Fast approximately timed simulation

International audienceIn this paper we present a technique for fast approximately timed simulation of software within a virtual prototyping framework. Our method performs a static analysis of the program control flow graph to construct annotations of the simulated program, combined with dynamic performance information. The static analysis estimates execution time based on a target architecture model. The delays introduced by instruction fetch and data cache misses are evaluated dynamically. At the end of each block, static and dynamic information are combined with branch target prediction to compute the total execution time of the blocks. As a result, we can provide approximate performance estimates with a high simulation speed that is still usable for software developers

Overview of Crosstalk Between Multiple Factor of Transcytosis in Blood Brain Barrier.

Blood brain barrier (BBB) conserves unique regulatory system to maintain barrier tightness while allowing adequate transport between neurovascular units. This mechanism possess a challenge for drug delivery, while abnormality may result in pathogenesis. Communication between vascular and neural system is mediated through paracellular and transcellular (transcytosis) pathway. Transcytosis itself showed dependency with various components, focusing on caveolae-mediated. Among several factors, intense communication between endothelial cells, pericytes, and astrocytes is the key for a normal development. Regulatory signaling pathway such as VEGF, Notch, S1P, PDGFβ, Ang/Tie, and TGF-β showed interaction with the transcytosis steps. Recent discoveries showed exploration of various factors which has been proven to interact with one of the process of transcytosis, either endocytosis, endosomal rearrangement, or exocytosis. As well as providing a hypothetical regulatory pathway between each factors, specifically miRNA, mechanical stress, various cytokines, physicochemical, basement membrane and junctions remodeling, and crosstalk between developmental regulatory pathways. Finally, various hypotheses and probable crosstalk between each factors will be expressed, to point out relevant research application (Drug therapy design and BBB-on-a-chip) and unexplored terrain

Content-specific auditing of a large scale anatomy ontology

Biomedical ontologies are envisioned to be usable in a range of research and clinical applications. The requirements for such uses include formal consistency, adequacy of coverage, and possibly other domain specific constraints. In this report we describe a case study that illustrates how application specific requirements may be used to identify modeling problems as well as data entry errors in ontology building and evolution. We have begun a project to use the UW Foundational Model of Anatomy (FMA) in a clinical application in radiation therapy planning. This application focuses mainly (but not exclusively) on the representation of the lymphatic system in the FMA, in order to predict the spread of tumor cells to regional metastatic sites. This application requires that the downstream relations associated with lymphatic system components must only be to other lymphatic chains or vessels, must be at the appropriate level of granularity, and that every path through the lymphatic system must terminate at one of the two well known trunks of the lymphatic system. It is possible through a programmable query interface to the FMA to write small programs that systematically audit the FMA for compliance with these constraints. We report on the design of some of these programs, and the results we obtained by applying them to the lymphatic system. The algorithms and approach are generalizable to other network organ systems in the FMA such as arteries and veins. In addition to illustrating exact constraint checking methods, this work illustrates how the details of an application may reflect back a requirement to revise the design of the ontology itself

Global simulation of EMIC wave excitation during the 21 April 2001 storm from coupled RCM-RAM-HOTRAY modeling

The global distribution and spectral properties of electromagnetic ion cyclotron (EMIC) waves in the He+ band are simulated for the 21 April 2001 storm using a combination of three different codes: the Rice Convection Model, the Ring current-Atmospheric interactions Model, and the HOTRAY ray tracing code (incorporated with growth rate solver). During the storm main phase, injected ions exhibit a non-Maxwellian distribution with pronounced phase space density minima at energies around a few keV. Ring current H+-injected from the plasma sheet provides the source of free energy for EMIC excitation during the storm. Significant wave gain is confined to a limited spatial region inside the storm time plume and maximizes at the eastward edge of the plume in the dusk and premidnight sector. The excited waves are also able to resonate and scatter relativistic electrons, but the minimum electron resonant energy is generally above 3 MeV

DNA methylation landscape of ocular tissue relative to matched peripheral blood

This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/Epigenetic variation is implicated in a range of non-communicable diseases, including those of the eye. However, investigating the role of epigenetic variation in central tissues, such as eye or brain, remains problematic and peripheral tissues are often used as surrogates. In this study, matched human blood and eye tissue (n = 8) were obtained post-mortem and DNA methylation profiling performed on blood, neurosensory retina, retinal pigment epithelium (RPE)/choroid and optic nerve tissue using the Illumina Infinium HumanMethylation450 platform. Unsupervised clustering and principal components analysis revealed tissue of origin as the main driver of methylation variation. Despite this, there was a strong correlation of methylation profiles between tissues with >255,000 CpG sites found to have similar methylation levels. An additional ~16,000 show similarity across ocular tissues only. A small proportion of probes showing inter-individual variation in blood co-varied with eye tissues within individuals, however much of this variation may be genetically driven. An improved understanding of the epigenetic landscape of the eye will have important implications for understanding eye disease. Despite a generally high correlation irrespective of origin, tissue type is the major driver of methylation variation, with only limited covariation between blood and any specific ocular tissue

Customer Analytics and New Product Performance: The Role of Contingencies

Drawing from the Knowledge Based View (KBV) of the firm and Contingency Theory, this paper examines the extent to which the relationship between Customer Analytics (CA) and new product performance is contingent on the strategic fit of CA with certain internal and external contingencies. The paper first conducts a multiple case study based on secondary data analysis. It then undertakes an empirical analysis based on a survey data of 249 high and medium tech firms based in China. We find that while some internal contingencies (such as exploitative learning strategy and market knowledge breadth) negatively moderate the effect of CA on new product performance, others (such as internal capability and knowledge integration mechanisms) mediate its effect on performance. Technological turbulence, as an external contingency, was found to reduce the positive impact of CA deployment on new product performance. This study contributed to the literature by focusing on how several internal and external contingencies of a firm may affect the relationship between CA and new product performance

Towards a Scientific Model Management System

Computational models of biological systems aim at accurately simulating in vivo phenomena. They have become a very powerful tool enabling scientists to study complex behavior. A side effect of their success Unfortunately exists and is observed as an increasing difficulty in managing data, metadata and a myriad of programs and tools used and produced during a research task. In this work we aim at supporting scientists during a research endeavour by using Scientific Models as a main guiding element for describing, searching and running computational models, as well as managing the corresponding results. We assume a data-oriented perspective for scientific model representation materialized into a data model with which users describe scientific models and corresponding computational models, and a query language with which a scientist specifies simulation queries. The model is grounded in XML and tightly related to domain ontologies, which provide formal domain descriptions and uniform terminology. Scientists may search for scientific models and run simulations that automatically invoke the underlying programs on provided inputs. The results of a simulation may generate complex data that can be queried in the context of the scientific model. Higher-level models can be specified through views that export a unified representation of underlying scientific models

Automatic benchmark profiling through advanced workflow-based trace analysis

International audienceBenchmarking has proven to be crucial for the investigation of the behavior and performances of a system. However, the choice of relevant benchmarks still remains a challenge. To help the process of comparing and choosing among benchmarks, we propose a solution for automatic benchmark profiling. It computes unified benchmark profiles reflecting benchmarks' duration, function repartition, stability, CPU efficiency, parallelization, and memory usage. Our approach identifies the needed system information for profile computation and collects it from execution traces captured without benchmark code modifications. It structures profile computation as a reproducible workflow for automatic trace analysis, which efficiently manages important trace volumes. In this paper, we report on the design and the implementation of our approach, which involves the collection and analysis of about 500 GB of trace data coming from 2 different platforms (an x86 desktop machine and the Juno SoC board). The computed benchmark profiles provide valuable insights about the benchmarks' behavior and help compare different benchmarks on the same platform as well as the behavior of the same benchmark on different platforms

Optimizing Nervous System-Specific Gene Targeting with Cre Driver Lines: Prevalence of Germline Recombination and Influencing Factors.

The Cre-loxP system is invaluable for spatial and temporal control of gene knockout, knockin, and reporter expression in the mouse nervous system. However, we report varying probabilities of unexpected germline recombination in distinct Cre driver lines designed for nervous system-specific recombination. Selective maternal or paternal germline recombination is showcased with sample Cre lines. Collated data reveal germline recombination in over half of 64 commonly used Cre driver lines, in most cases with a parental sex bias related to Cre expression in sperm or oocytes. Slight differences among Cre driver lines utilizing common transcriptional control elements affect germline recombination rates. Specific target loci demonstrated differential recombination; thus, reporters are not reliable proxies for another locus of interest. Similar principles apply to other recombinase systems and other genetically targeted organisms. We hereby draw attention to the prevalence of germline recombination and provide guidelines to inform future research for the neuroscience and broader molecular genetics communities