Effect of thiols on beta 2-adrenoceptors in human mononuclear leucocytes

The effect of the disulfide reducing agent dithiothreitol (DTT) and other thiols on binding of the beta-adrenoceptor antagonist (-)-125iodocyanopindolol (125ICYP) to human mononuclear leucocytes (MNL) was investigated. Saturation experiments and dissociation kinetics revealed two classes of specific 125ICYP binding sites, one of high and the other of low affinity, respectively. In intact MNL DTT caused a decrease in specific binding. This was due almost selectively to a decrease in the affinity of high affinity binding sites, which decreased gradually in a concentration-dependent manner to the affinity of low affinity binding sites. In MNL membranes DTT decreased not only the affinity but also the number of high affinity binding sites. The DTT effect was completely reversible by simple reoxidation on air. The structural isomers (+/-)-DTT. (-)-DTT and dithioerythritol revealed identical effects on specific binding, whereas the monothiols mercaptoethanol and alpha-monothioglycerol, having a lower redox potential, were considerably less effective. In the same concentration range that influenced specific binding. DTT stimulated intracellular cAMP production. These results suggest functionally important disulfide bridges which regulate the affinity of beta-adrenoceptor binding sites in human MNL. They stabilize the receptor in a high affinity state; their reduction causes the conversion of the high affinity state into a low affinity state in a process associated with stimulation of adenylate cyclase. Available evidence indicates that a similar transformation is made by beta-adrenoceptor agonists. Consequently low affinity 125ICYP binding sites preexistent in untreated cells could represent a reduced receptor state resulting from agonist-receptor interaction in vivo

Sputtering ion source Final report, 29 Mar. - 30 Sep. 1963

Modified sputtering ion source analyses of solid

Differential contractile response of critically ill patients to neuromuscular electrical stimulation

BACKGROUND: Neuromuscular electrical stimulation (NMES) has been investigated as a preventative measure for intensive care unit-acquired weakness. Trial results remain contradictory and therefore inconclusive. As it has been shown that NMES does not necessarily lead to a contractile response, our aim was to characterise the response of critically ill patients to NMES and investigate potential outcome benefits of an adequate contractile response. METHODS: This is a sub-analysis of a randomised controlled trial investigating early muscle activating measures together with protocol-based physiotherapy in patients with a SOFA score ≥ 9 within the first 72 h after admission. Included patients received protocol-based physiotherapy twice daily for 20 min and NMES once daily for 20 min, bilaterally on eight muscle groups. Electrical current was increased up to 70 mA or until a contraction was detected visually or on palpation. Muscle strength was measured by a blinded assessor at the first adequate awakening and ICU discharge. RESULTS: One thousand eight hundred twenty-four neuromuscular electrical stimulations in 21 patients starting on day 3.0 (2.0/6.0) after ICU admission were included in this sub-analysis. Contractile response decreased from 64.4% on day 1 to 25.0% on day 7 with a significantly lower response rate in the lower extremities and proximal muscle groups. The electrical current required to elicit a contraction did not change over time (day 1, 50.2 [31.3/58.8] mA; day 7, 45.3 [38.0/57.5] mA). The electrical current necessary for a contractile response was higher in the lower extremities. At the first awakening, patients presented with significant weakness (3.2 [2.5/3.8] MRC score). When dividing the cohort into responders and non-responders (> 50% vs. ≤ 50% contractile response), we observed a significantly higher SOFA score in non-responders. The electrical current necessary for a muscle contraction in responders was significantly lower (38.0 [32.8/42.9] vs. 54.7 [51.3/56.0] mA, p < 0.001). Muscle strength showed higher values in the upper extremities of responders at ICU discharge (4.4 [4.1/4.6] vs. 3.3 [2.8/3.8] MRC score, p = 0.036). CONCLUSION: Patients show a differential contractile response to NMES, which appears to be dependent on the severity of illness and also relevant for potential outcome benefits. TRIAL REGISTRATION: ISRCTN ISRCTN19392591 , registered 17 February 201

Comment on: ``Trace anomaly of dilaton coupled scalars in two dimensions''

The trace anomaly for nonminimally coupled scalars in spherically reduced gravity obtained by Bousso and Hawking (hep-th/9705236) is incorrect. We explain the reasons for the deviations from our correct (published) result which is supported by several other recent papers.Comment: 2 page

On the validity of statistical parametric mapping for nonuniformly and heterogeneously smooth one-dimensional biomechanical data

Nonuniform (non-constant) temporal smoothness can arise in biomechanical processes like impacts, and heterogeneous smoothness (unequal smoothness across observations) can arise in mechanically diverse comparisons such as padded vs. unpadded impacts, where padded dynamics are generally smoother than unpadded dynamics. It has been reported that statistical parametric mapping’s (SPM’s) probability values can be invalid for such cases. The purpose of this paper was to clarify the scope of validity for SPM analysis of nonuniformly and heterogeneously smooth one-dimensional (1D) data. We simulated a variety of nonuniformly and heterogeneously smooth Gaussian 1D data over a range of smoothness values, and computed Type I error rates across 10,000 simulation iterations for each smoothness type. Results showed that, in all cases, SPM accurately controlled error at the prescribed α=0.05. Moreover, the distribution of false positives was uniform across time, implying that all regions are equally likely to produce false positives, irrespective of local roughness. We nevertheless show that cluster-level inferences (i.e., p values specific to local regions of significance) may be over-or-underestimated by approximately 0.01 (for the currently simulated scenarios), but never exceed α by definition. We conclude that SPM’s null hypothesis rejection decisions are valid for both nonuniform and heterogeneous 1D data, but that clusters’ p values may be marginally too small/large in rough/smooth regions, respectively. Since cluster-level p values never exceed α, these p value errors are negligible for hypothesis testing purposes. Nevertheless, inter-cluster p value comparisons should be avoided. Implications for statistical power and general results interpretation are discussed

Magnetic polarizability of hadrons from lattice QCD

We extract the magnetic polarizability from the quadratic response of a hadron's mass shift in progressively small static magnetic fields. The calculation is done on a 24x12x12x24 lattice at a = 0.17 fm with an improved gauge action and the clover quark action. The results are compared to those from experiments and models where available.Comment: 3 pages, 3 figures, contribution to Lattice 2002 (spectrum

Dilaton driven Hawking radiation in AdS2_2 black hole

A recent study shows that Hawking radiation of the massless scalar field does not appear on the two-dimensional AdS$_2$ black hole background. We study this issue by investigating absorption and reflection coefficients under dilaton coupling with the matter field. If the scalar field does not couple to the dilaton, then it is fully absorbed into the black hole without any outgoing mode. On the other hand, once it couples to the dilaton field, the outgoing mode of the massless scalar field exists and the nontrivial Hawking radiation is obtained. Finally, we comment on this dilaton dependence of Hawking radiation in connection with a three-dimensional black hole.Comment: 13 pages, revtex, no figures, version to appear in Phys. Lett.