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

Novel Method to Process Cystic Fibrosis Sputum for Determination of Oxidative State

Background: Induced sputum is the most commonly used method to analyze airway inflammation in cystic fibrosis (CF) patients ex vivo. Due to the complex matrix of the sample material, precise and reliable analysis of sputum constituents depends critically on preanalytical issues. Objectives: Here we compared the commonly used method for sputum processing by dithiothreitol (DTT) with a novel mechanical method in regard to basal cellular parameters, neutrophil markers and glutathione (GSH) levels. Methods: Sputum samples from CF patients were processed in parallel with or without the use of DTT. The key improvement of the mechanical method was the processing in many very small aliquots. Cellular and humoral markers were assessed and compared according to Bland-Altman. Results: Total cell count, cell viability, differential cell count, neutrophil elastase levels and flow cytometrically analyzed neutrophil markers (CD63, CD11b, DHR) did not differ between the two methods. Intracellular and extracellular GSH levels were significantly higher in DTT-treated samples (p = 0.002). Conclusion: The mechanical sputum-processing method presented had a similar yield of cells and fluids as the conventional DTT method and the advantage of omitting the introduction of reducing agents. This method allows a more reliable analysis of redox-dependent airway inflammation in sputum cells and fluid from CF patients than methods utilizing DTT. Copyright (C) 2009 S. Karger AG, Base

Divergence-type 2+1 dissipative hydrodynamics applied to heavy-ion collisions

We apply divergence-type theory (DTT) dissipative hydrodynamics to study the 2+1 space-time evolution of the fireball created in Au+Au relativistic heavy-ion collisions at $\sqrt{s_{NN}}=$200 GeV. DTTs are exact hydrodynamic theories that do no rely on velocity gradient expansions and therefore go beyond second-order theories. We numerically solve the equations of motion of the DTT for Glauber initial conditions and compare the results with those of second-order theory based on conformal invariants (BRSS) and with data. We find that the charged-hadron minumum-bias elliptic flow reaches its maximum value at lower $p_T$ in the DTT, and that the DTT allows for a value of $\eta/s$ slightly larger than that of the BRSS. Our results show that the differences between viscous hydrodynamic formalisms are a significant source of uncertainty in the precise extraction of $\eta/s$ from experiments.Comment: v4: 29 pages, 12 figures, minor changes. Final version as published in Phys. Rev.

Simultaneous Distributed Sensor Self-Localization and Target Tracking Using Belief Propagation and Likelihood Consensus

We introduce the framework of cooperative simultaneous localization and tracking (CoSLAT), which provides a consistent combination of cooperative self-localization (CSL) and distributed target tracking (DTT) in sensor networks without a fusion center. CoSLAT extends simultaneous localization and tracking (SLAT) in that it uses also intersensor measurements. Starting from a factor graph formulation of the CoSLAT problem, we develop a particle-based, distributed message passing algorithm for CoSLAT that combines nonparametric belief propagation with the likelihood consensus scheme. The proposed CoSLAT algorithm improves on state-of-the-art CSL and DTT algorithms by exchanging probabilistic information between CSL and DTT. Simulation results demonstrate substantial improvements in both self-localization and tracking performance.Comment: 10 pages, 5 figure

Reaching Community Through School Going Children for Sickle Cell Disease in Zankhvav Village of Surat District, Western India

Objectives: The objective of the study was to explore a method to reach the community via school going adolescents for screening tribal people for Sickle Cell disease. Methodology: A cross-sectional study was conducted in a total of 1023 school going adolescents for Sickle Cell Disease screening by Dithionite Tube Turbidity (DTT) test with subsequent Hemoglobin Electrophoresis for confirmation among those testing positive for DTT. They were then advised to get their family members tested for the same. Results: 24.41% of school going adolescents tested positive by DTT test. 152 family members of those positive school children came forward for testing. On performing the DTT test on the family members, 53.94% tested positive. Out of those who tested positive, 61% belonged to Vasava caste; 36.6% belonged to Chaudhari caste followed by Gamit and Dhodhia Patel. On the subsequent Hemoglobin electrophoresis, 52.63% of the family members were found to be positive for Sickle Cell Trait and 1.97% tested positive for Sickle Cell Disease. Conclusions: School going children can be an effective medium to approach the community for the screening of Sickle Cell Disease

Age related diffusion and tractography changes in typically developing pediatric cervical and thoracic spinal cord

Background and objective: Diffusion tensor imaging (DTI) and diffusion tensor tractography (DTT) are two techniques that can measure white matter integrity of the spinal cord. Recently, DTI indices have been shown to change with age. The purpose of this study is (a) to evaluate the maturational states of the entire pediatric spinal cord using DTI and DTT indices including fractional anisotropy (FA), mean diffusivity (MD), mean length of white matter fiber tracts and tract density and (b) to analyze the DTI and DTT parameters along the entire spinal cord as a function of spinal cord levels and age. Method: A total of 23 typically developing (TD) pediatric subjects ranging in age from 6 to 16 years old (11.94 ± 3.26 (mean ± standard deviation), 13 females and 10 males) were recruited, and scanned using 3.0 T MR scanner. Reduced FOV diffusion tensor images were acquired axially in the same anatomical location prescribed for the T2-weighted images to cover the entire spinal cord (C1-mid L1 levels). To mitigate motion induced artifacts, diffusion directional images were aligned with the reference image (b0) using a rigid body registration algorithm performed by in-house software developed in Matlab (MathWorks, Natick, Massachusetts). Diffusion tensor maps (FA and MD) and streamline deterministic tractography were then generated from the motion corrected DTI dataset. DTI and DTT parameters were calculated by using ROIs drawn to encapsulate the whole cord along the entire spinal cord by an independent board certified neuroradiologist. These indices then were compared between two age groups (age group A = 6–11 years (n = 11) and age group B = 12–16 years (n = 12)) based on similar standards and age definitions used for reporting spinal cord injury in the pediatric population. Standard least squared linear regression based on a restricted maximum likelihood (REML) method was used to evaluate the relationship between age and DTI and DTT parameters. Results: An increase in FA (group A = 0.42 ± 0.097, group B = 0.49 ± 0.116), white matter tract density (group A = 368.01 ± 236.88, group B = 440.13 ± 245.24) and mean length of fiber tracts (group A = 48.16 ± 20.48 mm, group B = 60.28 ± 23.87 mm) and a decrease in MD (group A = 1.06 ± 0.23 × 10−3 mm2/s, group B = 0.82 ± 0.24 × 10−3 mm2/s) were observed with age along the entire spinal cord. Statistically significant increases have been shown in FA (p = 0.004, R2 = 0.57), tract density (p = 0.0004, R2 = 0.58), mean length of fiber tracts (p \u3c 0.001, R2 = 0.5) and a significant decrease has been shown in MD (p = 0.002, R2 = 0.59) between group A and group B. Also, it has been shown DTI and DTT parameters vary along the spinal cord as a function of intervertebral disk and mid-vertebral body level. Conclusion: This study provides an initial understanding of age related changes of DTI values as well as DTT metrics of the spinal cord. The results show significant differences in DTI and DTT parameters which may result from decreasing water content, myelination of fiber tracts, and the thickening diameter of fiber tracts during the maturation process. Consequently, when quantitative DTI and DTT of the spinal cord is undertaken in the pediatric population an age and level matched normative dataset should be used to accurately interpret the quantitative results. © 201

Microwave Background Anisotropies in Primeval Isocurvature Baryon Models: Constraints on the Cosmological Parameters

We have performed the most comprehensive predictions of the temperature fluctuations \dtt in the primeval isocurvature baryon models to see whether or not the models are consistent with the recent data on the cosmic microwave background anisotropies. More specifically, we computed the \dtt corresponding to the experimental set-up by the South-Pole and the Owens Valley experiments as well as the COBE satellite. The amplitudes of the predicted \dtt are normalized by means of the COBE 10$^\circ$ data. The resulting constraints on the models are presented on $n - \Omega_b$ plane in the case of $\lambda_0=1-\Omega_b$ (flat models) and $\lambda_0=0$ (open models), where $n$ is the primordial spectral index of entropy fluctuations and $\Omega_b$ is the present baryon density parameter. Our results imply that the PIB models cannot be reconciled with the current observations for any reasonable set of cosmological parameters.Comment: 10pages and 4figures compressed uuencoded postscript (with figures), UTAP-93-16