114 research outputs found

    Developing 21st century accreditation standards for teaching hospitals: the Taiwan experience

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    <p>Abstract</p> <p>Background</p> <p>The purpose of this study is to establish teaching hospital accreditation standards anew with the hope that Taiwan's teaching hospitals can live up to the expectations of our society and ensure quality teaching.</p> <p>Methods</p> <p>The development process lasted two years, 2005-2006, and was separated into three stages. The first stage centered on leadership meetings and consensus building, the second on drafting the new standards with expert focus groups, and the third on a pilot study and subsequent revision.</p> <p>Results</p> <p>Our new teaching hospital accreditation standards have six categories and 95 standards as follows: educational resources (20 items), teaching and training plans and outcomes (42 items), research and results (9 items), development of clinical faculty and continuing education (8 items), academic exchanges and community education (8 items), and administration (8 items).</p> <p>Conclusions</p> <p>The new standards have proven feasible and posed reasonable challenges in the pilot study. We hope the new standards will strengthen teaching and research, and improve the quality of hospital services at the same time.</p

    A model of feedback control for the charge-balanced suppression of epileptic seizures

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    Here we present several refinements to a model of feedback control for the suppression of epileptic seizures. We utilize a stochastic partial differential equation (SPDE) model of the human cortex. First, we verify the strong convergence of numerical solutions to this model, paying special attention to the sharp spatial changes that occur at electrode edges. This allows us to choose appropriate step sizes for our simulations; because the spatial step size must be small relative to the size of an electrode in order to resolve its electrical behavior, we are able to include a more detailed electrode profile in the simulation. Then, based on evidence that the mean soma potential is not the variable most closely related to the measurement of a cortical surface electrode, we develop a new model for this. The model is based on the currents flowing in the cortex and is used for a simulation of feedback control. The simulation utilizes a new control algorithm incorporating the total integral of the applied electrical potential. Not only does this succeed in suppressing the seizure-like oscillations, but it guarantees that the applied signal will be charge-balanced and therefore unlikely to cause cortical damage

    Impact of glucocorticoid receptor density on ligand-independent dimerization, cooperative ligand-binding and basal priming of transactivation: a cell culture model

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    Glucocorticoid receptor (GR) levels vary between tissues and individuals and are altered by physiological and pharmacological effectors. However, the effects and implications of differences in GR concentration have not been fully elucidated. Using three statistically different GR concentrations in transiently transfected COS-1 cells, we demonstrate, using co-immunoprecipitation (CoIP) and fluorescent resonance energy transfer (FRET), that high levels of wild type GR (wtGR), but not of dimerization deficient GR (GRdim), display ligand-independent dimerization. Whole-cell saturation ligand-binding experiments furthermore establish that positive cooperative ligand-binding, with a concomitant increased ligand-binding affinity, is facilitated by ligand-independent dimerization at high concentrations of wtGR, but not GRdim. The down-stream consequences of ligand-independent dimerization at high concentrations of wtGR, but not GRdim, are shown to include basal priming of the system as witnessed by ligand-independent transactivation of both a GRE-containing promoter-reporter and the endogenous glucocorticoid (GC)-responsive gene, GILZ, as well as ligand-independent loading of GR onto the GILZ promoter. Pursuant to the basal priming of the system, addition of ligand results in a significantly greater modulation of transactivation potency than would be expected solely from the increase in ligand-binding affinity. Thus ligand-independent dimerization of the GR at high concentrations primes the system, through ligand-independent DNA loading and transactivation, which together with positive cooperative ligand-binding increases the potency of GR agonists and shifts the bio-character of partial GR agonists. Clearly GR-levels are a major factor in determining the sensitivity to GCs and a critical factor regulating transcriptional programs

    Crystal structure of oxygen-evolving photosystem II at a resolution of 1.9 Å

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    Photosystem II is the site of photosynthetic water oxidation and contains 20 subunits with a total molecular mass of 350 kDa. The structure of photosystem II has been reported at resolutions from 3.8 to 2.9 angstrom. These resolutions have provided much information on the arrangement of protein subunits and cofactors but are insufficient to reveal the detailed structure of the catalytic centre of water splitting. Here we report the crystal structure of photosystem II at a resolution of 1.9 angstrom. From our electron density map, we located all of the metal atoms of the Mn(4)CaO(5) cluster, together with all of their ligands. We found that five oxygen atoms served as oxo bridges linking the five metal atoms, and that four water molecules were bound to the Mn(4)CaO(5) cluster; some of them may therefore serve as substrates for dioxygen formation. We identified more than 1,300 water molecules in each photosystem II monomer. Some of them formed extensive hydrogen-bonding networks that may serve as channels for protons, water or oxygen molecules. The determination of the high-resolution structure of photosystem II will allow us to analyse and understand its functions in great detail

    Depolarized resonance light scattering by porphyrin and chlorophyll a aggregates.

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    A quantum mechanical model is developed for the observed resonance enhancement of light scattering by aggregates of electronically interacting chromophores. Aggregate size, monomer oscillator strength, extent of electronic coupling, and aggregate geometry are all important determinants of intensity in resonance light scattering (RLS) spectra. The theory also predicts the value of the depolarization ratio (rho(v)(90)) of RLS for a given aggregate geometry. These results are used to interpret the RLS depolarization ratios of four aggregates: tetrakis(4-sulfonatophenyl)porphine aggregated at low pH (rho(v)(90) = 0.17 at 488 nm), trans-bis(N-methylpyridinium-4-yl)-diphenylporphinato copper(II) aggregated in 0.2 M NaCl solution (rho(v)(90) = 0.13 at 450 nm) and on calf thymus DNA (rho(v)(90) = 0.20 at 454 nm), and chlorophyll a aggregates in formamide/water (rho(v)(90) = 0.23 and 0.32 at 469 and 699 nm, respectively). The analysis is consistent with a J-aggregate geometry for all four systems. Furthermore, the specific values of rho(v)(90) allow us to estimate the orientation of the monomer transition dipoles with respect to the long axis of the aggregate. We conclude that depolarized resonance light scattering spectroscopy is a powerful probe of the geometric and electronic structures of extended aggregates of strong chromophores

    Calbindin D-28k EF-hand ligand binding and oligomerization: Four high-affinity sites-three modes of action

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    Calbindin D-28k, a highly conserved protein with Ca2+-sensing and Ca2+-buffering capabilities, is abundant in brain and sensory neurons. This protein contains six EF-hand subdomains, four of which bind Call with high affinity. Calbindin D28k can be reconstituted from six synthetic peptides corresponding to the six EF-hands, indicating a single-domain structure with multiple interactions between the EF-hand subdomains. In this study, we have undertaken a detailed characterization of the Ca2+-binding and oligomerization properties of each individual EF-hand peptide using CD spectroscopy and analytical ultracentrifugation. Under the conditions tested, EF2 is monomeric and does not bind Ca2+, whereas EF6, which binds Call weakly, aggregates severely. We have therefore focused this study on the high-affinity binding sites, EF-hands 1, 3, 4, and 5. Our sedimentation equilibrium data show that, in the presence of Call, EF-hands 1, 3, 4, and 5 all form dimers in solution in which the distribution between the monomer, dimer, and higher order oligomers differs. The processes of Call binding and oligomerization are linked to different degrees, and three main mechanisms emerge. For EF-hands 1 and 5, the dimer binds Ca2+ more strongly than the monomer and Call binding drives dimerization. For EF-hand 4, dimer formation requires only one of the monomers to be Ca2+-bound. In this case, the Call affinity is independent of dimerization. For EF-hand 3, dimerization occurs both in the absence and presence of Call, while oligomerization increases in the presence of Ca2+
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