Hypothalamic Protein Kinase C Regulates Glucose Production

OBJECTIVE—A selective rise in hypothalamic lipid metabolism and the subsequent activation of SUR1/Kir6.2 ATP-sensitive K+ (KATP) channels inhibit hepatic glucose production. The mechanisms that link the ability of hypothalamic lipid metabolism to the activation of KATP channels remain unknown

Material screening and selection for XENON100

Results of the extensive radioactivity screening campaign to identify materials for the construction of XENON100 are reported. This Dark Matter search experiment is operated underground at Laboratori Nazionali del Gran Sasso (LNGS), Italy. Several ultra sensitive High Purity Germanium detectors (HPGe) have been used for gamma ray spectrometry. Mass spectrometry has been applied for a few low mass plastic samples. Detailed tables with the radioactive contaminations of all screened samples are presented, together with the implications for XENON100.Comment: 8 pages, 1 figur

Machine Learning in Automated Text Categorization

The automated categorization (or classification) of texts into predefined categories has witnessed a booming interest in the last ten years, due to the increased availability of documents in digital form and the ensuing need to organize them. In the research community the dominant approach to this problem is based on machine learning techniques: a general inductive process automatically builds a classifier by learning, from a set of preclassified documents, the characteristics of the categories. The advantages of this approach over the knowledge engineering approach (consisting in the manual definition of a classifier by domain experts) are a very good effectiveness, considerable savings in terms of expert manpower, and straightforward portability to different domains. This survey discusses the main approaches to text categorization that fall within the machine learning paradigm. We will discuss in detail issues pertaining to three different problems, namely document representation, classifier construction, and classifier evaluation.Comment: Accepted for publication on ACM Computing Survey

Epigenome-wide association in adipose tissue from the METSIM cohort

Most epigenome-wide association studies to date have been conducted in blood. However, metabolic syndrome is mediated by a dysregulation of adiposity and therefore it is critical to study adipose tissue in order to understand the effects of this syndrome on epigenomes. To determine if natural variation in DNA methylation was associated with metabolic syndrome traits, we profiled global methylation levels in subcutaneous abdominal adipose tissue. We measured association between 32 clinical traits related to diabetes and obesity in 201 people from the Metabolic Syndrome in Men cohort. We performed epigenome-wide association studies between DNA methylation levels and traits, and identified associations for 13 clinical traits in 21 loci. We prioritized candidate genes in these loci using expression quantitative trait loci, and identified 18 high confidence candidate genes, including known and novel genes associated with diabetes and obesity traits. Using methylation deconvolution, we examined which cell types may be mediating the associations, and concluded that most of the loci we identified were specific to adipocytes. We determined whether the abundance of cell types varies with metabolic traits, and found that macrophages increased in abundance with the severity of metabolic syndrome traits. Finally, we developed a DNA methylation-based biomarker to assess type 2 diabetes risk in adipose tissue. In conclusion, our results demonstrate that profiling DNA methylation in adipose tissue is a powerful tool for understanding the molecular effects of metabolic syndrome on adipose tissue, and can be used in conjunction with traditional genetic analyses to further characterize this disorder

Barium in twilight zone suspended matter as a potential proxy for particulate organic carbon remineralization : results for the North Pacific

Author Posting. © Elsevier B.V., 2008. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Deep Sea Research Part II: Topical Studies in Oceanography 55 (2008): 1673-1683, doi:10.1016/j.dsr2.2008.04.020.This study focuses on the fate of exported organic carbon in the twilight zone at two contrasting environments in the North Pacific: the oligotrophic ALOHA site (22°45' N 158°W; Hawaii; studied during June–July 2004) and the mesotrophic Subarctic Pacific K2 site (47°N, 161°W; studied during July-August 2005). Earlier work has shown that non-lithogenic, excess particulate Ba (Baxs) in the mesopelagic water column is a potential proxy of organic carbon remineralization. In general Baxs contents were significantly larger at K2 than at ALOHA. At ALOHA the Baxs profiles from repeated sampling (5 casts) showed remarkable consistency over a period of three weeks, suggesting that the system was close to being at steady state. In contrast, more variability was observed at K2 (6 casts sampled) reflecting the more dynamic physical and biological conditions prevailing in this environment. While for both sites Baxs concentrations increased with depth, at K2 a clear maximum was present between the base of the mixed layer at around 50m and 500m, reflecting production and release of Baxs. Larger mesopelagic Baxs contents and larger bacterial production in the twilight zone at the K2 site indicate that more material was exported from the upper mixed layer for bacterial degradation deeper, compared to the ALOHA site. Furthermore, application of a published transfer function (Dehairs et al., 1997) relating oxygen consumption to the observed Baxs data indicated that the latter were in good agreement with bacterial respiration, calculated from bacterial production. These results corroborate earlier findings highlighting the potential of Baxs as a proxy for organic carbon remineralization. The range of POC remineralization rates calculated from twilight zone excess particulate Ba contents did also compare well with the depth dependent POC flux decrease as recorded by neutrally buoyant sediment traps, except in 1 case (out of 4). This discrepancy could indicate that differences in sinking velocities cause an 3 uncoupling of the processes occurring in the fine suspended particle pool from those affecting the larger particle pool which sustains the vertical flux, thus rendering comparison between both approaches risky.This research was supported by Federal Science Policy Office, Brussels through contracts EV/03/7A, SD/CA/03A, the Research Foundation Flanders through grant G.0021.04 and Vrije Universiteit Brussel via grant GOA 22, as well as the US National Science Foundation programs in Chemical and Biological Oceanography

Application-Layer Connector Synthesis

International audienceThe heterogeneity characterizing the systems populating the Ubiquitous Computing environment prevents their seamless interoperability. Heterogeneous protocols may be willing to cooperate in order to reach some common goal even though they meet dynamically and do not have a priori knowledge of each other. Despite numerous e orts have been done in the literature, the automated and run-time interoperability is still an open challenge for such environment. We consider interoperability as the ability for two Networked Systems (NSs) to communicate and correctly coordinate to achieve their goal(s). In this chapter we report the main outcomes of our past and recent research on automatically achieving protocol interoperability via connector synthesis. We consider application-layer connectors by referring to two conceptually distinct notions of connector: coordinator and mediator. The former is used when the NSs to be connected are already able to communicate but they need to be speci cally coordinated in order to reach their goal(s). The latter goes a step forward representing a solution for both achieving correct coordination and enabling communication between highly heterogeneous NSs. In the past, most of the works in the literature described e orts to the automatic synthesis of coordinators while, in recent years the focus moved also to the automatic synthesis of mediators. Within the Connect project, by considering our past experience on automatic coordinator synthesis as a baseline, we propose a formal theory of mediators and a related method for automatically eliciting a way for the protocols to interoperate. The solution we propose is the automated synthesis of emerging mediating connectors (i.e., mediators for short)

Perspectives in visual imaging for marine biology and ecology: from acquisition to understanding

Durden J, Schoening T, Althaus F, et al. Perspectives in Visual Imaging for Marine Biology and Ecology: From Acquisition to Understanding. In: Hughes RN, Hughes DJ, Smith IP, Dale AC, eds. Oceanography and Marine Biology: An Annual Review. 54. Boca Raton: CRC Press; 2016: 1-72

A new strategy for enhancing imputation quality of rare variants from next-generation sequencing data via combining SNP and exome chip data

Background: Rare variants have gathered increasing attention as a possible alternative source of missing heritability. Since next generation sequencing technology is not yet cost-effective for large-scale genomic studies, a widely used alternative approach is imputation. However, the imputation approach may be limited by the low accuracy of the imputed rare variants. To improve imputation accuracy of rare variants, various approaches have been suggested, including increasing the sample size of the reference panel, using sequencing data from study-specific samples (i.e., specific populations), and using local reference panels by genotyping or sequencing a subset of study samples. While these approaches mainly utilize reference panels, imputation accuracy of rare variants can also be increased by using exome chips containing rare variants. The exome chip contains 250 K rare variants selected from the discovered variants of about 12,000 sequenced samples. If exome chip data are available for previously genotyped samples, the combined approach using a genotype panel of merged data, including exome chips and SNP chips, should increase the imputation accuracy of rare variants. Results: In this study, we describe a combined imputation which uses both exome chip and SNP chip data simultaneously as a genotype panel. The effectiveness and performance of the combined approach was demonstrated using a reference panel of 848 samples constructed using exome sequencing data from the T2D-GENES consortium and 5,349 sample genotype panels consisting of an exome chip and SNP chip. As a result, the combined approach increased imputation quality up to 11 %, and genomic coverage for rare variants up to 117.7 % (MAF < 1 %), compared to imputation using the SNP chip alone. Also, we investigated the systematic effect of reference panels on imputation quality using five reference panels and three genotype panels. The best performing approach was the combination of the study specific reference panel and the genotype panel of combined data. Conclusions: Our study demonstrates that combined datasets, including SNP chips and exome chips, enhances both the imputation quality and genomic coverage of rare variants

The genetic architecture of the human cerebral cortex

INTRODUCTION The cerebral cortex underlies our complex cognitive capabilities. Variations in human cortical surface area and thickness are associated with neurological, psychological, and behavioral traits and can be measured in vivo by magnetic resonance imaging (MRI). Studies in model organisms have identified genes that influence cortical structure, but little is known about common genetic variants that affect human cortical structure. RATIONALE To identify genetic variants associated with human cortical structure at both global and regional levels, we conducted a genome-wide association meta-analysis of brain MRI data from 51,665 individuals across 60 cohorts. We analyzed the surface area and average thickness of the whole cortex and 34 cortical regions with known functional specializations. RESULTS We identified 306 nominally genome-wide significant loci (P < 5 × 10−8) associated with cortical structure in a discovery sample of 33,992 participants of European ancestry. Of the 299 loci for which replication data were available, 241 loci influencing surface area and 14 influencing thickness remained significant after replication, with 199 loci passing multiple testing correction (P < 8.3 × 10−10; 187 influencing surface area and 12 influencing thickness). Common genetic variants explained 34% (SE = 3%) of the variation in total surface area and 26% (SE = 2%) in average thickness; surface area and thickness showed a negative genetic correlation (rG = −0.32, SE = 0.05, P = 6.5 × 10−12), which suggests that genetic influences have opposing effects on surface area and thickness. Bioinformatic analyses showed that total surface area is influenced by genetic variants that alter gene regulatory activity in neural progenitor cells during fetal development. By contrast, average thickness is influenced by active regulatory elements in adult brain samples, which may reflect processes that occur after mid-fetal development, such as myelination, branching, or pruning. When considered together, these results support the radial unit hypothesis that different developmental mechanisms promote surface area expansion and increases in thickness. To identify specific genetic influences on individual cortical regions, we controlled for global measures (total surface area or average thickness) in the regional analyses. After multiple testing correction, we identified 175 loci that influence regional surface area and 10 that influence regional thickness. Loci that affect regional surface area cluster near genes involved in the Wnt signaling pathway, which is known to influence areal identity. We observed significant positive genetic correlations and evidence of bidirectional causation of total surface area with both general cognitive functioning and educational attainment. We found additional positive genetic correlations between total surface area and Parkinson’s disease but did not find evidence of causation. Negative genetic correlations were evident between total surface area and insomnia, attention deficit hyperactivity disorder, depressive symptoms, major depressive disorder, and neuroticism. CONCLUSION This large-scale collaborative work enhances our understanding of the genetic architecture of the human cerebral cortex and its regional patterning. The highly polygenic architecture of the cortex suggests that distinct genes are involved in the development of specific cortical areas. Moreover, we find evidence that brain structure is a key phenotype along the causal pathway that leads from genetic variation to differences in general cognitive function

Search for Gravitational Waves Associated with Gamma-Ray Bursts Detected by Fermi and Swift during the LIGO-Virgo Run O3b

We search for gravitational-wave signals associated with gamma-ray bursts (GRBs) detected by the Fermi and Swift satellites during the second half of the third observing run of Advanced LIGO and Advanced Virgo (2019 November 1 15:00 UTC-2020 March 27 17:00 UTC). We conduct two independent searches: A generic gravitational-wave transients search to analyze 86 GRBs and an analysis to target binary mergers with at least one neutron star as short GRB progenitors for 17 events. We find no significant evidence for gravitational-wave signals associated with any of these GRBs. A weighted binomial test of the combined results finds no evidence for subthreshold gravitational-wave signals associated with this GRB ensemble either. We use several source types and signal morphologies during the searches, resulting in lower bounds on the estimated distance to each GRB. Finally, we constrain the population of low-luminosity short GRBs using results from the first to the third observing runs of Advanced LIGO and Advanced Virgo. The resulting population is in accordance with the local binary neutron star merger rate. © 2022. The Author(s). Published by the American Astronomical Society