Targets for majority of drugs: G protein-coupled receptors - their structure and interaction with bioligands

G protein-coupled receptors (GPCRs) are the most frequent targets for many drugs. They form the largest superfamily of integral membrane proteins, of which more than 1000 members have the following common features: (i) All GPCRs form 7 hydrophobic a-helices of length ~38A (25 amino acids, 7 turns) along a single chain. The consecutive helices alternatively cross the membrane, starting from the extracellular side, so that they form a heptahelical transmembrane domain interwoven with 6 loops, of which the even ones plus the N-terminus create the receptor's extracellular domain while the odd ones plus the C-terminus form its intracellular domain. (ii) All GPCRs are stimulated by diverse extracellular (primary) signals. (iii) Stimulated GPCRs convey the primary signals via their transmembrane and intracellular domains to the cytosolic peripheral heterotrimeric GTP-binding proteins (G proteins), mediating the signal's further transduction to various cellular second messenger systems. A current status of structural studies on GPCRs, consisting of low ~7.5A resolution experimental structures and supplementary molecular modeling, is outlined. Subsequently, some results of authors' own work on studying essential interactions of the V2 vasopressin renal receptor (V2R) with its agonist [Arg8]Vasopressin (AVP) and selected antagonists are presented, as well as their possible impact on the biological signal transduction is discussed. Finally, perspectives for future developments are sketched

Electromagnetic Signal Propagation in a Lorentz Dispersive Medium

This work is concerned with the propagation of rapidly oscillating electromagnetic (EM) signal in a Lorentz dispersive medium. The problem considered here is 1-dimensional and its exact solution is described by a contour integral defined in a complex frequency plane. With the use of uniform asymptotic techniques, approximate representation for the total field consisting of the Sommerfeld and Brillouin precursors and the main signal is obtained. The effect of the rate of envelope changes, as well as of carrier frequency on the shape of the total signal is examined

Plane-wave diffraction by a wedge : a spectral domain approach

The canonical problem of plane wave diffraction by a wedge in the context of the spectral domain approach which exploits the relationship between the induced current on a scatterer and its far field is investigated. It is shown how the exact solution to the wedge diffraction problem can be manipulated in a form which enables one to interpret the far scattered field as the Fourier transform of the physical optics (PO) current on the two faces of the wedge augmented by the fringe current near the tip of the wedge. A uniform asymptotic expansion for the total field which slightly modifies the Ansatz in the uniform asymptotic theory of electromagnetic edge diffraction is constructed

“Porque Sentir es lo Primero”: Explorando la Dimensión Afectiva de los Exámenes de Licencia para Profesorado

Teacher licensure exams directly shape the racial demographics of the teaching profession. This is particularly the case for “basic skills” exams that are program entrance requirements in the United States and expanding into other countries. This qualitative study explored an important yet overlooked dimension of these exams for test takers: emotional and affective states. Specifically, we were interested in the affective dimension of the test-taking event. Our findings reveal a number of positive and negative affective states that both African American and White preservice teachers experience during the exam and the processes of appraisal that produce these states. Our findings also highlight the importance of preparation activities prior the exam to help alleviate negative affective states during the exam.Los exámenes de licencia para profesorado dan forma de manera directa a la demografía racial de la profesión docente. Éste es particularmente el caso de los exámenes de "habilidades básicas", que son requisitos de ingreso al programa en Estados Unidos y que están expandiéndose a otros países. Este estudio cualitativo exploró una dimensión importante pero poco explorada por los examinadores: los estados emocionales y afectivos. En concreto, nos interesamos por la dimensión afectiva del evento de realización de la prueba. Nuestros resultados revelan una serie de estados afectivos positivos y negativos experimentados tanto por los futuros profesores afroamericanos y blancos durante el examen, así como los procesos de evaluación que producen estos estados. Nuestros resultados también ponen de relieve la importancia de las actividades de preparación antes del examen para ayudar a aliviar los estados afectivos negativos durante el examen

Effects of carbon fillers in thermally conductive polypropylene based resins

The thermal conductivity of insulating polymers can be increased by adding conductive fillers. One potential market for these thermally conductive resins is for fuel cell bipolar plates. In this study, varying amounts of three different carbon fillers (carbon black, synthetic graphite particles, and carbon nanotubes) were added to polypropylene. The effects of single fillers and combinations of the different fillers were studied via a factorial design. Each single filler caused a statistically significant increase in composite through-plane thermal conductivity at the 95% confidence level, with synthetic graphite causing the largest increase. All of the composites containing combinations of the different fillers caused a statistically significant increase in composite through-plane thermal conductivity. It is possible that thermally conductive pathways are formed that \u27link\u27 these carbon fillers, which results in increased composite thermal conductivity. Composites containing 80 wt% synthetic graphite had an in-plane thermal conductivity of 28.0 W/m.K, which is desired for bipolar plates (\u3e 20 W/m.K)

The role of the L2 loop in the regulation and maintaining the proteolytic activity of HtrA (DegP) protein from Escherichia coli.

The aim of this study was to characterize the role of particular elements of the regulatory loop L2 in the activation process and maintaining the proteolytic activity of HtrA (DegP) from Escherichia coli. We measured the effects of various mutations introduced to the L2 loop's region (residues 228-238) on the stability of HtrA molecule and its proteolytic activity. We demonstrated that most mutations affected the activity of HtrA. In the case of the following substitutions: L229N, N235I, I238N, the proteolytic activity was undetectable. Thus, the majority of interactions mediated by the studied amino-acid residues seem to play important role in maintaining the active conformation. Formation of contacts between the apical parts (residues 231-234) of the L2 loops within the HtrA trimer, in particular the residues D232, was shown to play a crucial role in the activation process of HtrA. Stabilization of these intermolecular interactions by substitution of D232 with valine caused a stimulation of proteolytic activity whereas deletion of this region abolished the activity. Since the pathogenic E. coli strains require active HtrA for virulence, the apical part of L2 is of particular interest in terms of structure-based drug design for treatment E. coli infections