On contact loci of hyperplane arrangements

We give an explicit expression for the contact loci of hyperplane arrangements and show that their cohomology rings are combinatorial invariants. We also give an expression for the restricted contact loci in terms of Milnor fibers of associated hyperplane arrangements. We prove the degeneracy of a spectral sequence related to the restricted contact loci of a hyperplane arrangement and which conjecturally computes algebraically the Floer cohomology of iterates of the Milnor monodromy. We give formulas for the Betti numbers of contact loci and restricted contact loci in generic cases

QuantumATK: An integrated platform of electronic and atomic-scale modelling tools

QuantumATK is an integrated set of atomic-scale modelling tools developed since 2003 by professional software engineers in collaboration with academic researchers. While different aspects and individual modules of the platform have been previously presented, the purpose of this paper is to give a general overview of the platform. The QuantumATK simulation engines enable electronic-structure calculations using density functional theory or tight-binding model Hamiltonians, and also offers bonded or reactive empirical force fields in many different parametrizations. Density functional theory is implemented using either a plane-wave basis or expansion of electronic states in a linear combination of atomic orbitals. The platform includes a long list of advanced modules, including Green's-function methods for electron transport simulations and surface calculations, first-principles electron-phonon and electron-photon couplings, simulation of atomic-scale heat transport, ion dynamics, spintronics, optical properties of materials, static polarization, and more. Seamless integration of the different simulation engines into a common platform allows for easy combination of different simulation methods into complex workflows. Besides giving a general overview and presenting a number of implementation details not previously published, we also present four different application examples. These are calculations of the phonon-limited mobility of Cu, Ag and Au, electron transport in a gated 2D device, multi-model simulation of lithium ion drift through a battery cathode in an external electric field, and electronic-structure calculations of the composition-dependent band gap of SiGe alloys.Comment: Submitted to Journal of Physics: Condensed Matte

Identification of major dioxin-like compounds and androgen receptor antagonist in acid-treated tissue extracts of high trophic-level animals

We evaluated the applicability of combining in vitro bioassays with instrument analyses to identify potential endocrine disrupting pollutants in sulfuric acid-treated extracts of liver and/or blubber of high trophic-level animals. Dioxin-like and androgen receptor (AR) antagonistic activities were observed in Baikal seals, common cormorants, raccoon dogs, and finless porpoises by using a panel of rat and human cell-based chemical-activated luciferase gene expression (CALUX) reporter gene bioassays. On the other hand, no activity was detected in estrogen receptor α (ERα)-, glucocorticoid receptor (GR)-, progesterone receptor (PR)-, and peroxisome proliferator-activated receptor γ2 (PPARγ2)-CALUX assays with the sample amount applied. All individual samples (n = 66) showed dioxin-like activity, with values ranging from 21 to 5500 pg CALUX-2,3,7,8-tetrachlorodibenzo-p-dioxin equivalent (TEQ)/g-lipid. Because dioxins are expected to be strong contributors to CALUX-TEQs, the median theoretical contribution of dioxins calculated from the result of chemical analysis to the experimental CALUX-TEQs was estimated to explain up to 130% for all the tested samples (n = 54). Baikal seal extracts (n = 31), but not other extracts, induced AR antagonistic activities that were 8-150 μg CALUX-flutamide equivalent (FluEQ)/g-lipid. p,p′-DDE was identified as an important causative compound for the activity, and its median theoretical contribution to the experimental CALUX-FluEQs was 59% for the tested Baikal seal tissues (n = 25). Our results demonstrate that combining in vitro CALUX assays with instrument analysis is useful for identifying persistent organic pollutant-like compounds in the tissue of wild animals on the basis of in vitro endocrine disruption toxicity. © 2011 American Chemical Society

Processes Underlying Glycemic Deterioration in Type 2 Diabetes: An IMI DIRECT Study

Objective We investigated the processes underlying glycemic deterioration in type 2 diabetes (T2D). Research Design and Methods 732 recently diagnosed T2D patients from the IMI-DIRECT study were extensively phenotyped over three years, including measures of insulin sensitivity (OGIS), β-cell glucose sensitivity (GS) and insulin clearance (CLIm) from mixed meal tests, liver enzymes, lipid profiles, and baseline regional fat from MRI. The associations between the longitudinal metabolic patterns and HbA1c deterioration, adjusted for changes in BMI and in diabetes medications, were assessed via stepwise multivariable linear and logistic regression. Results Faster HbA1c progression was independently associated with faster deterioration of OGIS and GS, and increasing CLIm; visceral or liver fat, HDL-cholesterol and triglycerides had further independent, though weaker, roles (R2=0.38). A subgroup of patients with a markedly higher progression rate (fast progressors) was clearly distinguishable considering these variables only (discrimination capacity from AUROC=0.94). The proportion of fast progressors was reduced from 56% to 8-10% in subgroups in which only one trait among OGIS, GS and CLIm was relatively stable (odds ratios 0.07 to 0.09). T2D polygenic risk score and baseline pancreatic fat, GLP-1, glucagon, diet, and physical activity did not show an independent role. Conclusions Deteriorating insulin sensitivity and β-cell function, increasing insulin clearance, high visceral or liver fat, and worsening of the lipid profile are the crucial factors mediating glycemic deterioration of T2D patients in the initial phase of the disease. Stabilization of a single trait among insulin sensitivity, β-cell function, and insulin clearance may be relevant to prevent progression

Post-load glucose subgroups and associated metabolic traits in individuals with type 2 diabetes:An IMI-DIRECT study

AIM: Subclasses of different glycaemic disturbances could explain the variation in characteristics of individuals with type 2 diabetes (T2D). We aimed to examine the association between subgroups based on their glucose curves during a five-point mixed-meal tolerance test (MMT) and metabolic traits at baseline and glycaemic deterioration in individuals with T2D. METHODS: The study included 787 individuals with newly diagnosed T2D from the Diabetes Research on Patient Stratification (IMI-DIRECT) Study. Latent class trajectory analysis (LCTA) was used to identify distinct glucose curve subgroups during a five-point MMT. Using general linear models, these subgroups were associated with metabolic traits at baseline and after 18 months of follow up, adjusted for potential confounders. RESULTS: At baseline, we identified three glucose curve subgroups, labelled in order of increasing glucose peak levels as subgroup 1-3. Individuals in subgroup 2 and 3 were more likely to have higher levels of HbA1c, triglycerides and BMI at baseline, compared to those in subgroup 1. At 18 months (n = 651), the beta coefficients (95% CI) for change in HbA1c (mmol/mol) increased across subgroups with 0.37 (-0.18-1.92) for subgroup 2 and 1.88 (-0.08-3.85) for subgroup 3, relative to subgroup 1. The same trend was observed for change in levels of triglycerides and fasting glucose. CONCLUSIONS: Different glycaemic profiles with different metabolic traits and different degrees of subsequent glycaemic deterioration can be identified using data from a frequently sampled mixed-meal tolerance test in individuals with T2D. Subgroups with the highest peaks had greater metabolic risk

Profiles of glucose metabolism in different prediabetes phenotypes, classified by fasting glycemia, 2-hour OGTT, glycated hemoglobin, and 1-hour OGTT:An IMI DIRECT study

Differences in glucose metabolism among categories of prediabetes have not been systematically investigated. In this longitudinal study, participants (N = 2,111) underwent a 2-h 75-g oral glucose tolerance test (OGTT) at baseline and 48 months. HbA1c was also measured. We classified participants as having isolated prediabetes defect (impaired fasting glucose [IFG], impaired glucose tolerance [IGT], or HbA1c indicative of prediabetes [IA1c]), two defects (IFG+IGT, IFG+IA1c, or IGT+IA1c), or all defects (IFG+IGT+IA1c). β-Cell function (BCF) and insulin sensitivity were assessed from OGTT. At baseline, in pooling of participants with isolated defects, they showed impairment in both BCF and insulin sensitivity compared with healthy control subjects. Pooled groups with two or three defects showed progressive further deterioration. Among groups with isolated defect, those with IGT showed lower insulin sensitivity, insulin secretion at reference glucose (ISRr), and insulin secretion potentiation (P &lt; 0.002). Conversely, those with IA1c showed higher insulin sensitivity and ISRr (P &lt; 0.0001). Among groups with two defects, we similarly found differences in both BCF and insulin sensitivity. At 48 months, we found higher type 2 diabetes incidence for progressively increasing number of prediabetes defects (odds ratio &gt;2, P &lt; 0.008). In conclusion, the prediabetes groups showed differences in type/degree of glucometabolic impairment. Compared with the pooled group with isolated defects, those with double or triple defect showed progressive differences in diabetes incidence.</p

Eggs of the copepod Acartia tonsa Dana require hypoxic conditions to tolerate prolonged embryonic development arrest

Additional file 1. Raw data and calculations for all experiments as well as an overview of experiments in this study

The baseline characteristics and interim analyses of the high-risk sentinel cohort of the Vietnam Initiative on Zoonotic InfectiONS (VIZIONS)

The Vietnam Initiative for Zoonotic Infections (VIZIONS) includes community-based 'high-risk sentinel cohort' (HRSC) studies investigating individuals at risk of zoonotic infection due to occupational or residential exposure to animals. A total of 852 HRSC members were recruited between March 2013 and August 2014 from three provinces (Ha Noi, Dak Lak, and Dong Thap). The most numerous group (72.8%) corresponded to individuals living on farms, followed by slaughterers (16.3%) and animal health workers (8.5%). Nasal/pharyngeal and rectal swabs were collected from HRSC members at recruitment and after notifying illness. Exposure to exotic animals (including wild pigs, porcupine, monkey, civet, bamboo rat and bat) was highest for the Dak Lak cohort (53.7%), followed by Ha Noi (13.7%) and Dong Thap (4.0%). A total of 26.8% of individuals reported consumption of raw blood over the previous year; 33.6% slaughterers reported no use of protective equipment at work. Over 686 person-years of observation, 213 episodes of suspect infectious disease were notified, equivalent of 0.35 reports per person-year. Responsive samples were collected from animals in the farm cohort. There was noticeable time and space clustering of disease episodes suggesting that the VIZIONS set up is also suitable for the formal epidemiological investigation of disease outbreaks

Genetic analysis of blood molecular phenotypes reveals common properties in the regulatory networks affecting complex traits

We evaluate the shared genetic regulation of mRNA molecules, proteins and metabolites derived from whole blood from 3029 human donors. We find abundant allelic heterogeneity, where multiple variants regulate a particular molecular phenotype, and pleiotropy, where a single variant associates with multiple molecular phenotypes over multiple genomic regions. The highest proportion of share genetic regulation is detected between gene expression and proteins (66.6%), with a further median shared genetic associations across 49 different tissues of 78.3% and 62.4% between plasma proteins and gene expression. We represent the genetic and molecular associations in networks including 2828 known GWAS variants, showing that GWAS variants are more often connected to gene expression in trans than other molecular phenotypes in the network. Our work provides a roadmap to understanding molecular networks and deriving the underlying mechanism of action of GWAS variants using different molecular phenotypes in an accessible tissue