460 research outputs found
Quantitative Stability of Linear Infinite Inequality Systems under Block Perturbations with Applications to Convex Systems
The original motivation for this paper was to provide an efficient
quantitative analysis of convex infinite (or semi-infinite) inequality systems
whose decision variables run over general infinite-dimensional (resp.
finite-dimensional) Banach spaces and that are indexed by an arbitrary fixed
set . Parameter perturbations on the right-hand side of the inequalities are
required to be merely bounded, and thus the natural parameter space is
. Our basic strategy consists of linearizing the parameterized
convex system via splitting convex inequalities into linear ones by using the
Fenchel-Legendre conjugate. This approach yields that arbitrary bounded
right-hand side perturbations of the convex system turn on constant-by-blocks
perturbations in the linearized system. Based on advanced variational analysis,
we derive a precise formula for computing the exact Lipschitzian bound of the
feasible solution map of block-perturbed linear systems, which involves only
the system's data, and then show that this exact bound agrees with the
coderivative norm of the aforementioned mapping. In this way we extend to the
convex setting the results of [3] developed for arbitrary perturbations with no
block structure in the linear framework under the boundedness assumption on the
system's coefficients. The latter boundedness assumption is removed in this
paper when the decision space is reflexive. The last section provides the aimed
application to the convex case
Genome-wide signatures of convergent evolution in echolocating mammals
Evolution is typically thought to proceed through divergence of genes, proteins, and ultimately phenotypes(1-3). However, similar traits might also evolve convergently in unrelated taxa due to similar selection pressures(4,5). Adaptive phenotypic convergence is widespread in nature, and recent results from a handful of genes have suggested that this phenomenon is powerful enough to also drive recurrent evolution at the sequence level(6-9). Where homoplasious substitutions do occur these have long been considered the result of neutral processes. However, recent studies have demonstrated that adaptive convergent sequence evolution can be detected in vertebrates using statistical methods that model parallel evolution(9,10) although the extent to which sequence convergence between genera occurs across genomes is unknown. Here we analyse genomic sequence data in mammals that have independently evolved echolocation and show for the first time that convergence is not a rare process restricted to a handful of loci but is instead widespread, continuously distributed and commonly driven by natural selection acting on a small number of sites per locus. Systematic analyses of convergent sequence evolution in 805,053 amino acids within 2,326 orthologous coding gene sequences compared across 22 mammals (including four new bat genomes) revealed signatures consistent with convergence in nearly 200 loci. Strong and significant support for convergence among bats and the dolphin was seen in numerous genes linked to hearing or deafness, consistent with an involvement in echolocation. Surprisingly we also found convergence in many genes linked to vision: the convergent signal of many sensory genes was robustly correlated with the strength of natural selection. This first attempt to detect genome-wide convergent sequence evolution across divergent taxa reveals the phenomenon to be much more pervasive than previously recognised
A novel malaria vaccine candidate antigen expressed in Tetrahymena thermophila
Development of effective malaria vaccines is hampered by the problem of producing correctly folded Plasmodium proteins for use as vaccine components. We have investigated the use of a novel ciliate expression system, Tetrahymena thermophila, as a P. falciparum vaccine antigen platform. A synthetic vaccine antigen composed of N-terminal and C-terminal regions of merozoite surface protein-1 (MSP-1) was expressed in Tetrahymena thermophila. The recombinant antigen was secreted into the culture medium and purified by monoclonal antibody (mAb) affinity chromatography. The vaccine was immunogenic in MF1 mice, eliciting high antibody titers against both N- and C-terminal components. Sera from immunized animals reacted strongly with P. falciparum parasites from three antigenically different strains by immunofluorescence assays, confirming that the antibodies produced are able to recognize parasite antigens in their native form. Epitope mapping of serum reactivity with a peptide library derived from all three MSP-1 Block 2 serotypes confirmed that the MSP-1 Block 2 hybrid component of the vaccine had effectively targeted all three serotypes of this polymorphic region of MSP-1. This study has successfully demonstrated the use of Tetrahymena thermophila as a recombinant protein expression platform for the production of malaria vaccine antigens
Modulation of extracellular matrix by nutritional hepatotrophic factors in thioacetamide-induced liver cirrhosis in the rat
Nutritional substances associated to some hormones enhance liver regeneration when injected intraperitoneally, being denominated hepatotrophic factors (HF). Here we verified if a solution of HF (glucose, vitamins, salts, amino acids, glucagon, insulin, and triiodothyronine) can revert liver cirrhosis and how some extracellular matrices are affected. Cirrhosis was induced for 14 weeks in 45 female Wistar rats (200 mg) by intraperitoneal injections of thioacetamide (200 mg/kg). Twenty-five rats received intraperitoneal HF twice a day for 10 days (40 mL·kg-1·day-1) and 20 rats received physiological saline. Fifteen rats were used as control. The HF applied to cirrhotic rats significantly: a) reduced the relative mRNA expression of the genes: Col-α1 (-53%), TIMP-1 (-31.7%), TGF-β1 (-57.7%), and MMP-2 (-41.6%), whereas Plau mRNA remained unchanged; b) reduced GGT (-43.1%), ALT (-17.6%), and AST (-12.2%) serum levels; c) increased liver weight (11.3%), and reduced liver collagen (-37.1%), regenerative nodules size (-22.1%), and fibrous septum thickness. Progranulin protein (immunohistochemistry) and mRNA (in situ hybridization) were found in fibrous septa and areas of bile duct proliferation in cirrhotic livers. Concluding, HF improved the histology and serum biochemistry of liver cirrhosis, with an important reduction of interstitial collagen and increased extracelullar matrix degradation by reducing profibrotic gene expression
School-based physical education programs: evidence-based physical activity interventions for youth in Latin America
This article focuses on results of the systematic review from the Guide for
Useful Interventions for Activity in Latin America project related to
school-based physical education (PE) programs in Latin America. The aims of the
article are to describe five school-based PE programs from Latin America,
discuss implications for effective school-based PE recommendations, propose
approaches for implementing these interventions, and identify gaps in the
research literature related to physical activity promotion in Latin American
youth. Following the US Community Guide systematic review
process, five school-based PE intervention studies with sufficient quality of
design, execution and detail of intervention and outcomes were selected for full
abstraction. One study was conducted in Brazil, two studies were conducted in
Chile and two studies were conducted on the US/Mexico border. While studies
presented assorted outcomes, methods and duration of interventions, there were
consistent positive increases in physical activity levels for all outcomes
measured during PE classes, endurance and active transportation to school in all
three randomized studies. Except for one cohort from one study, the
non-randomized studies showed positive intervention effects for moderate and
vigorous physical activity levels during PE classes. The core elements of these
five interventions included capacity building and staff training (PE specialists
and/or classroom teachers); changes in the PE curricula; provision of equipment
and materials; and adjustment of the interventions to specific target
populations. In order to translate the strong evidence for school-based PE into
practice, systematic attention to policy and implementation issues is required.
(Global Health Promotion, 2010; 17(2): pp. 05–15
ANKRD54 preferentially selects Bruton's Tyrosine Kinase (BTK) from a Human Src-Homology 3 (SH3) domain library
Bruton's Tyrosine Kinase (BTK) is a cytoplasmic protein tyrosine kinase with a fundamental role in B-lymphocyte development and activation. The nucleocytoplasmic shuttling of BTK is specifically modulated by the Ankyrin Repeat Domain 54 (ANKRD54) protein and the interaction is known to be exclusively SH3-dependent. To identify the spectrum of the ANKRD54 SH3-interactome, we applied phage-display screening of a library containing all the 296 human SH3 domains. The BTK-SH3 domain was the prime interactor. Quantitative western blotting analysis demonstrated the accuracy of the screening procedure. Revealing the spectrum and specificity of ANKRD54-interactome is a critical step toward functional analysis in cells and tissues.Peer reviewe
Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector
Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02 TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1 μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos2Δϕ modulation for all ΣETPb ranges and particle pT
Novel Genetic Tools for Diaminopimelic Acid Selection in Virulence Studies of Yersinia pestis
Molecular studies of bacterial virulence are enhanced by expression of
recombinant DNA during infection to allow complementation of mutants and
expression of reporter proteins in vivo. For highly pathogenic
bacteria, such as Yersinia pestis, these studies are currently
limited because deliberate introduction of antibiotic resistance is restricted
to those few which are not human treatment options. In this work, we report the
development of alternatives to antibiotics as tools for host-pathogen research
during Yersinia pestis infections focusing on the
diaminopimelic acid (DAP) pathway, a requirement for cell wall synthesis in
eubacteria. We generated a mutation in the dapA-nlpB(dapX)
operon of Yersinia pestis KIM D27 and CO92 which eliminated the
expression of both genes. The resulting strains were auxotrophic for
diaminopimelic acid and this phenotype was complemented in
trans by expressing dapA in single and multi-copy.
In vivo, we found that plasmids derived from the p15a
replicon were cured without selection, while selection for DAP enhanced
stability without detectable loss of any of the three resident virulence
plasmids. The dapAX mutation rendered Y.
pestis avirulent in mouse models of bubonic and septicemic plague
which could be complemented when dapAX was inserted in single
or multi-copy, restoring development of disease that was indistinguishable from
the wild type parent strain. We further identified a high level, constitutive
promoter in Y. pestis that could be used to drive expression of
fluorescent reporters in dapAX strains that had minimal impact
to virulence in mouse models while enabling sensitive detection of bacteria
during infection. Thus, diaminopimelic acid selection for single or multi-copy
genetic systems in Yersinia pestis offers an improved
alternative to antibiotics for in vivo studies that causes
minimal disruption to virulence
Ancestral Informative Marker Selection and Population Structure Visualization Using Sparse Laplacian Eigenfunctions
Identification of a small panel of population structure informative markers can reduce genotyping cost and is useful in various applications, such as ancestry inference in association mapping, forensics and evolutionary theory in population genetics. Traditional methods to ascertain ancestral informative markers usually require the prior knowledge of individual ancestry and have difficulty for admixed populations. Recently Principal Components Analysis (PCA) has been employed with success to select SNPs which are highly correlated with top significant principal components (PCs) without use of individual ancestral information. The approach is also applicable to admixed populations. Here we propose a novel approach based on our recent result on summarizing population structure by graph Laplacian eigenfunctions, which differs from PCA in that it is geometric and robust to outliers. Our approach also takes advantage of the priori sparseness of informative markers in the genome. Through simulation of a ring population and the real global population sample HGDP of 650K SNPs genotyped in 940 unrelated individuals, we validate the proposed algorithm at selecting most informative markers, a small fraction of which can recover the similar underlying population structure efficiently. Employing a standard Support Vector Machine (SVM) to predict individuals' continental memberships on HGDP dataset of seven continents, we demonstrate that the selected SNPs by our method are more informative but less redundant than those selected by PCA. Our algorithm is a promising tool in genome-wide association studies and population genetics, facilitating the selection of structure informative markers, efficient detection of population substructure and ancestral inference
Search for the neutral Higgs bosons of the minimal supersymmetric standard model in pp collisions at root s=7 TeV with the ATLAS detector
A search for neutral Higgs bosons of the Minimal Supersymmetric Standard Model (MSSM) is reported. The analysis is based on a sample of proton-proton collisions at a centre-of-mass energy of 7TeV recorded with the ATLAS detector at the Large Hadron Collider. The data were recorded in 2011 and correspond to an integrated luminosity of 4.7 fb-1 to 4.8 fb-1. Higgs boson decays into oppositely-charged muon or τ lepton pairs are considered for final states requiring either the presence or absence of b-jets. No statistically significant excess over the expected background is observed and exclusion limits at the 95% confidence level are derived. The exclusion limits are for the production cross-section of a generic neutral Higgs boson, φ, as a function of the Higgs boson mass and for h/A/H production in the MSSM as a function of the parameters mA and tan β in the mhmax scenario for mA in the range of 90GeV to 500 GeV. Copyright CERN
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