OpenCL Actors - Adding Data Parallelism to Actor-based Programming with CAF

The actor model of computation has been designed for a seamless support of concurrency and distribution. However, it remains unspecific about data parallel program flows, while available processing power of modern many core hardware such as graphics processing units (GPUs) or coprocessors increases the relevance of data parallelism for general-purpose computation. In this work, we introduce OpenCL-enabled actors to the C++ Actor Framework (CAF). This offers a high level interface for accessing any OpenCL device without leaving the actor paradigm. The new type of actor is integrated into the runtime environment of CAF and gives rise to transparent message passing in distributed systems on heterogeneous hardware. Following the actor logic in CAF, OpenCL kernels can be composed while encapsulated in C++ actors, hence operate in a multi-stage fashion on data resident at the GPU. Developers are thus enabled to build complex data parallel programs from primitives without leaving the actor paradigm, nor sacrificing performance. Our evaluations on commodity GPUs, an Nvidia TESLA, and an Intel PHI reveal the expected linear scaling behavior when offloading larger workloads. For sub-second duties, the efficiency of offloading was found to largely differ between devices. Moreover, our findings indicate a negligible overhead over programming with the native OpenCL API.Comment: 28 page

Study of the bivariate survival data using frailty models based on Lévy processes

Frailty models allow us to take into account the non-observable inhomogeneity of individual hazard functions. Although models with time-independent frailty have been intensively studied over the last decades and a wide range of applications in survival analysis have been found, the studies based on the models with time-dependent frailty are relatively rare. In this paper, we formulate and prove two propositions related to the identifiability of the bivariate survival models with frailty given by a nonnegative bivariate Lévy process. We discuss parametric and semiparametric procedures for estimating unknown parameters and baseline hazard functions. Numerical experiments with simulated and real data illustrate these procedures. The statements of the propositions can be easily extended to the multivariate case

Discovery of Potent, Selective, and Orally Bioavailable Small-Molecule Modulators of the Mediator Complex-Associated Kinases CDK8 and CDK19.

The Mediator complex-associated cyclin-dependent kinase CDK8 has been implicated in human disease, particularly in colorectal cancer where it has been reported as a putative oncogene. Here we report the discovery of 109 (CCT251921), a potent, selective, and orally bioavailable inhibitor of CDK8 with equipotent affinity for CDK19. We describe a structure-based design approach leading to the discovery of a 3,4,5-trisubstituted-2-aminopyridine series and present the application of physicochemical property analyses to successfully reduce in vivo metabolic clearance, minimize transporter-mediated biliary elimination while maintaining acceptable aqueous solubility. Compound 109 affords the optimal compromise of in vitro biochemical, pharmacokinetic, and physicochemical properties and is suitable for progression to animal models of cancer

Risk-adjusted CUSUM control charts for shared frailty survival models with application to hip replacement outcomes: a study using the NJR dataset

Background:  Continuous monitoring of surgical outcomes after joint replacement is needed to detect which brands’ components have a higher than expected failure rate and are therefore no longer recommended to be used in surgical practice. We developed a monitoring method based on cumulative sum (CUSUM) chart specifically for this application.  Methods:  Our method entails the use of the competing risks model with the Weibull and the Gompertz hazard functions adjusted for observed covariates to approximate the baseline time-to-revision and time-to-death distributions, respectively. The correlated shared frailty terms for competing risks, corresponding to the operating unit, are also included in the model. A bootstrap-based boundary adjustment is then required for risk-adjusted CUSUM charts to guarantee a given probability of the false alarm rates. We propose a method to evaluate the CUSUM scores and the adjusted boundary for a survival model with the shared frailty terms. We also introduce a unit performance quality score based on the posterior frailty distribution. This method is illustrated using the 2003-2012 hip replacement data from the UK National Joint Registry (NJR). Results:  We found that the best model included the shared frailty for revision but not for death. This means that the competing risks of revision and death are independent in NJR data. Our method was superior to the standard NJR methodology. For one of the two monitored components, it produced alarms four years before the increased failure rate came to the attention of the UK regulatory authorities. The hazard ratios of revision across the units varied from 0.38 to 2.28. Conclusions:  An earlier detection of failure signal by our method in comparison to the standard method used by the NJR may be explained by proper risk-adjustment and the ability to accommodate time-dependent hazards. The continuous monitoring of hip replacement outcomes should include risk adjustment at both the individual and unit level

Comparison of Parallelisation Approaches, Languages, and Compilers for Unstructured Mesh Algorithms on GPUs

Efficiently exploiting GPUs is increasingly essential in scientific computing, as many current and upcoming supercomputers are built using them. To facilitate this, there are a number of programming approaches, such as CUDA, OpenACC and OpenMP 4, supporting different programming languages (mainly C/C++ and Fortran). There are also several compiler suites (clang, nvcc, PGI, XL) each supporting different combinations of languages. In this study, we take a detailed look at some of the currently available options, and carry out a comprehensive analysis and comparison using computational loops and applications from the domain of unstructured mesh computations. Beyond runtimes and performance metrics (GB/s), we explore factors that influence performance such as register counts, occupancy, usage of different memory types, instruction counts, and algorithmic differences. Results of this work show how clang's CUDA compiler frequently outperform NVIDIA's nvcc, performance issues with directive-based approaches on complex kernels, and OpenMP 4 support maturing in clang and XL; currently around 10% slower than CUDA

Endosialin (TEM1, CD248) is a marker of stromal fibroblasts and is not selectively expressed on tumour endothelium

AbstractFibroblasts are a diverse cell type and display clear topographic differentiation and positional memory. In a screen for fibroblast specific markers we have characterized four monoclonal antibodies to endosialin (TEM1/CD248). Previous studies have reported that endosialin is a tumour endothelium marker and is localized intracellularly. We demonstrate conclusively that endosialin is a cell surface glycoprotein and is predominantly expressed by fibroblasts and a subset of pericytes associated with tumour vessels but not by tumour endothelium. These novel antibodies will facilitate the isolation and classification of fibroblast and pericyte lineages as well as the further functional analysis of endosialin

Empire Ultimate Expansion: Resonances and Covariances.

The EMPIRE code system is being extended to cover the resolved and unresolved resonance region employing proven methodology used for the production of new evaluations in the recent Atlas of Neutron Resonances. Another directions of Empire expansion are uncertainties and correlations among them. These include covariances for cross sections as well as for model parameters. In this presentation we concentrate on the KALMAN method that has been applied in EMPIRE to the fast neutron range as well as to the resonance region. We also summarize role of the EMPIRE code in the ENDF/B-VII.0 development. Finally, large scale calculations and their impact on nuclear model parameters are discussed along with the exciting perspectives offered by the parallel supercomputing

Actin polymerization driven by WASH causes V-ATPase retrieval and vesicle neutralization before exocytosis

WASH coats mature lysosomes and is required for exocytosis of indigestible material

Balancing Selection of a Frame-Shift Mutation in the MRC2 Gene Accounts for the Outbreak of the Crooked Tail Syndrome in Belgian Blue Cattle

We herein describe the positional identification of a 2-bp deletion in the open reading frame of the MRC2 receptor causing the recessive Crooked Tail Syndrome in cattle. The resulting frame-shift reveals a premature stop codon that causes nonsense-mediated decay of the mutant messenger RNA, and the virtual absence of functional Endo180 protein in affected animals. Cases exhibit skeletal anomalies thought to result from impaired extracellular matrix remodeling during ossification, and as of yet unexplained muscular symptoms. We demonstrate that carrier status is very significantly associated with desired characteristics in the general population, including enhanced muscular development, and that the resulting heterozygote advantage caused a selective sweep which explains the unexpectedly high frequency (25%) of carriers in the Belgian Blue Cattle Breed