pinecone/core-2020-05-10-deduplication huggingface dataset:
Mitochondrial Protein Lipoylation and the 2-Oxoglutarate Dehydrogenase Complex Controls HIF1$\alpha$ Stability in Aerobic Conditions

Hypoxia-inducible transcription factors (HIFs) control adaptation to low oxygen environments by activating genes involved in metabolism, angiogenesis, and redox homeostasis. The finding that HIFs are also regulated by small molecule metabolites highlights the need to understand the complexity of their cellular regulation. Here we use a forward genetic screen in near-haploid human cells to identify genes that stabilize HIFs under aerobic conditions. We identify two mitochondrial genes, oxoglutarate dehydrogenase (OGDH) and lipoic acid synthase (LIAS), which when mutated stabilize HIF1$\alpha$ in a non-hydroxylated form. Disruption of OGDH complex activity in OGDH or LIAS mutants promotes L-2-hydroxyglutarate formation, which inhibits the activity of the HIF$\alpha$ prolyl hydroxylases (PHDs) and TET 2-oxoglutarate dependent dioxygenases. We also find that PHD activity is decreased in patients with homozygous germline mutations in lipoic acid synthesis, leading to HIF1 activation. Thus, mutations affecting OGDHC activity may have broad implications for epigenetic regulation and tumorigenesis.This work was supported by a Wellcome Trust Senior Clinical Research Fellowship to J.A.N. (102770/Z/13/Z), Wellcome Trust Principal Research Fellowship to P.J.L. (084957/Z/08/Z), and the Medical Research Council (A.S.H.C. and C.F.). The Cambridge Institute for Medical Research is in receipt of a Wellcome Trust Strategic Award (100140).This is the final version of the article. It first appeared from Elsevier (Cell Press) via https://doi.org/10.1016/j.cmet.2016.09.01
Adequate Inner Bound for Geometric Modeling with Compact Field Functions

Recent advances in implicit surface modeling now provide highly controllable blending effects.  These effects rely on the field functions of  R3→R in which the implicit surfaces are defined.  In these fields, there is an outside part in which blending is defined and an inside part.  The implicit surface is the interface between these two parts.  As recent operators often focus on blending, most efforts have been made on the outer part of field functions and little attention has been paid on the inner part.  Yet, the inner fields are important as soon as difference and intersection operators are used.  This makes its quality as crucial as the quality of the outside.  In this paper, we analyze these shortcomings, and deduce new constraints on field functions such that differences and intersections can be seamlessly applied without introducing discontinuities or field distortions.  In particular, we show how to adapt state of the art gradient-based union and blending operators to our new constraints.  Our approach enables a precise control of the  shape of both the inner or outer field boundaries.  We also introduce a new set of asymmetric operators tailored for the modeling of fine details while preserving the integrity of the resulting fields
Investigation on Al2O3-Reinforced Zinc-Aluminum Matrix Composites.

Composite materials obtained by adding particles to the metallic matrix (MMCs) have made remarkable progress in its development and applications in automotive and aerospace industries in recent decades. Among them the most current application is MMCs with zinc and aluminum matrix. The present work is focused on the study of the effect of the directional heat extraction on the alumina distribution inside the zinc-aluminum matrix and on the columnar – to – equiaxed (CET) phenomenon in samples directionally solidified. The ZA-27 alloy was reinforced with ceramic-particulates of alumina (Al2O3) and then vertically directionally solidified. The following parameters were measured: cooling rates, temperature gradients, interphase velocities. And the influence of heat transfer on the solidification microstructure of the MMCs was analyzed. Experimental results include transient metal/mould heat transfer coefficients, secondary dendrite arm spacings and particle distribution as a function of solidification conditions imposed by the metal/mould system. The results about the conditions for the CET in MMCs are compared with those obtained in directional solidification of Zn-Al alloysFil: Zurko, Marco. Universidad Nacional de Misiones; ArgentinaFil: Schvezov, Carlos Enrique. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico Nordeste. Instituto de Materiales de Misiones; ArgentinaFil: Ares, Alicia Esther. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico Nordeste. Instituto de Materiales de Misiones; Argentin
Using DNA profiling to investigate human-mediated translocations of an invasive species

AbstractThe reconstruction of invasion history is the goal or foundation of many investigations of biological invasions. This study applies DNA profiling to investigate the sources and vectors of new propagules, to detect illegal human-mediated translocations and to improve the management of invasions by identifying invasion pathways that can be targeted for more stringent control. We use the European invasion of the American Eastern grey squirrel as a focal example. Many human-mediated translocations of this species have occurred in Europe since the 19th century. We built a genotype database of 1421 individuals from 59 locations across Europe and one in the USA, with each individual genotyped at 12 highly polymorphic microsatellites. DNA from newly detected populations and individuals of unknown sources were compared with this database. Our results indicated illegal human-mediated translocations in Aberdeen, the Isle of Skye and Northumberland in the UK, and revealed precise details of illegal squirrel trade in Italy. We recommend that multi-locus genotype databases be set up for all major invasive species considered attractive or ornamental, as these are often subject to illegal translocations through human actions such as the pet trade
The Drosophila hnRNPA/B Homolog, Hrp48, Is Specifically Required for a Distinct Step in osk mRNA Localization

AbstractThe Staufen-dependent localization of oskar mRNA to the posterior of the Drosophila oocyte induces the formation of the pole plasm, which contains the abdominal and germline determinants. In a germline clone screen for mutations that disrupt the posterior localization of GFP-Staufen, we isolated three missense alleles in the hnRNPA/B homolog, Hrp48. These mutants specifically abolish osk mRNA localization, without affecting its translational control or splicing, or the localization of bicoid and gurken mRNAs and the organization of the microtubule cytoskeleton. Hrp48 colocalizes with osk mRNA throughout oogenesis, and interacts with its 5′ and 3′ regulatory regions, suggesting that it binds directly to oskar mRNA to mediate its posterior transport. The hrp48 alleles cause a different oskar mRNA localization defect from other mutants, and disrupt the formation of GFP-Staufen particles. This suggests a new step in the localization pathway, which may correspond to the assembly of Staufen/oskar mRNA transport particles
The Impact of IFN-γ Receptor on SLPI Expression in Active Tuberculosis Association with Disease Severity

Interferon (IFN)-γ displays a critical role in tuberculosis (TB), modulating the innate and adaptive immune responses. Previously, we reported that secretory leukocyte protease inhibitor (SLPI) is a pattern recognition receptor with anti-mycobacterial activity against Mycobacterium tuberculosis (Mtb). Herein, we determined whether IFN-γ modulated the levels of SLPI in TB patients. Plasma levels of SLPI and IFN-γ were studied in healthy donors (HDs) and TB patients. Peripheral blood mononuclear cells from HDs and patients with TB or defective IFN-γ receptor 1* were stimulated with Mtb antigen and SLPI, and IFN-γR expression levels were measured. Both SLPI and IFN-γ were significantly enhanced in plasma from those with TB compared with HDs. A direct association between SLPI levels and the severity of TB was detected. In addition, Mtb antigen stimulation decreased the SLPI produced by peripheral blood mononuclear cells from HDs, but not from TB or IFN-γR patients. Neutralization of IFN-γ reversed the inhibition of SLPI induced by Mtb antigen in HDs, but not in TB patients. Furthermore, recombinant IFN-γ was unable to modify the expression of SLPI in TB patients. Finally, IFN-γR expression was lower in TB compared with HD peripheral blood mononuclear cells. These results show that Mtb-induced IFN-γ down-modulated SLPI levels by signaling through the IFN-γR in HDs. This inhibitory mechanism was not observed in TB, probably because of the low expression of IFN-γR detected in these individuals
Galactic center GeV gamma-ray excess, from dark matter with gauged lepton numbers

AbstractThe recently observed excess in gamma-ray signal near the Galactic center suggests that dark matter particles may annihilate into charged fermions that produce gamma-ray to be observed. In this paper, we consider a leptonic dark matter, which annihilates into the standard model leptons, μ+μ− and τ+τ−, by the interaction of the gauged lepton number U(1)Lμ−Lτ and fits the observed excess. Interestingly, the necessary annihilation cross section for the observed gamma-ray flux provides a good fit to the value for the relic abundance of dark matter. We identify the preferred parameter space of the model after taking the existing experimental constraints from the precision measurements including the muon (g−2), tau decay, neutrino trident production, dark matter direct detection, LHC, and LEP experiments
The Default Mode Network is functionally and structurally disrupted in amnestic mild cognitive impairment — A bimodal MEG–DTI study

AbstractOver the past years, several studies on Mild Cognitive Impairment (MCI) and Alzheimer's disease (AD) have reported Default Mode Network (DMN) deficits. This network is attracting increasing interest in the AD community, as it seems to play an important role in cognitive functioning and in beta amyloid deposition. Attention has been particularly drawn to how different DMN regions are connected using functional or structural connectivity. To this end, most studies have used functional Magnetic Resonance Imaging (fMRI), Positron Emission Tomography (PET) or Diffusion Tensor Imaging (DTI). In this study we evaluated (1) functional connectivity from resting state magnetoencephalography (MEG) and (2) structural connectivity from DTI in 26 MCI patients and 31 age-matched controls. Compared to controls, the DMN in the MCI group was functionally disrupted in the alpha band, while no differences were found for delta, theta, beta and gamma frequency bands. In addition, structural disconnection could be assessed through a decreased fractional anisotropy along tracts connecting different DMN regions. This suggests that the DMN functional and anatomical disconnection could represent a core feature of MCI
Normal serum levels of immune complexes in postpolio patients

AbstractObjectiveThe pathophysiology of the postpolio syndrome is not fully understood. Increased cytokine levels in cerebrospinal fluid and peripheral blood indicate a systemic inflammatory process. Decreased cytokine levels and the clinical effect of intravenous immunoglobulin treatment further indicate an inflammatory/immunological pathogenesis. The aim of the present study was to evaluate whether an autoimmune process follows the initial infection, by means of analyzing immune complexes.Patients and methodsCirculating immune complexes were analyzed from blood samples of 20 postpolio patients and 95 healthy controls. To compensate for differences in age between patients and controls, a sub-analysis was performed using only the 30 oldest controls. Tumor necrosis factor-inducing properties of polyethylene glycol-precipitated immune complexes were compared between the postpolio patients and 10 healthy controls.ResultsWhen comparing levels in postpolio patients to the whole control group, including the 30 oldest investigated, there were no statistically significant differences. No difference was found in tumor necrosis factor levels induced by immune complexes when comparing patients and controls.ConclusionsThere was no increase in circulating immune complex or in tumor necrosis factor-inducing effects of circulating immune complex between postpolio patients and healthy controls, indicating that the postpolio syndrome is not due to an autoimmune reaction
Multivariate and repeated measures (MRM): A new toolbox for dependent and multimodal group-level neuroimaging data

AbstractRepeated measurements and multimodal data are common in neuroimaging research. Despite this, conventional approaches to group level analysis ignore these repeated measurements in favour of multiple between-subject models using contrasts of interest. This approach has a number of drawbacks as certain designs and comparisons of interest are either not possible or complex to implement. Unfortunately, even when attempting to analyse group level data within a repeated-measures framework, the methods implemented in popular software packages make potentially unrealistic assumptions about the covariance structure across the brain. In this paper, we describe how this issue can be addressed in a simple and efficient manner using the multivariate form of the familiar general linear model (GLM), as implemented in a new MATLAB toolbox. This multivariate framework is discussed, paying particular attention to methods of inference by permutation. Comparisons with existing approaches and software packages for dependent group-level neuroimaging data are made. We also demonstrate how this method is easily adapted for dependency at the group level when multiple modalities of imaging are collected from the same individuals. Follow-up of these multimodal models using linear discriminant functions (LDA) is also discussed, with applications to future studies wishing to integrate multiple scanning techniques into investigating populations of interest
Land use implications of future energy system trajectories—The case of the UK 2050 Carbon Plan

AbstractThe UK's 2008 Climate Change Act sets a legally binding target for reducing territorial greenhouse gas emissions by 80% by 2050, relative to 1990 levels. Four pathways to achieve this target have been developed by the Department of Energy and Climate Change, with all pathways requiring increased us of bioenergy. A significant amount of this could be indigenously sourced from crops, but will increased domestic production of energy crops conflict with other agricultural priorities?To address this question, a coupled analysis of the UK energy system and land use has been developed. The two systems are connected by the production of bioenergy, and are projected forwards in time under the energy pathways, accounting for various constraints on land use for agriculture and ecosystem services.The results show different combinations of crop yield and compositions for the pathways lead to the appropriation of between 7% and 61% of UK's agricultural land for bioenergy production. This could result in competition for land for food production and other land uses, as well as indirect land use change in other countries due to an increase in bioenergy imports. Consequently, the potential role of bioenergy in achieving UK emissions reduction targets may face significant deployment challenges
Measurement of the charge asymmetry in highly boosted top-quark pair production in s=8 TeV pp collision data collected by the ATLAS experiment

AbstractIn the pp→tt¯ process the angular distributions of top and anti-top quarks are expected to present a subtle difference, which could be enhanced by processes not included in the Standard Model. This Letter presents a measurement of the charge asymmetry in events where the top-quark pair is produced with a large invariant mass. The analysis is performed on 20.3 fb−1 of pp collision data at s=8TeV collected by the ATLAS experiment at the LHC, using reconstruction techniques specifically designed for the decay topology of highly boosted top quarks. The charge asymmetry in a fiducial region with large invariant mass of the top-quark pair (mtt¯>0.75 TeV) and an absolute rapidity difference of the top and anti-top quark candidates within −2<|yt|−|yt¯|<2 is measured to be 4.2±3.2%, in agreement with the Standard Model prediction at next-to-leading order. A differential measurement in three tt¯ mass bins is also presented
Bit-parallel (δ,γ)-matching and suffix automata

Abstract(δ,γ)-matching is a string matching problem with applications to music retrieval. The goal is, given a pattern P1…m and a text T1…n on an alphabet of integers, find the occurrences P′ of the pattern in the text such that (i) ∀1⩽i⩽m,|Pi−Pi′|⩽δ, and (ii) ∑1⩽i⩽m|Pi−Pi′|⩽γ. The problem makes sense for δ⩽γ⩽δm. Several techniques for (δ,γ)-matching have been proposed, based on bit-parallelism or on skipping characters. We first present an O(mnlog(γ)/w) worst-case time and O(n) average-case time bit-parallel algorithm (being w the number of bits in the computer word). It improves the previous O(mnlog(δm)/w) worst-case time algorithm of the same type. Second, we combine our bit-parallel algorithm with suffix automata to obtain the first algorithm that skips characters using both δ and γ. This algorithm examines less characters than any previous approach, as the others do just δ-matching and check the γ-condition on the candidates. We implemented our algorithms and drew experimental results on real music, showing that our algorithms are superior to current alternatives with high values of δ
Low-cost and Fast Wet-based Technique to Generate Nanostructured Organic Materials Layers and its Application to Chemiresistive Gas-sensing Devices

AbstractNanostructured materials for sensors and transducers are of great interest to the scientific community due to several advantages that these materials can provide (e.g., integration with large scale manufacturing technologies, enhanced performances, etc.). Nonetheless, large-area, low-cost and fast processing technologies for creating effective sensing nanostructures are still sought for. In this work, a recently described technique called Auxiliary Solvent-Based Sublimation-Aided NanoStructuring (ASB-SANS) has been used to generate poly(3-hexylthiophene) (P3HT, a well known semiconducting polymer) nanofilamentary structures onto interdigitated electrodes. These have been tested as gas sensing layers for volatile organic compounds, delivering promising results
Hot medium effects on J/ψ production in p+Pb collisions at sNN=5.02 TeV

AbstractBased on a kinetic description of J/ψ dissociation and production in an expanding quark–gluon plasma that is described by a 2+1 dimensional ideal hydrodynamics, we have studied the hot medium effects on J/ψ production in p+Pb collisions at sNN=5.02 TeV. Including also the cold nuclear matter effects, we are able to reproduce recent experimental results on the nuclear modification factor RpPb(J/ψ) measured by the ALICE Collaboration. We have also made predictions for the RpPb of J/ψ and the double ratio RpPbpro(ψ′)/RpPbpro(J/ψ) of prompt quarkonia produced in the most central 10% p+Pb collisions. We find that different from the cold nuclear matter effects, the RpPb(J/ψ) is slightly smaller than that in the minimum bias collisions, and the double ratio is significantly less than one at backward rapidity
ZFPIP/Zfp462 is maternally required for proper early Xenopus laevis development

AbstractZFPIP (Zinc Finger Pbx1 Interacting Protein) has been recently identified in our laboratory in a yeast two hybrid screen using an embryonic mouse cDNA library and PBX1 as a bait. This gene encodes a large protein (250 kDa) that contains a bipartite NLS, numerous C2H2 zinc fingers and is highly conserved amongst vertebrates. In order to address the role of ZFPIP during embryonic development, we analysed the expression pattern of the gene and performed morpholinos injections into Xenopus laevis embryos. We first showed that the ZFPIP protein was maternally present in oocytes. Then, ZFPIP was detected from morula to neurula stages in the nucleus of the cells, with a gradient from animal to vegetal pole. By injection of ZFPIP morpholinos, we showed that morphant embryos were unable to undergo proper gastrulation and subsequently exhibited a persistent opened blastopore. Analysis of molecular and cellular events that were altered in morphant embryos highlighted an impairment of cell division processes as illustrated by atypical mitosis with aberrant metaphase, anaphase or telophase, incomplete chromosome segregation or conjointed nuclei. The overall data presented here demonstrated that ZFPIP was a major developing gene that acts in the very first steps of embryonic development of Xenopus laevis
New members of the tomato ERF family show specific expression pattern and diverse DNA-binding capacity to the GCC box element

AbstractFour new members of the ERF (ethylene-response factor) family of plant-specific DNA-binding (GCC box) factors were isolated from tomato fruit (LeERF1–4). Phylogenetic analysis indicated that LeERF2 belongs to a new ERF class, characterized by a conserved N-terminal signature sequence. Expression patterns and cis/trans binding affinities differed between the LeERFs. Combining experimental data and modeled three-dimensional analysis, it was shown that binding affinity of the LeERFs was affected by both the variation of nucleotides surrounding the DNA cis-element sequence and the nature of critical amino acid residues within the ERF domain
The shape of extremal functions for Poincaré–Sobolev-type inequalities in a ball

AbstractWe study extremal functions for a family of Poincaré–Sobolev-type inequalities. These functions minimize, for subcritical or critical p⩾2, the quotient ‖∇u‖2/‖u‖p among all u∈H1(B)∖{0} with ∫Bu=0. Here B is the unit ball in RN. We show that the minimizers are axially symmetric with respect to a line passing through the origin. We also show that they are strictly monotone in the direction of this line. In particular, they take their maximum and minimum precisely at two antipodal points on the boundary of B. We also prove that, for p close to 2, minimizers are antisymmetric with respect to the hyperplane through the origin perpendicular to the symmetry axis, and that, once the symmetry axis is fixed, they are unique (up to multiplication by a constant). In space dimension two, we prove that minimizers are not antisymmetric for large p
Algorithms for combinatorial structures: Well-founded systems and Newton iterations

AbstractWe consider systems of recursively defined combinatorial structures. We give algorithms checking that these systems are well founded, computing generating series and providing numerical values. Our framework is an articulation of the constructible classes of Flajolet and Sedgewick with Joyalʼs species theory. We extend the implicit species theorem to structures of size zero. A quadratic iterative Newton method is shown to solve well-founded systems combinatorially. From there, truncations of the corresponding generating series are obtained in quasi-optimal complexity. This iteration transfers to a numerical scheme that converges unconditionally to the values of the generating series inside their disk of convergence. These results provide important subroutines in random generation. Finally, the approach is extended to combinatorial differential systems