The Experiment for Space Radiation Analysis: Probing the Earth\u27s Radiation Belts Using a CubeSat Platform

The Experiment for Space Radiation Analysis (ESRA) is the latest of a series of Demonstration and Validation missions built by the Los Alamos National Laboratory, with the focus on testing a new generation of plasma and energetic particle sensors. The primary motivation for the ESRA payloads is to minimize size, weight, power, and cost while still providing necessary mission data. These new instruments will be demonstrated by ESRA through testing and on-orbit operations to increase their technology readiness level such that they can support the evolution of technology and mission objectives. This project will leverage a commercial off-the-shelf CubeSat avionics bus and commercial satellite ground networks to reduce the cost and timeline associated with traditional DemVal missions. The system will launch as a ride share with the DoD Space Test Program to be inserted in Geosynchronous Transfer Orbit (GTO) and allow observations of the Earth’s radiation belts. The ESRA CubeSat consists of two science payloads and several subsystems: the Wide-field-of-view Plasma Spectrometer, the Energetic Charged Particle telescope, high voltage power supply, payload processor, flight software architecture, and distributed processor module. The ESRA CubeSat will provide measurements of the plasma and energetic charged particle populations in the GTO environment for ions ranging from ~100 eV to ~1000 MeV and electrons with energy ranging from 100 keV to 20 MeV. ESRA will utilize a commercial 12U bus and demonstrate a low-cost, rapidly deployable spaceflight platform with sufficient SWAP to enable efficient measurements of the energetic particle populations in the dynamic radiation belts

Plasma amyloid β levels are driven by genetic variants near APOE, BACE1, APP, PSEN2: A genome-wide association study in over 12,000 non-demented participants

INTRODUCTION: There is increasing interest in plasma amyloid beta (Aβ) as an endophenotype of Alzheimer's disease (AD). Identifying the genetic determinants of plasma Aβ levels may elucidate important biological processes that determine plasma Aβ measures. METHODS: We included 12,369 non-demented participants from eight population-based studies. Imputed genetic data and measured plasma Aβ1-40, Aβ1-42 levels and Aβ1-42/Aβ1-40 ratio were used to perform genome-wide association studies, and gene-based and pathway analyses. Significant variants and genes were followed up for their association with brain positron emission tomography Aβ deposition and AD risk. RESULTS: Single-variant analysis identified associations with apolipoprotein E (APOE) for Aβ1-42 and Aβ1-42/Aβ1-40 ratio, and BACE1 for Aβ1-40. Gene-based analysis of Aβ1-40 additionally identified associations for APP, PSEN2, CCK, and ZNF397. There was suggestive evidence for interaction between a BACE1 variant and APOE ε4 on brain Aβ deposition. DISCUSSION: Identification of variants near/in known major Aβ-processing genes strengthens the relevance of plasma-Aβ levels as an endophenotype of AD

Cerebral small vessel disease genomics and its implications across the lifespan

White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older individuals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were associated with altered white matter integrity (p = 2.5×10-7) in brain images from 1,738 young healthy adults, providing insight into the lifetime impact of SVD genetic risk. Mendelian randomization suggested causal association of increasing WMH-volume with stroke, Alzheimer-type dementia, and of increasing blood pressure (BP) with larger WMH-volume, notably also in persons without clinical hypertension. Transcriptome-wide colocalization analyses showed association of WMH-volume with expression of 39 genes, of which four encode known drug targets. Finally, we provide insight into BP-independent biological pathways underlying SVD and suggest potential for genetic stratification of high-risk individuals and for genetically-informed prioritization of drug targets for prevention trials.Peer reviewe

Novel genetic loci associated with hippocampal volume

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness

Genetic architecture of subcortical brain structures in 38,851 individuals

Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease

Novel genetic loci underlying human intracranial volume identified through genome-wide association

Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five novel loci for intracranial volume and confirmed two known signals. Four of the loci are also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (ρgenetic=0.748), which indicated a similar genetic background and allowed for the identification of four additional loci through meta-analysis (Ncombined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, Parkinson’s disease, and enriched near genes involved in growth pathways including PI3K–AKT signaling. These findings identify biological underpinnings of intracranial volume and provide genetic support for theories on brain reserve and brain overgrowth

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Middle East - North Africa and the millennium development goals : implications for German development cooperation

          Closed-loop controlled combustion is a promising technique to improve the overall performance of internal combustion engines and Diesel engines in particular. In order for this technique to be implemented some form of feedback from the combustion process is required. The feedback signal is processed and from it combustionrelated parameters are computed. These parameters are then fed to a control process which drives a series of outputs (e.g. injection timing in Diesel engines) to control their values. This paper’s focus lies on the processing and computation that is needed on the feedback signal before this is ready to be fed to the control process as well as on the electronics necessary to support it. A number of feedback alternatives are briefly discussed and for one of them, the in-cylinder pressure sensor, the CA50 (crank angle in which the integrated heat release curve reaches its 50% value) and the IMEP (Indicated Mean Effective Pressure) are identified as two potential control variables. The hardware architecture of a system capable of calculating both of them on-line is proposed and necessary feasibility size and speed considerations are made by implementing critical blocks in VHDL targeting a flash-based Actel ProASIC3 automotive-grade FPGA