370 research outputs found

    Computing Fixed Point Floer Homology

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    In the summer of 2009, our group developed a computer program that computes Hochschild Homology, a topological invariant. While we must assume that the reader has at least encountered algebraic topology, in this paper we provide the mathematical background and motivation for our algorithm. After presenting a number of definitions, we will explain how the algorithm works. Specifically, we first define the Floer complex of two curves on surface; the resulting homology is invariant under isotopies. Then, we introduce the Fukaya category associated to a sequence of curves. Next, we define the Hochschild complex of the Fukaya category. And finally, we describe an algorithm for computing Hochschild Homology and provide some examples

    Immune DNA signature of T-cell infiltration in breast tumor exomes.

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    Tumor infiltrating lymphocytes (TILs) have been associated with favorable prognosis in multiple tumor types. The Cancer Genome Atlas (TCGA) represents the largest collection of cancer molecular data, but lacks detailed information about the immune environment. Here, we show that exome reads mapping to the complementarity-determining-region 3 (CDR3) of mature T-cell receptor beta (TCRB) can be used as an immune DNA (iDNA) signature. Specifically, we propose a method to identify CDR3 reads in a breast tumor exome and validate it using deep TCRB sequencing. In 1,078 TCGA breast cancer exomes, the fraction of CDR3 reads was associated with TILs fraction, tumor purity, adaptive immunity gene expression signatures and improved survival in Her2+ patients. Only 2/839 TCRB clonotypes were shared between patients and none associated with a specific HLA allele or somatic driver mutations. The iDNA biomarker enriches the comprehensive dataset collected through TCGA, revealing associations with other molecular features and clinical outcomes

    Optofluidic applications with lithium niobate nanowires

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    We report the hydrothermal synthesis of free-standing lithium niobate nanowires. We show that the versatile properties of bulk lithium niobate such as nonlinear optical effects can be exploited at the nanoscale. We describe the fabrication of polydimethylsiloxane (PDMS) microfluidics as well as indium tin oxide (ITO) electrodes with different design for dedicated applications. The control of microfluidic channel dimensions and the corresponding particle concentration is explored. Finally, the selection of fluidic conductivity for optimal dielectrophoretic trapping conditions is discussed

    Second harmonic nanoparticles in imaging applications

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    Nanocrystals with second harmonic response is a new class of nonlinear optical nanoprobes with dramatically different properties from fluorescent agents. Compared with two-photon fluorescence, second harmonic generation is an ultrafast, lossless, and coherent process. In particular, the absence of photobleaching and emission intermittency in the optical response of the second harmonic nanoparticles is likely to complement the fluorescent agents widely used today in many imaging applications. Furthermore, the coherent emission from the second harmonic generation process provides unique opportunities for the application of coherence domain techniques that are not available with fluorescent agents. We review the application of the second harmonic nanocrystals in imaging applications, especially those pertaining to biomedicine

    The RCSB Protein Data Bank: views of structural biology for basic and applied research and education.

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    The RCSB Protein Data Bank (RCSB PDB, http://www.rcsb.org) provides access to 3D structures of biological macromolecules and is one of the leading resources in biology and biomedicine worldwide. Our efforts over the past 2 years focused on enabling a deeper understanding of structural biology and providing new structural views of biology that support both basic and applied research and education. Herein, we describe recently introduced data annotations including integration with external biological resources, such as gene and drug databases, new visualization tools and improved support for the mobile web. We also describe access to data files, web services and open access software components to enable software developers to more effectively mine the PDB archive and related annotations. Our efforts are aimed at expanding the role of 3D structure in understanding biology and medicine

    Nutrition provider confidence in the Massachusetts Childhood Obesity Research Demonstration (MA-CORD) study

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    Objective: The multi-sector, multi-level Massachusetts Childhood Obesity Research Demonstration (MA-CORD) study resulted in improvements in obesity risk factors among children age 2-4 years enrolled in the Special Supplemental Nutrition program for Women, Infants, and Children (WIC). The goal of this study was to examine whether the MA-CORD intervention increased WIC provider confidence in their ability to identify childhood obesity and obesity-related behaviors. Methods: As part of the MA-CORD intervention conducted from 2012 to 2015, we implemented WIC practice changes focused on childhood obesity prevention within two Massachusetts communities. We examined changes in provider confidence to assess childhood obesity risk factors and practice frequency among WIC practices located in MA-CORD intervention communities over a 3-year period, compared to non-intervention sites. We measured provider confidence on a continuous scale using questions previously developed to assess provider and parent confidence to make weight-related behavior change (range 0 to 24). Results: There were 205 providers at baseline and 165 at follow-up. WIC providers at intervention sites reported greater confidence in their ability to identify childhood obesity and obesity-related behaviors compared to the usual care sites (β = 1.01, standard error = 0.13). These findings persisted after adjusting for provider gender, years in practice, highest education level, and WIC position. Conclusions: The MA-CORD intervention was associated with increased WIC provider confidence to assess children's obesity risk. Interventions that increase confidence in assessing obesity-related behaviors may have salutary effects within WIC programs that serve low-income families

    Virulence determinants, drug resistance and mobile genetic elements of Laribacter hongkongensis: a genome-wide analysis

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    <p>Abstract</p> <p>Background</p> <p><it>Laribacter hongkongensis </it>is associated with community-acquired gastroenteritis and traveler's diarrhea. In this study, we performed an in-depth annotation of the genes in its genome related to the various steps in the infective process, drug resistance and mobile genetic elements.</p> <p>Results</p> <p>For acid and bile resistance, <it>L. hongkongensis </it>possessed a urease gene cassette, two <it>arc </it>gene clusters and bile salt efflux systems. For intestinal colonization, it possessed a putative adhesin of the autotransporter family homologous to those of diffusely adherent <it>Escherichia coli </it>(<it>E. coli</it>) and enterotoxigenic <it>E. coli</it>. To evade from host defense, it possessed superoxide dismutase and catalases. For lipopolysaccharide biosynthesis, it possessed the same set of genes that encode enzymes for synthesizing lipid A, two Kdo units and heptose units as <it>E. coli</it>, but different genes for its symmetrical acylation pattern, and nine genes for polysaccharide side chains biosynthesis. It contained a number of CDSs that encode putative cell surface acting (RTX toxin and hemolysins) and intracellular cytotoxins (patatin-like proteins) and enzymes for invasion (outer membrane phospholipase A). It contained a broad variety of antibiotic resistance-related genes, including genes related to β-lactam (n = 10) and multidrug efflux (n = 54). It also contained eight prophages, 17 other phage-related CDSs and 26 CDSs for transposases.</p> <p>Conclusions</p> <p>The <it>L. hongkongensis </it>genome possessed genes for acid and bile resistance, intestinal mucosa colonization, evasion of host defense and cytotoxicity and invasion. A broad variety of antibiotic resistance or multidrug resistance genes, a high number of prophages, other phage-related CDSs and CDSs for transposases, were also identified.</p

    Transport genes and chemotaxis in Laribacter hongkongensis: a genome-wide analysis

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    <p>Abstract</p> <p>Background</p> <p><it>Laribacter hongkongensis </it>is a Gram-negative, sea gull-shaped rod associated with community-acquired gastroenteritis. The bacterium has been found in diverse freshwater environments including fish, frogs and drinking water reservoirs. Using the complete genome sequence data of <it>L. hongkongensis</it>, we performed a comprehensive analysis of putative transport-related genes and genes related to chemotaxis, motility and quorum sensing, which may help the bacterium adapt to the changing environments and combat harmful substances.</p> <p>Results</p> <p>A genome-wide analysis using Transport Classification Database TCDB, similarity and keyword searches revealed the presence of a large diversity of transporters (n = 457) and genes related to chemotaxis (n = 52) and flagellar biosynthesis (n = 40) in the <it>L. hongkongensis </it>genome. The transporters included those from all seven major transporter categories, which may allow the uptake of essential nutrients or ions, and extrusion of metabolic end products and hazardous substances. <it>L. hongkongensis </it>is unique among closely related members of <it>Neisseriaceae </it>family in possessing higher number of proteins related to transport of ammonium, urea and dicarboxylate, which may reflect the importance of nitrogen and dicarboxylate metabolism in this assacharolytic bacterium. Structural modeling of two C<sup><sub>4</sub></sup>-dicarboxylate transporters showed that they possessed similar structures to the determined structures of other DctP-TRAP transporters, with one having an unusual disulfide bond. Diverse mechanisms for iron transport, including hemin transporters for iron acquisition from host proteins, were also identified. In addition to the chemotaxis and flagella-related genes, the <it>L. hongkongensis </it>genome also contained two copies of <it>qseB/qseC </it>homologues of the AI-3 quorum sensing system.</p> <p>Conclusions</p> <p>The large number of diverse transporters and genes involved in chemotaxis, motility and quorum sensing suggested that the bacterium may utilize a complex system to adapt to different environments. Structural modeling will provide useful insights on the transporters in <it>L. hongkongensis</it>.</p

    Pregnancy cohorts and biobanking in sub-Saharan Africa: a systematic review

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    Background: Technological advances and high throughput biological assays can facilitate discovery science in biobanks from population cohorts, including pregnant women. Biological pathways associated with health outcomes differ depending on geography, and high-income country data may not generalise to low-resource settings. We conducted a systematic review to identify prospective pregnancy cohorts in sub-Saharan Africa (SSA) that include biobanked samples with potential to enhance discovery science opportunity. Methods: Inclusion criteria were prospective data collection during pregnancy, with associated biobanking in SSA. Data sources included: scientific databases (with comprehensive search terms), grey literature, hand searching applicable reference lists and expert input. Results were screened in a three-stage process based on title, abstract and full text by two independent reviewers. The review is registered on PROSPERO (CRD42019147483). Results: Fourteen SSA studies met the inclusion criteria from database searches (n=8), reference list searches (n=2) and expert input (n=4). Three studies have ongoing data collection. The most represented countries were South Africa and Mozambique (Southern Africa) (n=3), Benin (Western Africa) (n=4) and Tanzania (Eastern Africa) (n=4); including an estimated 31 763 women. Samples commonly collected were blood, cord blood and placenta. Seven studies collected neonatal samples. Common clinical outcomes included maternal and perinatal mortality, malaria and preterm birth. Conclusions: Increasingly numerous pregnancy cohorts in SSA that include biobanking are generating a uniquely valuable resource for collaborative discovery science, and improved understanding of the high regional risks of maternal, fetal and neonatal morbidity and mortality. Future studies should align protocols and consider their added value and distinct contributions

    The Lick AGN Monitoring Project: Reverberation Mapping of Optical Hydrogen and Helium Recombination Lines

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    We have recently completed a 64-night spectroscopic monitoring campaign at the Lick Observatory 3-m Shane telescope with the aim of measuring the masses of the black holes in 12 nearby (z < 0.05) Seyfert 1 galaxies with expected masses in the range ~10^6-10^7M_sun and also the well-studied nearby active galactic nucleus (AGN) NGC 5548. Nine of the objects in the sample (including NGC 5548) showed optical variability of sufficient strength during the monitoring campaign to allow for a time lag to be measured between the continuum fluctuations and the response to these fluctuations in the broad Hbeta emission, which we have previously reported. We present here the light curves for the Halpha, Hgamma, HeII 4686, and HeI 5876 emission lines and the time lags for the emission-line responses relative to changes in the continuum flux. Combining each emission-line time lag with the measured width of the line in the variable part of the spectrum, we determine a virial mass of the central supermassive black hole from several independent emission lines. We find that the masses are generally consistent within the uncertainties. The time-lag response as a function of velocity across the Balmer line profiles is examined for six of the AGNs. Finally we compare several trends seen in the dataset against the predictions from photoionization calculations as presented by Korista & Goad. We confirm several of their predictions, including an increase in responsivity and a decrease in the mean time lag as the excitation and ionization level for the species increases. Further confirmation of photoionization predictions for broad-line gas behavior will require additional monitoring programs for these AGNs while they are in different luminosity states. [abridged]Comment: 37 pages, 18 figures and 15 tables, accepted for publication in the Astrophysical Journa
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