Space Science and Microsatellites - A Case Study Observations of the Near-Earth Radiation Environment using the Cosmic-Ray Effects and Dosimetry (CREDO) Payload On-Board UoSAT-3

The University of Surrey\u27s technology demonstration microsatellite: UoSAT-3 launched in January 1990. carries on-board a Cosmic-Ray Effects and Dosimetry (CREDO) payload for characterizing the low-Earth orbit (LEO) radiation environment. Measurements made with this payload are correlated with radiation effects observed in the spacecraft\u27s microelectronics, in particular, the occurrence of single event upsets (SEUs) in solid-state memory devices. The CREDO payload consists of two Sub-systems, the Cosmic Particle Experiment (CPE) and the Total-Dose Experiment (TDE). The CPE houses an array of large-area PIN diode detectors, connected to a pulse-height analysis network. Particles incident on the detector are counted and logged according to their linear-energy transfer (LET). Results are integrated over five minute intervals and the data are stored in the PACSAT Communications Experiment (PCE) memory. The TDE consists of specially manufactured p-channel MOSFETs which are monitored for changes in threshold voltage due to accumulated radiation dose. During the first year\u27s operation, CREDO has provided measurements of the cosmic-ray background, the trapped particle population of the South Atlantic Anomaly (SAA), and has observed a number of large solar proton events - most recently, the major events of June 1991. This paper reviews the results obtained so far and comments on the suitability of microsatellites for this kind of small-scale space science mission

Spatio-temporal genetic tagging of a cosmopolitan planktivorous shark provides insight to gene flow, temporal variation and site-specific re-encounters

Migratory movements in response to seasonal resources often influence population structure and dynamics. Yet in mobile marine predators, population genetic consequences of such repetitious behaviour remain inaccessible without comprehensive sampling strategies. Temporal genetic sampling of seasonally recurring aggregations of planktivorous basking sharks, Cetorhinus maximus, in the Northeast Atlantic (NEA) affords an opportunity to resolve individual re-encounters at key sites with population connectivity and patterns of relatedness. Genetic tagging (19 microsatellites) revealed 18% of re-sampled individuals in the NEA demonstrated inter/multi-annual site-specific re-encounters. High genetic connectivity and migration between aggregation sites indicate the Irish Sea as an important movement corridor, with a contemporary effective population estimate (Ne) of 382 (CI = 241–830). We contrast the prevailing view of high gene flow across oceanic regions with evidence of population structure within the NEA, with early-season sharks off southwest Ireland possibly representing genetically distinct migrants. Finally, we found basking sharks surfacing together in the NEA are on average more related than expected by chance, suggesting a genetic consequence of, or a potential mechanism maintaining, site-specific re-encounters. Long-term temporal genetic monitoring is paramount in determining future viability of cosmopolitan marine species, identifying genetic units for conservation management, and for understanding aggregation structure and dynamics

Meta-analysis of type 2 Diabetes in African Americans Consortium

Type 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry. In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis. Single nucleotide polymorphisms (SNPs) association analysis was conducted in each study under the additive model after adjustment for age, sex, study site, and principal components. Meta-analysis of approximately 2.6 million genotyped and imputed SNPs in all studies was conducted using an inverse variance-weighted fixed effect model. Replications were performed to follow up 21 loci in up to 6,061 cases and 5,483 controls in African Americans, and 8,130 cases and 38,987 controls of European ancestry. We identified three known loci (TCF7L2, HMGA2 and KCNQ1) and two novel loci (HLA-B and INS-IGF2) at genome-wide significance (4.15 × 10(-94)<P<5 × 10(-8), odds ratio (OR)  = 1.09 to 1.36). Fine-mapping revealed that 88 of 158 previously identified T2D or glucose homeostasis loci demonstrated nominal to highly significant association (2.2 × 10(-23) < locus-wide P<0.05). These novel and previously identified loci yielded a sibling relative risk of 1.19, explaining 17.5% of the phenotypic variance of T2D on the liability scale in African Americans. Overall, this study identified two novel susceptibility loci for T2D in African Americans. A substantial number of previously reported loci are transferable to African Americans after accounting for linkage disequilibrium, enabling fine mapping of causal variants in trans-ethnic meta-analysis studies.Peer reviewe

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Fifth personnel dosimetry intercomparison study

The fifth Personnel Dosimetry Intercomparison Study (PDIS) was conducted at the Oak Ridge National Laboratory's (ORNL) Dosimetry Applications Research (DOSAR) facility on March 20-22, 1979. This study is the latest PDIS in the continuing series started at the DOSAR facility in 1974. The PDIS is a three day study, typically in March, where personnel dosimeters are mailed to the DOSAR facility, exposed to a range of low-level neutron radiation doses (1 to 15 mSv or equivalently, 100 to 1500 mrem) and neutron-to-gamma ratios (1:1-10:1) using the Health Physics Research Reactor (HPRR) as the radiation source, and returned to the participants for evaluation. This report is a summary and analysis of the results reported by the various participants. The participants are able to intercompare their results with those of others who made dose measurements under identical experimental conditions

Collection and analysis of Health Physics Research Reactor operational and use data

The Health Physics Research Reactor (HPRR) is the primary research tool at the Dosimetry Applications Research (DOSAR) Facility. In addition to use by the DOSAR staff, the HPRR is used by a wide segment of the scientific community for a variety of experimental purposes. This report is a compilation and analysis of data concerning HPRR uses, users, and operations through the end of FY 1984. 17 refs., 12 tabs.