pinecone/core-2020-05-10-deduplication huggingface dataset:
Metformin increases APP expression and processing via oxidative stress,\ud
mitochondrial dysfunction and NF-κB activation: Use of insulin to attenuate\ud
metformin's effect.

Clinical and experimental biomedical studies have shown Type 2 diabetes mellitus (T2DM) to be a risk factor for the development of Alzheimer's disease (AD). This study demonstrates the effect of metformin, a therapeutic biguanide administered for T2DM therapy, on β-amyloid precursor protein (APP) metabolism in in vitro, ex vivo and in vivo models. Furthermore, the protective role of insulin against metformin is also demonstrated. In LAN5 neuroblastoma cells, metformin increases APP and presenilin levels, proteins involved in AD. Overexpression of APP and presenilin 1 (Pres 1) increases APP cleavage and intracellular accumulation of β-amyloid peptide (Aβ), which, in turn, promotes aggregation of Aβ. In the experimental conditions utilized the drug causes oxidative stress, mitochondrial damage, decrease of Hexokinase-II levels and cytochrome C release, all of which lead to cell death. Several changes in oxidative stress-related genes following metformin treatment were detected by PCR arrays specific for the oxidative stress pathway. These effects of metformin were found to be antagonized by the addition of insulin, which reduced Aβ levels, oxidative stress, mitochondrial dysfunction and cell death. Similarly, antioxidant molecules, such as ferulic acid and curcumin, are able to revert metformin's effect. Comparable results were obtained using peripheral blood mononuclear cells. Finally, the involvement of NF-κB transcription factor in regulating APP and Pres 1 expression was investigated. Upon metformin treatment, NF-κB is activated and translocates from the cytoplasm to the nucleus, where it induces increased APP and Pres 1 transcription. The use of Bay11-7085 inhibitor suppressed the effect of metformin on APP and Pres 1 expression
No Identical ‘‘Mesenchymal Stem Cells’’ at Different Times and Sites: Human Committed Progenitors of Distinct Origin and Differentiation Potential Are Incorporated as Adventitial Cells in Microvessels

A widely shared view reads that mesenchymal stem/stromal cells ("MSCs") are ubiquitous in human connective tissues, can be defined by a common in vitro phenotype, share a skeletogenic potential as assessed by in vitro differentiation assays, and coincide with ubiquitous pericytes. Using stringent in vivo differentiation assays and transcriptome analysis, we show that human cell populations from different anatomical sources, regarded as "MSCs" based on these criteria and assumptions, actually differ widely in their transcriptomic signature and in vivo differentiation potential. In contrast, they share the capacity to guide the assembly of functional microvessels in vivo, regardless of their anatomical source, or in situ identity as perivascular or circulating cells. This analysis reveals that muscle pericytes, which are not spontaneously osteochondrogenic as previously claimed, may indeed coincide with an ectopic perivascular subset of committed myogenic cells similar to satellite cells. Cord blood-derived stromal cells, on the other hand, display the unique capacity to form cartilage in vivo spontaneously, in addition to an assayable osteogenic capacity. These data suggest the need to revise current misconceptions on the origin and function of so-called "MSCs," with important applicative implications. The data also support the view that rather than a uniform class of "MSCs," different mesoderm derivatives include distinct classes of tissue-specific committed progenitors, possibly of different developmental origin
Solutions to large B and L breaking in the Randall–Sundrum model

AbstractThe stability of proton and neutrino masses are discussed in the Randall–Sundrum model. We show that relevant operators should be suppressed, if the hierarchical Yukawa matrices are explained only by configurations of wavefunctions for fermions and the Higgs field along the extra dimension. We assume a ZN discrete gauge symmetry to suppress those operators. In the Dirac neutrino case, there is an infinite number of symmetries which may forbid the dangerous operators. In the Majorana neutrino case, the discrete gauge symmetries should originate from U(1)X gauge symmetries which are broken on the Planck brane. We also comment on the n−n¯ oscillation as a phenomenon which can distinguish those discrete gauge symmetries
Lie-algebra expansions, Chern–Simons theories and the Einstein–Hilbert Lagrangian

AbstractStarting from gravity as a Chern–Simons action for the AdS algebra in five dimensions, it is possible to modify the theory through an expansion of the Lie algebra that leads to a system consisting of the Einstein–Hilbert action plus non-minimally coupled matter. The modified system is gauge invariant under the Poincaré group enlarged by an Abelian ideal. Although the resulting action naively looks like general relativity plus corrections due to matter sources, it is shown that the non-minimal couplings produce a radical departure from GR. Indeed, the dynamics is not continuously connected to the one obtained from Einstein–Hilbert action. In a matter-free configuration and in the torsionless sector, the field equations are too strong a restriction on the geometry as the metric must satisfy both the Einstein and pure Gauss–Bonnet equations. In particular, the five-dimensional Schwarzschild geometry fails to be a solution; however, configurations corresponding to a brane-world with positive cosmological constant on the worldsheet are admissible when one of the matter fields is switched on. These results can be extended to higher odd dimensions
Computing desirable partitions in additively separable hedonic games

AbstractAn important aspect in systems of multiple autonomous agents is the exploitation of synergies via coalition formation. Additively separable hedonic games are a fundamental class of coalition formation games in which each player has a value for any other player and the value of a coalition to a particular player is simply the sum of the values he assigns to the members of his coalition. In this paper, we consider a number of solution concepts from cooperative game theory, welfare theory, and social choice theory as criteria for desirable partitions in hedonic games. We then conduct a detailed computational analysis of computing, checking the existence of, and verifying stable, fair, optimal, and popular partitions for additively separable hedonic games
Irregular wave runup statistics on plane beaches: Application of a Boussinesq-type model incorporating a generating–absorbing sponge layer and second-order wave generation

AbstractEfficient absorption of reflected waves at the offshore boundary is a prerequisite for the accurate physical or theoretical modelling of long-duration irregular wave runup statistics at uniform, gently sloped beaches. This paper presents an implementation of the method suggested by Zhang et al. (2014) to achieve reflected wave absorption and simultaneous generation and propagation of incident waves in an existing numerical wave flume incorporating a moving boundary wavemaker. A generating–absorbing layer is incorporated within this 1DH hybrid Boussinesq-nonlinear shallow water equation model such that inshore-travelling incident waves, encompassing bound-wave structure approximately correct to second order, propagate unhindered while offshore-travelling reflected waves are absorbed. Once validated, the method is used to compile random wave runup statistics on uniform beach slopes broadly representative of dissipative, intermediate, and reflective beaches. Analyses of the individual runup time series, ensemble statistics and comparison to an empirical formula based on experimental runup data suggest that the main aspects of runup observed in the field are properly represented by the model. Existence of an upper limit on maximum runup is investigated using a simple extreme-value statistical analysis. Spectral saturation is examined by considering ensemble-averaged swash spectra for three representative beach slopes subject to incident waves with two different offshore significant wave heights. All spectra show f−4 roll-off at high frequencies in agreement with many previous field studies. The effect is also investigated of the swash motions preceding one particular extreme runup event on the eventual maximum runup elevation
Conformal SO(2, 4) transformations of the one-cusp Wilson loop surface

AbstractBy applying the conformal SO(2, 4) transformations to the elementary one-cusp Wilson loop surface we construct various two-cusp and four-cusp Wilson loop surface configurations in AdS5 and demonstrate that they solve the string equations of the Nambu–Goto string action. The conformal boosts of the basic four-cusp Wilson loop surface with a square-form projection generate various four-cusp Wilson loop surfaces with projections of the rescaled square, the rhombus and the trapezium, on which surfaces the classical Euclidean Nambu–Goto string actions in the IR dimensional regularization are evaluated
F-GUTs with Mordell–Weil U(1)'s

AbstractIn this note we study the constraints on F-theory GUTs with extra U(1)'s in the context of elliptic fibrations with rational sections. We consider the simplest case of one abelian factor (Mordell–Weil rank one) and investigate the conditions that are induced on the coefficients of its Tate form. Converting the equation representing the generic hypersurface P112 to this Tate's form we find that the presence of a U(1), already in this local description, is consistent with the exceptional E6 and E7 non-abelian singularities. We briefly comment on a viable E6×U(1) effective F-theory model
Lymphotoxin-Dependent B Cell-FRC Crosstalk Promotes De Novo Follicle Formation and Antibody Production following Intestinal Helminth Infection

SummarySecondary lymphoid tissues provide specialized niches for the initiation of adaptive immune responses and undergo a remarkable expansion in response to inflammatory stimuli. Although the formation of B cell follicles was previously thought to be restricted to the postnatal period, we observed that the draining mesenteric lymph nodes (mLN) of helminth-infected mice form an extensive number of new, centrally located, B cell follicles in response to IL-4Rα-dependent inflammation. IL-4Rα signaling promoted LTα1β2 (lymphotoxin) expression by B cells, which then interacted with CCL19 positive stromal cells to promote lymphoid enlargement and the formation of germinal center containing B cell follicles. Importantly, de novo follicle formation functioned to promote both total and parasite-specific antibody production. These data reveal a role for type 2 inflammation in promoting stromal cell remodeling and de novo follicle formation by promoting B cell-stromal cell crosstalk
Stochastic R matrix for Uq(An(1))

AbstractWe show that the quantum R matrix for symmetric tensor representations of Uq(An(1)) satisfies the sum rule required for its stochastic interpretation under a suitable gauge. Its matrix elements at a special point of the spectral parameter are found to factorize into the form that naturally extends Povolotsky's local transition rate in the q-Hahn process for n=1. Based on these results we formulate new discrete and continuous time integrable Markov processes on a one-dimensional chain in terms of n species of particles obeying asymmetric stochastic dynamics. Bethe ansatz eigenvalues of the Markov matrices are also given
Amalgamations of factorizations of complete equipartite graphs

AbstractLet t be a positive integer, and let L=(l1,…,lt) and K=(k1,…,kt) be collections of nonnegative integers. A graph has a (t,K,L) factorization if it can be represented as the edge-disjoint union of factors F1,…,Ft where, for 1⩽i⩽t, Fi is ki-regular and at least li-edge-connected. In this paper we consider (t,K,L)-factorizations of complete equipartite graphs. First we show precisely when they exist. Then we solve two embedding problems: we show when a factorization of a complete σ-partite graph can be embedded in a (t,K,L)-factorization of a complete s-partite graph, σ<s, and also when a factorization of Ka,b can be embedded in a (t,K,L)-factorization of Kn,n, a,b⩽n. Our proofs use the technique of amalgamations of graphs
Hard exclusive electroproduction of π+π− pairs

AbstractHard exclusive electroproduction of π+π− pairs off hydrogen and deuterium targets has been studied by the HERMES experiment at DESY. Legendre moments 〈P1〉 and 〈P3〉 of the angular distributions of π+ mesons in the center-of-mass frame of the pair have been measured for the first time. Their dependence on the π+π− invariant mass can be understood as being due to the interference between relative P-wave (isovector) and S-, D-wave (isoscalar) states of the two pions. The increase in magnitude of 〈P1〉 as Bjorken x increases is interpreted in the framework of generalized parton distributions as an enhancement of flavour non-singlet qq¯ exchange for larger values of x, which leads to a sizable admixture of isoscalar and isovector pion pairs. In addition, the interference between P-wave and D-wave states separately for transverse and longitudinal pion pairs has been studied. The data indicate that in the f2(1270) region at 〈Q2〉=3 GeV2 higher-twist effects can be as large as the leading-twist longitudinal component
Production of antimatter 5,6Li nuclei in central Au+Au collisions at sNN=200 GeV

AbstractCombining the covariant coalescence model and a blast-wave-like analytical parametrization for (anti-)nucleon phase–space freezeout configuration, we explore light (anti-)nucleus production in central Au+Au collisions at sNN=200 GeV. Using the nucleon freezeout configuration (denoted by FO1) determined from the measured spectra of protons (p), deutrons (d) and 3He, we find the predicted yield of 4He is significantly smaller than the experimental data. We show this disagreement can be removed by using a nucleon freezeout configuration (denoted by FO2) in which the nucleons are assumed to freeze out earlier than those in FO1 to effectively consider the effect of large binding energy value of 4He. Assuming the binding energy effect also exists for the production of 5Li, Li‾5, 6Li and Li‾6 due to their similar binding energy values as 4He, we find the yields of these heavier (anti-)nuclei can be enhanced by a factor of about one order, implying that although the stable (anti-)6Li nucleus is unlikely to be observed, the unstable (anti-)5Li nucleus could be produced in observable abundance in Au+Au collisions at sNN=200 GeV where it may be identified through the p–4He (p‾–He‾4) invariant mass spectrum. The future experimental measurement on (anti-)5Li would be very useful to understand the production mechanism of heavier antimatter
The pre- and post-somatic segments of the human type I spiral ganglion neurons – Structural and functional considerations related to cochlear implantation

AbstractHuman auditory nerve afferents consist of two separate systems; one is represented by the large type I cells innervating the inner hair cells and the other one by the small type II cells innervating the outer hair cells. Type I spiral ganglion neurons (SGNs) constitute 96% of the afferent nerve population and, in contrast to other mammals, their soma and pre- and post-somatic segments are unmyelinated. Type II nerve soma and fibers are unmyelinated. Histopathology and clinical experience imply that human SGNs can persist electrically excitable without dendrites, thus lacking connection to the organ of Corti. The biological background to this phenomenon remains elusive. We analyzed the pre- and post-somatic segments of the type I human SGNs using immunohistochemistry and transmission electron microscopy (TEM) in normal and pathological conditions. These segments were found surrounded by non-myelinated Schwann cells (NMSCs) showing strong intracellular expression of laminin-β2/collagen IV. These cells also bordered the perikaryal entry zone and disclosed surface rugosities outlined by a folded basement membrane (BM) expressing laminin-β2 and collagen IV. It is presumed that human large SGNs are demarcated by three cell categories: (a) myelinated Schwann cells, (b) NMSCs and (c) satellite glial cells (SGCs). Their BMs express laminin-β2/collagen IV and reaches the BM of the sensory epithelium at the habenula perforata. We speculate that the NMSCs protect SGNs from further degeneration following dendrite loss. It may give further explanation why SGNs can persist as electrically excitable monopolar cells even after long-time deafness, a blessing for the deaf treated with cochlear implantation
DNA-Protein Cooperative Binding through Variable-Range Elastic Coupling

AbstractCooperativity plays an important role in the action of proteins bound to DNA. A simple mechanism for cooperativity, in the form of a tension-mediated interaction between proteins bound to DNA at two different locations, is proposed. These proteins are not in direct physical contact. DNA segments intercalating bound proteins are modeled as a worm-like chain, which is free to deform in two dimensions. The tension-controlled protein-protein interaction is the consequence of two effects produced by the protein binding. The first is the introduction of a bend in the host DNA and the second is the modification of the bending modulus of the DNA in the immediate vicinity of the bound protein. The interaction between two bound proteins may be either attractive or repulsive, depending on their relative orientation on the DNA. Applied tension controls both the strength and the range of protein-protein interactions in this model. Properties of the cooperative interaction are discussed, along with experimental implications
Menopause as a predictor of new-onset asthma: A longitudinal Northern European population study

BackgroundThere is limited and conflicting evidence on the effect of menopause on asthma.ObjectivesWe sought to study whether the incidence of asthma and respiratory symptoms differ by menopausal status in a longitudinal population-based study with an average follow-up of 12 years.MethodsThe Respiratory Health in Northern Europe study provided questionnaire data pertaining to respiratory and reproductive health at baseline (1999-2001) and follow-up (2010-2012). The study cohort included women aged 45 to 65 years at follow-up, without asthma at baseline, and not using exogenous hormones (n = 2322). Menopausal status was defined as nonmenopausal, transitional, early postmenopausal, and late postmenopausal. Associations with asthma (defined by the use of asthma medication, having asthma attacks, or both) and respiratory symptoms scores were analyzed by using logistic (asthma) and negative binomial (respiratory symptoms) regressions, adjusting for age, body mass index, physical activity, smoking, education, and study center.ResultsThe odds of new-onset asthma were increased in women who were transitional (odds ratio, 2.40; 95% CI, 1.09-5.30), early postmenopausal (odds ratio, 2.11; 95% CI, 1.06-4.20), and late postmenopausal (odds ratio, 3.44; 95% CI, 1.31-9.05) at follow-up compared with nonmenopausal women. The risk of respiratory symptoms increased in early postmenopausal (coefficient, 0.40; 95% CI, 0.06-0.75) and late postmenopausal (coefficient, 0.69; 95% CI, 0.15-1.23) women. These findings were consistent irrespective of smoking status and across study centers.ConclusionsNew-onset asthma and respiratory symptoms increased in women becoming postmenopausal in a longitudinal population-based study. Clinicians should be aware that respiratory health might deteriorate in women during reproductive aging
TRIC-A Channels in Vascular Smooth Muscle Contribute to Blood Pressure Maintenance

SummaryTRIC channel subtypes, namely TRIC-A and TRIC-B, are intracellular monovalent cation channels postulated to mediate counter-ion movements facilitating physiological Ca2+ release from internal stores. Tric-a-knockout mice developed hypertension during the daytime due to enhanced myogenic tone in resistance arteries. There are two Ca2+ release mechanisms in vascular smooth muscle cells (VSMCs); incidental opening of ryanodine receptors (RyRs) generates local Ca2+ sparks to induce hyperpolarization, while agonist-induced activation of inositol trisphosphate receptors (IP3Rs) evokes global Ca2+ transients causing contraction. Tric-a gene ablation inhibited RyR-mediated hyperpolarization signaling to stimulate voltage-dependent Ca2+ influx, and adversely enhanced IP3R-mediated Ca2+ transients by overloading Ca2+ stores in VSMCs. Moreover, association analysis identified single-nucleotide polymorphisms (SNPs) around the human TRIC-A gene that increase hypertension risk and restrict the efficiency of antihypertensive drugs. Therefore, TRIC-A channels contribute to maintaining blood pressure, while TRIC-A SNPs could provide biomarkers for constitutional diagnosis and personalized medical treatment of essential hypertension
MOMP from Campylobacter jejuni Is a Trimer of 18-Stranded β-Barrel Monomers with a Ca2+ Ion Bound at the Constriction Zone

AbstractThe Gram-negative organism Campylobacter jejuni is the major cause of food poisoning. Unlike Escherichia coli, which has two major porins, OmpC and OmpF, C. jejuni has one, termed major outer membrane protein (MOMP) through which nutrients and antibiotics transit. We report the 2.1-Å crystal structure of C. jejuni MOMP expressed in E. coli and a lower resolution but otherwise identical structure purified directly from C. jejuni. The 2.1-Å resolution structure of recombinant MOMP showed that although the protein has timeric arrangement similar to OmpC, it is an 18-stranded, not 16-stranded, β-barrel. The structure has identified a Ca2+ bound at the constriction zone, which is functionally significant as suggested by molecular dynamics and single-channel experiments. The water-filled channel of MOMP has a narrow constriction zone, and single-molecule studies show a monomeric conductivity of 0.7±0.2 nS and a trimeric conductance of 2.2±0.2 nS. The ion neutralizes negative charges at the constriction zone, reducing the transverse electric field and reversing ion selectivity. Modeling of the transit of ciprofloxacin, an antibiotic of choice for treating Campylobacter infection, through the pore of MOMP reveals a trajectory that is dependent upon the presence metal ion
${\cal PT}$ deformation of angular Calogero models

The rational Calogero model based on an arbitrary rank-$n$ Coxeter root
system is spherically reduced to a superintegrable angular model of a particle
moving on $S^{n-1}$ subject to a very particular potential singular at the
reflection hyperplanes. It is outlined how to find conserved charges and to
construct intertwining operators. We deform these models in a ${\cal
PT}$-symmetric manner by judicious complex coordinate transformations, which
render the potential less singular. The ${\cal PT}$ deformation does not change
the energy eigenvalues but in some cases adds a previously unphysical tower of
states. For integral couplings the new and old energy levels coincide, which
roughly doubles the previous degeneracy and allows for a conserved nonlinear
supersymmetry charge. We present the details for the generic rank-two ($A_2$,
$G_2$) and all rank-three Coxeter systems ($AD_3$, $BC_3$ and $H_3$), including
a reducible case ($A_1^{\otimes 3}$).Comment: 1+41 pages, 12 figure
The InterLACE study: design, data harmonization and characteristics across 20 studies on women\u27s health

The International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events (InterLACE) project is a global research collaboration that aims to advance understanding of women\u27s reproductive health in relation to chronic disease risk by pooling individual participant data from several cohort and cross-sectional studies. The aim of this paper is to describe the characteristics of contributing studies and to present the distribution of demographic and reproductive factors and chronic disease outcomes in InterLACE