5,366 research outputs found
Some discussions on the Read Paper "Beyond subjective and objective in statistics" by A. Gelman and C. Hennig
This note is a collection of several discussions of the paper "Beyond
subjective and objective in statistics", read by A. Gelman and C. Hennig to the
Royal Statistical Society on April 12, 2017, and to appear in the Journal of
the Royal Statistical Society, Series A
Application of Peptides Containing the Cleavage Sequence of Pro-TNFα in Assessing TACE Activity of Whole Cells
Tumor necrosis factor-α (TNFα) is presumably shed from cell membranes by TNFα-cleaving enzyme (TACE). The peptides SPLAQAVRSSSR and Dabcyl-LAQAVRSSSR-Edans, each encompassing the cleavage sequence of pro-TNFα recognized by TACE, were applied to intact umbilical vein endothelium (HUVEC), peripheral blood leukocytes (PBL) and the mast cell line HMC-1, which express TACE, to homogenates of rat heart tissue and to membrane and cytoplasmic extracts of PBL. Formation of SPLAQA (specific cleavage) was determined by HPLC, while cleavage (specific plus non-specific) of Dabcyl-TNFα-Edans was followed over time by measuring fluorescence. Participation of TACE was assessed from inhibition due to the drug TAPI-2. Incubation with recombinant human TACE gave specific cleavage, fully inhibitable by TAPI-2 (IC50<0.1 μM). HUVEC rapidly degraded TNFα-peptide, but in a non-specific manner (no SPLAQA detectable) and 50 μM TAPI-2 was without effect. Fluorescence was evoked when Dabcyl-
LAQAVRSSSR-Edans was incubated with HMC-1 or PBL and also with cytoplasmic and membrane fractions of lysed PBL, but in no case was there significant inhibition by TAPI-2. However, marginal (10%) inhibition of fluorescence by 50 μM TAPI-2 was observed with homogenized heart tissue. This contained TACE, about 75% of which was without the inhibitory cysteine switch (Western blot). In conclusion, simple peptide analogs of pro-TNFα cannot be employed as substrates for measuring membrane TACE activity, largely due to extensive non-specific proteolytic cleavage by whole cells and cell extracts
Consumption and asset prices with homothetic recursive preferences
When preferences are homothetic, utility can be expressed in terms of current consumption and a variable that captures all information about future opportunities. We use this observation to express the differential equation that characterizes utility as a restriction on the information variable in terms of the dynamics of consumption. We derive the supporting price system and returns process and thereby characterize optimal consumption and portfolio decisions. We provide a fast and accurate numerical solution method and illustrate its use with a number of Markovian models. In addition, we provide insight by changing the numeraire from units of consumption to units of the consumption process. In terms of the new units, the wealth-consumption ratio (which is closely related to the information variable) is the value of a coupon bond and the existence of an infinite-horizon solution depends on the positivity of the asymptotic forward rate
Regularization in regression: comparing Bayesian and frequentist methods in a poorly informative situation
Using a collection of simulated an real benchmarks, we compare Bayesian and
frequentist regularization approaches under a low informative constraint when
the number of variables is almost equal to the number of observations on
simulated and real datasets. This comparison includes new global noninformative
approaches for Bayesian variable selection built on Zellner's g-priors that are
similar to Liang et al. (2008). The interest of those calibration-free
proposals is discussed. The numerical experiments we present highlight the
appeal of Bayesian regularization methods, when compared with non-Bayesian
alternatives. They dominate frequentist methods in the sense that they provide
smaller prediction errors while selecting the most relevant variables in a
parsimonious way
Release of TNF-α during myocardial reperfusion depends on oxidative stress and is prevented by mast cell stabilizers
Objectives: Our study sought to elucidate the role of oxidative stress for shedding of tumor necrosis factor-α (TNF-α) and for activating TNF-α-converting enzyme (TACE). Background: TNF-α, a central inflammatory cytokine, is discussed as one of the mediators of reperfusion injury. Shedding of membrane-bound pro-TNF-α is thought to be largely due to TNF-α-converting enzyme (TACE). Methods: Release of TNF-α and TACE dependency were studied in isolated rat hearts and in the human mast cell line HMC-1. Results: In reperfused hearts, interstitial release of TNF-α occurred in two phases (2–10 and >45 min). It depended on the presence of oxygen during reperfusion and was attenuated by reduced glutathione. Infusion of the oxidants H2O2 or HOCl elicited release in non-ischemic hearts. TNF-α release was inhibited in hearts treated with degranulation inhibitors ketotifen or cromoglycate, suggesting mast cells as major source for myocardial TNF-α. This was confirmed by tissue staining. Post-ischemic release of histamine, however, did not parallel that of TNF-α. Heart tissue contained mainly mature TACE. HMC-1 expressed abundant pro-TACE and cleaved the pro-TNF-α-peptide Ac-SPLAQAVRSSSR-NH2. However, cleavage was nonspecific and only partly inhibited by TACE inhibitor TAPI-2 (10–100 μmol/l), while it was stimulated by H2O2 and HOCl and fully blocked by the nonspecific metalloprotease inhibitor o-phenanthroline. Conclusions: The mechanism underlying TNF-α release from post-ischemic myocardium is oxidation-dependent but largely independent of activation of TACE. Mast cell stabilizers may be useful in preventing TNF-α release during reperfusion
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