Altered ligand dissociation rates in thyrotropin-releasing hormone receptors mutated in glutamine 105 of transmembrane helix III

Glutamine 105 in the third transmembrane helix of the thyrotropin-releasing hormone receptor (TRH-R) occupies a position equivalent to a conserved negatively charged residue in receptors for biogenic amines where it acts as counterion interacting with the cationic amine moiety of the ligand. Maximum levels of response to TRH in oocytes expressing wild-type TRH-Rs were indistinguishable from those of oocytes expressing receptors mutated to Glu, Asn, or Asp in position 105. However, the EC50 values for activation of oocyte responses increased more than 500 times in oocytes expressing mutant Glu105 receptors, in which the amido group of Gln105 has been removed by site-directed mutagenesis. Charge effects do not seem to be involved in the huge effect of mutating Gln105 to Glu, since mutation of Gln105 to Asp induces only a 15-fold increase in EC50. Furthermore, no change in EC50 is observed after mutation of Asn110 to Asp. The affinity shift (identified by changes in EC50 values for systems of comparable efficacy) in Glu105 mutant receptors was partially recovered in oocytes expressing Asn105 mutant receptors. These results and those obtained after substitution of Lys, Leu, Tyr, and Ser for Gln105 suggest that the presence and the correct position of the Gln hydrogen bond-donor amido group are important for normal functionality of the receptor. In wild type or Asp105 mutant receptors showing the same maximal responses, decreases in affinity with TRH and methyl-histidyl-TRH correlated with increased dissociation rates of hormone from the receptor. Rapid dilution experiments following subsecond stimulation indicate that the TRH-R is converted rapidly from a form showing fast dissociation kinetics to a form from which the hormone dissociates slowly. Mutation of residue 105 impairs the receptor shift between these two forms. This effect was demonstrated in a direct way by comparing [3H]methyl-histidyl-TRH dissociation rates in COS-7 cells transfected with either wild type or Asp105 mutant TRH-Rs. Thus, residues located in transmembrane helix III positions equivalent to those of the counterions for biogenic amines, regulate hormone-receptor interactions in the TRH receptor (and perhaps other receptors). Furthermore, the nature of the amino acid in these positions may also play a role, directly or indirectly, in conformational changes leading to receptor activation, and hence to signal transduction.     

Integrating supercomputing clusters into education: a case study in biotechnology

The Journal of Supercomputing - The integration of a Supercomputer in the educational process improves student’s technological skills. The aim of the paper is to study the interaction between...     

Gain‐scheduled dynamic output feedback control for discrete‐time LPV systems

This paper presents synthesis conditions for the design of gain‐scheduled dynamic output feedback controllers for discrete‐time linear parameter‐varying systems. The state‐space matrix representation of the plant and of the controller can have a homogeneous polynomial dependency of arbitrary degree on the scheduling parameter. As an immediate extension, conditions for the synthesis of a multiobjective ??_∞ and ??₂ gain‐scheduled dynamic feedback controller are also provided. The scheduling parameters vary inside a polytope and are assumed to be a priori unknown, but measured in real‐time. If bounds on the rate of parameter variation are known, they can be taken into account, providing less conservative results. The geometric properties of the uncertainty domain are exploited to derive finite sets of linear matrix inequalities based on the existence of a homogeneous polynomially parameter‐dependent Lyapunov function. An application of the control design to a realistic engineering problem illustrates the benefits of the proposed approach. Copyright © 2011 John Wiley & Sons, Ltd.     

Durability of sheet molding compounds: Influence of hydrothermal aging on morphology and molecular mobility at microscopic scale

The physicochemical aging for parts of Sheet Molding Compound should be considered for their lifetime management and reusability. This material has a complex morphology and contains porosity due to the process and to shrinkage compensation. This SMC study has two complementary approaches. One describes the morphological consequences of water uptake, showing the decrease in the total amount and the fractal dimension of micro-voids by scanning electron microscopy and image processing. The other shows, by mechanical spectrometry, the effect of water on physical or chemical bonds. In both cases, the “low profile agent” in SMC plays an important role. The molecular mobility was taken as a sensor parameter for the structural changes at the molecular scale, highlighting and quantifying the first steps of the aging. The loss factor level increases, and the activation energies are modified, even for the first aging days. The analysis shows recovery for the material near the relaxation peak of the low profile agent, since the curve recovers its initial shape.     

Heat Induced Structure Modifications in Polymer‐Layered Silicate Nanocomposites

Summary: The success of the use of layered silicates in polymer nanocomposites, to improve physical and chemical properties is strictly related to a deeper knowledge of the mechanistic aspects on which the final features are grounded. This work shows the temperature induced structural rearrangements of nanocomposites based on poly[ethylene‐co‐(vinyl acetate)] (EVA) intercalated‐organomodified clay (at 3–30 wt.‐% silicate addition) which occur in the range between 75 and 350 °C. In situ high temperature X‐ray diffraction (HT‐XRD) studies have been performed under both nitrogen and air to monitor the modifications of the nanocomposite structure at increasing temperatures under inert/oxidative atmosphere. Heating between 75 and 225 °C, under nitrogen or air, causes the layered silicate to migrate towards the nanocomposite surface and to increase its interlayer distance. The degradation of both the clay organomodifier and the VA units of the EVA polymer seems to play a key role in driving the evolution of the silicate phase in the low temperature range. The structural modifications of the nanocomposites in the high temperature range (250–350 °C), depended on the atmosphere, either inert or oxidizing, in which the samples were heated. Heating under nitrogen led to deintercalation and thus a decrease of the silicate interlayer space, whereas exfoliation was the main process under air leading to an increase of the silicate interlayer space.

Heat induced structural modification of EVA‐clay nanocomposite under nitrogen and air.     

A genetic solution based on lexicographical goal programming for a multiobjective job shop with uncertainty

In this work we consider a multiobjective job shop problem with uncertain durations and crisp due dates. Ill-known durations are modelled as fuzzy numbers. We take a fuzzy goal programming approach to propose a generic multiobjective model based on lexicographical minimisation of expected values. To solve the resulting problem, we propose a genetic algorithm searching in the space of possibly active schedules. Experimental results are presented for several problem instances, solved by the GA according to the proposed model, considering three objectives: makespan, tardiness and idleness. The results illustrate the potential of the proposed multiobjective model and genetic algorithm.     

Occurrence of salmonellae in retail chicken carcasses and their products in Spain

This study examined the incidence of Salmonella in Spanish poultry products. Samples included chicken carcasses, chicken parts (wings, legs and giblets-livers and hearts) and processed chicken products (red sausages, white sausages and hamburgers). The average detection rate was 49%, with the highest (55%) in chicken carcasses (skin) and the lowest (20%) in hamburgers. The chicken carcasses purchased in supermarkets were more contaminated (75%) than those from poulterers shops (25%). Salmonella Enteritidis, S. Poona, S. Paratyphi B and S. Worthington were isolated in 34.3%, 11.4%, 2.8% and 1.4% of the samples, respectively. One (1.4%) red sausage sample harboured two serotypes (S. Enteritidis and S. Worthington). This fact emphasizes the usefulness of subtyping several Salmonella isolates from the same sample in epidemiological studies.     

Interpolating model identification for SISO linear parameter-varying systems

This paper presents a new method to estimate linear parameter-varying (LPV) state-space models for single-input single-output systems whose dynamics depend on one or more time-varying parameters, called scheduling parameters. The method is based on the interpolation of linear time-invariant models that are identified for fixed operating conditions of the system, that is, for constant values of the scheduling parameters. The proposed method can account for multiple scheduling parameters and yields either a polynomial or an affine LPV model that is numerically well-conditioned and therefore suitable for LPV control synthesis. The underlying interpolation technique is formulated as a nonlinear least-squares optimization problem that can be solved efficiently by standard solvers. The new interpolation method is applied to an electromechanical system that depends on two scheduling parameters. The numerical results are compared to existing techniques in the literature, demonstrating the potential and advantages of the proposed method.     

Hydroxypropylmethylcellulose at the oil–water interface. Part II. Submicron-emulsions as affected by pH

The emulsifying behavior of four different commercial types of hydroxypropylmethylcellulose (HPMC) was studied and correlated with the properties of the interfacial films.