1,509 research outputs found

    Factors Influencing Bike Share Among Underserved Populations: Evidence from Three US Cities

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    There is evidence that lower-income and people of color (POC) in the U.S. do not use bike share as much as higher-income and white people. Using data from residents living near stations in New York, Chicago, and Philadelphia, our analysis examines reasons for these disparities. While smaller shares of POC are members (vs higher-income white people), large shares of POC are interested in bike share. Among POC, having positive attitudes about bicycling and having family and friends that use bike share are strong predictors of interest in bike share. POC are also motivated to use bike share for recreational reasons. Receiving information from interactive sources may be effective at increasing bike share use and interest, though it is not clear whether these efforts have affected POC. Cost is a barrier for people who have tried bike share and are interested in using it in the future but are not members

    Annexin-A5 assembled into two-dimensional arrays promotes cell membrane repair

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    Eukaryotic cells possess a universal repair machinery that ensures rapid resealing of plasma membrane disruptions. Before resealing, the torn membrane is submitted to considerable tension, which functions to expand the disruption. Here we show that annexin-A5 (AnxA5), a protein that self-assembles into two-dimensional (2D) arrays on membranes upon Ca2+ activation, promotes membrane repair. Compared with wild-type mouse perivascular cells, AnxA5-null cells exhibit a severe membrane repair defect. Membrane repair in AnxA5-null cells is rescued by addition of AnxA5, which binds exclusively to disrupted membrane areas. In contrast, an AnxA5 mutant that lacks the ability of forming 2D arrays is unable to promote membrane repair. We propose that AnxA5 participates in a previously unrecognized step of the membrane repair process: triggered by the local influx of Ca2+, AnxA5 proteins bind to torn membrane edges and form a 2D array, which prevents wound expansion and promotes membrane resealing

    Exploring the correlation between lipid packaging in lipoplexes and their transfection efficacy

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    Whilst there is a large body of evidence looking at the design of cationic liposomes as transfection agents, correlates of formulation to function remain elusive. In this research, we investigate if lipid packaging can give further insights into transfection efficacy. DNA lipoplexes composed of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) or 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) in combination with 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) or 1,2-stearoyl-3-trimethylammonium-propane (DSTAP) were prepared by the lipid hydration method. Each of the formulations was prepared by hydration in dH2O or phosphate buffer saline (PBS) to investigate the effect of buffer salts on lipoplex physicochemical characteristics and in vitro transfection. In addition, Langmuir monolayer studies were performed to investigate any possible correlation between lipid packaging and liposome attributes. Using PBS, rather than dH2O, to prepare the lipoplexes increased the size of vesicles in most of formulations and resulted in variation in transfection efficacies. However, one combination of lipids (DSPE:DOTAP) could not form liposomes in PBS, whilst the DSPE:DSTAP combination could not form liposomes in either aqueous media. Monolayer studies demonstrated saturated lipid combinations offered dramatically closer molecular packing compared to the other combinations which could suggest why this lipid combination could not form vesicles. Of the lipoplexes prepared, those formulated with DSTAP showed higher transfection efficacy, however, the effect of buffer on transfection efficiency was formulation dependent

    Circuit Quantum Electrodynamics with a Spin Qubit

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    Circuit quantum electrodynamics allows spatially separated superconducting qubits to interact via a "quantum bus", enabling two-qubit entanglement and the implementation of simple quantum algorithms. We combine the circuit quantum electrodynamics architecture with spin qubits by coupling an InAs nanowire double quantum dot to a superconducting cavity. We drive single spin rotations using electric dipole spin resonance and demonstrate that photons trapped in the cavity are sensitive to single spin dynamics. The hybrid quantum system allows measurements of the spin lifetime and the observation of coherent spin rotations. Our results demonstrate that a spin-cavity coupling strength of 1 MHz is feasible.Comment: Related papers at http://pettagroup.princeton.edu

    Promotion of plasma membrane repair by vitamin E

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    Severe vitamin E deficiency results in lethal myopathy in animal models. Membrane repair is an important myocyte response to plasma membrane disruption injury as when repair fails, myocytes die and muscular dystrophy ensues. Here we show that supplementation of cultured cells with α-tocopherol, the most common form of vitamin E, promotes plasma membrane repair. Conversely, in the absence of α-tocopherol supplementation, exposure of cultured cells to an oxidant challenge strikingly inhibits repair. Comparative measurements reveal that, to promote repair, an anti-oxidant must associate with membranes, as α-tocopherol does, or be capable of α-tocopherol regeneration. Finally, we show that myocytes in intact muscle cannot repair membranes when exposed to an oxidant challenge, but show enhanced repair when supplemented with vitamin E. Our work suggests a novel biological function for vitamin E in promoting myocyte plasma membrane repair. We propose that this function is essential for maintenance of skeletal muscle homeostasis

    A vine copula mixed effect model for trivariate meta-analysis of diagnostic test accuracy studies accounting for disease prevalence

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    A bivariate copula mixed model has been recently proposed to synthesize diagnostic test accuracy studies and it has been shown that it is superior to the standard generalized linear mixed model in this context. Here, we call trivariate vine copulas to extend the bivariate meta-analysis of diagnostic test accuracy studies by accounting for disease prevalence. Our vine copula mixed model includes the trivariate generalized linear mixed model as a special case and can also operate on the original scale of sensitivity, specificity, and disease prevalence. Our general methodology is illustrated by re-analyzing the data of two published meta-analyses. Our study suggests that there can be an improvement on trivariate generalized linear mixed model in fit to data and makes the argument for moving to vine copula random effects models especially because of their richness, including reflection asymmetric tail dependence, and computational feasibility despite their three dimensionality

    Hsp90 governs dispersion and drug resistance of fungal biofilms

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    Fungal biofilms are a major cause of human mortality and are recalcitrant to most treatments due to intrinsic drug resistance. These complex communities of multiple cell types form on indwelling medical devices and their eradication often requires surgical removal of infected devices. Here we implicate the molecular chaperone Hsp90 as a key regulator of biofilm dispersion and drug resistance. We previously established that in the leading human fungal pathogen, Candida albicans, Hsp90 enables the emergence and maintenance of drug resistance in planktonic conditions by stabilizing the protein phosphatase calcineurin and MAPK Mkc1. Hsp90 also regulates temperature-dependent C. albicans morphogenesis through repression of cAMP-PKA signalling. Here we demonstrate that genetic depletion of Hsp90 reduced C. albicans biofilm growth and maturation in vitro and impaired dispersal of biofilm cells. Further, compromising Hsp90 function in vitro abrogated resistance of C. albicans biofilms to the most widely deployed class of antifungal drugs, the azoles. Depletion of Hsp90 led to reduction of calcineurin and Mkc1 in planktonic but not biofilm conditions, suggesting that Hsp90 regulates drug resistance through different mechanisms in these distinct cellular states. Reduction of Hsp90 levels led to a marked decrease in matrix glucan levels, providing a compelling mechanism through which Hsp90 might regulate biofilm azole resistance. Impairment of Hsp90 function genetically or pharmacologically transformed fluconazole from ineffectual to highly effective in eradicating biofilms in a rat venous catheter infection model. Finally, inhibition of Hsp90 reduced resistance of biofilms of the most lethal mould, Aspergillus fumigatus, to the newest class of antifungals to reach the clinic, the echinocandins. Thus, we establish a novel mechanism regulating biofilm drug resistance and dispersion and that targeting Hsp90 provides a much-needed strategy for improving clinical outcome in the treatment of biofilm infections

    The GALNTL6 Gene rs558129 Polymorphism Is Associated With Power Performance

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    Diaz, J, alvarez Herms, J, Castaneda, A, Larruskain, J, Ramirez de la Piscina, X, Borisov, OV, Semenova, EA, Kostryukova, ES, Kulemin, NA, Andryushchenko, ON, Larin, AK, Andryushchenko, LB, Generozov, EV, Ahmetov, II, and Odriozola, A. The GALNTL6 gene rs558129 polymorphism is associated with power performance. J Strength Cond Res 34(11): 3031-3036, 2020-The largest genome-wide association study to date in sports genomics showed that endurance athletes were 1.23 times more likely to possess the C allele of the single nucleotide polymorphism rs558129 of N-acetylgalactosaminyltransferase-like 6 gene (GALNTL6), compared with controls. Nevertheless, no further study has investigated GALNTL6 gene in relation to physical performance. Considering that previous research has shown that the same polymorphism can be associated with both endurance and power phenotypes (ACTN3, ACE, and PPARA), we investigated the association between GALNTL6 rs558129 polymorphism and power performance. According to this objective we conducted 2 global studies regarding 2 different communities of athletes in Spain and Russia. The first study involved 85 Caucasian physically active men from the north of Spain to perform a Wingate anaerobic test (WAnT). In the second study we compared allelic frequencies between 173 Russian power athletes (49 strength and 124 speed-strength athletes), 169 endurance athletes, and 201 controls. We found that physically active men with the T allele of GALNTL6 rs558129 had 5.03-6.97% higher power values compared with those with the CC genotype (p < 0.05). Consistent with these findings, we have shown that the T allele was over-represented in power athletes (37.0%) compared with endurance athletes (29.3%; OR = 1.4, p = 0.032) and controls (28.6%; OR = 1.5, p = 0.015). Furthermore, the highest frequency of the T allele was observed in strength athletes (43.9%; odds ratio [OR] = 1.9, p = 0.0067 compared with endurance athletes; OR = 2.0, p = 0.0036 compared with controls). In conclusion, our data suggest that the GALNTL6 rs558129 T allele can be favorable for anaerobic performance and strength athletes. In addition, we propose a new possible functional role of GALNTL6 rs558129, gut microbiome regarding short-chain fatty acid regulation and their anti-inflammatory and resynthesis functions. Nevertheless, further studies are required to understand the mechanisms involved.The authors would like to thank all the staff and athletes who participated in the study and the ZuOK Center where sports testing were performed. J. Larruskain was supported by a PhD Studentship from the Vice-Chancellorship for Basque of the University of the Basque Country UPV/EHU (EuskararenarlokoErrektoreordetza). J. Diaz and J. Alvarez Herms have contributed equally to this manuscrip
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