Preclinical species gene expression database: Development and meta-analysis

The evaluation of toxicity in preclinical species is important for identifying potential safety liabilities of experimental medicines. Toxicology studies provide translational insight into potential adverse clinical findings, but data interpretation may be limited due to our understanding of cross-species biological differences. With the recent technological advances in sequencing and analyzing omics data, gene expression data can be used to predict cross species biological differences and improve experimental design and toxicology data interpretation. However, interpreting the translational significance of toxicogenomics analyses can pose a challenge due to the lack of comprehensive preclinical gene expression datasets. In this work, we performed RNA-sequencing across four preclinical species/strains widely used for safety assessment (CD1 mouse, Sprague Dawley rat, Beagle dog, and Cynomolgus monkey) in ∼50 relevant tissues/organs to establish a comprehensive preclinical gene expression body atlas for both males and females. In addition, we performed a meta-analysis across the large dataset to highlight species and tissue differences that may be relevant for drug safety analyses. Further, we made these databases available to the scientific community. This multi-species, tissue-, and sex-specific transcriptomic database should serve as a valuable resource to enable informed safety decision-making not only during drug development, but also in a variety of disciplines that use these preclinical species

A Roadmap for HEP Software and Computing R&D for the 2020s

Particle physics has an ambitious and broad experimental programme for the coming decades. This programme requires large investments in detector hardware, either to build new facilities and experiments, or to upgrade existing ones. Similarly, it requires commensurate investment in the R&D of software to acquire, manage, process, and analyse the shear amounts of data to be recorded. In planning for the HL-LHC in particular, it is critical that all of the collaborating stakeholders agree on the software goals and priorities, and that the efforts complement each other. In this spirit, this white paper describes the R&D activities required to prepare for this software upgrade.Peer reviewe

Identification of VEGF Signaling Inhibition-Induced Glomerular Injury in Rats through Site-Specific Urinary Biomarkers

Cancer therapies targeting the vascular endothelial growth factor (VEGF) signaling pathway can lead to renal damage by disrupting the glomerular ultrafiltration apparatus. The objective of the current study was to identify sensitive biomarkers for VEGF inhibition-induced glomerular changes in rats. Male Sprague-Dawley rats were administered an experimental VEGF receptor (VEGFR) inhibitor, ABT-123, for seven days to investigate the correlation of several biomarkers with microscopic and ultrastructural changes. Glomeruli obtained by laser capture microdissection were also subjected to gene expression analysis to investigate the underlying molecular events of VEGFR inhibition in glomerulus. ABT-123 induced characteristic glomerular ultrastructural changes in rats, including fusion of podocyte foot processes, the presence of subendothelial electron-dense deposits, and swelling and loss of fenestrations in glomerular endothelium. The subtle morphological changes cannot be detected with light microscopy or by changes in standard clinical chemistry and urinalysis. However, urinary albumin increased 44-fold as early as Day three. Urinary β2-microglobulin levels were also increased. Other urinary biomarkers that are typically associated with tubular injury were not significantly impacted. Such patterns in urinary biomarkers can provide valuable diagnostic insight to VEGF inhibition therapy-induced glomeruli injuries

Correlation of Neonatal Intensive Care Unit Performance Across Multiple Measures of Quality of Care

This find is registered at Portable Antiquities of the Netherlands with number PAN-0007661

Overview of NASA's Solar Electric Propulsion Project

NASA is continuing to develop and qualify a state of the art 13 kW-class Advanced Electric Propulsion System (AEPS) for NASA exploration missions through a contract with Aerojet Rocketdyne (AR). An objective of the AEPS project is accelerate the adoption of high power electric propulsion technologies by reducing the risk and uncertainty of integrating Solar Electric Propulsion (SEP) technologies into space flight systems. NASA and AR have recently initiated testing of engineering hardware including the Hall Current Thruster (HCT), Power Processing Unit (PPU), and Xenon Flow Controller (XFC) at both the component and system levels. The successful completion of these tests will provide the required information to advance the AEPS system towards Critical Design Review. In support of the AEPS contract, NASA and JPL have been performing risk reduction activities to address specific concerns of this higher power Hall thruster propulsion system. These risk reduction activities have included long duration wear testing of the Technology Demonstration Unit (TDU) Hall thruster and cathode hardware, thermal cycling of TDU cathode heaters and coils, plasma plume measurements, and performed early circuit testing of the AEPS PPU design. In addition to the propulsion system development, the SEP project is developing the Plasma Diagnostic Package (PDP) and the SEP Testbed. The PDP is designed for use in conjunction with a high-powered electric propulsion (EP) system to characterize in-space operation. The SEP Testbed system is being developed to demonstrate integrated SEP system performance. The paper presents an overview of the NASA and the AEPS contract activities and a summary of the associated NASA in-house activities

A Roadmap for HEP Software and Computing R&D for the 2020s

Particle physics has an ambitious and broad experimental programme for the coming decades. This programme requires large investments in detector hardware, either to build new facilities and experiments, or to upgrade existing ones. Similarly, it requires commensurate investment in the R&D of software to acquire, manage, process, and analyse the shear amounts of data to be recorded. In planning for the HL-LHC in particular, it is critical that all of the collaborating stakeholders agree on the software goals and priorities, and that the efforts complement each other. In this spirit, this white paper describes the R&D activities required to prepare for this software upgrade