First Measurement of Coherent Elastic Neutrino-Nucleus Scattering on Argon

We report the first measurement of coherent elastic neutrino-nucleus scattering (\cevns) on argon using a liquid argon detector at the Oak Ridge National Laboratory Spallation Neutron Source. Two independent analyses prefer \cevns over the background-only null hypothesis with greater than $3\sigma$ significance. The measured cross section, averaged over the incident neutrino flux, is (2.2 $\pm$ 0.7) $\times$10$^{-39}$ cm$^2$ -- consistent with the standard model prediction. The neutron-number dependence of this result, together with that from our previous measurement on CsI, confirms the existence of the \cevns process and provides improved constraints on non-standard neutrino interactions.Comment: 8 pages, 5 figures with 2 pages, 6 figures supplementary material V3: fixes to figs 3,4 V4: fix typo in table 1, V5: replaced missing appendix, V6: fix Eq 1, new fig 3, V7 final version, updated with final revision

Mapping the genetic architecture of gene expression in human liver

Genetic variants that are associated with common human diseases do not lead directly to disease, but instead act on intermediate, molecular phenotypes that in turn induce changes in higher-order disease traits. Therefore, identifying the molecular phenotypes that vary in response to changes in DNA and that also associate with changes in disease traits has the potential to provide the functional information required to not only identify and validate the susceptibility genes that are directly affected by changes in DNA, but also to understand the molecular networks in which such genes operate and how changes in these networks lead to changes in disease traits. Toward that end, we profiled more than 39,000 transcripts and we genotyped 782,476 unique single nucleotide polymorphisms (SNPs) in more than 400 human liver samples to characterize the genetic architecture of gene expression in the human liver, a metabolically active tissue that is important in a number of common human diseases, including obesity, diabetes, and atherosclerosis. This genome-wide association study of gene expression resulted in the detection of more than 6,000 associations between SNP genotypes and liver gene expression traits, where many of the corresponding genes identified have already been implicated in a number of human diseases. The utility of these data for elucidating the causes of common human diseases is demonstrated by integrating them with genotypic and expression data from other human and mouse populations. This provides much-needed functional support for the candidate susceptibility genes being identified at a growing number of genetic loci that have been identified as key drivers of disease from genome-wide association studies of disease. By using an integrative genomics approach, we highlight how the gene RPS26 and not ERBB3 is supported by our data as the most likely susceptibility gene for a novel type 1 diabetes locus recently identified in a large-scale, genome-wide association study. We also identify SORT1 and CELSR2 as candidate susceptibility genes for a locus recently associated with coronary artery disease and plasma low-density lipoprotein cholesterol levels in the process. © 2008 Schadt et al

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

As above, so below: whole transcriptome profiling demonstrates strong molecular similarities between avian dorsal and ventral pallial subdivisions

Over the last two decades, beginning withthe Avian Brain Nomenclature Forum in2000, major revisions have been made to our understanding of the organization andnomenclature of the avian brain. However, there are still unresolved questions on avianpallial organization, particularly whether the cells above the vestigial ventricle representdistinct populations to those below it or similar populations. To test these two hypothe-ses, we profiled the transcriptomes of the major avian pallial subdivisions dorsal and ven-tral to the vestigial ventricle boundary using RNA sequencing and a new zebra finchgenome assembly containing about 22,000annotated, complete genes. We found thatthe transcriptomes of neural populations above and below the ventricle were remarkablysimilar. Each subdivision in dorsal pallium (Wulst) had a corresponding molecular counter-part in the ventral pallium (dorsal ventricularridge). In turn, each corresponding subdivi-sion exhibited shared gene co-expression modules that contained gene sets enriched infunctional specializations, such as anatomical structure development, synaptic transmis-sion, signaling, and neurogenesis. Thesefindings are more in line with the continuumhypothesis of avian brain subdivision organization above and below the vestigial ventriclespace, with the pallium as a whole consisting offour major cell populations (intercalatedpallium, mesopallium, hyper-nidopallium, andarcopallium) instead of seven (hyperpalliumapicale, interstitial hyperpallium apicale, intercalated hyperpallium, hyperpalliumdensocellare, mesopallium, nidopallium, and arcopallium). We suggest adopting a morestreamlined hierarchical naming system thatreflects the robust similarities in geneexpression, neural connectivity motifs, and function. These findings have important impli-cations for our understanding of overall vertebrate brain evolution

Planning, implementation, and scientific goals of the studies of emissions and atmospheric composition, clouds and climate coupling by regional surveys (SEAC\u3csup\u3e4\u3c/sup\u3eRS) field mission

The Studies of Emissions and Atmospheric Composition, Clouds and Climate Coupling by Regional Surveys (SEAC4RS) fieldmission based at Ellington Field, Texas, during August and September 2013 employed the most comprehensive airborne payload to date to investigate atmospheric composition over North America. The NASA ER-2, DC-8, and SPEC Inc. Learjet flew 57 science flights fromthe surface to 20 km. The ER-2 employed seven remote sensing instruments as a satellite surrogate and eight in situ instruments. The DC-8 employed 23 in situ and five remote sensing instruments for radiation, chemistry, and microphysics. The Learjet used 11 instruments to explore cloud microphysics. SEAC4RS launched numerous balloons, augmented AErosol RObotic NETwork, and collaborated with many existing ground measurement sites. Flights investigating convection included close coordination of all three aircraft. Coordinated DC-8 and ER-2 flights investigated the optical properties of aerosols, the influence of aerosols on clouds, and the performance of new instruments for satellite measurements of clouds and aerosols. ER-2 sorties sampled stratospheric injections of water vapor and other chemicals by local and distant convection. DC-8 flights studied seasonally evolving chemistry in the Southeastern U.S., atmospheric chemistry with lower emissions of NOx and SO2 than in previous decades, isoprene chemistry under high and low NOx conditions at different locations, organic aerosols, air pollution near Houston and in petroleum fields, smoke from wildfires in western forests and from agricultural fires in the Mississippi Valley, and the ways in which the chemistry in the boundary layer and the upper troposphere were influenced by vertical transport in convective clouds

Altered DNA Methylation in Leukocytes with Trisomy 21

The primary abnormality in Down syndrome (DS), trisomy 21, is well known; but how this chromosomal gain produces the complex DS phenotype, including immune system defects, is not well understood. We profiled DNA methylation in total peripheral blood leukocytes (PBL) and T-lymphocytes from adults with DS and normal controls and found gene-specific abnormalities of CpG methylation in DS, with many of the differentially methylated genes having known or predicted roles in lymphocyte development and function. Validation of the microarray data by bisulfite sequencing and methylation-sensitive Pyrosequencing (MS-Pyroseq) confirmed strong differences in methylation (p<0.0001) for each of 8 genes tested: TMEM131, TCF7, CD3Z/CD247, SH3BP2, EIF4E, PLD6, SUMO3, and CPT1B, in DS versus control PBL. In addition, we validated differential methylation of NOD2/CARD15 by bisulfite sequencing in DS versus control T-cells. The differentially methylated genes were found on various autosomes, with no enrichment on chromosome 21. Differences in methylation were generally stable in a given individual, remained significant after adjusting for age, and were not due to altered cell counts. Some but not all of the differentially methylated genes showed different mean mRNA expression in DS versus control PBL; and the altered expression of 5 of these genes, TMEM131, TCF7, CD3Z, NOD2, and NPDC1, was recapitulated by exposing normal lymphocytes to the demethylating drug 5-aza-2′deoxycytidine (5aza-dC) plus mitogens. We conclude that altered gene-specific DNA methylation is a recurrent and functionally relevant downstream response to trisomy 21 in human cells

Detecting supraglacial debris thickness with GPR under suboptimal conditions

The thickness of a supraglacial layer is critical to the magnitude and time frame of glacier melt. Field-based, short pulse, ground-penetrating radar (GPR) has successfully measured debris thickness during a glacier\u27s melt season, when there is a strong return from the ice-debris interface, but profiling with GPR in the absence of a highly reflective ice interface has not been explored. We investigated the performance of 960 MHz signals over 2 km of transects on Changri Nup Glacier, Nepal, during the post-monsoon. We also performed laboratory experiments to interpret the field data and investigate electromagnetic wave propagation into dry rocky debris. Laboratory tests confirmed wave penetration into the glacier ice and suggest that the ice-debris interface return was missing in field data because of a weak dielectric contrast between solid ice and porous dry debris. We developed a new method to estimate debris thicknesses by applying a statistical approach to volumetric backscatter, and our backscatter-based calculated thickness retrievals gave reasonable agreement with debris depths measured manually in the field (10-40 cm). We conclude that, when melt season profiling is not an option, a remote system near 1 GHz could allow dry debris thickness to be estimated based on volumetric backscatter

DNA methylation-based classification of central nervous system tumours.

Accurate pathological diagnosis is crucial for optimal management of patients with cancer. For the approximately 100 known tumour types of the central nervous system, standardization of the diagnostic process has been shown to be particularly challenging-with substantial inter-observer variability in the histopathological diagnosis of many tumour types. Here we present a comprehensive approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups, and demonstrate its application in a routine diagnostic setting. We show that the availability of this method may have a substantial impact on diagnostic precision compared to standard methods, resulting in a change of diagnosis in up to 12% of prospective cases. For broader accessibility, we have designed a free online classifier tool, the use of which does not require any additional onsite data processing. Our results provide a blueprint for the generation of machine-learning-based tumour classifiers across other cancer entities, with the potential to fundamentally transform tumour pathology

Side-Channel Expectation-Maximization Attacks

Block ciphers are protected against side-channel attacks by masking. On one hand, when the leakage model is unknown, second-order correlation attacks are typically used. On the other hand, when the leakage model can be profiled, template attacks are prescribed. But what if the profiled model does not exactly match that of the attacked device? One solution consists in regressing on-the-fly the scaling parameters from the model. In this paper, we leverage an Expectation-Maximization (EM) algorithm to implement such an attack. The resulting unprofiled EM attack, termed U-EM, is shown to be both efficient (in terms of number of traces) and effective (computationally speaking). Based on synthetic and real traces, we introduce variants of our U-EM attack to optimize its performance, depending on trade-offs between model complexity and epistemic noise. We show that the approach is flexible, in that it can easily be adapted to refinements such as different points of interest and number of parameters in the leakage model