The Near-Earth Space Radiation Environment During Solar Cycle 25: Consequences for the Alabama Burst Energetics eXplorer

The Alabama Burst Energetics eXplorer (ABEX) is a 12U mission to enhance the detection of low energy Gamma Ray Burst (GRB) components and provide improved, rapid localization of short GRBs for multiwavelength follow up via GRB measurements outside the Van Allen Belts (VAB). The ABEX launch date is Q4 2024 during the peak of solar cycle 25; the ABEX science orbit is 300 km perigee by 60,000 km apogee with an inclination of 27°. This orbit defines distinct radiation environments in Low Earth Orbit, crossing the VABs, performing science operations outside the VABs, and Coronal Mass Ejection (CME) conditions. Numerical trajectory data was generated in AGI’s Systems Tool Kit and provided to the Space Environment Information System (SPENVIS). VAB trapped particle, Solar Energetic Particle, and Galactic Cosmic Ray particle fluxes were determined for the ABEX orbit. Empirical fits for Total Ionizing Dose are provided per particle source. Solar cell degradation as a function of Non-Ionizing Energy Loss was calculated per coverglass thickness with mass implications. Charged Particle Heating is characterized in a full thermal radiation model. Single Event Effects and surface charging are not discussed in the context of particle flux

Blanchfield and Seifert algebra in high-dimensional boundary link theory I: Algebraic K-theory

The classification of high-dimensional mu-component boundary links motivates decomposition theorems for the algebraic K-groups of the group ring A[F_mu] and the noncommutative Cohn localization Sigma^{-1}A[F_mu], for any mu>0 and an arbitrary ring A, with F_mu the free group on mu generators and Sigma the set of matrices over A[F_mu] which become invertible over A under the augmentation A[F_mu] to A. Blanchfield A[F_mu]-modules and Seifert A-modules are abstract algebraic analogues of the exteriors and Seifert surfaces of boundary links. Algebraic transversality for A[F_mu]-module chain complexes is used to establish a long exact sequence relating the algebraic K-groups of the Blanchfield and Seifert modules, and to obtain the decompositions of K_*(A[F_mu]) and K_*(Sigma^{-1}A[F_mu]) subject to a stable flatness condition on Sigma^{-1}A[F_mu] for the higher K-groups.Comment: This is the version published by Geometry & Topology on 2 November 200

Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use.

Tobacco and alcohol use are leading causes of mortality that influence risk for many complex diseases and disorders1. They are heritable2,3 and etiologically related4,5 behaviors that have been resistant to gene discovery efforts6-11. In sample sizes up to 1.2 million individuals, we discovered 566 genetic variants in 406 loci associated with multiple stages of tobacco use (initiation, cessation, and heaviness) as well as alcohol use, with 150 loci evidencing pleiotropic association. Smoking phenotypes were positively genetically correlated with many health conditions, whereas alcohol use was negatively correlated with these conditions, such that increased genetic risk for alcohol use is associated with lower disease risk. We report evidence for the involvement of many systems in tobacco and alcohol use, including genes involved in nicotinic, dopaminergic, and glutamatergic neurotransmission. The results provide a solid starting point to evaluate the effects of these loci in model organisms and more precise substance use measures

Deregulation of TDP-43 in amyotrophic lateral sclerosis triggers nuclear factor κB–mediated pathogenic pathways

TDP-43 interacts with and coactivates NF-κB p65 in the spinal cord of amyotrophic lateral sclerosis (ALS) patients, and an NF-κB inhibitor suppresses ALS disease symptoms and neuromuscular junction denervation in an ALS mouse model

Longitudinal Associations Between Perceived Parent-Adolescent Attachment Relationship Quality and Generalized Anxiety Disorder Symptoms in Adolescence

This longitudinal study examined the direction of effects between adolescents’ generalized anxiety disorder (GAD) symptoms and perceived parent-adolescent attachment relationship quality, as well as the moderating role of gender and age. 1,313 Dutch adolescents (48.5% boys) from two age cohorts of early (n = 923, Mage = 12 at W1) and middle (n = 390, Mage = 16 at W1) adolescents completed questionnaires regarding their attachment relationship to parents and GAD symptoms in four waves. Cross-lagged path analyses demonstrated that adolescents’ GAD symptoms and perceived father-adolescent attachment relationship quality bidirectionally negatively affected each other over time. For mothers, adolescents’ GAD symptoms negatively predicted perceived mother-adolescent attachment relationship quality over time. The within-wave correlated residuals between perceived attachment relationship quality with fathers and GAD symptoms were stronger for boys than for girls and stronger for the cohort of middle adolescents than for the cohort of early adolescents. This study demonstrates that both the parents’ and the adolescents’ gender as well as the adolescents’ age affects the relation between adolescents’ GAD symptoms and perceived parent-adolescent attachment relationship quality

Within-sibship genome-wide association analyses decrease bias in estimates of direct genetic effects

Estimates from genome-wide association studies (GWAS) of unrelated individuals capture effects of inherited variation (direct effects), demography (population stratification, assortative mating) and relatives (indirect genetic effects). Family-based GWAS designs can control for demographic and indirect genetic effects, but large-scale family datasets have been lacking. We combined data from 178,086 siblings from 19 cohorts to generate population (between-family) and within-sibship (within-family) GWAS estimates for 25 phenotypes. Within-sibship GWAS estimates were smaller than population estimates for height, educational attainment, age at first birth, number of children, cognitive ability, depressive symptoms and smoking. Some differences were observed in downstream SNP heritability, genetic correlations and Mendelian randomization analyses. For example, the within-sibship genetic correlation between educational attainment and body mass index attenuated towards zero. In contrast, analyses of most molecular phenotypes (for example, low-density lipoprotein-cholesterol) were generally consistent. We also found within-sibship evidence of polygenic adaptation on taller height. Here, we illustrate the importance of family-based GWAS data for phenotypes influenced by demographic and indirect genetic effects

Trans-ethnic Meta-analysis and Functional Annotation Illuminates the Genetic Architecture of Fasting Glucose and Insulin

Knowledge of the genetic basis of the type 2 diabetes (T2D)-related quantitative traits fasting glucose (FG) and insulin (FI) in African ancestry (AA) individuals has been limited. In non-diabetic subjects of AA (n = 20,209) and European ancestry (EA; n = 57,292), we performed trans-ethnic (AA+EA) fine-mapping of 54 established EA FG or FI loci with detailed functional annotation, assessed their relevance in AA individuals, and sought previously undescribed loci through trans-ethnic (AA+EA) meta-analysis. We narrowed credible sets of variants driving association signals for 22/54 EA-associated loci; 18/22 credible sets overlapped with active islet-specific enhancers or transcription factor (TF) binding sites, and 21/22 contained at least one TF motif. Of the 54 EA-associated loci, 23 were shared between EA and AA. Replication with an additional 10,096 AA individuals identified two previously undescribed FI loci, chrX FAM133A (rs213676) and chr5 PELO (rs6450057). Trans-ethnic analyses with regulatory annotation illuminate the genetic architecture of glycemic traits and suggest gene regulation as a target to advance precision medicine for T2D. Our approach to utilize state-of-the-art functional annotation and implement trans-ethnic association analysis for discovery and fine-mapping offers a framework for further follow-up and characterization of GWAS signals of complex trait loc