The National Criticality Experiments Research Center and its role in support of advanced reactor design

The National Criticality Experiments Research Center (NCERC) located at the Nevada National Security Site (NNSS) in the Device Assembly Facility (DAF) and operated by Los Alamos National Laboratory (LANL) is the only general purpose critical experiments facility in the United States. Experiments from subcritical to critical and above prompt critical are carried out at NCERC on a regular basis. In recent years, NCERC has become more involved in experiments related to nuclear energy, including the Kilopower/KRUSTY demonstration and the recent Hypatia experiment. Multiple nuclear energy related projects are currently ongoing at NCERC. This paper discusses NCERC’s role in advanced reactor design and how that role may change in the future

Genetic diversity fuels gene discovery for tobacco and alcohol use

Tobacco and alcohol use are heritable behaviours associated with 15% and 5.3% of worldwide deaths, respectively, due largely to broad increased risk for disease and injury(1-4). These substances are used across the globe, yet genome-wide association studies have focused largely on individuals of European ancestries(5). Here we leveraged global genetic diversity across 3.4 million individuals from four major clines of global ancestry (approximately 21% non-European) to power the discovery and fine-mapping of genomic loci associated with tobacco and alcohol use, to inform function of these loci via ancestry-aware transcriptome-wide association studies, and to evaluate the genetic architecture and predictive power of polygenic risk within and across populations. We found that increases in sample size and genetic diversity improved locus identification and fine-mapping resolution, and that a large majority of the 3,823 associated variants (from 2,143 loci) showed consistent effect sizes across ancestry dimensions. However, polygenic risk scores developed in one ancestry performed poorly in others, highlighting the continued need to increase sample sizes of diverse ancestries to realize any potential benefit of polygenic prediction.Peer reviewe

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis

BioTIME 2.0 : expanding and improving a database of biodiversity time series

Funding: H2020 European Research Council (Grant Number(s): GA 101044975, GA 101098020).Motivation: Here, we make available a second version of the BioTIME database, which compiles records of abundance estimates for species in sample events of ecological assemblages through time. The updated version expands version 1.0 of the database by doubling the number of studies and includes substantial additional curation to the taxonomic accuracy of the records, as well as the metadata. Moreover, we now provide an R package (BioTIMEr) to facilitate use of the database. Main Types of Variables: Included The database is composed of one main data table containing the abundance records and 11 metadata tables. The data are organised in a hierarchy of scales where 11,989,233 records are nested in 1,603,067 sample events, from 553,253 sampling locations, which are nested in 708 studies. A study is defined as a sampling methodology applied to an assemblage for a minimum of 2 years. Spatial Location and Grain: Sampling locations in BioTIME are distributed across the planet, including marine, terrestrial and freshwater realms. Spatial grain size and extent vary across studies depending on sampling methodology. We recommend gridding of sampling locations into areas of consistent size. Time Period and Grain: The earliest time series in BioTIME start in 1874, and the most recent records are from 2023. Temporal grain and duration vary across studies. We recommend doing sample-level rarefaction to ensure consistent sampling effort through time before calculating any diversity metric. Major Taxa and Level of Measurement: The database includes any eukaryotic taxa, with a combined total of 56,400 taxa. Software Format: csv and. SQL.Peer reviewe

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

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

Histone H3.3 beyond cancer: Germline mutations in Histone 3 Family 3A and 3B cause a previously unidentified neurodegenerative disorder in 46 patients

Although somatic mutations in Histone 3.3 (H3.3) are well-studied drivers of oncogenesis, the role of germline mutations remains unreported. We analyze 46 patients bearing de novo germline mutations in histone 3 family 3A (H3F3A) or H3F3B with progressive neurologic dysfunction and congenital anomalies without malignancies. Molecular modeling of all 37 variants demonstrated clear disruptions in interactions with DNA, other histones, and histone chaperone proteins. Patient histone posttranslational modifications (PTMs) analysis revealed notably aberrant local PTM patterns distinct from the somatic lysine mutations that cause global PTM dysregulation. RNA sequencing on patient cells demonstrated up-regulated gene expression related to mitosis and cell division, and cellular assays confirmed an increased proliferative capacity. A zebrafish model showed craniofacial anomalies and a defect in Foxd3-derived glia. These data suggest that the mechanism of germline mutations are distinct from cancer-associated somatic histone mutations but may converge on control of cell proliferation

BioTIME 2.0 : expanding and improving a database of biodiversity time series

Motivation. Here, we make available a second version of the BioTIME database, which compiles records of abundance estimates for species in sample events of ecological assemblages through time. The updated version expands version 1.0 of the database by doubling the number of studies and includes substantial additional curation to the taxonomic accuracy of the records, as well as the metadata. Moreover, we now provide an R package (BioTIMEr) to facilitate use of the database. Main Types of Variables Included. The database is composed of one main data table containing the abundance records and 11 metadata tables. The data are organised in a hierarchy of scales where 11,989,233 records are nested in 1,603,067 sample events, from 553,253 sampling locations, which are nested in 708 studies. A study is defined as a sampling methodology applied to an assemblage for a minimum of 2 years. Spatial Location and Grain. Sampling locations in BioTIME are distributed across the planet, including marine, terrestrial and freshwater realms. Spatial grain size and extent vary across studies depending on sampling methodology. We recommend gridding of sampling locations into areas of consistent size. Time Period and Grain. The earliest time series in BioTIME start in 1874, and the most recent records are from 2023. Temporal grain and duration vary across studies. We recommend doing sample-level rarefaction to ensure consistent sampling effort through time before calculating any diversity metric. Major Taxa and Level of Measurement. The database includes any eukaryotic taxa, with a combined total of 56,400 taxa. Software Format. csv and. SQL

The Moral Roots of Partisan Division: How Moral Conviction Heightens Affective Polarization

Partisan bias and hostility have increased substantially over the last few decades in the American electorate, and previous work shows that partisan strength and sorting help drive this trend. Drawing on insights from moral psychology, however, we posit that partisan moral convictions heighten affective polarization beyond the effects of partisanship, increasing partisan animosity and copartisan favoritism. Testing this theory using data from two national samples and novel measures of affective polarization in everyday life, we find that people who tend to moralize politics display more partisan bias, distance and hostility, irrespective of partisan strength. These results shed light on a different moral divide that separates the American public and raise key normative questions about moral conviction and electoral politics.</jats:p