pinecone/core-2020-05-10-deduplication huggingface dataset:
Mitochondrialuncouplingprotein-2isnotinvolvedin palmitate-induced impairmentofglucose-stimulatedinsulinsecretion in INS-1Einsulinomacellsandisnotneededfortheamplification of insulin release

WehaverecentlyshownthatovernightexposureofINS-1Einsulinomacellstopalmitateinthepresence of highglucosecausesdefectsinbothmitochondrialenergymetabolismandglucose-stimulatedinsulin secretion (GSIS).Herewereportexperimentsdesignedtotesttheinvolvementofmitochondrial uncoupling protein-2(UCP2)intheseglucolipotoxiceffects.Measuringreal-timeoxygenconsumption in siRNA-transfectedINS-1Ecells,weshowthatdeleteriouseffectsofpalmitateontheglucosesensitivity of mitochondrialrespirationandonthecouplingefficiency ofoxidativephosphorylationareindepen- dent ofUCP2.Consistently,palmitateimpairsGSIStothesameextentincellswithandwithoutUCP2. Furthermore,weknockeddownUCP2inspheroidINS-1Ecellclusters(pseudoislets)totestwhetheror not UCP2regulatesinsulinsecretionduringprolongedglucoseexposure.Wedemonstratethatthereare no differencesintemporalGSISkineticsbetweenperifusedpseudoisletswithandwithoutUCP2.We conclude thatUCP2isnotinvolvedinpalmitate-inducedimpairmentofGSISinINS-1Einsulinomacells and isnotneededfortheamplification ofinsulinrelease.Theseconclusionsinformongoingdebateon the disputedbiochemicalandphysiologicalfunctionsofthebetacellUCP2
An analytic method for S-Expansion involving resonance and reduction

In this paper we describe an analytic method able to give the multiplication table(s) of the set(s) involved in an S-expansion process (with either resonance or 0_S-resonant-reduction) for reaching a target Lie (super)algebra from a starting one, after having properly chosen the partitions over subspaces of the considered (super)algebras. This analytic method gives us a simple set of expressions to find the subset decomposition of the set(s) involved in the process. Then, we use the information coming from both the initial (super)algebra and the target one for reaching the multiplication table(s) of the mentioned set(s). Finally, we check associativity with an auxiliary computational algorithm, in order to understand whether the obtained set(s) can describe semigroup(s) or just abelian set(s) connecting two (super)algebras. We also give some interesting examples of application, which check and corroborate our analytic procedure and also generalize some result already presented in the literature
Asset-liability modelling and pension schemes: the application of robust optimization to USS

yesThis paper uses a novel numerical optimization technique – robust optimization – that is well suited to
solving the asset–liability management (ALM) problem for pension schemes. It requires the estimation
of fewer stochastic parameters, reduces estimation risk and adopts a prudent approach to asset allocation.
This study is the first to apply it to a real-world pension scheme, and the first ALM model of a pension
scheme to maximize the Sharpe ratio. We disaggregate pension liabilities into three components –
active members, deferred members and pensioners, and transform the optimal asset allocation into the
scheme’s projected contribution rate. The robust optimization model is extended to include liabilities and
used to derive optimal investment policies for the Universities Superannuation Scheme (USS), benchmarked
against the Sharpe and Tint, Bayes–Stein and Black–Litterman models as well as the actual USS
investment decisions. Over a 144-month out-of-sample period, robust optimization is superior to the four
benchmarks across 20 performance criteria and has a remarkably stable asset allocation – essentially
fix-mix. These conclusions are supported by six robustness checks
MC1R gene variants and non-melanoma skin cancer: a pooled-analysis from the M-SKIP project.

The melanocortin-1-receptor (MC1R) gene regulates human pigmentation and is highly polymorphic in populations of European origins. The aims of this study were to evaluate the association between MC1R variants and the risk of non-melanoma skin cancer (NMSC), and to investigate whether risk estimates differed by phenotypic characteristics.Data on 3527 NMSC cases and 9391 controls were gathered through the M-SKIP Project, an international pooled-analysis on MC1R, skin cancer and phenotypic characteristics. We calculated summary odds ratios (SOR) with random-effect models, and performed stratified analyses.Subjects carrying at least one MC1R variant had an increased risk of NMSC overall, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC): SOR (95%CI) were 1.48 (1.24-1.76), 1.39 (1.15-1.69) and 1.61 (1.35-1.91), respectively. All of the investigated variants showed positive associations with NMSC, with consistent significant results obtained for V60L, D84E, V92M, R151C, R160W, R163Q and D294H: SOR (95%CI) ranged from 1.42 (1.19-1.70) for V60L to 2.66 (1.06-6.65) for D84E variant. In stratified analysis, there was no consistent pattern of association between MC1R and NMSC by skin type, but we consistently observed higher SORs for subjects without red hair.Our pooled-analysis highlighted a role of MC1R variants in NMSC development and suggested an effect modification by red hair colour phenotype
A computational tool to predict the evolutionarily conserved protein-protein interaction hot-spot residues from the structure of the unbound protein

Identifying hot-spot residues – residues that are critical to protein–protein binding – can help to elucidate a protein's function and assist in designing therapeutic molecules to target those residues. We present a novel computational tool, termed spatial-interaction-map (SIM), to predict the hot-spot residues of an evolutionarily conserved protein–protein interaction from the structure of an unbound protein alone. SIM can predict the protein hot-spot residues with an accuracy of 36–57%. Thus, the SIM tool can be used to predict the yet unknown hot-spot residues for many proteins for which the structure of the protein–protein complexes are not available, thereby providing a clue to their functions and an opportunity to design therapeutic molecules to target these proteins.Novartis (Firm)Singapore-MIT Alliance for Research and Technolog
Degrees of chloroquine resistance in Plasmodium - Is the redox system involved?

Chloroquine (CQ) was once a very effective antimalarial drug that, at its peak, was consumed in the hundreds of millions of doses per year. The drug acts against the Plasmodium parasite during the asexual intra-erythrocytic phase of its lifecycle. Unfortunately, clinical resistance to this drug is now widespread. Questions remain about precisely how CQ kills malaria parasites, and by what means some CQ-resistant (CQR) parasites can withstand much higher concentrations of the drug than others that also fall in the CQR category. In this review we investigate the evidence for and against the proposal that CQ kills parasites by generating oxidative stress. Further, we examine a long-held idea that the glutathione system of malaria parasites plays a role in CQ resistance. We conclude that there is strong evidence that glutathione levels modulate CQ response in the rodent malaria species Plasmodium berghei, but that a role for redox in contributing to the degree of CQ resistance in species infectious to humans has not been firmly established.Adele M. Lehane, Christopher A. McDevitt, Kiaran Kirk, David A. Fidoc
Measurement of the hadronic activity in events with a Z and two jets and extraction of the cross section for the electroweak production of a Z with two jets in pp collisions at sqrt(s) = 7 TeV

The first measurement of the electroweak production cross section of a Z boson with two jets (Zjj) in pp collisions at sqrt(s) = 7 TeV is presented, based on a data sample recorded by the CMS experiment at the LHC with an integrated luminosity of 5 inverse femtobarns. The cross section is measured for the lljj (l = e, mu) final state in the kinematic region m[ll] &gt;50 GeV, m[jj] &gt; 120 GeV, transverse momenta pt[j] &gt; 25 GeV and pseudorapidity abs(eta[j]) &lt; 4.0. The measurement, combining the muon and electron channels, yields sigma = 154 +/- 24 (stat.) +/- 46 (exp. syst.) +/- 27 (th. syst.) +/- 3 (lum.) fb, in agreement with the theoretical cross section. The hadronic activity, in the rapidity interval between the jets, is also measured. These results establish an important foundation for the more general study of vector boson fusion processes, of relevance for Higgs boson searches and for measurements of electroweak gauge couplings and vector boson scattering
Remarks on the pion–nucleon σ-term

The pion–nucleon σ-term can be stringently constrained by the combination of analyticity, unitarity, and crossing symmetry with phenomenological information on the pion–nucleon scattering lengths. Recently, lattice calculations at the physical point have been reported that find lower values by about 3σ with respect to the phenomenological determination. We point out that a lattice measurement of the pion–nucleon scattering lengths could help resolve the situation by testing the values extracted from spectroscopy measurements in pionic atoms
Cyber-physical production systems combined with logistic models - a learning factory concept for an improved production planning and control

Nowadays, production enterprises are faced with an array of challenges including increasing pressure regarding costs, demands for individualized products as well as the growing significance of logistic performance and costs, to name just a few. These in turn give rise to special requirements that the production planning, control and monitoring, among others, need to meet with suitable methods and techniques. Within this context, developments such as Industry 4.0 and cyber-physical production systems on the technology side, and approaches such as innovative learning factories for training employees hold great potential. This paper clarifies the advantages of cyber-physical systems in view of production planning, controlling and monitoring. Based on that, using the concept of IFA's Learning Factory, it describes how these can be specifically utilized in applying logistic models to improve order processing
Real-time Monitoring of Wind Turbine Blade Alignment Using Laser Measurement

AbstractThe aim of this paper is focused on using laser based metrology techniques to capture the positional changes of wind turbines in service and aligning drivelines in the turbines. In this way the mechanical operation, and therefore the aerodynamic design and loading predictions, of the turbine can be more accurately predicted and thus lead to greater optimization and improved efficiencies.In order to perform real-time blade alignment, a laboratory test rig has been created that operates at the typical rotational rates of a wind turbine. This test will be conducted on both the radial misalignment and axial angular misalignment for a range of rotational speeds and torque loads. As such, a relationship for variation in alignment by rotational speed and torque will be determined, as well as presenting a method for real-time analysis of wind turbine blade alignment. Tests will also be conducted showing misalignment, and hence will show when the blade enters a state of requiring re-alignment
Levels of insulin and HOMA-IR in adolescents in Saltillo, Coahuila, Mexico

AbstractIntroductionAn alarming rise of obesity in adolescents has been observed, placing them at risk of developing resistance to insulin (IR) and its adverse metabolic consequences such as diabetes mellitus type 2 (DM2), metabolic syndrome and cardiovascular disease.ObjectiveTo know the prevalence of obesity, and the levels of glucose, insulin and HOMA-IR and its association with the BMIz, waist circumference and the pubertal stage in a random sample of adolescents.Materials and methods292 adolescents between 12 and 15 years (152 female and 140 male), whose anthropometric measurements (weight, height and waist circumference) were taken, body mass index calculated and Z-score determined. Blood glucose and insulin levels were evaluated from a sample of blood and their HOMA-IR was determined.ResultsThe results showed that 32.5% were obese, 22.3% were overweight and 23.6% showed adolescent central obesity. Glucose levels (p=0.016), insulin (p=0.0001) and HOMA-IR (p=0.0001) showed significant differences in the group with obesity. Values of the three parameters were increased with the stage of puberty. We found significant differences in the levels of glucose (p=0.0388), insulin (p=0.0005) and HOMA-IR (p=0.0001) between the prepubertal and postpubertal stages.ConclusionThe results showed that the presence of central obesity, overweightness and obesity are closely associated with the prevalence of IR, and may be significant predictors of DM2
β+/EC decay rates of deformed neutron-deficient nuclei in the deformed QRPA with realistic interactions

AbstractThe weak-decay (β+ and EC) rates of neutron-deficient Kr, Sr, Zr, and Mo isotopes are investigated within the deformed quasiparticle random-phase approximation with realistic nucleon–nucleon interactions. The particle–particle and particle–hole channels of residual interactions are handled in large single-particle model spaces, based on the Brückner G-matrix with charge-dependent Bonn nucleon–nucleon forces. Contributions from allowed Gamow–Teller and Fermi transitions as well as first-forbidden transitions are calculated. The calculated half-lives show good agreement with the experimental data over a wide range of magnitude, from 10−2 to 107 s. Moreover, predictions of β-decay half-lives are made for some extremely proton-rich isotopes, which could be useful for future experiments
Airway inflammation in patients affected by obstructive sleep apnea syndrome

AbstractObstructive sleep apnea syndrome (OSAS) has been shown to be associated to upper airway inflammation. The object of the present study was to establish the presence of bronchial inflammation in OSAS subjects.In 16 subjects affected by OSAS, and in 14 healthy volunteers, airway inflammation was detected by the cellular analysis of the induced sputum.OSAS patients, as compared to control subjects, showed a higher percentage of neutrophils (66.7±18.9 vs. 25.8±15.6) (P<0.001) and a lower percentage of macrophages (29.4±18.4 vs. 70.8±15.3) (P<0.001). The percentage of eosinophils and lymphocytes were not significantly different in the two groups.OSAS subjects show bronchial inflammation characterized by a significant increase in neutrophils
Associated production of a Kaluza–Klein excitation of a gluon with a tt¯ pair at the LHC

AbstractIn certain model-realizations of the Randall–Sundrum scenario, the Kaluza–Klein (KK) excitations of the gluon, gKK have enhanced couplings to right-handed top quarks. In the absence of a gggKK coupling in these models, the single production of a gKK from an initial gg state is not possible. The search for other production mechanisms at the LHC, therefore, becomes important. We suggest that the associated production of a gKK with a tt¯ pair is such a mechanism. Our parton-level study, which neglects detection efficiencies, shows that through this process the LHC can probe KK gluon masses in the range of 2.8–3.0 TeV
Expansion of Intronic GGCCTG Hexanucleotide Repeat in NOP56 Causes SCA36, a Type of Spinocerebellar Ataxia Accompanied by Motor Neuron Involvement

Autosomal-dominant spinocerebellar ataxias (SCAs) are a heterogeneous group of neurodegenerative disorders. In this study, we performed genetic analysis of a unique form of SCA (SCA36) that is accompanied by motor neuron involvement. Genome-wide linkage analysis and subsequent fine mapping for three unrelated Japanese families in a cohort of SCA cases, in whom molecular diagnosis had never been performed, mapped the disease locus to the region of a 1.8 Mb stretch (LOD score of 4.60) on 20p13 (D20S906–D20S193) harboring 37 genes with definitive open reading frames. We sequenced 33 of these and observed a large expansion of an intronic GGCCTG hexanucleotide repeat in NOP56 and an unregistered missense variant (Phe265Leu) in C20orf194, but we found no mutations in PDYN and TGM6. The expansion showed complete segregation with the SCA phenotype in family studies, whereas Phe265Leu in C20orf194 did not. Screening of the expansions in the SCA cohort cases revealed four additional occurrences, but none were revealed in the cohort of 27 Alzheimer disease cases, 154 amyotrophic lateral sclerosis cases, or 300 controls. In total, nine unrelated cases were found in 251 cohort SCA patients (3.6%). A founder haplotype was confirmed in these cases. RNA foci formation was detected in lymphoblastoid cells from affected subjects by fluorescence in situ hybridization. Double staining and gel-shift assay showed that (GGCCUG)n binds the RNA-binding protein SRSF2 but that (CUG)6 does not. In addition, transcription of MIR1292, a neighboring miRNA, was significantly decreased in lymphoblastoid cells of SCA patients. Our finding suggests that SCA36 is caused by hexanucleotide repeat expansions through RNA gain of function
Hippocampal subfield volumetry in mild cognitive impairment, Alzheimer's disease and semantic dementia

AbstractBackgroundHippocampal atrophy is a well-known feature of Alzheimer's disease (AD), but sensitivity and specificity of hippocampal volumetry are limited. Neuropathological studies have shown that hippocampal subfields are differentially vulnerable to AD; hippocampal subfield volumetry may thus prove to be more accurate than global hippocampal volumetry to detect AD.MethodsCA1, subiculum and other subfields were manually delineated from 40 healthy controls, 18 AD, 17 amnestic Mild Cognitive Impairment (aMCI), and 8 semantic dementia (SD) patients using a previously developed high resolution MRI procedure. Non-parametric group comparisons and receiver operating characteristic (ROC) analyses were conducted. Complementary analyses were conducted to evaluate differences of hemispheric asymmetry and anterior-predominance between AD and SD patients and to distinguish aMCI patients with or without β-amyloid deposition as assessed by Florbetapir-TEP.ResultsGlobal hippocampi were atrophied in all three patient groups and volume decreases were maximal in the CA1 subfield (22% loss in aMCI, 27% in both AD and SD; all p<0.001). In aMCI, CA1 volumetry was more accurate than global hippocampal measurement to distinguish patients from controls (areas under the ROC curve=0.88 and 0.76, respectively; p=0.05) and preliminary analyses suggest that it was independent from the presence of β-amyloid deposition. In patients with SD, whereas the degree of CA1 and subiculum atrophy was similar to that found in AD patients, hemispheric and anterior–posterior asymmetry were significantly more marked than in AD with greater involvement of the left and anterior hippocampal subfields.ConclusionsThe findings suggest that CA1 measurement is more sensitive than global hippocampal volumetry to detect structural changes at the pre-dementia stage, although the predominance of CA1 atrophy does not appear to be specific to AD pathophysiological processes
Functional Expression Cloning of Nanog, a Pluripotency Sustaining Factor in Embryonic Stem Cells

AbstractEmbryonic stem (ES) cells undergo extended proliferation while remaining poised for multilineage differentiation. A unique network of transcription factors may characterize self-renewal and simultaneously suppress differentiation. We applied expression cloning in mouse ES cells to isolate a self-renewal determinant. Nanog is a divergent homeodomain protein that directs propagation of undifferentiated ES cells. Nanog mRNA is present in pluripotent mouse and human cell lines, and absent from differentiated cells. In preimplantation embryos, Nanog is restricted to founder cells from which ES cells can be derived. Endogenous Nanog acts in parallel with cytokine stimulation of Stat3 to drive ES cell self-renewal. Elevated Nanog expression from transgene constructs is sufficient for clonal expansion of ES cells, bypassing Stat3 and maintaining Oct4 levels. Cytokine dependence, multilineage differentiation, and embryo colonization capacity are fully restored upon transgene excision. These findings establish a central role for Nanog in the transcription factor hierarchy that defines ES cell identity
Global dynamics above the ground state energy for the focusing nonlinear Klein–Gordon equation

AbstractThe analysis of global dynamics of nonlinear dispersive equations has a long history starting from small solutions. In this paper we study the focusing, cubic, nonlinear Klein–Gordon equation in R3 with large radial data in the energy space. This equation admits a unique positive stationary solution Q, called the ground state. In 1975 Payne and Sattinger showed that solutions u(t) with energy E[u,u˙] strictly below that of the ground state are divided into two classes, depending on a suitable functional K(u): If K(u)<0, then one has finite time blow-up, if K(u)⩾0 global existence; moreover, these sets are invariant under the flow. Recently, Ibrahim, Masmoudi and the first author [22] improved this result by establishing scattering to zero for K[u]⩾0 by means of a variant of the Kenig–Merle method (Kenig and Merle, 2006, 2008 [25,26]). In this paper we go slightly beyond the ground state energy and we give a complete description of the evolution in that case. For example, in a small neighborhood of Q one encounters the following trichotomy: On one side of a center-stable manifold one has finite time blow-up for t⩾0, on the other side scattering to zero, and on the manifold itself one has scattering to Q, both as t→+∞. In total, the class of data with energy at most slightly above that of Q is divided into nine disjoint non-empty sets each displaying different asymptotic behavior as t→±∞, which includes solutions blowing up in one time direction and scattering to zero on the other. The analogue of the solutions found by Duyckaerts and Merle (2009, 2008) [13,14] for the energy critical wave and Schrödinger equations appear here as the unique one-dimensional stable/unstable manifolds approaching ±Q exponentially as t→∞ or t→−∞, respectively. The main technical ingredient in our proof is a “one-pass” theorem which excludes the existence of (almost) homoclinic orbits between Q (as well as −Q) and (almost) heteroclinic orbits connecting Q with −Q. In a companion paper (Nakanishi and Schlag, 2010 [31]) we establish analogous properties for the NLS equation
Contractions from osp(1|32)⊕osp(1|32) to the M-theory superalgebra extended by additional fermionic generators

AbstractWe study here the generalized Weimar-Woods contractions of the superalgebra osp(1|32)⊕osp(1|32) in order to obtain a suitable algebra that could describe the gauge group of D=11 supergravity. The contracted superalgebras are assumed to be given in terms of fermionic extensions of the M-theory superalgebra. We show that the only superalgebra of this type obtained by contraction is the only one for which the three-form of D=11 supergravity cannot be trivialized. Therefore, D=11 supergravity cannot be connected in this way with a contraction of osp(1|32)⊕osp(1|32)