13,858 research outputs found

    Establishing an Ion Pair Interaction in the Homomeric {rho}1 {gamma}-Aminobutyric Acid Type A Receptor That Contributes to the Gating Pathway

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    {gamma}-Aminobutyric acid type A (GABAA) receptors are members of the Cys-loop superfamily of ligand-gated ion channels. Upon agonist binding, the receptor undergoes a structural transition from the closed to the open state, but the mechanism of gating is not well understood. Here we utilized a combination of conventional mutagenesis and the high precision methodology of unnatural amino acid incorporation to study the gating interface of the human homopentameric {rho}1 GABAA receptor. We have identified an ion pair interaction between two conserved charged residues, Glu92 in loop 2 of the extracellular domain and Arg258 in the pre-M1 region. We hypothesize that the salt bridge exists in the closed state by kinetic measurements and free energy analysis. Several other charged residues at the gating interface are not critical to receptor function, supporting previous conclusions that it is the global charge pattern of the gating interface that controls receptor function in the Cys-loop superfamily

    The Effect Of Spatiotemporally-Dependent Air Pollution Exposure On Birthweight In The Lanzhou Birth Cohort

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    Introduction: Low birthweight serves as a proxy risk factor for a number of conditions later in development. Of China’s urban centers, Lanzhou has long been considered one of the worst-affected cities by air pollution. Objectives: This study uses spatial heterogeneity in air pollution exposure across addresses in Lanzhou and temporal heterogeneity resulting from the differential timing of pregnancy in the Lanzhou Birth Cohort to investigate the association between PM10 exposure and birthweight. Methods: The study population consisted of 4,865 mother-child pairs from the Gansu Provincial Maternity and Child Care Hospital. Participants completed an epidemiological questionnaire and patient data were collected from hospital records. Environmental data from four monitoring stations were provided by the Gansu Provincial Environmental Monitoring Central Station. Linear regressions were used to model the relationship between mean PM10 exposure during the whole pregnancy and birthweight. Results: The lowest PM10 exposure quartiles had a mean birthweight of 3396 g, compared to a mean birthweight of 3373 g for the highest PM10 exposure quartiles. A 10 µg/m3 increase in mean PM10 exposure during the 2nd trimester was associated with an 8 g (sd 2 g) decrease in birthweight (P=0.0002) and the same increase during the 3rd trimester was associated with a 4 g (sd 1 g) decrease in birthweight (P=0.0019). Mean PM10 exposure during the whole pregnancy was not found to have significant interactions with income, maternal BMI, newborn sex, or dietary factors. Conclusion: PM10 exposure, especially during the 2nd and 3rd trimesters, may be associated with decreased birthweight. Though Lanzhou long topped lists of cities most affected by air pollution in China, the local government launched a major initiative in 2012 to significantly reduce air pollution presenting opportunities for natural experiments to understand the burden of air pollution. The findings of this study may serve as a reference for comparison of future results

    Implementation and Outcome Evaluation of the Intensive Aftercare Program: Final Report

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    This Report presents the findings from a 5-year, multisite evaluation of the implementation and outcomes of the Intensive Aftercare Program (IAP), which was sponsored by the Office of Juvenile Justice and Delinquency Prevention (OJJDP). IAP was a major initiative in aftercare programming during the 1990s and has received considerable national attention. It addresses a critical problem facing the nation's juvenile justice system: how to effectively intervene with high-risk, incarcerated juvenile offenders who have demonstrated high recidivism rates and continue to offend as adults

    Phase Structure of the Random-Plaquette Z_2 Gauge Model: Accuracy Threshold for a Toric Quantum Memory

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    We study the phase structure of the random-plaquette Z_2 lattice gauge model in three dimensions. In this model, the "gauge coupling" for each plaquette is a quenched random variable that takes the value \beta with the probability 1-p and -\beta with the probability p. This model is relevant for the recently proposed quantum memory of toric code. The parameter p is the concentration of the plaquettes with "wrong-sign" couplings -\beta, and interpreted as the error probability per qubit in quantum code. In the gauge system with p=0, i.e., with the uniform gauge couplings \beta, it is known that there exists a second-order phase transition at a certain critical "temperature", T(\equiv \beta^{-1}) = T_c =1.31, which separates an ordered(Higgs) phase at T<T_c and a disordered(confinement) phase at T>T_c. As p increases, the critical temperature T_c(p) decreases. In the p-T plane, the curve T_c(p) intersects with the Nishimori line T_{N}(p) at the certain point (p_c, T_{N}(p_c)). The value p_c is just the accuracy threshold for a fault-tolerant quantum memory and associated quantum computations. By the Monte-Carlo simulations, we calculate the specific heat and the expectation values of the Wilson loop to obtain the phase-transition line T_c(p) numerically. The accuracy threshold is estimated as p_c \simeq 0.033.Comment: 24 pages, 14 figures, some clarification

    Charging performance of a COâ‚‚ semi-clathrate hydrate based PCM in a lab-scale cold storage system

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    Cold thermal energy storage aids in the efficient deployment of thermal energy whenever there is a mismatch between energy generation and energy use. In this study, a lab-scale demonstration of cold storage system was built to investigate the performance of CO₂ semi-clathrate hydrate as a cold storage material in the charge of a realistic cold thermal storage. The experimental rig was basically a vessel equipped with an external loop and an ultrasonic crystallizer to boost the hydrate formation. The hydrate was formed from a salt solution composed of tetra-n-butyl ammonium bromide 20 wt%, tetra-n-butyl ammonium fluoride 0.25 wt% and sodium decyl sulfate 0.15 wt%. At a constant pressure condition of 5.0 bar, the hydrate formation was triggered by the heat transfer fluid at 7.5 °C. The charged cooling capacity of two control strategies, namely ‘constant pressure’ and ‘constant mass’, were compared. The repeatability and stability of hydrate formation conditions were studied. It was indicated that CO₂ semi-clathrate hydrate could serve in cold storage systems effectively. However, it was also found that under the experimental conditions, hydrate formation was hard to thoroughly complete due to the lack of sufficient driving force or heat/mass transfer
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