OpenCRG models from different data sources to support vehicle simulations

Digital twins of road surfaces support multiple engineering applications. Remote sensing technologies provide information from the entire surface of the pavement by high accuracy point clouds. Pavement errors and differences from designed geometry can be detected and assessed using such datasets, while OpenCRG models derived from point clouds support transportation applications. High-resolution CRG (Curved Regular Grid) models enable analyzing vehicle suspension systems in vehicle dynamics simulation environments. Furthermore, such models also support creating the digital twins of vehicle suspensions and improve the development and research of models related to vehicle dynamics. The paper presents how the suspension digital twin was obtained applying a genetic algorithm and how it was assessed. The quality of raw data and that of the derived methods are analyzed in the case of multiple mapping technologies (terrestrial, mobile, and aerial laser scanning). CRG models were created from all datasets, and their applicability was investigated to support vehicle simulations with high accuracy demand. Other important vehicle-related use cases are also mentioned in the paper

Prediction of Graft-Versus-Host Disease in Humans by Donor Gene-Expression Profiling

BACKGROUND: Graft-versus-host disease (GVHD) results from recognition of host antigens by donor T cells following allogeneic hematopoietic cell transplantation (AHCT). Notably, histoincompatibility between donor and recipient is necessary but not sufficient to elicit GVHD. Therefore, we tested the hypothesis that some donors may be “stronger alloresponders” than others, and consequently more likely to elicit GVHD. METHODS AND FINDINGS: To this end, we measured the gene-expression profiles of CD4(+) and CD8(+) T cells from 50 AHCT donors with microarrays. We report that pre-AHCT gene-expression profiling segregates donors whose recipient suffered from GVHD or not. Using quantitative PCR, established statistical tests, and analysis of multiple independent training-test datasets, we found that for chronic GVHD the “dangerous donor” trait (occurrence of GVHD in the recipient) is under polygenic control and is shaped by the activity of genes that regulate transforming growth factor-β signaling and cell proliferation. CONCLUSIONS: These findings strongly suggest that the donor gene-expression profile has a dominant influence on the occurrence of GVHD in the recipient. The ability to discriminate strong and weak alloresponders using gene-expression profiling could pave the way to personalized transplantation medicine

SimFlex: a fast, accurate, flexible full-system simulation framework for performance evaluation of server architecture

The new focus on commercial workloads in simulation studies of server systems has caused a drastic increase in the complexity and decrease in the speed of simulation tools. The complexity of a large-scale full-system model makes development of a monolithic simulation tool a prohibitively difficult task. Furthermore, detailed full-system models simulate so slowly that experimental results must be based on simulations of only fractions of a second of execution of the modelled system. This paper presents SimFlex, a simulation framework which uses component-based design and rigorous statistical sampling to enable development of complex models and ensure representative measurement results with fast simulation turnaround. The novelty of SimFlex lies in its combination of a unique, compile-time approach to component interconnection and a methodology for obtaining accurate results from sampled simulations on a platform capable of evaluating unmodified commercial workload

Convergence of TCR and cytokine signaling leads to FOXO3a phosphorylation and drives the survival of CD4+ central memory T cells

The molecular events involved in the establishment and maintenance of CD4+ central memory and effector memory T cells (TCM and TEM, respectively) are poorly understood. In this study, we demonstrate that ex vivo isolated TCM are more resistant to both spontaneous and Fas-induced apoptosis than TEM and have an increased capacity to proliferate and persist in vitro. Using global gene expression profiling, single cell proteomics, and functional assays, we show that the survival of CD4+ TCM depends, at least in part, on the activation and phosphorylation of signal transducer and activator of transcription 5a (STAT5a) and forkhead box O3a (FOXO3a). TCM showed a significant increase in the levels of phosphorylation of STAT5a compared with TEM in response to both IL-2 (P < 0.04) and IL-7 (P < 0.002); the latter is well known for its capacity to enhance T cell survival. Moreover, ex vivo TCM express higher levels of the transcriptionally inactive phosphorylated forms of FOXO3a and concomitantly lower levels of the proapoptotic FOXO3a target, Bim. Experiments aimed at blocking FOXO3a phosphorylation confirmed the role of this phosphoprotein in protecting TCM from apoptosis. Our results provide, for the first time in humans, an insight into molecular mechanisms that could be responsible for the longevity and persistence of CD4+ TCM

Yellow fever vaccine induces integrated multilineage and polyfunctional immune responses

Correlates of immune-mediated protection to most viral and cancer vaccines are still unknown. This impedes the development of novel vaccines to incurable diseases such as HIV and cancer. In this study, we have used functional genomics and polychromatic flow cytometry to define the signature of the immune response to the yellow fever (YF) vaccine 17D (YF17D) in a cohort of 40 volunteers followed for up to 1 yr after vaccination. We show that immunization with YF17D leads to an integrated immune response that includes several effector arms of innate immunity, including complement, the inflammasome, and interferons, as well as adaptive immunity as shown by an early T cell response followed by a brisk and variable B cell response. Development of these responses is preceded, as demonstrated in three independent vaccination trials and in a novel in vitro system of primary immune responses (modular immune in vitro construct [MIMIC] system), by the coordinated up-regulation of transcripts for specific transcription factors, including STAT1, IRF7, and ETS2, which are upstream of the different effector arms of the immune response. These results clearly show that the immune response to a strong vaccine is preceded by coordinated induction of master transcription factors that lead to the development of a broad, polyfunctional, and persistent immune response that integrates all effector cells of the immune system