for second-line therapy was significantly lower than for first-line therapy (0.35±0.74 vs. 2.13±0.87, p=0.00005). Median of EDSS progression with first-line therapy was significantly higher than that with natalizumab or fingolimod treatment (p=0.00002). The mean number of new or enlarged T2 and Gd+ lesions in MRI after one-year second-line treatment was significantly lower in comparison to lesions in MRI performed at the end of the first-line therapy (for T2: 0.61 vs. 4.56, p=0.0004; for Gd+: 0.13 vs. 1.98, p=0.0009). No significant differences in the clinical data, MRI results, and side effects between fingolimod and natalizumab patients have been observed. CONCLUSIONS Treatment with natalizumab or fingolimod as a second-line therapy in RRMS patients is safe and effective. Less restrictive criteria for switching should be considered.

Puget Sound Area Electric Reliability Plan : Appendix E, Transmission Reinforcement Analysis.

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

United States. Bonneville Power Administration.

1992-04-01

The purpose of this appendix to the draft environmental impact statement (EIS) report is to provide an update of the latest study work done on transmission system options for the Puget Sound Area Electric Reliability Plan. Also included in the attachments to the EIS are 2 reports analyzing the voltage stability of the Puget Sound transmission system and a review by Power Technologies, Inc. of the BPA voltage stability analysis and reactive options. Five transmission line options and several reactive options are presently being considered as possible solutions to the PSAFRP by the Transmission Team. The first two line optionsmore » would be built on new rights-of way adjacent (as much as possible) to existing corridors. The reactive options would optimize the existing transmission system capability by adding new stations for series capacitors and/or switchgear. The other three line options are rebuilds or upgrades of existing cross mountain transmission lines. These options are listed below and include a preliminary assessment of the additional transmission system reinforcement required to integrate the new facilities into the existing transmission system. Plans were designed to provide at least 500 MVAR reactive margin.« less

Quantifying Stability in Complex Networks: From Linear to Basin Stability

NASA Astrophysics Data System (ADS)

Kurths, Jürgen

The human brain, power grids, arrays of coupled lasers and the Amazon rainforest are all characterized by multistability. The likelihood that these systems will remain in the most desirable of their many stable states depends on their stability against significant perturbations, particularly in a state space populated by undesirable states. Here we claim that the traditional linearization-based approach to stability is in several cases too local to adequately assess how stable a state is. Instead, we quantify it in terms of basin stability, a new measure related to the volume of the basin of attraction. Basin stability is non-local, nonlinear and easily applicable, even to high-dimensional systems. It provides a long-sought-after explanation for the surprisingly regular topologies of neural networks and power grids, which have eluded theoretical description based solely on linear stability. Specifically, we employ a component-wise version of basin stability, a nonlinear inspection scheme, to investigate how a grid's degree of stability is influenced by certain patterns in the wiring topology. Various statistics from our ensemble simulations all support one main finding: The widespread and cheapest of all connection schemes, namely dead ends and dead trees, strongly diminish stability. For the Northern European power system we demonstrate that the inverse is also true: `Healing' dead ends by addition of transmission lines substantially enhances stability. This indicates a crucial smart-design principle for tomorrow's sustainable power grids: add just a few more lines to avoid dead ends. Further, we analyse the particular function of certain network motifs to promote the stability of the system. Here we uncover the impact of so-called detour motifs on the appearance of nodes with a poor stability score and discuss the implications for power grid design. Moreover, it will be shown that basin stability enables uncovering the mechanism for explosive synchronization and understanding of evolving networks. Reference: P. Menck, J. Heitzig, N. Marwan, and J. Kurths, Nature Physics 9, 89 (2013) P. Menck, J. Heitzig, J. Kurths, and H. Schellnhuber, Nature Communication 5, 3969 (2014) P. Schultz, J. Heitzig, and J. Kurths, New Journal Physics 16, 125001 (2014) V. Kohar, P. Ji, A. Choudhary, S. Sinha, and J. Kurths, Phys. Rev. E 90, 022812 (2014) Y. Zou, T. Pereira, M. Small, Z. Liu, and J. Kurths, Phys. Rev. Lett. 112, 114102 (2014)

78 FR 56612 - Seagoing Barges

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-13

..., measured parallel to the centerline. \\2\\ Subchapters E (Load Lines), F (Marine Engineering), J (Electrical Engineering), N (Dangerous Cargoes), S (Subdivision and Stability), and W (Lifesaving Appliances and...

Stability analysis of BWR nuclear-coupled thermal-hyraulics using a simple model

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

Karve, A.A.; Rizwan-uddin; Dorning, J.J.

1995-09-01

A simple mathematical model is developed to describe the dynamics of the nuclear-coupled thermal-hydraulics in a boiling water reactor (BWR) core. The model, which incorporates the essential features of neutron kinetics, and single-phase and two-phase thermal-hydraulics, leads to simple dynamical system comprised of a set of nonlinear ordinary differential equations (ODEs). The stability boundary is determined and plotted in the inlet-subcooling-number (enthalpy)/external-reactivity operating parameter plane. The eigenvalues of the Jacobian matrix of the dynamical system also are calculated at various steady-states (fixed points); the results are consistent with those of the direct stability analysis and indicate that a Hopf bifurcationmore » occurs as the stability boundary in the operating parameter plane is crossed. Numerical simulations of the time-dependent, nonlinear ODEs are carried out for selected points in the operating parameter plane to obtain the actual damped and growing oscillations in the neutron number density, the channel inlet flow velocity, and the other phase variables. These indicate that the Hopf bifurcation is subcritical, hence, density wave oscillations with growing amplitude could result from a finite perturbation of the system even where the steady-state is stable. The power-flow map, frequently used by reactor operators during start-up and shut-down operation of a BWR, is mapped to the inlet-subcooling-number/neutron-density (operating-parameter/phase-variable) plane, and then related to the stability boundaries for different fixed inlet velocities corresponding to selected points on the flow-control line. The stability boundaries for different fixed inlet subcooling numbers corresponding to those selected points, are plotted in the neutron-density/inlet-velocity phase variable plane and then the points on the flow-control line are related to their respective stability boundaries in this plane.« less

Variable TERRA abundance and stability in cervical cancer cells.

PubMed

Oh, Bong-Kyeong; Keo, Ponnarath; Bae, Jaeman; Ko, Jung Hwa; Choi, Joong Sub

2017-06-01

Telomeres are transcribed into long non-coding RNA, referred to as telomeric repeat-containing RNA (TERRA), which plays important roles in maintaining telomere integrity and heterochromatin formation. TERRA has been well characterized in HeLa cells, a type of cervical cancer cell. However, TERRA abundance and stability have not been examined in other cervical cancer cells, at least to the best of our knowledge. Thus, in this study, we measured TERRA levels and stability, as well as telomere length in 6 cervical cancer cell lines, HeLa, SiHa, CaSki, HeLa S3, C-33A and SNU-17. We also examined the association between the TERRA level and its stability and telomere length. We found that the TERRA level was several fold greater in the SiHa, CaSki, HeLa S3, C-33A and SNU-17 cells, than in the HeLa cells. An RNA stability assay of actinomycin D-treated cells revealed that TERRA had a short half-life of ~4 h in HeLa cells, which was consistent with previous studies, but was more stable with a longer half-life (>8 h) in the other 5 cell lines. Telomere length varied from 4 to 9 kb in the cells and did not correlate significantly with the TERRA level. On the whole, our data indicate that TERRA abundance and stability vary between different types of cervical cancer cells. TERRA degrades rapidly in HeLa cells, but is maintained stably in other cervical cancer cells that accumulate higher levels of TERRA. TERRA abundance is associated with the stability of RNA in cervical cancer cells, but is unlikely associated with telomere length.

A Comprehensive Strategy for the Assessment of Stability Conditions in Porous Media at Varying Levels of Water Saturation

NASA Astrophysics Data System (ADS)

Mihalache, Constance

Assessing the potential for instability in non-saturated geomaterials is of critical importance for the prevention of disastrous failures that occur through these materials, from natural hazards such as rainfall-induced flow slides, to underwater sediment collapse due to methane hydrate dissociation, to the failure of key infrastructure components. In particular, the gaseous and liquid phases present within the pores of a geomaterial play a vital role in its overall behavior, and consequently must be considered in stability analyses. In this work, analytical techniques are presented to evaluate material stability for the different saturation states that occur during a wetting process, where soils progress from unsaturated conditions in the funicular regime, to quasi-saturated conditions in the insular regime, to complete saturation. Each of these different saturation states involves different interactions between the pore fluids and the solid skeleton hosting them. For example, while unsaturated soil behavior is characterized by the capillary effects from the interface between the gaseous and liquid phases, the dominant effect of isolated bubbles within the quasi-saturated regime is to increase the compressibility of the interstitial fluid mixture. By considering the different characteristics of these saturation states, energy-based work input expressions are developed and then used to derive criteria for loss of controllability of the material response. These criteria are then used to assess the stability of geomaterials under various loading configurations. Then, to unite the funicular and insular saturation regimes, the same methodology is adapted to the derivation of comprehensive three-phase criteria for non-saturated soils. An alternative interpretation of such constitutive singularities is also derived, with reference to the ill-posedness of the mass balance equations that control the transient flow of the fluid constituents of a deformable multiphase porous medium. Lastly, the concepts considered throughout the study are applied to the solution of boundary-value problems, using a finite element approach. Overall, it is shown that depending on the considered saturation regime, different stability criteria need to be applied for the accurate interpretation of material behavior. These techniques provide a mechanistic interpretation for a range of processes, such as the nature of so-called "wetting-collapse" events, the variability of the instability line for flow failures acting through gassy sediments, and the onset of runaway failures at the transition between funicular and insular states.

A novel triple repeat mutant tau transgenic model that mimics aspects of pick's disease and fronto-temporal tauopathies.

PubMed

Rockenstein, Edward; Overk, Cassia R; Ubhi, Kiren; Mante, Michael; Patrick, Christina; Adame, Anthony; Bisquert, Alejandro; Trejo-Morales, Margarita; Spencer, Brian; Masliah, Eliezer

2015-01-01

Tauopathies are a group of disorders leading to cognitive and behavioral impairment in the aging population. While four-repeat (4R) Tau is more abundant in corticobasal degeneration, progressive supranuclear palsy, and Alzheimer's disease, three-repeat (3R) Tau is the most abundant splice, in Pick's disease. A number of transgenic models expressing wild-type and mutant forms of the 4R Tau have been developed. However, few models of three-repeat Tau are available. A transgenic mouse model expressing three-repeat Tau was developed bearing the mutations associated with familial forms of Pick's disease (L266V and G272V mutations). Two lines expressing high (Line 13) and low (Line 2) levels of the three-repeat mutant Tau were analyzed. By Western blot, using antibodies specific to three-repeat Tau, Line 13 expressed 5-times more Tau than Line 2. The Tau expressed by these mice was most abundant in the frontal-temporal cortex and limbic system and was phosphorylated at residues detected by the PHF-1, AT8, CP9 and CP13 antibodies. The higher-expressing mice displayed hyperactivity, memory deficits in the water maze and alterations in the round beam. The behavioral deficits started at 6-8 months of age and were associated with a progressive increase in the accumulation of 3R Tau. By immunocytochemistry, mice from Line 13 displayed extensive accumulation of 3R Tau in neuronal cells bodies in the pyramidal neurons of the neocortex, CA1-3 regions, and dentate gyrus of the hippocampus. Aggregates in the granular cells had a globus appearance and mimic Pick's-like inclusions. There were abundant dystrophic neurites, astrogliosis and synapto-dendritic damage in the neocortex and hippocampus of the higher expresser line. The hippocampal lesions were moderately argyrophilic and Thioflavin-S negative. By electron microscopy, discrete straight filament aggregates were detected in some neurons in the hippocampus. This model holds promise for better understanding the natural history and progression of 3R tauopathies and their relationship with mitochondrial alterations and might be suitable for therapeutical testing.

Astaxanthin Inhibits Proliferation of Human Gastric Cancer Cell Lines by Interrupting Cell Cycle Progression

PubMed Central

Kim, Jung Ha; Park, Jong-Jae; Lee, Beom Jae; Joo, Moon Kyung; Chun, Hoon Jai; Lee, Sang Woo; Bak, Young-Tae

2016-01-01

Background/Aims Astaxanthin is a carotenoid pigment that has antioxidant, antitumoral, and anti-inflammatory properties. In this in vitro study, we investigated the mechanism of anticancer effects of astaxanthin in gastric carcinoma cell lines. Methods The human gastric adenocarcinoma cell lines AGS, KATO-III, MKN-45, and SNU-1 were treated with various concentrations of astaxanthin. A cell viability test, cell cycle analysis, and immunoblotting were performed. Results The viability of each cancer cell line was suppressed by astaxanthin in a dose-dependent manner with significantly decreased proliferation in KATO-III and SNU-1 cells. Astaxanthin increased the number of cells in the G0/G1 phase but reduced the proportion of S phase KATO-III and SNU-1 cells. Phosphorylated extracellular signal-regulated kinase (ERK) was decreased in an inverse dose-dependent correlation with astaxanthin concentration, and the expression of p27kip-1 increased the KATO-III and SNU-1 cell lines in an astaxanthin dose-dependent manner. Conclusions Astaxanthin inhibits proliferation by interrupting cell cycle progression in KATO-III and SNU-1 gastric cancer cells. This may be caused by the inhibition of the phosphorylation of ERK and the enhanced expression of p27kip-1. PMID:26470770

Integration of high-risk human papillomavirus into cellular cancer-related genes in head and neck cancer cell lines.

PubMed

Walline, Heather M; Goudsmit, Christine M; McHugh, Jonathan B; Tang, Alice L; Owen, John H; Teh, Bin T; McKean, Erin; Glover, Thomas W; Graham, Martin P; Prince, Mark E; Chepeha, Douglas B; Chinn, Steven B; Ferris, Robert L; Gollin, Susanne M; Hoffmann, Thomas K; Bier, Henning; Brakenhoff, Ruud; Bradford, Carol R; Carey, Thomas E

2017-05-01

Human papillomavirus (HPV)-positive oropharyngeal cancer is generally associated with excellent response to therapy, but some HPV-positive tumors progress despite aggressive therapy. The purpose of this study was to evaluate viral oncogene expression and viral integration sites in HPV16- and HPV18-positive squamous cell carcinoma lines. E6/E7 alternate transcripts were assessed by reverse transcriptase-polymerase chain reaction (RT-PCR). Detection of integrated papillomavirus sequences (DIPS-PCR) and sequencing identified viral insertion sites and affected host genes. Cellular gene expression was assessed across viral integration sites. All HPV-positive cell lines expressed alternate HPVE6/E7 splicing indicative of active viral oncogenesis. HPV integration occurred within cancer-related genes TP63, DCC, JAK1, TERT, ATR, ETV6, PGR, PTPRN2, and TMEM237 in 8 head and neck squamous cell carcinoma (HNSCC) lines but UM-SCC-105 and UM-GCC-1 had only intergenic integration. HPV integration into cancer-related genes occurred in 7 of 9 HPV-positive cell lines and of these 6 were from tumors that progressed. HPV integration into cancer-related genes may be a secondary carcinogenic driver in HPV-driven tumors. © 2017 Wiley Periodicals, Inc. Head Neck 39: 840-852, 2017. © 2017 Wiley Periodicals, Inc.

On-Line Synthesis and Analysis by Mass Spectrometry

ERIC Educational Resources Information Center

Bain, Ryan M.; Pulliam, Christopher J.; Raab, Shannon A.; Cooks, R. Graham

2015-01-01

In this laboratory experiment, students learn how to use ESI to accelerate chemical synthesis and to couple it with on-line mass spectrometry for structural analysis. The Hantzsch synthesis of symmetric 1,4-dihydropyridines is a classic example of a one-pot reaction in which multiple intermediates can serve to indicate the progress of the reaction…

Bionic Vision-Based Intelligent Power Line Inspection System

PubMed Central

Ma, Yunpeng; He, Feijia; Xu, Jinxin

2017-01-01

Detecting the threats of the external obstacles to the power lines can ensure the stability of the power system. Inspired by the attention mechanism and binocular vision of human visual system, an intelligent power line inspection system is presented in this paper. Human visual attention mechanism in this intelligent inspection system is used to detect and track power lines in image sequences according to the shape information of power lines, and the binocular visual model is used to calculate the 3D coordinate information of obstacles and power lines. In order to improve the real time and accuracy of the system, we propose a new matching strategy based on the traditional SURF algorithm. The experimental results show that the system is able to accurately locate the position of the obstacles around power lines automatically, and the designed power line inspection system is effective in complex backgrounds, and there are no missing detection instances under different conditions. PMID:28203269

Hepatocyte growth factor activator inhibitor type-2 (HAI-2)/SPINT2 contributes to invasive growth of oral squamous cell carcinoma cells.

PubMed

Yamamoto, Koji; Kawaguchi, Makiko; Shimomura, Takeshi; Izumi, Aya; Konari, Kazuomi; Honda, Arata; Lin, Chen-Yong; Johnson, Michael D; Yamashita, Yoshihiro; Fukushima, Tsuyoshi; Kataoka, Hiroaki

2018-02-20

Hepatocyte growth factor activator inhibitor (HAI)-1/ SPINT1 and HAI-2/ SPINT2 are membrane-anchored protease inhibitors having homologous Kunitz-type inhibitor domains. They regulate membrane-anchored serine proteases, such as matriptase and prostasin. Whereas HAI-1 suppresses the neoplastic progression of keratinocytes to invasive squamous cell carcinoma (SCC) through matriptase inhibition, the role of HAI-2 in keratinocytes is poorly understood. In vitro homozygous knockout of the SPINT2 gene suppressed the proliferation of two oral SCC (OSCC) lines (SAS and HSC3) but not the growth of a non-tumorigenic keratinocyte line (HaCaT). Reversion of HAI-2 abrogated the growth suppression. Matrigel invasion of both OSCC lines was also suppressed by the loss of HAI-2. The levels of prostasin protein were markedly increased in HAI-2-deficient cells, and knockdown of prostasin alleviated the HAI-2 loss-induced suppression of OSCC cell invasion. Therefore, HAI-2 has a pro-invasive role in OSCC cells through suppression of prostasin. In surgically resected OSCC tissues, HAI-2 immunoreactivity increased along with neoplastic progression, showing intense immunoreactivities in invasive OSCC cells. In summary, HAI-2 is required for invasive growth of OSCC cells and may contribute to OSCC progression.

miR-17 inhibitor suppressed osteosarcoma tumor growth and metastasis via increasing PTEN expression

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

Gao, Yong, E-mail: gaoyongunion@163.com; Luo, Ling-hui; Li, Shuai

2014-02-07

Highlights: • miR-17 was increased in OS tissues and cell lines. • Inhibition of miR-17 suppressed OS cell proliferation. • Inhibition of miR-17 suppressed OS cell migration and invasion. • PTEN was a target of miR-17. • miR-17 was negatively correlated with PTEN in OS tissues. - Abstract: MicroRNAs (miRNAs) play essential roles in cancer development and progression. Here, we investigated the role of miR-17 in the progression and metastasis of osteosarcoma (OS). miR-17 was frequently increased in OS tissues and cell lines. Inhibition of miR-17 in OS cell lines substantially suppressed cell proliferation, migration, and invasion. Phosphatase and tensinmore » homolog (PTEN) was identified as a target of miR-17, and ectopic expression of miR-17 inhibited PTEN by direct binding to its 3′-untranslated region (3′-UTR). Expression of miR-17 was negatively correlated with PTEN in OS tissues. Together, these findings indicate that miR-17 acts as an oncogenic miRNA and may contribute to the progression and metastasis of OS, suggesting miR-17 as a potential novel diagnostic and therapeutic target of OS.« less

Kinetics, prognostic and predictive values of ESR1 circulating mutations in metastatic breast cancer patients progressing on aromatase inhibitor

PubMed Central

Clatot, Florian; Perdrix, Anne; Augusto, Laetitia; Beaussire, Ludivine; Delacour, Julien; Calbrix, Céline; Sefrioui, David; Viailly, Pierre-Julien; Bubenheim, Michael; Moldovan, Cristian; Alexandru, Cristina; Tennevet, Isabelle; Rigal, Olivier; Guillemet, Cécile; Leheurteur, Marianne; Gouérant, Sophie; Petrau, Camille; Théry, Jean-Christophe; Picquenot, Jean-Michel; Veyret, Corinne; Frébourg, Thierry; Jardin, Fabrice

2016-01-01

Purpose To assess the prognostic and predictive value of circulating ESR1 mutation and its kinetics before and after progression on aromatase inhibitor (AI) treatment. Patients and methods ESR1 circulating D538G and Y537S/N/C mutations were retrospectively analyzed by digital droplet PCR after first-line AI failure in patients treated consecutively from 2010 to 2012 for hormone receptor-positive metastatic breast cancer. Progression-free survival (PFS) and overall survival (OS) were analyzed according to circulating mutational status and subsequent lines of treatment. The kinetics of ESR1 mutation before (3 and 6 months) and after (3 months) AI progression were determined in the available archive plasmas. Results Circulating ESR1 mutations were found at AI progression in 44/144 patients included (30.6%). Median follow-up from AI initiation was 40 months (range 4-94). The median OS was decreased in patients with circulating ESR1 mutation than in patients without mutation (15.5 versus 23.8 months, P=0.0006). The median PFS was also significantly decreased in patients with ESR1 mutation than in patients without mutation (5.9 vs 7 months, P=0.002). After AI failure, there was no difference in outcome for patients receiving chemotherapy (n = 58) versus non-AI endocrine therapy (n=51) in patients with and without ESR1 mutation. ESR1 circulating mutations were detectable in 75% of all cases before AI progression, whereas the kinetics 3 months after progression did not correlate with outcome. Conclusion ESR1 circulating mutations are independent risk factors for poor outcome after AI failure, and are frequently detectable before clinical progression. Interventional studies based on ESR1 circulating status are warranted. PMID:27801670

Kinetics, prognostic and predictive values of ESR1 circulating mutations in metastatic breast cancer patients progressing on aromatase inhibitor.

PubMed

Clatot, Florian; Perdrix, Anne; Augusto, Laetitia; Beaussire, Ludivine; Delacour, Julien; Calbrix, Céline; Sefrioui, David; Viailly, Pierre-Julien; Bubenheim, Michael; Moldovan, Cristian; Alexandru, Cristina; Tennevet, Isabelle; Rigal, Olivier; Guillemet, Cécile; Leheurteur, Marianne; Gouérant, Sophie; Petrau, Camille; Théry, Jean-Christophe; Picquenot, Jean-Michel; Veyret, Corinne; Frébourg, Thierry; Jardin, Fabrice; Sarafan-Vasseur, Nasrin; Di Fiore, Frédéric

2016-11-15

To assess the prognostic and predictive value of circulating ESR1 mutation and its kinetics before and after progression on aromatase inhibitor (AI) treatment. ESR1 circulating D538G and Y537S/N/C mutations were retrospectively analyzed by digital droplet PCR after first-line AI failure in patients treated consecutively from 2010 to 2012 for hormone receptor-positive metastatic breast cancer. Progression-free survival (PFS) and overall survival (OS) were analyzed according to circulating mutational status and subsequent lines of treatment. The kinetics of ESR1 mutation before (3 and 6 months) and after (3 months) AI progression were determined in the available archive plasmas. Circulating ESR1 mutations were found at AI progression in 44/144 patients included (30.6%). Median follow-up from AI initiation was 40 months (range 4-94). The median OS was decreased in patients with circulating ESR1 mutation than in patients without mutation (15.5 versus 23.8 months, P=0.0006). The median PFS was also significantly decreased in patients with ESR1 mutation than in patients without mutation (5.9 vs 7 months, P=0.002). After AI failure, there was no difference in outcome for patients receiving chemotherapy (n = 58) versus non-AI endocrine therapy (n=51) in patients with and without ESR1 mutation. ESR1 circulating mutations were detectable in 75% of all cases before AI progression, whereas the kinetics 3 months after progression did not correlate with outcome. ESR1 circulating mutations are independent risk factors for poor outcome after AI failure, and are frequently detectable before clinical progression. Interventional studies based on ESR1 circulating status are warranted.

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

G.Y. Fu; L.P. Ku; M.H. Redi

A key issue for compact stellarators is the stability of beta-limiting MHD modes, such as external kink modes driven by bootstrap current and pressure gradient. We report here recent progress in MHD stability studies for low-aspect-ratio Quasi-Axisymmetric Stellarators (QAS) and Quasi-Omnigeneous Stellarators (QOS). We find that the N = 0 periodicity-preserving vertical mode is significantly more stable in stellarators than in tokamaks because of the externally generated rotational transform. It is shown that both low-n external kink modes and high-n ballooning modes can be stabilized at high beta by appropriate 3D shaping without a conducting wall. The stabilization mechanism formore » external kink modes in QAS appears to be an enhancement of local magnetic shear due to 3D shaping. The stabilization of ballooning mode in QOS is related to a shortening of the normal curvature connection length.« less

Clinical management and outcome of patients with advanced NSCLC carrying EGFR mutations in Spain.

PubMed

Arriola, Edurne; García Gómez, Ramón; Diz, Pilar; Majem, Margarita; Martínez Aguillo, Maite; Valdivia, Javier; Paredes, Alfredo; Sánchez-Torres, José Miguel; Peralta Muñoz, Sergio; Barneto, Isidoro; Gutierrez, Vanesa; Andrade Santiago, Jesús Manuel; Aparisi, Francisco; Isla, Dolores; Ponce, Santiago; Vicente Baz, David; Artal, Angel; Amador, Mariluz; Provencio, Mariano

2018-01-30

Although the benefit of first-line epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitors (TKIs) over chemotherapy has been demonstrated in several clinical trials, data from clinical practice is lacking and the optimal EGFR TKI to be used remains unclear. This study aims to assess the real-life diagnostic and clinical management and outcome of patients with advanced non-small-cell lung cancer (NSCLC) carrying EGFR mutations in Spain. All consecutive patients recently diagnosed with advanced or metastatic NSCLC from April 2010 to December 2011 in 18 Spanish hospitals and carrying EGFR mutations were retrospectively evaluated. Between March and November 2013, a total of 187 patients were enrolled (98.3% Caucasian, 61.9% female, 54.9% never-smokers, 89.0% adenocarcinoma). Mutation testing was mainly performed on biopsy tumour tissue specimens (69.0%) using a qPCR-based test (90%) (47.0% Therascreen EGFR PCR Kit). Common sensitising mutations were detected in 79.8% of patients: 57.1% had exon 19 deletions and 22.6% exon 21 L858R point mutations. The vast majority of patients received first-line therapy (n = 168; 92.8%). EGFR TKIs were the most commonly used first-line treatment (81.5%), while chemotherapy was more frequently administered as a second- and third-line option (51.9% and 56.0%, respectively). Of 141 patients who experienced disease progression, 79 (56.0%) received second-line treatment. After disease progression on first-line TKIs (n = 112), 33.9% received chemotherapy, 8.9% chemotherapy and a TKI, and 9.8% continued TKI therapy. Most patients received first-line gefitinib (83.0%), while erlotinib was more frequently used in the second-line setting (83.0%). Progression-free survival (PFS) and overall survival (OS) in patients harbouring common mutations were 11.1 months and 20.1 months respectively (exon 19 deletions: 12.4 and 21.4 months; L858R: 8.3 and 14.5 months), and 3.9 months and 11.1 months respectively for those with rare mutations. EGFR TKIs (gefitinib and erlotinib) are used as the preferred first-line treatment while chemotherapy is more frequently administered as a second- and third-line option in routine clinical practice in Spain. In addition, efficacy data obtained in the real-life setting seem to concur with data from EGFR TKI phase III pivotal studies in NSCLC.

Progress Report on Rotating Liquid Liner Implosion Experiment, 1 June to 31 December 1975.

DTIC Science & Technology

A critical question in the use of imploding liner flux compression for controlled fusion has been the stability of the inner surface of the liner ...To study the problem experimentally, the existing NRL Imploding Liner Facility was modified to allow the implosion of rotating liquid metal liners ...Rotational stabilization of lthe inner surface of a decelerating liquid sodium-potassium liner has been demonstrated, with excellent circularity of the

A short review of relativistic iron lines from stellar-mass black holes

NASA Astrophysics Data System (ADS)

Miller, J. M.

2006-12-01

% In this contribution, I briefly review recent progress in detecting and measuring the properties of relativistic iron lines observed in stellar-mass black hole systems, and the aspects of these lines that are most relevant to studies of similar lines in Seyfert-1 AGN. In particular, the lines observed in stellar-mass black holes are not complicated by complex low-energy absorption or partial-covering of the central engine, and strong lines are largely independent of the model used to fit the underlying broad-band continuum flux. Indeed, relativistic iron lines are the most robust diagnostic of black hole spin that is presently available to observers, with specific advantages over the systematics-plagued disk continuum. If accretion onto stellar-mass black holes simply scales with mass, then the widespread nature of lines in stellar-mass black holes may indicate that lines should be common in Seyfert-1 AGN, though perhaps harder to detect.

Optimising the use of cetuximab in the continuum of care for patients with metastatic colorectal cancer.

PubMed

Goldberg, Richard M; Montagut, Clara; Wainberg, Zev A; Ronga, Philippe; Audhuy, François; Taieb, Julien; Stintzing, Sebastian; Siena, Salvatore; Santini, Daniele

2018-01-01

The anti-epidermal growth factor receptor (EGFR) monoclonal antibody cetuximab in combination with chemotherapy is a standard of care in the first-line treatment of RAS wild-type (wt) metastatic colorectal cancer (mCRC) and has demonstrated efficacy in later lines. Progressive disease (PD) occurs when tumours develop resistance to a therapy, although controversy remains about whether PD on a combination of chemotherapy and targeted agents implies resistance to both components. Here, we propose that some patients may gain additional clinical benefit from the reuse of cetuximab after having PD on regimens including cetuximab in an earlier treatment line. We conducted a non-systematic literature search in PubMed and reviewed published and ongoing clinical trials, focusing on later-line cetuximab reuse in patients with mCRC. Evidence from multiple studies suggests that cetuximab can be an efficacious and tolerable treatment when continued or when fit patients with mCRC are retreated with it after a break from anti-EGFR therapy. Furthermore, on the basis of available preclinical and clinical evidence, we propose that longitudinal monitoring of RAS status may identify patients suitable for such a strategy. Patients who experience progression on cetuximab plus chemotherapy but have maintained RAS wt tumour status may benefit from continuation of cetuximab with a chemotherapy backbone switch because they have probably developed resistance to the chemotherapeutic agents rather than the biologic component of the regimen. Conversely, patients whose disease progresses on cetuximab-based therapy due to drug-selected clonal expansion of RAS- mutant tumour cells may regain sensitivity to cetuximab following a defined break from anti-EGFR therapy. Looking to the future, we propose that RAS status determination at disease progression by liquid, needle or excisional biopsy may identify patients eligible for cetuximab continuation and rechallenge. With this approach, treatment benefit can be extended, adding to established continuum-of-care strategies in patients with mCRC.

Efficacy and influence factors of icotinib hydrochloride in treating advanced non-small cell lung cancer.

PubMed

Ma, X-H; Tian, T-D; Liu, H-M; Li, Q-J; Gao, Q-L; Li, L; Shi, B

2017-01-01

To evaluate the efficacy and safety of icotinib hydrochloride in the treatment of patients with advanced non-small cell lung cancer (NSCLC) and discuss the influence factors on efficacy. 120 treatment-experienced patients confirmed by pathology or cytology with stage III B-IV non-small cell lung cancer took icotinib hydrochloride and erlotinib orally until the occurrence of disease progression or serious adverse reactions. Then, the efficacy of icotinib hydrochloride and the related influence factors were analyzed. In icotinib hydrochloride group, the response rate and the disease control rate were 30.00% and 65.00%, and the median progression-free survival time was 179 days (95% CI: 103.21-254.78); in erlotinib group, the response rate and the disease control rate were 25.00% and 56.70%, and the median progression-free survival time was 121 days (95% CI: 95.05-146.94). Moreover, the objective response rate and the disease control rate of second-line therapy were both superior to the third-line and above therapy. The objective response rate of patients with complete response/partial response/stable disease after the first-line therapy was higher than that of patients without response after the first-line therapy (p<0.05), and the significant differences existed in the objective response rate and the disease control rate among mutant group, wild-type group, and unknown group (p<0.05). The response rate and the disease control rate of erythra group were higher than those of non-erythra group (p<0.05). It was showed in the univariate analysis that the progression-free survival was correlated with the smoking status and the epidermal growth factor receptor gene mutations. The icotinib hydrochloride is effective and safe in treating the treatment-experienced patients with advanced NSCLC, especially for patients with sensitive mutations.