pinecone/core-2020-05-10-deduplication huggingface dataset:
Genome-wide Regional Heritability Mapping Identifies a Locus Within the TOX2 Gene Associated With Major Depressive Disorder.

Major depressive disorder (MDD) is the second largest cause of global disease burden. It has an estimated heritability of 37%, but published genome-wide association studies have so far identified few risk loci. Haplotype-block-based regional heritability mapping (HRHM) estimates the localized genetic variance explained by common variants within haplotype blocks, integrating the effects of multiple variants, and may be more powerful for identifying MDD-associated genomic regions.
We applied HRHM to Generation Scotland: The Scottish Family Health Study, a large family- and population-based Scottish cohort (N = 19,896). Single-single nucleotide polymorphism (SNP) and haplotype-based association tests were used to localize the association signal within the regions identified by HRHM. Functional prediction was used to investigate the effect of MDD-associated SNPs within the regions.
A haplotype block across a 24-kb region within the TOX2 gene reached genome-wide significance in HRHM. Single-SNP- and haplotype-based association tests demonstrated that five of nine genotyped SNPs and two haplotypes within this block were significantly associated with MDD. The expression of TOX2 and a brain-specific long noncoding RNA RP1-269M15.3 in frontal cortex and nucleus accumbens basal ganglia, respectively, were significantly regulated by MDD-associated SNPs within this region. Both the regional heritability and single-SNP associations within this block were replicated in the UK-Ireland group of the most recent release of the Psychiatric Genomics Consortium (PGC), the PGC2-MDD (Major Depression Dataset). The SNP association was also replicated in a depressive symptom sample that shares some individuals with the PGC2-MDD.
This study highlights the value of HRHM for MDD and provides an important target within TOX2 for further functional studies
Measurement of the t̄t production cross section in the all-jet final state in pp collisions at √s=7 TeV

A measurement is presented of the t̄t production cross section σt̄t in proton-proton collisions at a centre-of-mass energy of 7 TeV, in the all-jet final state that contains at least six jets, two of which are tagged as originating from b quarks. The data correspond to an integrated luminosity of 3.54 fb-1, collected with the CMS detector at the LHC. The cross section is determined through an unbinned maximum likelihood fit of background and t̄t signal to the reconstructed mass spectrum of t̄t candidates in the data, in which events are subjected to a kinematic fit assuming a t̄t → W+bW-̄b → 6 jets hypothesis. The measurement yields σt̄t = 139±10(stat.)±26(syst.)±3(lum.)pb, a result consistent with those obtained in other t̄t decay channels, as well as with predictions of the standard model. © 2013 CERN for the benefit of the CMS collaboration.The Scientific and Technical Research Council of Turkey, and Turkish Atomic Energy Authorit
Inhibition of PTP1B disrupts cell–cell adhesion and induces anoikis in breast epithelial cells

Protein tyrosine phosphatase 1B (PTP1B) is a well-known inhibitor of insulin signaling pathways and inhibitors against PTP1B are being developed as promising drug candidates for treatment of obesity. PTP1B has also been linked to breast cancer both as a tumor suppressor and as an oncogene. Furthermore, PTP1B has been shown to be a regulator of cell adhesion and migration in normal and cancer cells. In this study, we analyzed the PTP1B expression in normal breast tissue, primary breast cells and the breast epithelial cell line D492. In normal breast tissue and primary breast cells, PTP1B is widely expressed in both epithelial and stromal cells, with highest expression in myoepithelial cells and fibroblasts. PTP1B is widely expressed in branching structures generated by D492 when cultured in 3D reconstituted basement membrane (3D rBM). Inhibition of PTP1B in D492 and another mammary epithelial cell line HMLE resulted in reduced cell proliferation and induction of anoikis. These changes were seen when cells were cultured both in monolayer and in 3D rBM. PTP1B inhibition affected cell attachment, expression of cell adhesion proteins and actin polymerization. Moreover, epithelial to mesenchymal transition (EMT) sensitized cells to PTP1B inhibition. A mesenchymal sublines of D492 and HMLE (D492M and HMLEmes) were more sensitive to PTP1B inhibition than D492 and HMLE. Reversion of D492M to an epithelial state using miR-200c-141 restored resistance to detachment induced by PTP1B inhibition. In conclusion, we have shown that PTP1B is widely expressed in the human breast gland with highest expression in myoepithelial cells and fibroblasts. Inhibition of PTP1B in D492 and HMLE affects cell–cell adhesion and induces anoikis-like effects. Finally, cells with an EMT phenotype are more sensitive to PTP1B inhibitors making PTP1B a potential candidate for further studies as a target for drug development in cancer involving the EMT phenotype.This work was supported by Grants from Landspitali University Hospital Science Fund, University of Iceland Research Fund, Icelandic Science and Technology Policy Council Research Fund no. 1103010061 and Icelandic Science and Technology Policy - Grant of Excellence: 152144051. ‘Göngum saman’, a supporting group for breast cancer research in Iceland (www.gongumsaman.is). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer Reviewe
The semiclassical-Sobolev orthogonal polynomials: a general approach

We say that the polynomial sequence (Q(λ)n) is a semiclassical Sobolev polynomial sequence when it is orthogonal with respect to the inner product
<p,r>S=<u,pr>+λ<u,DpDr>,
where u is a semiclassical linear functional, D is the differential, the difference or the q--difference operator, and λ is a positive constant. In this paper we get algebraic and differential/difference properties for such polynomials as well as algebraic relations between them and the polynomial sequence orthogonal with respect to the semiclassical functional u. The main goal of this article is to give a general approach to the study of the polynomials orthogonal with respect to the above nonstandard inner product regardless of the type of operator D considered. Finally, we illustrate our results by applying them to some known families of Sobolev orthogonal polynomials as well as to some new ones introduced in this paper for the first time
Probability of digits by dividing random numbers: a psi and zeta functions approach

This paper begins with the statistics of the decimal digits of n/d with n, d randomly chosen. Starting with a statement by E. Cesàro on probabilistic number theory  we evaluate, through the Euler psi  function, an integral appearing there. Furthermore the probabilistic statement itself is proved, using a different approach.The theorem is then generalized to real numbers (Theorem 1) and to the alpha-th power of the ratio of integers (Theorem 2), via an elementary approach involving  the psi function and the Hurwitz zeta function. The article provides historic remarks, numerical examples, and original theoretical contributions: also it complements the recent renewed interest in Benford's law among number theorists
Search for dark matter produced with an energetic jet or a hadronically decaying W or Z boson at $\sqrt{s}=13$ TeV

A search for dark matter particles is performed using events with large missing transverse momentum, at least one energetic jet, and no leptons, in proton-proton collisions at $\sqrt{s}=13$ TeV collected with the CMS detector at the LHC. The data sample corresponds to an integrated luminosity of 12.9 $fb^{−1}$. The search includes events with jets from the hadronic decays of a W or Z boson. The data are found to be in agreement with the predicted background contributions from standard model processes. The results are presented in terms of simplified models in which dark matter particles are produced through interactions involving a vector, axial-vector, scalar, or pseudoscalar mediator. Vector and axial-vector mediator particles with masses up to 1.95 TeV, and scalar and pseudoscalar mediator particles with masses up to 100 and 430 GeV respectively, are excluded at 95% confidence level. The results are also interpreted in terms of the invisible decays of the Higgs boson, yielding an observed (expected) 95% confidence level upper limit of 0.44 (0.56) on the corresponding branching fraction. The results of this search provide the strongest constraints on the dark matter pair production cross section through vector and axial-vector mediators at a particle collider. When compared to the direct detection experiments, the limits obtained from this search provide stronger constraints for dark matter masses less than 5, 9, and 550 GeV, assuming vector, scalar, and axial-vector mediators, respectively. The search yields stronger constraints for dark matter masses less than 200 GeV, assuming a pseudoscalar mediator, when compared to the indirect detection results from Fermi-LAT
Body size but not warning signal luminance influences predation risk in recently metamorphosed poison frogs.

This is the final version of the article. Available from Wiley via the DOI in this record.During early development, many aposematic species have bright and conspicuous warning appearance, but have yet to acquire chemical defenses, a phenotypic state which presumably makes them vulnerable to predation. Body size and signal luminance in particular are known to be sensitive to variation in early nutrition. However, the relative importance of these traits as determinants of predation risk in juveniles is not known. To address this question, we utilized computer-assisted design (CAD) and information on putative predator visual sensitivities to produce artificial models of postmetamorphic froglets that varied in terms of body size and signal luminance. We then deployed the artificial models in the field and measured rates of attack by birds and unknown predators. Our results indicate that body size was a significant predictor of artificial prey survival. Rates of attack by bird predators were significantly higher on smaller models. However, predation by birds did not differ between artificial models of varying signal luminance. This suggests that at the completion of metamorphosis, smaller froglets may be at a selective disadvantage, potentially because predators can discern they have relatively low levels of chemical defense compared to larger froglets. There is likely to be a premium on efficient foraging, giving rise to rapid growth and the acquisition of toxins from dietary sources in juvenile poison frogs.This study was supported by a PhD
scholarship (IFARHU-SENACYT program) and
a research grant No. APY-NI-010-006B/
SENACYT both awarded to EEF by the
Government of Panama, and by a Royal
Society University Research Fellowship to JDB.
MS was supported by a Biotechnology and
Biological Sciences Research Council David
Phillips Research Fellowship (BB/G022887/1).
HMR was supported by a Junior Research
Fellowship from Churchill College,
Cambridge. Special thanks to Rachel Page at
STRI for supporting EEF with the grant
application, Sistema Nacional de
Investigacion de Panama (SNI), and the
People of Santa Fe for their collaboration
during the stud
Inactivation of SACE_3446, a TetR family transcriptional regulator, stimulates erythromycin production in Saccharopolyspora erythraea.

Erythromycin A is a widely used antibiotic produced by Saccharopolyspora erythraea; however, its biosynthetic cluster lacks a regulatory gene, limiting the yield enhancement via regulation engineering of S. erythraea. Herein, six TetR family transcriptional regulators (TFRs) belonging to three genomic context types were individually inactivated in S. erythraea A226, and one of them, SACE_3446, was proved to play a negative role in regulating erythromycin biosynthesis. EMSA and qRT-PCR analysis revealed that SACE_3446 covering intact N-terminal DNA binding domain specifically bound to the promoter regions of erythromycin biosynthetic gene eryAI, the resistant gene ermE and the adjacent gene SACE_3447 (encoding a long-chain fatty-acid CoA ligase), and repressed their transcription. Furthermore, we explored the interaction relationships of SACE_3446 and previously identified TFRs (SACE_3986 and SACE_7301) associated with erythromycin production. Given demonstrated relatively independent regulation mode of SACE_3446 and SACE_3986 in erythromycin biosynthesis, we individually and concomitantly inactivated them in an industrial S. erythraea WB. Compared with WB, the WBΔ3446 and WBΔ3446Δ3986 mutants respectively displayed 36% and 65% yield enhancement of erythromycin A, following significantly elevated transcription of eryAI and ermE. When cultured in a 5 L fermentor, erythromycin A of WBΔ3446 and WBΔ3446Δ3986 successively reached 4095 mg/L and 4670 mg/L with 23% and 41% production improvement relative to WB. The strategy reported here will be useful to improve antibiotics production in other industrial actinomycete
Prednisolone with vs without pentoxifylline and survival of patients with severe alcoholic hepatitis: a randomized clinical trial.

IMPORTANCE: Prednisolone or pentoxifylline is recommended for severe alcoholic hepatitis, a life-threatening disease. The benefit of their combination is unknown.
OBJECTIVE: To determine whether the addition of pentoxifylline to prednisolone is more effective than prednisolone alone.
DESIGN, SETTING, AND PARTICIPANTS: Multicenter, randomized, double-blind clinical trial conducted between December 2007 and March 2010 in 1 Belgian and 23 French hospitals of 270 patients aged 18 to 70 years who were heavy drinkers with severe biopsy-proven alcoholic hepatitis, as indicated by recent onset of jaundice in the prior 3 months and a Maddrey score of at least 32. Duration of follow-up was 6 months. The last included patient completed the study in October 2010. None of the patients were lost to follow-up for the main outcome.
INTERVENTION: Patients were randomly assigned to receive either a combination of 40 mg of prednisolone once a day and 400 mg of pentoxifylline 3 times a day (n=133) for 28 days, or 40 mg of prednisolone and matching placebo (n=137) for 28 days.
MAIN OUTCOMES AND MEASURES: Six-month survival, with secondary end points of development of hepatorenal syndrome and response to therapy based on the Lille model, which defines treatment nonresponders after 7 days of initiation of treatment.
RESULTS: In intention-to-treat analysis, 6-month survival was not different in the pentoxifylline-prednisolone and placebo-prednisolone groups (69.9% [95% CI, 62.1%-77.7%] vs 69.2% [95% CI; 61.4%-76.9%], P = .91), corresponding to 40 vs 42 deaths, respectively. In multivariable analysis, only the Lille model and the Model for End-Stage Liver Disease score were independently associated with 6-month survival. At 7 days, response to therapy assessed by the Lille model was not significantly different between the 2 groups (Lille model score, 0.41 [95% CI, 0.36-0.46] vs 0.40 [95% CI, 0.35-0.45], P = .80). The probability of being a responder was not different in both groups (62.6% [95% CI, 53.9%-71.3%] vs 61.9% [95% CI, 53.7%-70.3%], P = .91). The cumulative incidence of hepatorenal syndrome at 6 months was not significantly different in the pentoxifylline-prednisolone and the placebo-prednisolone groups (8.4% [95% CI, 4.8%-14.8%] vs 15.3% [95% CI, 10.3%-22.7%], P = .07).
CONCLUSION AND RELEVANCE: In patients with alcoholic hepatitis, 4-week treatment with pentoxifylline and prednisolone, compared with prednisolone alone, did not result in improved 6-month survival. The study may have been underpowered to detect a significant difference in incidence of hepatorenal syndrome, which was less frequent in the group receiving pentoxifylline.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01214226
One-loop calculations on the wess-zumino-witten anomalous functional at finite-temperature

We analyze the finite temperature (T) extension of the Wess-Zumino-Witten functional, discussed in a previous work, to one loop in chiral perturbation theory. As a phenomenological application, we calculate finite temperature corrections to the amplitude of pi0 decay into two photons. This calculation is performed in three limits : i) T/M(pi) << 1, ii) the chiral limit at finite T and iii) T/M(pi) >> 1 (M(pi) being the pion mass). The T-corrections tend to vanish in the chiral limit, where only the kaon contribution remains (although it is exponentially suppressed)
Rate of escape and central limit theorem for the supercritical Lamperti
  problem

The study of discrete-time stochastic processes on the half-line with mean
drift at $x$ given by $\mu_1 (x) \to 0$ as $x \to \infty$ is known as
Lamperti's problem. We give sharp almost-sure bounds for processes of this type
in the case where $\mu_1 (x)$ is of order $x^{-\beta}$ for some $\beta \in
(0,1)$. The bounds are of order $t^{1/(1+\beta)}$, so the process is
super-diffusive but sub-ballistic (has zero speed). We make minimal assumptions
on the moments of the increments of the process (finiteness of
$(2+2\beta+\varepsilon)$-moments for our main results, so 4th moments certainly
suffice) and do not assume that the process is time-homogeneous or Markovian.
In the case where $x^\beta \mu_1 (x)$ has a finite positive limit, our results
imply a strong law of large numbers, which strengthens and generalizes earlier
results of Lamperti and Voit. We prove an accompanying central limit theorem,
which appears to be new even in the case of a nearest-neighbour random walk,
although our result is considerably more general. This answers a question of
Lamperti. We also prove transience of the process under weaker conditions than
those that we have previously seen in the literature. Most of our results also
cover the case where $\beta =0$. We illustrate our results with applications to
birth-and-death chains and to multi-dimensional non-homogeneous random walks.Comment: 24 pages; v2: minor revisio
Observation of Long-Range Near-Side Angular Correlations in
  Proton-Proton Collisions at the LHC

Results on two-particle angular correlations for charged particles emitted in
proton-proton collisions at center-of-mass energies of 0.9, 2.36, and 7 TeV are
presented, using data collected with the CMS detector over a broad range of
pseudorapidity (eta) and azimuthal angle (phi). Short-range correlations in
Delta(eta), which are studied in minimum bias events, are characterized using a
simple "independent cluster" parametrization in order to quantify their
strength (cluster size) and their extent in eta (cluster decay width).
Long-range azimuthal correlations are studied differentially as a function of
charged particle multiplicity and particle transverse momentum using a 980
inverse nb data set at 7 TeV. In high multiplicity events, a pronounced
structure emerges in the two-dimensional correlation function for particle
pairs with intermediate transverse momentum of 1-3 GeV/c, 2.0< |Delta(eta)|
<4.8 and Delta(phi) near 0. This is the first observation of such a long-range,
near-side feature in two-particle correlation functions in pp or p p-bar
collisions
Effective partitioning method for computing weighted Moore-Penrose
  inverse

We introduce a method and an algorithm for computing the weighted
Moore-Penrose inverse of multiple-variable polynomial matrix and the related
algorithm which is appropriated for sparse polynomial matrices. These methods
and algorithms are generalizations of algorithms developed in [M.B. Tasic, P.S.
Stanimirovic, M.D. Petkovic, Symbolic computation of weighted Moore-Penrose
inverse using partitioning method, Appl. Math. Comput. 189 (2007) 615-640] to
multiple-variable rational and polynomial matrices and improvements of these
algorithms on sparse matrices. Also, these methods are generalizations of the
partitioning method for computing the Moore-Penrose inverse of rational and
polynomial matrices introduced in [P.S. Stanimirovic, M.B. Tasic, Partitioning
method for rational and polynomial matrices, Appl. Math. Comput. 155 (2004)
137-163; M.D. Petkovic, P.S. Stanimirovic, Symbolic computation of the
Moore-Penrose inverse using partitioning method, Internat. J. Comput. Math. 82
(2005) 355-367] to the case of weighted Moore-Penrose inverse. Algorithms are
implemented in the symbolic computational package MATHEMATICA
Comments on Yang-Mills thermodynamics, the Hagedorn spectrum and the
  gluon gas

We discuss the dependence of pure Yang-Mills equation of state on the choice
of gauge algebra. In the confined phase, we generalize to an arbitrary simple
gauge algebra Meyer's proposal of modelling the Yang-Mills matter by an ideal
glueball gas in which the high-lying glueball spectrum is approximated by a
Hagedorn spectrum of closed-bosonic-string type. Such a formalism is undefined
above the Hagedorn temperature, corresponding to the phase transition toward a
deconfined state of matter in which gluons are the relevant degrees of freedom.
Under the assumption that the adjoint string tension and the typical energy
scale of the running coupling are gauge-algebra independent, we discuss about
how the behavior of thermodynamical quantities such as the trace anomaly should
depend on the gauge algebra in both the confined and deconfined phase. The
obtained results compare favourably with recent and accurate lattice data in
the $\mathfrak{su}(3)$ case and support the idea that the more the gauge
algebra has generators, the more the phase transition is of first-order type.Comment: Discussion extended in v2 ; to appear in Phys Lett
WW Production Cross Section and W Branching Fractions in e+e- Collisions
  at 189 GeV

From a data sample of 183 pb^-1 recorded at a center-of-mass energy of roots
= 189 GeV with the OPAL detector at LEP, 3068 W-pair candidate events are
selected. Assuming Standard Model W boson decay branching fractions, the W-pair
production cross section is measured to be sigmaWW = 16.30 +- 0.34(stat.) +-
0.18(syst.) pb. When combined with previous OPAL measurements, the W boson
branching fraction to hadrons is determined to be 68.32 +- 0.61(stat.) +-
0.28(syst.) % assuming lepton universality. These results are consistent with
Standard Model expectations.Comment: 22 pages, 5 figures, submitted to Phys. Lett.
Measurement of the single-top-quark t-channel cross section in pp
  collisions at sqrt(s) = 7 TeV

A measurement of the single-top-quark t-channel production cross section in
pp collisions at sqrt(s) = 7 TeV with the CMS detector at the LHC is presented.
Two different and complementary approaches have been followed. The first
approach exploits the distributions of the pseudorapidity of the recoil jet and
reconstructed top-quark mass using background estimates determined from control
samples in data. The second approach is based on multivariate analysis
techniques that probe the compatibility of the candidate events with the
signal. Data have been collected for the muon and electron final states,
corresponding to integrated luminosities of 1.17 and 1.56 inverse femtobarns,
respectively. The single-top-quark production cross section in the t-channel is
measured to be 67.2 +/- 6.1 pb, in agreement with the approximate
next-to-next-to-leading-order standard model prediction. Using the standard
model electroweak couplings, the CKM matrix element abs(V[tb]]) is measured to
be 1.020 +/- 0.046 (meas.) +/- 0.017 (theor.).Comment: Replaced with published version. Added journal reference and DO