pinecone/core-2020-05-10-deduplication huggingface dataset:
Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson’s disease

We conducted a meta analysis of Parkinson’s disease genome-wide association studies using a common set of 7,893,274 variants across 13,708 cases and 95,282 controls. Twenty-six loci were identified as genome-wide significantthese and six additional previously reported loci were then tested in an independent set of 5,353 cases and 5,551 controls. Of the 32 tested SNPs, 24 replicated, including 6 novel loci. Conditional analyses within loci show four loci including GBA, GAK/DGKQ, SNCA, and HLA contain a secondary independent risk variant. In total we identified and replicated 28 independent risk variants for Parkinson disease across 24 loci. While the effect of each individual locus is small, a risk profile analysis revealed a substantial cummulative risk in a comparison highest versus lowest quintiles of genetic risk (OR=3.31, 95% CI: 2.55, 4.30p-value = 2×10−16). We also show 6 risk loci associated with proximal gene expression or DNA methylation
Cryptic quantitative evolution of the vulva intercellular signaling network in caenorhabditis.

International audienceBACKGROUND: The Caenorhabditis vulva is formed from a row of Pn.p precursor cells, which adopt a spatial cell-fate pattern-3 degrees 3 degrees 2 degrees 1 degrees 2 degrees 3 degrees -centered on the gonadal anchor cell. This pattern is robustly specified by an intercellular signaling network including EGF/Ras induction from the anchor cell and Delta/Notch signaling between the precursor cells. It is unknown how the roles and quantitative contributions of these signaling pathways have evolved in closely related Caenorhabditis species. RESULTS: Cryptic evolution in the network is uncovered by quantification of cell-fate-pattern frequencies obtained after displacement of the system out of its normal range, either by anchor-cell ablations or through LIN-3/EGF overexpression. Silent evolution in the Caenorhabditis genus covers a large neutral space of cell-fate patterns. Direct induction of the 1 degrees fate as in C. elegans appeared within the genus. C. briggsae displays a graded induction of 1 degrees and 2 degrees fates, with 1 degrees fate induction requiring a longer time than in C. elegans, and a reduced lateral inhibition of adjacent 1 degrees fates. C. remanei displays a strong lateral induction of 2 degrees fates relative to vulval-fate activation in the central cell. This evolution in cell-fate pattern space can be experimentally reconstituted by mild variations of Ras, Wnt, and Notch pathway activities in C. elegans and C. briggsae. CONCLUSIONS: Quantitative evolution in the roles of graded induction by LIN-3/EGF and Notch signaling is demonstrated for the Caenorhabditis vulva signaling network. This evolutionary system biology approach provides a quantitative view of the variational properties of this biological system
Measurement of the forward-backward asymmetry of electron and muon pair-production in pp collisions at root s = 7 TeV with the ATLAS detector

Çetin, Serkant Ali (Dogus Author)This paper presents measurements from the ATLAS experiment of the forward-backward asymmetry in the reaction pp → Z/γ* → l+l−, with l being electrons or muons, and the extraction of the effective weak mixing angle. The results are based on the full set of data collected in 2011 in pp collisions at the LHC at (Formula presented.), corresponding to an integrated luminosity of 4.8 fb−1. The measured asymmetry values are found to be in agreement with the corresponding Standard Model predictions. The combination of the muon and electron channels yields a value of the effective weak mixing angle of sin2θefflept = 0.2308 ± 0.0005(stat.) ± 0.0006(syst.) ± 0.0009(PDF), where the first uncertainty corresponds to data statistics, the second to systematic effects and the third to knowledge of the parton density functions. This result agrees with the current world average from the Particle Data Group fit
Adipose-derived stem cells from the brown bear (Ursus arctos) spontaneously undergo chondrogenic and osteogenic differentiation

Dette er post-print versjonen av artikkelen. Den trykte versjonen kan leses her: http://www.sciencedirect.com/science/article/pii/S1873506111000286In the den, hibernating brown bears do not develop tissue atrophy or organ damage, despite
almost no physical activity. Mesenchymal stem cells could play an important role in tissue repair and
regeneration in brown bears. Our objective was to determine if adipose tissue-derived stem cells
(ASCs) can be recovered from adipose tissue of wild Scandinavian brown bears and characterize
osteogenic, chondrogenic, and adipogenic differentiation in the cells. Following immobilization of 8
wild brown bears 7-10 days after leaving the den in mid-April, adipose tissue biopsies (5-8 ml) were
obtained subcutaneously from 7 bears. ASCs were recovered and characterized. Adipose stem cell
cultures were established from 6 of 7 bears. Adipose tissue-derived stem cells from yearlings
spontaneously formed bone-like nodules surrounded by cartilaginous deposits, suggesting
differentiation into osteogenic and chondrogenic lineages. This ability appears to be lost gradually with
age. This is the first study to demonstrate stem cell recovery and growth from brown bears, and it is
the first report of ASCs spontaneously differentiating into osteocytes and chondrocytes. These findings
could have implications for the use of hibernating brown bears as a model to study osteoporosis
Fock model and Segal-Bargmann transform for minimal representations of
  Hermitian Lie groups

For any Hermitian Lie group G of tube type we construct a Fock model of its
minimal representation. The Fock space is defined on the minimal nilpotent
K_C-orbit X in p_C and the L^2-inner product involves a K-Bessel function as
density. Here K is a maximal compact subgroup of G, and g_C=k_C+p_C is a
complexified Cartan decomposition. In this realization the space of k-finite
vectors consists of holomorphic polynomials on X. The reproducing kernel of the
Fock space is calculated explicitly in terms of an I-Bessel function. We
further find an explicit formula of a generalized Segal-Bargmann transform
which intertwines the Schroedinger and Fock model. Its kernel involves the same
I-Bessel function. Using the Segal--Bargmann transform we also determine the
integral kernel of the unitary inversion operator in the Schroedinger model
which is given by a J-Bessel function.Comment: 77page
Controlled non uniform random generation of decomposable structures

International audienceConsider a class of decomposable combinatorial structures, using different types of atoms ${\cal Z} = \{z_1,\ldots ,z_{|{\cal Z}|}\}$. We address the random generation of such structures with respect to a size $n$ and a targeted distribution in $k$ of its \emph{distinguished} atoms. We consider two variations on this problem. In the first alternative, the targeted distribution is given by $k$ real numbers $\mu_1, \ldots, \mu_k$ such that $0 < \mu_i < 1$ for all $i$ and $\mu_1+\cdots+\mu_k \leq 1$. We aim to generate random structures among the whole set of structures of a given size $n$, in such a way that the {\em expected} frequency of any distinguished atom $z_i$ equals $\mu_i$. We address this problem by weighting the atoms with a $k$-tuple $\pi$ of real-valued weights, inducing a weighted distribution over the set of structures of size $n$. We first adapt the classical recursive random generation scheme into an algorithm taking ${\cal O}(n^{1+o(1)}+mn\log{n})$ arithmetic operations to draw $m$ structures from the $\pi$-weighted distribution. Secondly, we address the analytical computation of weights such that the targeted frequencies are achieved asymptotically, i. e. for large values of $n$. We derive systems of functional equations whose resolution gives an explicit relationship between $\pi$ and $\mu_1, \ldots, \mu_k$. Lastly, we give an algorithm in ${\cal O}(k n^4)$ for the inverse problem, {\it i.e.} computing the frequencies associated with a given $k$-tuple $\pi$ of weights, and an optimized version in ${\cal O}(k n^2)$ in the case of context-free languages. This allows for a heuristic resolution of the weights/frequencies relationship suitable for complex specifications. In the second alternative, the targeted distribution is given by a $k$ natural numbers $n_1, \ldots, n_k$ such that $n_1+\cdots+n_k+r=n$ where $r \geq 0$ is the number of undistinguished atoms. The structures must be generated uniformly among the set of structures of size $n$ that contain {\em exactly} $n_i$ atoms $z_i$ ($1 \leq i \leq k$). We give a ${\cal O}(r^2\prod_{i=1}^k n_i^2 +m n k \log n)$ algorithm for generating $m$ structures, which simplifies into a ${\cal O}(r\prod_{i=1}^k n_i +m n)$ for regular specifications
Search for supersymmetry in the vector-boson fusion topology in proton-proton collisions at sqrt(s) = 8 TeV

The first search for supersymmetry in the vector-boson fusion topology is presented. The search targets final states with at least two leptons, large missing transverse momentum, and two jets with a large separation in rapidity. The data sample corresponds to an integrated luminosity of 19.7 fb−1 of proton-proton collisions at s√=8 TeV collected with the CMS detector at the CERN LHC. The observed dijet invariant mass spectrum is found to be consistent with the expected standard model prediction. Upper limits are set on the cross sections for chargino and neutralino production with two associated jets, assuming the supersymmetric partner of the τ lepton to be the lightest slepton and the lightest slepton to be lighter than the charginos. For a so-called compressed-mass-spectrum scenario in which the mass difference between the lightest supersymmetric particle χ~01 and the next lightest, mass-degenerate, gaugino particles χ~02 and χ~±1 is 50 GeV, a mass lower limit of 170 GeV is set for these latter two particles
Synthesis of pure stereoisomers of benzo[b]thienyldehydrophenylalanines by Suzuki cross-coupling : preliminary studies of antimicrobial activity

Several benzo[b]thienyldehydrophenylalanines were synthesized from pure stereoisomers of the methyl ester of N-(tert-butoxycarbonyl)-beta-bromodehydrophenylalanine as an extension of our previously reported method for the synthesis of dehydrotryptophan analogues to dehydrophenylalanine derivatives. The latter were obtained in high yields by N-deprotection and bromination of N,N-bis-(tert-butoxycarbonyl)-(Z)-dehydrophenylalanine using TFA and NBS. This was carried out in two steps or in a one pot procedure resulting in different E/Z ratios. These compounds were coupled under Suzuki cross-coupling conditions [Pd(PPh3)4, Na2CO3, DME/H2O] with several boronic benzo[b]thienyl acids in good to high yields maintaining the stereochemistry of the starting materials. The best yields were obtained when the boronic acid was in position 7 of the benzo[b]thiophene and with the E isomer of the brominated dehydrophenylalanine. In some cases it was possible to increase the lower yields by changing the Pd source to PdCl2(PPh)2. A model dipeptide was prepared coupling a benzo[b]thienyldehydrophenylalanine with the methyl ester of alanine. Preliminary antimicrobial studies were performed with both isomers of one of the beta,beta-diaryldehydroalanines obtained. The results show that the compounds are selective and very active (very low MICs) against Gram positive bacteria (B. cereus and B. subtilis) the Z-isomer being more active. The compounds are also active against Candida albicans presenting similar MICs.Fundação para a Ciência e Tecnologia - POCTI/1999/QUI/32689, SFRH/BD/4709/2001
Search for direct production of charginos, neutralinos and sleptons in final states with two leptons and missing transverse momentum in pp collisions at s√= 8 TeV with the ATLAS detector

Searches for the electroweak production of charginos, neutralinos and sleptons in final states characterized by the presence of two leptons (electrons and muons) and missing transverse momentum are performed using 20.3 fb-1 of proton-proton collision data at sqrt(s) = 8 TeV recorded with the ATLAS experiment at the Large Hadron Collider. No significant excess beyond Standard Model expectations is observed. Limits are set on the masses of the lightest chargino, next-to-lightest neutralino and sleptons for different lightest-neutralino mass hypotheses in simplified models. Results are also interpreted in various scenarios of the phenomenological Minimal Supersymmetric Standard Model.We acknowledge the support of ANPCyT, Argentina; YerPhI, Armenia; ARC, Australia; BMWF and FWF, Austria; ANAS, Azerbaijan; SSTC, Belarus; CNPq and FAPESP, Brazil; NSERC, NRC and CFI, Canada; CERN; CONICYT, Chile; CAS, MOST and NSFC, China; COLCIENCIAS, Colombia; MSMT CR, MPO CR and VSC CR, Czech Republic; DNRF, DNSRC and Lundbeck Foundation, Denmark; EPLANET, ERC and NSRF, European Union; IN2P3-CNRS, CEA-DSM/IRFU, France; GNSF, Georgia; BMBF, DFG, HGF, MPG and AvH Foundation, Germany; GSRT and NSRF, Greece; ISF, MINERVA, GIF, I-CORE and Benoziyo Center, Israel; INFN, Italy; MEXT and JSPS, Japan; CNRST, Morocco; FOM and NWO, Netherlands; BRF and RCN, Norway; MNiSW and NCN, Poland; GRICES and FCT, Portugal; MNE/IFA, Romania; MES of Russia and ROSATOM, Russian Federation; JINR; MSTD, Serbia; MSSR, Slovakia; ARRS and MIZ. S, Slovenia; DST/NRF, South Africa; MINECO, Spain; SRC and Wallenberg Foundation, Sweden; SER, SNSF and Cantons of Bern and Geneva, Switzerland; NSC, Taiwan; TAEK, Turkey; STFC, the Royal Society and Leverhulme Trust, United Kingdom; DOE and NSF, United States of America
Neutron-driven collectivity in light tin isotopes: proton inelastic scattering from 104Sn

Inelastic scattering cross sections to individual bound excited states of Sn-104 were measured at 150 MeV/u beam energy and analyzed to evaluate the contribution of neutron and proton collectivity. State-of-the-art Quasi-Particle Random Phase Approximation (QRPA) with the D1M Gogny interaction reproduces the experimental proton collectivity and our inelastic scattering cross sections once used as input for a reaction calculation together with the Jeukenne-Lejeune-Mahaux (JLM) potentials. Experimental inelastic scattering cross section decreases by 40(24)% from Sn-112 to Sn-104. The present work shows that (i) proton and neutron collectivities are proportional over a large range of tin isotopes (including Sn-104), as is typical for isoscalar excitations, and (ii) the neutron collectivity dominates. It suggests that the plateau in the mass range A = 106-112 displayed by E2 transition probabilities is driven by neutron collectivity
Combined results of searches for the standard model Higgs boson in pp collisions at s=7 TeV

Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si le hubiere, y los autores pertenecientes a la UAMCombined results are reported from searches for the standard model Higgs boson in proton–proton collisions at √ s = 7 TeV in five Higgs boson decay modes: γγ, bb, ττ, WW, and ZZ. The explored Higgs boson mass range is 110–600 GeV. The analysed data correspond to an integrated luminosity of 4.6–4.8 fb−1. The expected excluded mass range in the absence of the standard model Higgs boson is 118–543 GeV at 95% CL. The observed results exclude the standard model Higgs boson in the mass range 127–600 GeV at 95% CL, and in the mass range 129–525 GeV at 99% CL. An excess of events above the expected standard model background is observed at the low end of the explored mass range making the observed limits weaker than expected in the absence of a signal. The largest excess, with a local significance of 3.1σ, is observed for a Higgs boson mass hypothesis of 124 GeV. The global significance of observing an excess with a local significance ≥3.1σ anywhere in the search range 110–600 (110– 145) GeV is estimated to be 1.5σ (2.1σ). More data are required to ascertain the origin of the observed excessWe wish to congratulate our colleagues in the CERN accelerator departments for the excellent performance of the LHC machine. We thank the technical and administrative staff at CERN and other CMS institutes, and acknowledge support from: FMSR (Austria); FNRS and FWO (Belgium); CNPq, CAPES, FAPERJ, and FAPESP (Brazil); MES (Bulgaria); CERN; CAS, MoST, and NSFC (China); COLCIENCIAS (Colombia); MSES (Croatia); RPF (Cyprus); Academy of Sciences and NICPB (Estonia); Academy of Finland, MEC, and HIP (Finland); CEA and CNRS/IN2P3 (France); BMBF, DFG, and HGF (Germany); GSRT (Greece); OTKA and NKTH (Hungary); DAE and DST (India); IPM (Iran); SFI (Ireland); INFN (Italy); NRF and WCU (Korea); LAS (Lithuania); CINVESTAV, CONACYT, SEP, and UASLPFAI (Mexico); MSI (New Zealand); PAEC (Pakistan); MSHE and NSC (Poland); FCT (Portugal); JINR (Armenia, Belarus, Georgia, Ukraine, Uzbekistan); MON, RosAtom, RAS and RFBR (Russia); MSTD (Serbia); MICINN and CPAN (Spain); Swiss Funding Agencies (Switzerland); NSC (Taipei); TUBITAK and TAEK (Turkey); STFC (United Kingdom); DOE and NSF (USA
Rethinking dog domestication by integrating genetics,\ud
archeology, and biogeography.

The dog was the first domesticated animal but it remains uncertain\ud
when the domestication process began and whether it occurred just\ud
once or multiple times across the Northern Hemisphere. To ascertain\ud
the value of modern genetic data to elucidate the origins of dog\ud
domestication, we analyzed 49,024 autosomal SNPs in 1,375 dogs\ud
(representing 35 breeds) and 19 wolves. After combining our data\ud
with previously published data,we contrasted the genetic signatures\ud
of 121 breeds with a worldwide archeological assessment of the\ud
earliest dog remains. Correlating the earliest archeological dogswith\ud
the geographic locations of 14 so-called “ancient” breeds (defined by\ud
their genetic differentiation) resulted in a counterintuitive pattern.\ud
First, none of the ancient breeds derive fromregionswhere the oldest\ud
archeological remains have been found. Second, three of the ancient\ud
breeds (Basenjis, Dingoes, and New Guinea Singing Dogs) come from\ud
regions outside the natural range of Canis lupus (the dog’s wild ancestor)\ud
and where dogs were introduced more than 10,000 y after\ud
domestication. These results demonstrate that the unifying characteristic\ud
among all genetically distinct so-called ancient breeds is a lack\ud
of recent admixturewith other breeds likely facilitated by geographic\ud
and cultural isolation. Furthermore, these genetically distinct ancient\ud
breeds only appear so because of their relative isolation, suggesting\ud
that studies of modern breeds have yet to shed light on dog origins.\ud
We conclude by assessing the limitations of past studies and how\ud
next-generation sequencing of modern and ancient individuals may\ud
unravel the history of dog domestication
Exploring the potential of antiangiogenic strategies targeting the TGF-β family in the tumor microenvironment

Members of the transforming growth factor (TGF)-β family exert their effect on
virtually all cell types in the body, producing diverse and complex cellular
responses. Additionally, TGF-β signaling is deregulated and hyperactive in many
malignant conditions, making it an appealing target in the combat of cancer
disease. The predominantly endothelial TGF-β receptors, ALK1 and endoglin,
which are activated during neoangiogenesis both during development and
pathological conditions, pose attractive modulating opportunities to impair tumor
vessel formation and cancer progression. However, the precise function of TGF-β
family signaling in endothelial cells is difficult to predict, as it appears highly
context dependent due to a myriad of ligands and receptors influencing the final
outcome. Furthermore, TGF-β is involved in autocrine and intricate dynamic
paracrine signaling events in the context of the tumor microenvironment. 
Pharmacological inhibitors for ALK1 and endoglin have been developed and will
facilitate more comprehensive studies on the exact function of the TGF-β family in
the tumor-associated endothelium. Here, we summarize the current knowledge on
TGF-β signaling in the regulation of the vascular network as alternative targets to
VEGF and incorporate our novel and promising findings in the field. Our two
studies aiming at dissecting the independent role of ALK1 and endoglin resulted in
very distinctive outcomes. While ALK1 suppression results in sustained tumor
growth by affecting the tumor neovasculature, endoglin impairment generates a
weakened and increasingly lenient vasculature to the passage of malignant cells to
and from the bloodstream. Our both seemingly contradictory studies challenge the
current view of a strong interconnection between ALK1 and endoglin in the
vasculature.



The ongoing clinical trials of inhibitors affecting ALK1 and endoglin involvement
in vascular formation during malignant progression will further clarify the
valuable potential of targeting alternative pathways to VEGF
Assesing use and suitability of scanning electron microscopy in the analysis of micro remains in dental calculus

Dental calculus is increasingly recognized as a major reservoir of dietary information. Palaeodietary studies using plant and animal micro remains (e.g. phytoliths, pollen, sponge spicules, and starch grains) trapped in calculus have the potential to revise our knowledge of the dietary role of plants in past populations. The conventional methods used to isolate and identify these micro remains rely on removing them from their microenvironment in the calculus, thus the microenvironment that traps and preserves micro remains is not understood. By using scanning electron microscopy and energy dispersive X-ray spectroscopy (SEMeEDX) on modern chimpanzee calculus from the Taï Forest, Côte d¿Ivoire, and human calculus from the Chalcolithic site of Camino del Molino, Spain, we present the first reported observations on characteristics of the matrix setting that are conducive to the survival of starch in dental calculus. We also assess the potential for SEMeEDX to detect starch and differentiate it from structurally and molecularly similar substrates. We demonstrate that SEMeEDX may offer a nondestructive technique for studying micro remains in certain contexts. Finally, we compare traditional optical analytical techniques (OM) with less invasive electron microscopy. The results indicate that SEM-EDX and OM are both effective for observing micro remains in calculus, but differ in their analytical resolution to identify different micro remains, and we therefore recommend a sequential use of both techniques
Measurement of the energy spectrum of cosmic rays above 10(18) eV using the Pierre Auger Observatory

We report a measurement of the flux of cosmic rays with unprecedented precision and statistics using the Pierre Auger Observatory. Based on fluorescence observations in coincidence with at least one surface detector we derive a spectrum for energies above 10^18 eV. We also update the previously published energy spectrum obtained with the surface detector array. The two spectra are combined addressing the systematic uncertainties and, in particular, the influence of the energy resolution on the spectral shape. The spectrum can be described by a broken power law E^-gamma with index gamma=3.3 below the ankle which is measured at log10(E/eV) = 18.6. Above the ankle the spectrum is described by a power law with index 2.6 followed by a flux suppression, above about log10(E/eV) = 19.5, detected with high statistical significance