Numerical analysis of a model of ligand-induced B-cell antigen-receptor clustering. Implications for simple models of B-cell activation in an immune network

Experimental measures of responsiveness to painful and non-painful stimuli as well as measures of typical and present clinical pain were assessed in 26 female patients with fibromyalgia and in an equal number of age-matched healthy women. Pressure pain thresholds, determined by means of a dolorimeter, were lower in the patients compared to the control subjects both at a tender point (trapezius) and at a non-tender control point (inner forearm). The same was true for the heat pain thresholds, measured using a contact thermode. In contrast, the pain thresholds for electrocutaneous stimuli were decreased only at the tender point. The detection thresholds for non-painful stimuli (warmth, cold and electrical stimuli) seemed to be less affected in the fibromyalgia patients, with only the detection threshold for cold being lower at both sites. Tender points were more sensitive than control points for mechanical pressure. The reverse was found for the other modalities which were tested. Although the 3 experimental pain thresholds showed patterns of either generalized or site-specific pain hyperresponsiveness, the between-methods correlations were not very high. While the correlations between the experimental pain thresholds and the various measures of clinical pain (Localized Pain Rating, McGill Pain Questionnaire) in the patients were generally low, there were significant negative correlations between pressure pain thresholds at the two sites and the level of present pain assessed by the Localized Pain Rating. We conclude that a pattern of pain hyperresponsiveness, generalized across the site of noxious stimulation and across the physical nature of the stressor, is associated with fibromyalgia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparative study of the effects of clozapine and clothiapine in different preparations of guinea pig and rat isolated organs

1. A study has been made to know the effects of clozapine and clothiapine on the responses of rat isolated vas deferens to norepinephrine, dopamine and potassium, those of the rat isolated uterus to serotonin and potassium, and that of guinea pig isolated ileum to histamine. 2. Clozapine was a noncompetitive antagonist to norepinephrine, dopamine, serotonin and histamine; it inhibited potassium-induced contraction in isolated rat uterus and vas deferens. 3. Clothiapine was a competitive antagonist to serotonin and a noncompetitive antagonist to norepinephrine, dopamine and histamine; it inhibited potassium-induced contractions in isolated rat uterus and vas deferens.     

Using real-coded genetic algorithms for Weibull parameter estimation

Genetic algorithms (GAs) represent a class of adaptive search techniques based on a direct analogy to Darwinian natural selection and mutations in biological systems. “Standard” GAs have emphasized the utilization of binary codes. However, recent empirical results have indicated that a chromosome representation which utilizes real values have enhanced the performance of these GAs in certain engineering problems. A real-valued Genetic Algorithm method described in this paper estimates the parameter values from an unconstrained population of data points for a Weibull distribution function using a simultaneous random search function by integrating the principles of the Genetic Algorithm and the method of Maximum Likelihood Estimation. The results of the real-coded GA technique for parameter estimation are compared to the results of the Newton-Raphson Algorithm.     

Malonyl-CoA-independent acute control of hepatic carnitine palmitoyltransferase I activity. Role of Ca2+/calmodulin-dependent protein kinase II and cytoskeletal components

The mechanism of malonyl-CoA-independent acute control of hepatic carnitine palmitoyltransferase I (CPT-I) activity was investigated. In a first series of experiments, the possible involvement of the cytoskeleton in the control of CPT-I activity was studied. The results of these investigations can be summarized as follows. (i) Very mild treatment of permeabilized hepatocytes with trypsin produced around 50% stimulation of CPT-I activity. This effect was absent in cells that had been pretreated with okadaic acid (OA) and seemed to be due to the action of trypsin on cell component(s) distinct from CPT-I. (ii) Incubation of intact hepatocytes with 3, 3'-iminodipropionitrile, a disruptor of intermediate filaments, increased CPT-I activity in a non-additive manner with respect to OA. Taxol, a stabilizer of the cytoskeleton, prevented the OA- and 3, 3'-iminodipropionitrile-induced stimulation of CPT-I. (iii) CPT-I activity in isolated mitochondria was depressed in a dose-dependent fashion by the addition of a total cytoskeleton fraction and a cytokeratin-enriched cytoskeletal fraction, the latter being 3 times more potent than the former. In a second series of experiments, the possible link between Ca2+/calmodulin-dependent protein kinase II (Ca2+/CM-PKII) and the cytoskeleton was studied in the context of CPT-I regulation. The data of these experiments indicate that (i) purified Ca2+/CM-PKII activated CPT-I in permeabilized hepatocytes but not in isolated mitochondria, (ii) purified Ca2+/CM-PKII abrogated the inhibition of CPT-I of isolated mitochondria induced by a cytokeratin-enriched fraction, and (iii) the Ca2+/CM-PKII inhibitor KN-62 prevented the OA-induced phosphorylation of cytokeratins in intact hepatocytes. Results thus support a novel mechanism of short-term control of hepatic CPT-I activity which may rely on the cascade Ca2+/CM-PKII activation --> cytokeratin phosphorylation --> CPT-I de-inhibition.     

Gene structure and expression analysis of the drought- and abscisic acid-responsive CDeT11-24 gene family from the resurrection plant Craterostigma plantagineum Hochst

In order to understand the molecular mechanisms which are responsible for desiccation tolerance in the resurrection plant Craterostigma plantagineum Hochst. a thorough analysis of the CDeT11-24 gene family was performed. CDeT11-24 comprises a small gene family whose genes are expressed in response to dehydration, salt stress and abscisic acid (ABA) treatment in leaves. The gene products are constitutively expressed in roots and disappear only when the plants are transferred to water. It is therefore suggested that the proteins are involved in sensing water status. The predicted proteins are very hydrophilic; they share some features with late-embryogenesis-abundant proteins, and sequence similarities were found with two ABA- and drought-regulated Arabidopsis genes. The analysis of beta-glucuronidase reporter genes driven by the CDeT11-24 promoter showed high activity in mature seeds in both transgenic Arabidopsis and tobacco. In vegetative tissues the promoter activity in response to ABA was restricted to young Arabidosis seedlings. The responsiveness to ABA during later developmental stages was regained in the presence of the Arabidopsis gene product ABI3. Dehydration-induced promoter activity was only observed in Arabidopsis leaves at a particular developmental stage. This analysis indicates that some components in the signal transduction pathway of the resurrection plant are not active in tobacco or Arabidopsis.     

Effect of Explotab on the tabletability of a poorly soluble drug

OBJECTIVE: To examine what is known about engaging and maintaining suicidal individuals in treatment and what can be learned from the randomized, controlled trials of psychosocial interventions concerning the reduction of suicidal behaviours. METHOD: Review of the relevant literature. RESULTS: Treatment follow-through is low among those who attempt suicide. The evidence to date is inconclusive as to whether psychosocial interventions can reduce the repetition of suicidal behaviour. CONCLUSIONS: Certain groups may benefit from psychosocial interventions. Future research must overcome several methodological issues. As treatment relies on adequate follow-through, changes in the delivery of care may enhance treatment effectiveness.     

Effect on wear resistance of nanoparticles addition to a powder polyester coating through ball milling

The wear properties of a textured polyester powder coating with pyrogenic silica nanoparticles addition were evaluated. Raw powders of a commercial, textured polyester organic coating were mixed with low amounts of SiO₂ nanoparticles (0.5–3 wt%) using ball milling, a simple and economical method. Nanoparticles were mixed into the powder of thermoset organic coating for 10 min in a two-body planetary ball mill. Particle size distribution of the powder was measured to evaluate the milling effect. The coatings were applied and cured in an industrial installation on aluminum substrates. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) images of the coatings were taken to analyze the homogeneity of the organic coating. Roughness, gloss and color were measured in order to evaluate their appearance. The effect of nanoparticles on abrasive and erosion wear performances was measured. Pin-on-disk wear tests were carried out. Erosion measurements were performed with free fall of sand on the samples, a test based on ASTM D968 standard. The results showed that the milling process provides a good distribution of nanoparticles as no agglomerates were found. The addition of 0.5 wt% silica nanoparticles allows for improvement of the wear resistance of the coatings.     

Quartz Tuning Fork Pressure Gauge for High-Pressure Liquid Helium

We have measured the quality factor Q and the frequency f of a 32-kHz quartz tuning fork immersed in liquid \(^4\)He between 0.9 and 3.0 K, over pressures ranging from the saturated vapor pressure to \(\approx \)25 atm. At constant pressure, as a function of temperature, the quality factor and frequency have strong features related to the temperature dependence of the superfluid fraction. At constant temperature, Q depends on the superfluid fraction, while the frequency is a smooth function of pressure. The behavior is explained using a simple hydrodynamic model. The liquid helium viscosity is obtained from measured values of Q, and together with tabulated values of the helium density as a function of pressure and temperature, the frequency shift can be parameterized as a function of temperature and pressure. The observed sensitivity is \(\approx \)7.8 Hz/atm. The quartz tuning fork provides a compact low power method of measuring the pressure in the bulk liquid.