14,707 research outputs found

    A tight coupling between Ī²\u3csub\u3e2\u3c/sub\u3eY97 and Ī²\u3csub\u3e2\u3c/sub\u3eF200 of the GABA\u3csub\u3eA\u3c/sub\u3e receptor mediates GABA binding

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    The GABAA receptor is an oligopentameric chloride channel that is activated via conformation changes induced upon the binding of the endogenous ligand, GABA, to the extracellular inter-subunit interfaces. Although dozens of amino acid residues at the Ī±/Ī² interface have been implicated in ligand binding, the structural elements that mediate ligand binding and receptor activation are not yet fully described. In this study, double-mutant cycle analysis was employed to test for possible interactions between several arginines (Ī±1R67, Ī±1R120, Ī±1R132, and Ī²2R207) and two aromatic residues (Ī²2Y97 and Ī²2F200) that are present in the ligand-binding pocket and are known to influence GABA affinity. Our results show that neither Ī±1R67 nor Ī±1R120 is functionally coupled to either of the aromatics, whereas a moderate coupling exists between Ī±1R132 and both aromatic residues. Significant functional coupling between Ī²2R207 and both Ī²2Y97 and Ī²2F200 was found. Furthermore, we identified an even stronger coupling between the two aromatics, Ī²2Y97 and Ī²2F200, and for the first time provided direct evidence for the involvement of Ī²2Y97 and Ī²2F200 in GABA binding. As these residues are tightly linked, and mutation of either has similar, severe effects on GABA binding and receptor kinetics, we believe they form a single functional unit that may directly coordinate GABA

    A spatial analysis of state banking regulation

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    We use a spatial model to investigate a stateā€™s choice of branch banking and interstate banking regimes as a function of the regime choices made by other states and other variables suggested in the literature. We extend the basic spatial econometric model by allowing spatial dependence to vary by geographic region. Our findings reveal that spatial effects have a large, statistically significant impact on state regulatory regime decisions. The importance of spatial correlation in the setting of state banking policies suggests the need to consider spatial effects in empirical models of state policies in general.Banks and banking ; Bank supervision

    Regional disparities in the spatial correlation of state income growth

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    This paper presents new evidence of spatial correlation in U.S. state income growth. We extend the basic spatial econometric model used in the growth literature by allowing spatial correlation in state income growth to vary across geographic regions. We find positive spatial correlation in income growth rates across neighboring states, but that the strength of this spatial correlation varies considerably by region. Spatial correlation in income growth is highest for states located in the Northeast and the South. Our findings have policy implications both at the state and national level, and also suggest that growth models may benefit from incorporating more complex forms of spatial correlation.Regional economics ; Income distribution

    Safety verification of a fault tolerant reconfigurable autonomous goal-based robotic control system

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    Fault tolerance and safety verification of control systems are essential for the success of autonomous robotic systems. A control architecture called Mission Data System (MDS), developed at the Jet Propulsion Laboratory, takes a goal-based control approach. In this paper, a method for converting goal network control programs into linear hybrid systems is developed. The linear hybrid system can then be verified for safety in the presence of failures using existing symbolic model checkers. An example task is simulated in MDS and successfully verified using HyTech, a symbolic model checking software for linear hybrid systems

    Effects of photoperiod extension on clock gene and neuropeptide RNA expression in the SCN of the Soay sheep

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    In mammals, changing daylength (photoperiod) is the main synchronizer of seasonal functions. The photoperiodic information is transmitted through the retino-hypothalamic tract to the suprachiasmatic nuclei (SCN), site of the master circadian clock. To investigate effects of day length change on the sheep SCN, we used in-situ hybridization to assess the daily temporal organization of expression of circadian clock genes (Per1, Per2, Bmal1 and Fbxl21) and neuropeptides (Vip, Grp and Avp) in animals acclimated to a short photoperiod (SP; 8h of light) and at 3 or 15 days following transfer to a long photoperiod (LP3, LP15, respectively; 16h of light), achieved by an acute 8-h delay of lights off. We found that waveforms of SCN gene expression conformed to those previously seen in LP acclimated animals within 3 days of transfer to LP. Mean levels of expression for Per1-2 and Fbxl21 were nearly 2-fold higher in the LP15 than in the SP group. The expression of Vip was arrhythmic and unaffected by photoperiod, while, in contrast to rodents, Grp expression was not detectable within the sheep SCN. Expression of the circadian output gene Avp cycled robustly in all photoperiod groups with no detectable change in phasing. Overall these data suggest that synchronizing effects of light on SCN circadian organisation proceed similarly in ungulates and in rodents, despite differences in neuropeptide gene expression

    Introduction: School-to-Work Policies in Industrialized Countries as Responses to Push and Pull

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    Two main forces propel policies that aim to improve the transition from school to stable employment. First is a high level of joblessness, which pushes policy makers to find solutions as quickly as possible. Because unemployment rates in most countries stay persistently higher for young people than for adults, youth unemployment in particular remains a chronic concern for public policy. This concern intensifies when demographic waves or economic recessions drive unemployment upward

    Direct Measurement of 2D and 3D Interprecipitate Distance Distributions from Atom-Probe Tomographic Reconstructions

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    Edge-to-edge interprecipitate distance distributions are critical for predicting precipitation strengthening of alloys and other physical phenomena. A method to calculate this 3D distance and the 2D interplanar distance from atom-probe tomographic data is presented. It is applied to nanometer-sized Cu-rich precipitates in an Fe-1.7 at.% Cu alloy. Experimental interprecipitate distance distributions are discussed
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