Cooperative parallel SAT local search with path relinking

In this paper, we propose the use of path relinking to improve the performance of parallel portfolio-based local search solvers for the Boolean Satisfiability problem. In the portfolio-based framework several algorithms explore the search space in parallel, either independently or cooperatively with some communication between the solvers. Path relinking is a method to maintain an appropriate balance between diversification and intensification (and explore paths that aggregate elite solutions) to properly craft a new assignment for the variables to restart from. We present an empirical study that suggest that path relinking outperforms a set of well-known parallel portfolio-based local search algorithms with and without cooperation

Quantitative Multicolor Compositional Imaging Resolves Molecular Domains in Cell-Matrix Adhesions

Background: Cellular processes occur within dynamic and multi-molecular compartments whose characterization requires analysis at high spatio-temporal resolution. Notable examples for such complexes are cell-matrix adhesion sites, consisting of numerous cytoskeletal and signaling proteins. These adhesions are highly variable in their morphology, dynamics, and apparent function, yet their molecular diversity is poorly defined. Methodology/Principal Findings: We present here a compositional imaging approach for the analysis and display of multicomponent compositions. This methodology is based on microscopy-acquired multicolor data, multi-dimensional clustering of pixels according to their composition similarity and display of the cellular distribution of these composition clusters. We apply this approach for resolving the molecular complexes associated with focal-adhesions, and the time-dependent effects of Rho-kinase inhibition. We show here compositional variations between adhesion sites, as well as ordered variations along the axis of individual focal-adhesions. The multicolor clustering approach also reveals distinct sensitivities of different focaladhesion-associated complexes to Rho-kinase inhibition. Conclusions/Significance: Multicolor compositional imaging resolves ‘‘molecular signatures’ ’ characteristic to focaladhesions and related structures, as well as sub-domains within these adhesion sites. This analysis enhances the spatial information with additional ‘‘contents-resolved’ ’ dimensions. We propose that compositional imaging can serve as

Nanomechanical investigation of soft biological cell adhesion using atomic force microscopy

Mechanical coupling between living cells is a complex process that is important for a variety of biological processes. In this study the effects of specific biochemical treatment on cell-to-cell adhesion and single cell mechanics were systematically investigated using atomic force microscopy (AFM) single cell force spectroscopy. Functionalised AFM tipless cantilevers were used for attaching single suspended cells that were brought in contact with substrate cells. Cell-to-cell adhesion parameters, such as maximum unbinding force (F max) and work or energy of detachment (W D), were extracted from the retraction force–displacement (F–d) curves. AFM indentation experiments were performed by indenting single cells with a spherical microbead attached to the cantilever. Hertzian contact model was applied to determine the elastic modulus (E) of single cells. Following treatment of the cells with neutralising antibody for epithelial (E)-cadherin, F max was increased by 25%, whereas W D decreased by 11% in response to a 43% increase in E. The results suggest that although the adhesion force between cells was increased after treatment, the energy of adhesion was decreased due to the reduced displacement separation as manifested by the loss of elastic deformation. Conclusively, changes in single cell mechanics are important underlying factors contributing to cell-to-cell adhesion and hence cytomechanical characterization is critical for cell adhesion measurements

Ubiquitin Carboxyl-Terminal Esterase LI (UCHLI) SI8Y Polymorphism in Patients with Cataracts

Background: Cataract is characterized by light-scattering protein aggregates. The ubiquitin-proteasome system has been proposed a role in proteolytic removal of these protein aggregates. Ubiquitin carboxyl-terminal esterase L1 (UCHL1) is a de-ubiquitinating enzyme wit

Evidence based post graduate training. A systematic review of reviews based on the WFME quality framework

<p>Abstract</p> <p>Background</p> <p>A framework for high quality in post graduate training has been defined by the World Federation of Medical Education (WFME). The objective of this paper is to perform a systematic review of reviews to find current evidence regarding aspects of quality of post graduate training and to organise the results following the 9 areas of the WFME framework.</p> <p>Methods</p> <p>The systematic literature review was conducted in 2009 in Medline Ovid, EMBASE, ERIC and RDRB databases from 1995 onward. The reviews were selected by two independent researchers and a quality appraisal was based on the SIGN tool.</p> <p>Results</p> <p>31 reviews met inclusion criteria. The majority of the reviews provided information about the training process (WFME area 2), the assessment of trainees (WFME area 3) and the trainees (WFME area 4). One review covered the area 8 'governance and administration'. No review was found in relation to the mission and outcomes, the evaluation of the training process and the continuous renewal (respectively areas 1, 7 and 9 of the WFME framework).</p> <p>Conclusions</p> <p>The majority of the reviews provided information about the training process, the assessment of trainees and the trainees. Indicators used for quality assessment purposes of post graduate training should be based on this evidence but further research is needed for some areas in particular to assess the quality of the training process.</p

Internal Jugular Vein Cross-Sectional Area and Cerebrospinal Fluid Pulsatility in the Aqueduct of Sylvius: A Comparative Study between Healthy Subjects and Multiple Sclerosis Patients

Objectives Constricted cerebral venous outflow has been linked with increased cerebrospinal fluid (CSF) pulsatility in the aqueduct of Sylvius in multiple sclerosis (MS) patients and healthy individuals. This study investigates the relationship between CSF pulsatility and internal jugular vein (IJV) cross-sectional area (CSA) in these two groups, something previously unknown. Methods 65 relapsing-remitting MS patients (50.8% female; mean age = 43.8 years) and 74 healthy controls (HCs) (54.1% female; mean age = 43.9 years) were investigated. CSF flow quantification was performed on cine phase-contrast MRI, while IJV-CSA was calculated using magnetic resonance venography. Statistical analysis involved correlation, and partial least squares correlation analysis (PLSCA). Results PLSCA revealed a significant difference (p<0.001; effect size = 1.072) between MS patients and HCs in the positive relationship between CSF pulsatility and IJV-CSA at C5-T1, something not detected at C2-C4. Controlling for age and cardiovascular risk factors, statistical trends were identified in HCs between: increased net positive CSF flow (NPF) and increased IJV-CSA at C5-C6 (left: r = 0.374, p = 0.016; right: r = 0.364, p = 0.019) and C4 (left: r = 0.361, p = 0.020); and increased net negative CSF flow and increased left IJV-CSA at C5-C6 (r = -0.348, p = 0.026) and C4 (r = -0.324, p = 0.039), whereas in MS patients a trend was only identified between increased NPF and increased left IJV-CSA at C5-C6 (r = 0.351, p = 0.021). Overall, correlations were weaker in MS patients (p = 0.015). Conclusions In healthy adults, increased CSF pulsatility is associated with increased IJV-CSA in the lower cervix (independent of age and cardiovascular risk factors), suggesting a biomechanical link between the two. This relationship is altered in MS patients

Exoplanet diversity in the era of space-based direct imaging missions

Community White Paper: submitted to the National Academy of Sciences Exoplanet Science StrategyThis white paper discusses the diversity of exoplanets that could be detected by future observations, so that comparative exoplanetology can be performed in the upcoming era of large space-based flagship missions. The primary focus will be on characterizing Earth-like worlds around Sun-like stars. However, we will also be able to characterize companion planets in the system simultaneously. This will not only provide a contextual picture with regards to our Solar system, but also presents a unique opportunity to observe size dependent planetary atmospheres at different orbital distances. We propose a preliminary scheme based on chemical behavior of gases and condensates in a planet's atmosphere that classifies them with respect to planetary radius and incident stellar flux

Clinical impact of HLA class I expression in rectal cancer

Contains fulltext : 69499.pdf (publisher's version ) (Open Access)PURPOSE: To determine the clinical impact of human leukocyte antigen (HLA) class I expression in irradiated and non-irradiated rectal carcinomas. EXPERIMENTAL DESIGN: Tumor samples in tissue micro array format were collected from 1,135 patients. HLA class I expression was assessed after immunohistochemical staining with two antibodies (HCA2 and HC10). RESULTS: Tumors were split into two groups: (1) tumors with >50% of tumor cells expressing HLA class I (high) and (2) tumors with < or =50% of tumor cells expressing HLA class I (low). No difference in distribution or prognosis of HLA class I expression was found between irradiated and non-irradiated patients. Patients with low expression of HLA class I (15% of all patients) showed an independent significantly worse prognosis with regard to overall survival and disease-free survival. HLA class I expression had no effect on cancer-specific survival or recurrence-free survival. CONCLUSIONS: Down-regulation of HLA class I in rectal cancer is associated with poor prognosis. In contrast to our results, previous reports on HLA class I expression in colorectal cancer described a large population of patients with HLA class I negative tumors, having a good prognosis. This difference might be explained by the fact that a large proportion of HLA negative colon tumors are microsatellite instable (MSI). MSI tumors are associated with a better prognosis than microsatellite stable (MSS). As rectal tumors are mainly MSS, our results suggest that it is both, oncogenic pathway and HLA class I expression, that dictates patient's prognosis in colorectal cancer. Therefore, to prevent confounding in future prognostic analysis on the impact of HLA expression in colorectal tumors, separate analysis of MSI and MSS tumors should be performed