A Novel 110-kDa Receptor Protein is Involved in Endocytic Uptake of Decorin by Human Skin Fibroblasts

The small leucine-rich proteoglycan (SLRP) decorin is efficiently internalized by a variety of cultured cells. A 51-kDa protein has previously been described as a receptor mediating endocytosis of decorin and of the structurally related SLRP biglycan. Recent findings suggest that endocytosis of SLRPs may also be mediated by additional receptors. The class-A scavenger receptor, the endocytic mannose receptor, the epidermal growth factor receptor, and insulin-like growth factor-I receptor have emerged as candidates. We used a combined approach of immunoprecipitation and photoactivated cross-linking to identify endocytosis receptors for decorin in human skin fibroblasts. Decorin was purified by HPLC-DEAE-ion exchange chromatography from the secretions of human skin fibroblasts under nondenaturing conditions. Confocal immunofluorescence microscopy revealed that both biotinylated decorin and decorin conjugated to the heterobifunctional cross-linker sulfosuccinimidyl 2-(p-azidosalicylamido)ethyl-1-3'-dithiopropionate (SASD) were endocytosed with equal efficiency. SASD-conjugated decorin was added to [35S]-methionine-labeled fibroblasts and cross-linked intracellularly to receptor molecules by photoactivation on endocytic uptake. Cross-linked decorin-receptor complexes were purified from the extracts of trypsin-treated fibroblasts by anion exchange chromatography and immunoprecipitation with a decorin-specific antiserum. Analysis by 2D electrophoresis and autoradiography revealed that decorin was specifically cross-linked to a protein of 110 kDa, which exhibited an isoelectric point of 5.5. In a second approach, unlabeled fibroblasts were subjected to decorin endocytosis and photoactivated cross-linking followed by Western blotting of DEAE-purified cell extracts. A shift of biotinylated decorin immunoreactivity from 165 kDa (decorin-receptor complex) to 54 kDa (SASD-conjugated biotinylated decorin) was noted on reductive cleavage of the cross-linker, representing a difference in molecular weight of approximately 110 kDa. The identification of a 110-kDa protein as a novel endocytosis receptor for decorin provides further support for the emerging concept of a redundancy of receptor molecules in the endocytosis of SLRP

Incentive payments are not related to expected health gain in the pay for performance scheme for UK primary care: cross-sectional analysis

Background: The General Medical Services primary care contract for the United Kingdom financially rewards performance in 19 clinical areas, through the Quality and Outcomes Framework. Little is known about how best to determine the size of financial incentives in pay for performance schemes. Our aim was to test the hypothesis that performance indicators with larger population health benefits receive larger financial incentives. Methods: We performed cross sectional analyses to quantify associations between the size of financial incentives and expected health gain in the 2004 and 2006 versions of the Quality and Outcomes Framework. We used non-parametric two-sided Spearman rank correlation tests. Health gain was measured in expected lives saved in one year and in quality adjusted life years. For each quality indicator in an average sized general practice we tested for associations first, between the marginal increase in payment and the health gain resulting from a one percent point improvement in performance and second, between total payment and the health gain at the performance threshold for maximum payment. Results: Evidence for lives saved or quality adjusted life years gained was found for 28 indicators accounting for 41% of the total incentive payments. No statistically significant associations were found between the expected health gain and incentive gained from a marginal 1% increase in performance in either the 2004 or 2006 version of the Quality and Outcomes Framework. In addition no associations were found between the size of financial payment for achievement of an indicator and the expected health gain at the performance threshold for maximum payment measured in lives saved or quality adjusted life years. Conclusions: In this subgroup of indicators the financial incentives were not aligned to maximise health gain. This disconnection between incentive and expected health gain risks supporting clinical activities that are only marginally effective, at the expense of more effective activities receiving lower incentives. When designing pay for performance programmes decisions about the size of the financial incentive attached to an indicator should be informed by information on the health gain to be expected from that indicator

The role of thermal energy accommodation and atomic recombination probabilities in low pressure oxygen plasmas

International audienceSurface interaction probabilities are critical parameters that determine the behaviour of low pressure plasmas and so are crucial input parameters for plasma simulations that play a key role in determining their accuracy. However, these parameters are difficult to estimate without in situ measurements. In this work, the role of two prominent surface interaction probabilities, the atomic oxygen recombination coefficient ? O and the thermal energy accommodation coefficient ? E in determining the plasma properties of low pressure inductively coupled oxygen plasmas are investigated using two-dimensional fluid-kinetic simulations. These plasmas are the type used for semiconductor processing. It was found that ? E plays a crucial role in determining the neutral gas temperature and neutral gas density. Through this dependency, the value of ? E also determines a range of other plasma properties such as the atomic oxygen density, the plasma potential, the electron temperature, and ion bombardment energy and neutral-to-ion flux ratio at the wafer holder. The main role of ? O is in determining the atomic oxygen density and flux to the wafer holder along with the neutral-to-ion flux ratio. It was found that the plasma properties are most sensitive to each coefficient when the value of the coefficient is small causing the losses of atomic oxygen and thermal energy to be surface interaction limited rather than transport limited