pinecone/core-2020-05-10-deduplication huggingface dataset:
The Neutrophil NLRC4 Inflammasome Selectively Promotes IL-1β Maturation without Pyroptosis during Acute Salmonella Challenge

SummaryThe macrophage NLRC4 inflammasome drives potent innate immune responses against Salmonella by eliciting caspase-1-dependent proinflammatory cytokine production (e.g., interleukin-1β [IL-1β]) and pyroptotic cell death. However, the potential contribution of other cell types to inflammasome-mediated host defense against Salmonella was unclear. Here, we demonstrate that neutrophils, typically viewed as cellular targets of IL-1β, themselves activate the NLRC4 inflammasome during acute Salmonella infection and are a major cell compartment for IL-1β production during acute peritoneal challenge in vivo. Importantly, unlike macrophages, neutrophils do not undergo pyroptosis upon NLRC4 inflammasome activation. The resistance of neutrophils to pyroptotic death is unique among inflammasome-signaling cells so far described and allows neutrophils to sustain IL-1β production at a site of infection without compromising the crucial inflammasome-independent antimicrobial effector functions that would be lost if neutrophils rapidly lysed upon caspase-1 activation. Inflammasome pathway modification in neutrophils thus maximizes host proinflammatory and antimicrobial responses during pathogen challenge
Quantifying three dimensional reconnection in fragmented current layers.

There is growing evidence that when magnetic reconnection occurs in high Lundquist number plasmas such as in the Solar Corona or the Earth's Magnetosphere it does so within a fragmented, rather than a smooth current layer. Within the extent of these fragmented current regions, the associated magnetic flux transfer and energy release occur simultaneously in many different places. This investigation focusses on how best to quantify the rate at which reconnection occurs in such layers. An analytical theory is developed which describes the manner in which new connections form within fragmented current layers in the absence of magnetic nulls. It is shown that the collective rate at which new connections form can be characterized by two measures; a total rate which measures the true rate at which new connections are formed and a net rate which measures the net change of connection associated with the largest value of the integral of E ||  \ud
E||\ud
 through all of the non-ideal regions. Two simple analytical models are presented which demonstrate how each should be applied and what they quantify
On the nucleus of the Grassmann embedding of the symplectic dual polar space DSp(2n,F), char(F)=2

AbstractLet n≥3 and let F be a field of characteristic 2. Let DSp(2n,F) denote the dual polar space associated with the building of type Cn over F and let Gn−2 denote the (n−2)-Grassmannian of type Cn. Using the bijective correspondence between the points of Gn−2 and the quads of DSp(2n,F), we construct a full projective embedding of Gn−2 into the nucleus of the Grassmann embedding of DSp(2n,F). This generalizes a result of an earlier paper [I. Cardinali, G. Lunardon, A geometric description of the spin-embedding of symplectic dual polar spaces of rank 3, J. Combin. Theory Ser. A (in press)] which contains an alternative proof of this fact in the case when n=3 and F is finite
Complex flavour couplings in supersymmetry and unexpected CP violation in the decay B→φK

AbstractComplex flavour couplings (off-diagonal mass terms) in the squark sector of supersymmetric theories may drastically alter both the rate and the CP-violating asymmetry of certain B-meson decays. We consider the effects of couplings that induce b→s transitions and lead to final state with strangeness one. We investigate the bounds that must be satisfied by the new terms and explore the possible implications on direct and mixing induced asymmetries in the charged and neutral B→J/ΨK and B→φK decays
Exploring viral infection using single-cell sequencing

AbstractSingle-cell sequencing (SCS) has emerged as a valuable tool to study cellular heterogeneity in diverse fields, including virology. By studying the viral and cellular genome and/or transcriptome, the dynamics of viral infection can be investigated at single cell level. Most studies have explored the impact of cell-to-cell variation on the viral life cycle from the point of view of the virus, by analyzing viral sequences, and from the point of view of the cell, mainly by analyzing the cellular host transcriptome. In this review, we will focus on recent studies that use single-cell sequencing to explore viral diversity and cell variability in response to viral replication
The golden strip of correlated top quark, gaugino, and vector-like mass in no-scale, no-parameter F-SU(5)

AbstractWe systematically establish the hyper-surface within the tanβ, top quark mass mt, universal gaugino mass M1/2, and vector-like mass MV parameter volume which is compatible with the application of the no-scale supergravity boundary conditions, particularly the vanishing of the Higgs bilinear soft term Bμ, near to the Planck mass at the point MF of ultimate F-lipped SU(5) unification. MF is elevated from the penultimate partial unification near the traditional GUT scale at a mass M32 by the inclusion of extra F-theory derived heavy vector-like multiplets. We demonstrate that simultaneous adherence to all current experimental constraints, most importantly contributions to the muon anomalous magnetic moment (g−2)μ, the branching ratio limit on (b→sγ), and the 7-year WMAP relic density measurement, dramatically reduces the allowed solutions to a highly non-trivial “golden strip” with tanβ≃15, mt=173.0–174.4 GeV, M1/2=455–481 GeV, and MV=691–1020 GeV, effectively eliminating all extraneously tunable model parameters. We emphasize that the consonance of the theoretically viable mt range with the experimentally established value is an independently correlated “postdiction”. The predicted range of MV is testable at the Large Hadron Collider (LHC). The partial lifetime for proton decay in the leading (e|μ)+π0 channels falls around 4.6×1034 Y, testable at the future DUSEL and Hyper-Kamiokande facilities
A robust Bayesian approach to modeling epistemic uncertainty in common-cause failure models

AbstractIn a standard Bayesian approach to the alpha-factor model for common-cause failure, a precise Dirichlet prior distribution models epistemic uncertainty in the alpha-factors. This Dirichlet prior is then updated with observed data to obtain a posterior distribution, which forms the basis for further inferences.In this paper, we adapt the imprecise Dirichlet model of Walley to represent epistemic uncertainty in the alpha-factors. In this approach, epistemic uncertainty is expressed more cautiously via lower and upper expectations for each alpha-factor, along with a learning parameter which determines how quickly the model learns from observed data. For this application, we focus on elicitation of the learning parameter, and find that values in the range of 1 to 10 seem reasonable. The approach is compared with Kelly and Atwood's minimally informative Dirichlet prior for the alpha-factor model, which incorporated precise mean values for the alpha-factors, but which was otherwise quite diffuse.Next, we explore the use of a set of Gamma priors to model epistemic uncertainty in the marginal failure rate, expressed via a lower and upper expectation for this rate, again along with a learning parameter. As zero counts are generally less of an issue here, we find that the choice of this learning parameter is less crucial.Finally, we demonstrate how both epistemic uncertainty models can be combined to arrive at lower and upper expectations for all common-cause failure rates. Thereby, we effectively provide a full sensitivity analysis of common-cause failure rates, properly reflecting epistemic uncertainty of the analyst on all levels of the common-cause failure model
An optical labeling-based proliferation assay system reveals the paracrine effect of interleukin-6 in breast cancer

AbstractProliferation analysis is one of the basic approaches to characterize various cell types. In conventional cell proliferation assays, the same sample cannot be observed over time, nor can a specific group within a heterogeneous population of cells, for example, cancerous cells, be analyzed separately. To overcome these limitations, we established an optical labeling-based proliferation assay system with the Kaede protein, whose fluorescence can be irreversibly photoconverted from green to red by irradiation. After a single non-toxic photoconversion event, the intensity of red fluorescence in each cell is reduced by cell division. From this, we developed a simple method to quantify cell proliferation by monitoring reduction of red fluorescence over time. This study shows that the optical labeling-based proliferation assay is a viable novel method to analyze cell proliferation, and could enhance our understanding of mechanisms regulating cell proliferation machinery. We used this newly established system to analyze the functions of secreted interleukin-6 (IL-6) in cancer cell proliferation, which had not been fully characterized. Reduction in proliferation was observed following IL-6 knockdown. However, after co-culturing with IL-6-expressing cells, the proliferation of Kaede-labeled IL-6-knockdown cells was restored. These data indicate that in basal-like breast cancer cells, IL-6 exhibits a paracrine effect to positively regulate cell proliferation. Our results thus demonstrate that cancer cells can secrete signaling molecules, such as IL-6, to support the proliferation of other cancer cells
Improving the DISPGB algorithm using the discriminant ideal

AbstractIn 1992, V. Weispfenning proved the existence of Comprehensive Gröbner Bases (CGB) and gave an algorithm for computing one. That algorithm was not very efficient and not canonical. Using his suggestions, A. Montes obtained in 2002 a more efficient algorithm (DISPGB) for Discussing Parametric Gröbner Bases. Inspired by its philosophy, V. Weispfenning defined, in 2002, how to obtain a Canonical Comprehensive Gröbner Basis (CCGB) for parametric polynomial ideals, and provided a constructive method.In this paper we use Weispfenning’s CCGB ideas to make substantial improvements on Montes’ DISPGB algorithm. It now includes rewriting of the discussion tree using the discriminant ideal and provides a compact and effective discussion. We also describe the new algorithms in the DPGB library containing the improved DISPGB as well as new routines for checking whether a given basis is a CGB or not, and for obtaining a CGB. Examples and tests are also provided
Safety evaluation of substituted thiophenes used as flavoring ingredients

AbstractThis publication is the second in a series by the Expert Panel of the Flavor and Extract Manufacturers Association summarizing the conclusions of its third systematic re-evaluation of the safety of flavorings previously considered to be generally recognized as safe (GRAS) under conditions of intended use. Re-evaluation of GRAS status for flavorings is based on updated considerations of exposure, structural analogy, metabolism, pharmacokinetics and toxicology and includes a comprehensive review of the scientific information on the flavorings and structurally related substances. Of the 12 substituted thiophenes reviewed here, 11 were reaffirmed as GRAS based on their rapid absorption, metabolism and excretion in humans and animals; the low estimated dietary exposure from flavor use; the wide margins of safety between the conservative estimates of intake and the no-observed-adverse effect levels; and the lack of significant genotoxic and mutagenic potential. For one of the substituted thiophenes, 3-acetyl-2,5-dimethylthiophene, it was concluded that more detailed exposure information, comparative metabolism studies and comprehensive toxicity data, including an in-depth evaluation of the mechanism of action for any adverse effects observed, are required for continuation of its FEMA GRAS™ status. In the absence of these data, the compound was removed from the FEMA GRAS list
RETRACTED: A Pleiotropically Acting MicroRNA, miR-31, Inhibits Breast Cancer Metastasis

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy).This article has been retracted at the request of the authors. Our study reported that miR-31 is a regulator of multiple mRNAs important for different aspects of breast cancer metastasis. We recently identified concerns with several figure panels in which original data were compiled from different replicate experiments in order to assemble the presented figure. The scope of the figure preparation issues includes compiling data from independent experiments to present them as one internally controlled experiment, statistical analyses based on technical replicates that are not reflective of the biological replicates, and comparisons of selectively chosen data points from multiple experiments. As many of the published figures are therefore not appropriate or accurate representations of the original data, we believe that the responsible course of action is to retract the paper. We apologize for any inconvenience we have caused
The Cerebral Cavernous Malformation Pathway Controls Cardiac Development via Regulation of Endocardial MEKK3 Signaling and KLF Expression

SummaryThe cerebral cavernous malformation (CCM) pathway is required in endothelial cells for normal cardiovascular development and to prevent postnatal vascular malformations, but its molecular effectors are not well defined. Here we show that loss of CCM signaling in endocardial cells results in mid-gestation heart failure associated with premature degradation of cardiac jelly. CCM deficiency dramatically alters endocardial and endothelial gene expression, including increased expression of the Klf2 and Klf4 transcription factors and the Adamts4 and Adamts5 proteases that degrade cardiac jelly. These changes in gene expression result from increased activity of MEKK3, a mitogen-activated protein kinase that binds CCM2 in endothelial cells. MEKK3 is both necessary and sufficient for expression of these genes, and partial loss of MEKK3 rescues cardiac defects in CCM-deficient embryos. These findings reveal a molecular mechanism by which CCM signaling controls endothelial gene expression during cardiovascular development that may also underlie CCM formation
The triple alpha reaction rate and the 2+ resonances in 12C

AbstractThe triple alpha rate is obtained from the three-body bound and continuum states computed in a large box. The results from this genuine full three-body calculation are compared with standard reference rates obtained by two sequential two-body processes. The fairly good agreement relies on two different assumptions about the lowest 2+ resonance energy. With the same 2+ energy the rates from the full three-body calculation are smaller than those of the standard reference. We discuss the rate dependence on the experimentally unknown 2+ energy. Substantial deviations from previous results appear for temperatures above 3 GK
Overdamping phenomena near the critical point in O(N) model

AbstractWe consider the dynamic critical behavior of the propagating mode for the order parameter fluctuation of the O(N) Ginzburg–Landau theory, involving the canonical momentum as a degree of freedom. We reexamine the renormalization group analysis of the Langevin equation for the propagating mode. We find the fixed point for the propagating mode as well as that for the diffusive one, the former of which is unstable to the latter. This indicates that the propagating mode becomes overdamped near the critical point. We thus can have a sufficient understanding of the phonon mode in the structural phase transition of solids. We also discuss the implication for the chiral phase transition
Spin–orbit force from lattice QCD

AbstractWe present a first attempt to determine nucleon–nucleon potentials in the parity-odd sector, which appear in the P11, P03, P13, P23–F23 channels, in Nf=2 lattice QCD simulations. These potentials are constructed from the Nambu–Bethe–Salpeter wave functions for JP=0−,1− and 2−, which correspond to the A1−, T1− and T2−⊕E− representation of the cubic group, respectively. We have found a large and attractive spin–orbit potential VLS(r) in the isospin-triplet channel, which is qualitatively consistent with the phenomenological determination from the experimental scattering phase shifts. The potentials obtained from lattice QCD are used to calculate the scattering phase shifts in the P11, P03, P13 and P23–F23 channels. The strong attractive spin–orbit force and a weak repulsive central force in spin-triplet P-wave channels lead to an attraction in the P23 channel, which is related to the P-wave neutron paring in neutron stars
Search for the standard model Higgs boson decaying to bottom quarks in pp collisions at s=7 TeV

AbstractA search for the standard model Higgs boson (H) decaying to bb¯ when produced in association with weak vector bosons (V) is reported for the following modes: W(μν)H, W(eν)H, Z(μμ)H, Z(ee)H and Z(νν)H. The search is performed in a data sample corresponding to an integrated luminosity of 4.7 fb−1, recorded by the CMS detector in proton–proton collisions at the LHC with a center-of-mass energy of 7 TeV. No significant excess of events above the expectation from background is observed. Upper limits on the VH production cross section times the H→bb¯ branching ratio, with respect to the expectations for a standard model Higgs boson, are derived for a Higgs boson in the mass range 110–135 GeV. In this range, the observed 95% confidence level upper limits vary from 3.4 to 7.5 times the standard model prediction; the corresponding expected limits vary from 2.7 to 6.7 times the standard model prediction
Bystander-Activated Memory CD8 T Cells Control Early Pathogen Load in an Innate-like, NKG2D-Dependent Manner

SummaryDuring an infection the antigen-nonspecific memory CD8 T cell compartment is not simply an inert pool of cells, but becomes activated and cytotoxic. It is unknown how these cells contribute to the clearance of an infection. We measured the strength of T cell receptor (TCR) signals that bystander-activated, cytotoxic CD8 T cells (BA-CTLs) receive in vivo and found evidence of limited TCR signaling. Given this marginal contribution of the TCR, we asked how BA-CTLs identify infected target cells. We show that target cells express NKG2D ligands following bacterial infection and demonstrate that BA-CTLs directly eliminate these target cells in an innate-like, NKG2D-dependent manner. Selective inhibition of BA-CTL-mediated killing led to a significant defect in pathogen clearance. Together, these data suggest an innate role for memory CD8 T cells in the early immune response before the onset of a de novo generated, antigen-specific CD8 T cell response
Low post-glacial rebound rates in the Weddell Sea due to Late Holocene ice-sheet readvance

AbstractMany ice-sheet reconstructions assume monotonic Holocene retreat for the West Antarctic Ice Sheet, but an increasing number of glaciological observations infer that some portions of the ice sheet may be readvancing, following retreat behind the present-day margin. A readvance in the Weddell Sea region can reconcile two outstanding problems: (i) the present-day widespread occurrence of seemingly stable ice streams grounded on beds that deepen inland; and (ii) the inability of models of glacial isostatic adjustment to match present-day uplift rates. By combining a suite of ice loading histories that include a readvance with a model of glacial isostatic adjustment we report substantial improvements to predictions of present-day uplift rates, including reconciling one problematic observation of land sinking. We suggest retreat behind present grounding lines occurred when the bed was lower, and isostatic recovery has since led to shallowing, ice sheet re-grounding and readvance. The paradoxical existence of grounding lines in apparently unstable configurations on reverse bed slopes may be resolved by invoking the process of unstable advance, in accordance with our load modelling
Revisiting the ‘disaster and development’ debate – Toward a broader understanding of macroeconomic risk and resilience

AbstractDebate regarding the relationship between socioeconomic development and natural disasters remains at the fore of global discussions, as the potential risk from climate extremes and uncertainty pose an increasing threat to developmental prospects. This study reviews statistical investigations of disaster and development linkages, across topics of macroeconomic growth, public governance and others to identify key challenges to the current approach to macro-level statistical investigation. Both theoretically and qualitatively, disaster is known to affect development through a number of channels: haphazard development, weak institutions, lack of social safety nets and short-termism of our decision-making practices are some of the factors that drive natural disaster risk. Developmental potentials, including the prospects for sustainable and equitable growth, are in turn threatened by such accumulation of disaster risks. However, quantitative evidence regarding these complex causality chains remains contested due to several reasons. A number of theoretical and methodological limitations have been identified, including the use of GDP as a proxy measurement of welfare, issues with natural disaster damage reporting and the adoption of ad hoc model specifications and variables, which render interpretation and cross-comparison of statistical analysis difficult. Additionally, while greater attention is paid to economic and institutional parameters such as GDP, remittance, corruption and public expenditure as opposed to hard-to-quantify yet critical factors such as environmental conditions and social vulnerabilities. These are gaps in our approach that hamper our comprehensive understanding of the disaster-development nexus. Important areas for further research are identified, including recognizing and addressing the data constraints, incorporating sustainability and equity concerns through alternatives to GDP, and finding novel approaches to examining the complex and dynamic relationships between risk, vulnerability, resilience, adaptive capacity and development
Battery System Development – Assembly Planning between Lightweight Design and High Volume Production

AbstractBattery systems of electric vehicles suffer from low energy densities as well as high masses and geometrical complexity. The absence of standards for battery cells and peripheral components in combination with large and distributed design spaces within passenger vehicles open up innumerable possibilities to design battery systems. The results are product specific and uneconomical assembly systems.This paper describes the work of the TU Braunschweig to create a methodology that generates and evaluates modular and easy to assemble battery systems based upon user requirements. This methodology gathers and links requirements between the priorities “lightweight design” and “high volume production” including a partly automated generation of CAD data. The generated concepts are directly used for assembly planning. The presented methodology therefore represents a simultaneous engineering approach that shortens development time and supports design engineers as well as process planners