416 research outputs found
A Report on the Preliminary design of Composite Cocured LCA Fin
A report on the preliminary design of composite cocured LCA fin is presented. A six spar structural configuration involving laminated carbon composite construction is employed in the design of torsion box. The design studies are carried out using a strength of materials based analysis. Three critical loading cases have been considered in the investigation. Results for various cases studied are presented and discussed
Geometric multiaxial representation of N-qubit mixed symmetric separable states
Study of an N qubit mixed symmetric separable states is a long standing challenging problem as there exist no unique separability criterion. In this regard, we take up the N-qubit mixed symmetric separable states for a detailed study as these states are of experimental importance and offer elegant mathematical analysis since the dimension of the Hilbert space reduces from 2N to N + 1. Since there exists a one to one correspondence between spin-j system and an N-qubit symmetric state, we employ Fano statistical tensor parameters for the parametrization of spin density matrix. Further, we use geometric multiaxial representation (MAR) of density matrix to characterize the mixed symmetric separable states. Since separability problem is NP hard, we choose to study it in the continuum limit where mixed symmetric separable states are characterized by the P-distribution function λ (ᶿ, Φ) We show that the N-qubit mixed symmetric separable state can be visualized as a uniaxial system if the distribution function is independent of ᶿ, and Φ. We further choose distribution function to be the most general positive function on a sphere and observe that the statistical tensor parameters characterizing the N-qubit symmetric system are the expansion coefficients of the distribution function. As an example for the discrete case, we investigate the MAR of a uniformly weighted two qubit mixed symmetric separable state. We also observe that there exists a correspondence between separability and classicality of states
Magnetic stress as a driving force of structural distortions: the case of CrN
We show that the observed transition from rocksalt to orthorhombic P
symmetry in CrN can be understood in terms of stress anisotropy. Using local
spin density functional theory, we find that the imbalance between stress
stored in spin-paired and spin-unpaired Cr nearest neighbors causes the
rocksalt structure to be unstable against distortions and justifies the
observed antiferromagnetic ordering. This stress has a purely magnetic origin,
and may be important in any system where the coupling between spin ordering and
structure is strong.Comment: 4 pages (two columns) 4 figure
Competition between Magnetic and Structural Transition in CrN
CrN is observed to undergo a paramagnetic to antiferromagnetic transition
accompanied by a shear distortion from cubic NaCl-type to orthorhombic
structure. Our first-principle plane wave and ultrasoft pseudopotential
calculations confirm that the distorted antiferromagnetic phase with spin
configuration arranged in double ferromagnetic sheets along [110] is the most
stable. Antiferromagnetic ordering leads to a large depletion of states around
Fermi level, but it does not open a gap. Simultaneous occurence of structural
distortion and antiferromagnetic order is analyzed.Comment: 10 pages, 10 figure
Uncertainty quantification in graph-based classification of high dimensional data
Classification of high dimensional data finds wide-ranging applications. In
many of these applications equipping the resulting classification with a
measure of uncertainty may be as important as the classification itself. In
this paper we introduce, develop algorithms for, and investigate the properties
of, a variety of Bayesian models for the task of binary classification; via the
posterior distribution on the classification labels, these methods
automatically give measures of uncertainty. The methods are all based around
the graph formulation of semi-supervised learning.
We provide a unified framework which brings together a variety of methods
which have been introduced in different communities within the mathematical
sciences. We study probit classification in the graph-based setting, generalize
the level-set method for Bayesian inverse problems to the classification
setting, and generalize the Ginzburg-Landau optimization-based classifier to a
Bayesian setting; we also show that the probit and level set approaches are
natural relaxations of the harmonic function approach introduced in [Zhu et al
2003].
We introduce efficient numerical methods, suited to large data-sets, for both
MCMC-based sampling as well as gradient-based MAP estimation. Through numerical
experiments we study classification accuracy and uncertainty quantification for
our models; these experiments showcase a suite of datasets commonly used to
evaluate graph-based semi-supervised learning algorithms.Comment: 33 pages, 14 figure
Single-inhaler triple therapy fluticasone furoate/umeclidinium/vilanterol versus fluticasone furoate/vilanterol and umeclidinium/vilanterol in patients with COPD:results on cardiovascular safety from the IMPACT trial
BACKGROUND: This analysis of the IMPACT study assessed the cardiovascular (CV) safety of single-inhaler triple therapy with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus FF/VI and UMEC/VI dual therapy. METHODS: IMPACT was a 52-week, randomized, double-blind, multicenter Phase III study comparing the efficacy and safety of FF/UMEC/VI 100/62.5/25 mcg with FF/VI 100/25 mcg or UMEC/VI 62.5/25 mcg in patients ≥40 years of age with symptomatic chronic obstructive pulmonary disease (COPD) and ≥1 moderate/severe exacerbation in the previous year. The inclusion criteria for the study were intentionally designed to permit the enrollment of patients with significant concurrent CV disease/risk. CV safety assessments included proportion of patients with and exposure-adjusted rates of on-treatment CV adverse events of special interest (CVAESI) and major adverse cardiac events (MACE), as well as time-to-first (TTF) CVAESI, and TTF CVAESI resulting in hospitalization/prolonged hospitalization or death. RESULTS: Baseline CV risk factors were similar across treatment groups. Overall, 68% of patients (n = 7012) had ≥1 CV risk factor and 40% (n = 4127) had ≥2. At baseline, 29% of patients reported a current/past cardiac disorder and 58% reported a current/past vascular disorder. The proportion of patients with on-treatment CVAESI was 11% for both FF/UMEC/VI and UMEC/VI, and 10% for FF/VI. There was no statistical difference for FF/UMEC/VI versus FF/VI or UMEC/VI in TTF CVAESI (hazard ratio [HR]: 0.98, 95% confidence interval [CI]: 0.85, 1.11; p = 0.711 and HR: 0.92, 95% CI: 0.78, 1.08; p = 0.317, respectively) nor TTF CVAESI leading to hospitalization/prolonged hospitalization or death (HR: 1.19, 95% CI: 0.93, 1.51; p = 0.167 and HR: 0.96, 95% CI: 0.72, 1.27; p = 0.760, respectively). On-treatment MACE occurred in ≤3% of patients across treatment groups, with similar prevalence and rates between treatments. CONCLUSIONS: In a symptomatic COPD population with a history of exacerbations and a high rate of CV disease/risk, the proportion of patients with CVAESI and MACE was 10-11% and 1-3%, respectively, across treatment arms, and the risk of CVAESI was low and similar across treatment arms. There was no statistically significant increased CV risk associated with the use of FF/UMEC/VI versus FF/VI or UMEC/VI, and UMEC/VI versus FF/VI. TRIAL REGISTRATION: NCT02164513 (GSK study number CTT116855)
Diacylglycerol-Stimulated Endocytosis of Transferrin in Trypanosomatids Is Dependent on Tyrosine Kinase Activity
Small molecule regulation of cell function is an understudied area of trypanosomatid biology. In Trypanosoma brucei diacylglycerol (DAG) stimulates endocytosis of transferrin (Tf). However, it is not known whether other trypanosomatidae respond similarly to the lipid. Further, the biochemical pathways involved in DAG signaling to the endocytic system in T. brucei are unknown, as the parasite genome does not encode canonical DAG receptors (e.g. C1-domains). We established that DAG stimulates endocytosis of Tf in Leishmania major, and we evaluated possible effector enzymes in the pathway with multiple approaches. First, a heterologously expressed glycosylphosphatidylinositol phospholipase C (GPI-PLC) activated endocytosis of Tf 300% in L. major. Second, exogenous phorbol ester and DAGs promoted Tf endocytosis in L. major. In search of possible effectors of DAG signaling, we discovered a novel C1-like domain (i.e. C1_5) in trypanosomatids, and we identified protein Tyr kinases (PTKs) linked with C1_5 domains in T. brucei, T. cruzi, and L. major. Consequently, we hypothesized that trypanosome PTKs might be effector enzymes for DAG signaling. General uptake of Tf was reduced by inhibitors of either Ser/Thr or Tyr kinases. However, DAG-stimulated endocytosis of Tf was blocked only by an inhibitor of PTKs, in both T. brucei and L. major. We conclude that (i) DAG activates Tf endocytosis in L. major, and that (ii) PTKs are effectors of DAG-stimulated endocytosis of Tf in trypanosomatids. DAG-stimulated endocytosis of Tf may be a T. brucei adaptation to compete effectively with host cells for vertebrate Tf in blood, since DAG does not enhance endocytosis of Tf in human cells
The conserved C-terminus of the PcrA/UvrD helicase interacts directly with RNA polymerase
Copyright: © 2013 Gwynn et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was supported by a Wellcome Trust project grant to MD (Reference: 077368), an ERC starting grant to MD (Acronym: SM-DNA-REPAIR) and a BBSRC project grant to PM, NS and MD (Reference: BB/I003142/1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD
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