212 research outputs found

    Optical Tools for Single-Cell Manipulation and Analysis

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    Factors Related to Accelerometer-determined Patterns of Physical Activity in Adults: The Houston TRAIN Study

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    Meeting U.S. Physical Activity (PA) Guidelines has health benefits. Yet, little is known about the factors related to changes in PA over time, particularly among minority populations. PURPOSE: To examine sociodemographic, PA preferences, and health factors related to accelerometer-derived patterns of 1-year PA change in the Houston Travel Related Activity in Neighborhoods (TRAIN) Study, a majority-minority cohort. METHODS: Participants wore an ActiGraph wGT3X-BT monitor and completed self-report surveys at baseline and follow-up. Valid wear time was defined as ≥ 4 days, ≥ 10 hrs/day. PA was stratified by meeting Guidelines using total MVPA, defined by Freedson. Four PA patterns were defined: (i) ‘maintain high’ activity above Guidelines, (ii) ‘increased’ to meet Guidelines, (iii) ‘decreased’ from meet to not meet Guidelines, and (iv) ‘maintained low’ activity. Multinomial logistic regression was used to examine associations between studied factors and each PA pattern, with the ‘maintain high’ group as referent. RESULTS: Complete data were available for 153 adults (19% maintained high activity, 8.5% increased, 13% decreased, 59.5% maintained low activity). Controlling for all variables, males (OR = 0.3, 95% CI = 0.1, 0.9) had lower odds of being in the ‘maintain low’ group. Blacks (vs. whites, OR = 18.8, 95% CI = 2.6, 275.0), those liking biking (vs. strongly liking, OR = 4.6, 95% CI = 1.3, 15.6), and older participants (vs. younger, on continuous scale, OR = 1.1, 95% CI = 1.0, 1.1) had higher odds of being in the ‘maintain low’ group. Factors directly associated with being in the ‘increased’ group were being black (vs. white, OR = 17.9, 95% CI = 1.3, 120.9), strong dislike for biking (vs. strongly liking OR = 25.2, 95% CI = 1.6, 401.3), and having more chronic diseases (vs. less, on continuous scale, 95% CI = 1.5, 11.7). Having low educational attainment (vs. high, OR = 0.04, 95% CI = 0.0, 0.9) was inversely associated with being in the ‘increased’ group. No studied factors were significantly associated with being in the ‘decreased’ group. CONCLUSION: PA patterns are dynamic and suggest that sociodemographic, PA preferences, and health factors relate to change patterns over time. Future studies should examine the role of these factors over longer follow-up periods, and consider these factors when designing interventions

    The impact of diabetes on the pathogenesis of sepsis

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    Diabetes is associated with an increased susceptibility to infection and sepsis. Conflicting data exist on whether the mortality of patients with sepsis is influenced by the presence of diabetes, fuelling the ongoing debate on the benefit of tight glucose regulation in patients with sepsis. The main reason for which diabetes predisposes to infection appears to be abnormalities of the host response, particularly in neutrophil chemotaxis, adhesion and intracellular killing, defects that have been attributed to the effect of hyperglycaemia. There is also evidence for defects in humoral immunity, and this may play a larger role than previously recognised. We review the literature on the immune response in diabetes and its potential contribution to the pathogenesis of sepsis. In addition, the effect of diabetes treatment on the immune response is discussed, with specific reference to insulin, metformin, sulphonylureas and thiazolidinediones

    Integrated high-content quantification of intracellular ROS levels and mitochondrial morphofunction

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    Oxidative stress arises from an imbalance between the production of reactive oxygen species (ROS) and their removal by cellular antioxidant systems. Especially under pathological conditions, mitochondria constitute a relevant source of cellular ROS. These organelles harbor the electron transport chain, bringing electrons in close vicinity to molecular oxygen. Although a full understanding is still lacking, intracellular ROS generation and mitochondrial function are also linked to changes in mitochondrial morphology. To study the intricate relationships between the different factors that govern cellular redox balance in living cells, we have developed a high-contentmicroscopy-based strategy for simultaneous quantification of intracellular ROS levels and mitochondrial morphofunction. Here, we summarize the principles of intracellular ROS generation and removal, and we explain the major considerations for performing quantitative microscopy analyses of ROS and mitochondrial morphofunction in living cells. Next, we describe our workflow, and finally, we illustrate that a multiparametric readout enables the unambiguous classification of chemically perturbed cells as well as laminopathy patient cells

    Combined Forward-Backward Asymmetry Measurements in Top-Antitop Quark Production at the Tevatron

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    The CDF and D0 experiments at the Fermilab Tevatron have measured the asymmetry between yields of forward- and backward-produced top and antitop quarks based on their rapidity difference and the asymmetry between their decay leptons. These measurements use the full data sets collected in proton-antiproton collisions at a center-of-mass energy of s=1.96\sqrt s =1.96 TeV. We report the results of combinations of the inclusive asymmetries and their differential dependencies on relevant kinematic quantities. The combined inclusive asymmetry is AFBttˉ=0.128±0.025A_{\mathrm{FB}}^{t\bar{t}} = 0.128 \pm 0.025. The combined inclusive and differential asymmetries are consistent with recent standard model predictions

    Politics, 1641-1660

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    Multi-messenger observations of a binary neutron star merger

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    On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

    Multimessenger Search for Sources of Gravitational Waves and High-Energy Neutrinos: Results for Initial LIGO-Virgo and IceCube

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    We report the results of a multimessenger search for coincident signals from the LIGO and Virgo gravitational-wave observatories and the partially completed IceCube high-energy neutrino detector, including periods of joint operation between 2007-2010. These include parts of the 2005-2007 run and the 2009-2010 run for LIGO-Virgo, and IceCube's observation periods with 22, 59 and 79 strings. We find no significant coincident events, and use the search results to derive upper limits on the rate of joint sources for a range of source emission parameters. For the optimistic assumption of gravitational-wave emission energy of 10210^{-2}\,M_\odotc2^2 at 150\sim 150\,Hz with 60\sim 60\,ms duration, and high-energy neutrino emission of 105110^{51}\,erg comparable to the isotropic gamma-ray energy of gamma-ray bursts, we limit the source rate below 1.6×1021.6 \times 10^{-2}\,Mpc3^{-3}yr1^{-1}. We also examine how combining information from gravitational waves and neutrinos will aid discovery in the advanced gravitational-wave detector era

    Finishing the euchromatic sequence of the human genome

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    The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead
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