MODULATION OF CALCIUM CHANNELS IN ARTERIAL SMOOTH-MUSCLE CELLS BY DIHYDROPYRIDINE ENANTIOMERS

The actions of the optical enantiomers of BAY K 8644 and Sandoz 202,791 were studied on barium inward currents recorded using the whole-cell configuration of the patch clamp technique from enzymatically isolated smooth muscle cells from the rabbit ear artery. The enantiomers were applied by bath perfusion or rapidly by a concentration jump technique, which enabled the study of drug action under equilibrium and nonequilibrium conditions. A larger effect of agonists was seen on peak inward current in 110 mM Ba when small rather than large depolarizations were applied. The midpoint voltage of the steady-state inactivation curve of IBa was -12.8 +/- 1.9 mV (n = 4) in the absence of drug, -16.4 +/- 2.5 mV (n = 4) in 1 microM (+)202,791, and -31.4 +/- 0.4 mV (n = 4) in 1 microM (-)202,791. The rate of onset of action of the agonist and antagonist enantiomers of BAY K 8644 and Sandoz 202,791 was studied by rapid application during 20-ms depolarizing steps from different holding potentials to +30 mV at 1 or 0.2 Hz. The drugs were applied as concentration jumps between two single pulses of a pulse train. The rates of onset of drug action on peak IBa during a 1-Hz pulse train were concentration dependent over the range of 100 nM-3 microM for both (+) and (-)202,791. The rate of onset of inhibition of peak current by antagonist enantiomers was not significantly influenced by the test pulse frequency. At a holding potential of -60 mV, the onset rate of the increase in peak IBa on application of 1 microM of agonist enantiomers (+)202,791 or (-)BAY K 8644 during a train of pulses occurred with mean time constants of 2.1 +/- 0.7 s (n = 7) and 2.3 +/- 0.2 s (n = 4), respectively. The onset of current increase on application of 1 microM (+)202,791 during a single voltage clamp step to 20 mV was faster, with a mean time constant of 380 +/- 80 ms (n = 3)

Crystal structure of the 3C protease from South African Territories type 2 foot-and-mouth disease virus

The replication of foot-and-mouth disease virus (FMDV) is dependent on the virus-encoded 3C protease (3Cpro). As in other picornaviruses, 3Cpro performs most of the proteolytic processing of the polyprotein expressed from the single open reading frame in the RNA genome of the virus. Previous work revealed that the 3Cpro from serotype A – one of the seven serotypes of FMDV – adopts a trypsin-like fold. Phylogenetically the FMDV serotypes are grouped into two clusters, with O, A, C, and Asia 1 in one, and the three South African Territories serotypes, (SAT-1, SAT-2 and SAT-3) in another. We report here the cloning, expression and purification of 3C proteases from four SAT serotype viruses (SAT2/GHA/8/91, SAT1/NIG/5/81, SAT1/UGA/1/97, and SAT2/ZIM/7/83) and the crystal structure at 3.2 Å resolution of 3Cpro from SAT2/GHA/8/91)

Contextuality-by-Default: A Brief Overview of Ideas, Concepts, and Terminology

This paper is a brief overview of the concepts involved in measuring the degree of contextuality and detecting contextuality in systems of binary measurements of a finite number of objects. We discuss and clarify the main concepts and terminology of the theory called "contextuality-by-default," and then discuss a possible generalization of the theory from binary to arbitrary measurements.Comment: Lecture Notes in Computer Science 9535 (with the corrected list of authors) (2016

Sensitivity of land surface parameterization on Regional Spectral Model forecasts

Experiments were carried out to study the impact of different land surface schemes on a Regional Spectral Model (RSM) forecasts. RSM is based on the perturbation method of NCEP, where the dependent variables are the differences between the regional and global model fields called 'perturbations'. The perturbation method ensures the use of global model values as the base fields all over the domain and predicts the mesoscale features embedded in the base field forecasts. The first version of RSM has a land surface scheme with a single layer of soil moisture, which is the same as the operational global model with which it is nested. The second version of RSM has a land surface scheme with two layers of soil moisture and a more complex treatment of evaporation. The model was integrated for five days nested with the operational global spectral model during August 2001. The RSM with 2-layer soil moisture scheme was found to have slightly less easterly bias over north India. However, the two-layer scheme showed higher evaporation and precipitation over Andhra Pradesh region. Additionally, major differences were also observed in all the components of the surface energy balance over the same region

Systematic study of breakup effects on complete fusion at energies above the Coulomb barrier

A large number of complete fusion excitation functions of reactions including the breakup channel were measured in recent decades, especially in the last few years. It allows us to investigate the systematic behavior of the breakup effects on the complete fusion cross sections. To this end, we perform a systematic study of the breakup effects on the complete fusion cross sections at energies above the Coulomb barrier. The reduced fusion functions F(x) are compared with the universal fusion functions which are used as a uniform standard reference. The complete fusion cross sections at energies above the Coulomb barrier are suppressed by the breakup of projectiles. This suppression effect for reactions induced by the same projectile is independent of the target and mainly determined by the lowest energy breakup channel of the projectile. There holds a good exponential relation between the suppression factor and the energy corresponding to the lowest breakup threshold.Comment: 10 pages, 9 figures; Fig. 9 and related discussions modifie

Clearance of human papillomavirus related anal condylomas after oral and endorectal multistrain probiotic supplementation in an HIV positive male: A case report.

Abstract Go to: Introduction: Here we present the case of a 56-year-old human immunodeficiency virus (HIV)-infected man with multiple anal condylomas and positivity for human papilloma virus (HPV) 18 on anal brushing. Biopsies of the anal mucosa led to the diagnosis of Bowen's disease and a subsequent pelvic magnetic resonance imaging (MRI) scan evidenced multiple reactive lymphoadenopathies and large intra-anal condylomas. The patient was treated with a complete excision of Bowen's lesion and with a 4 months course of supplementation with a high concentration multistrain probiotic formulation administered orally and by rectal instillation with the purpose to reduce local inflammation and to enhance local mucosal immunity. Go to: Conclusion: An MRI performed at the end of the supplementation period evidenced the clearance of the anal condylomas previously described and no evidence of residual lymphadenopathies. Trials are therefore required to confirm this therapeutic possibility and for a better understanding of the mechanisms by which this specific probiotic formulation interacts with local epithelium when administered by the anal route

Desenvolvimentos recentes no comportamento à fadiga de conectores metálicos

A presente comunicação recolhe a mais recente investigação, realizada em torno da avaliação experimental do comportamento à fadiga de vários tipos de conectores metálicos, como sejam os pernos de cabeça, conector C, os conectores pós-instalados, o Perfobond e o Crestbond. Com base num conjunto vasto de resultados experimentais obtidos por diversos investigadores, discutem-se aspectos como a vida de fadiga, a resistência residual ou a evolução do escorregamento e comparam-se os vários resultados obtidos. A partir da comparação entre resultados analisados, é possível definir um plano de ensaios para avaliar o comportamento à fadiga de um novo tipo de conector metálico, o Crestbond, recentemente desenvolvido por dois autores deste artigo. O objectivo final é o de obter a curva S-N para este conector

Niet kerende grondbewerking (NKG)

Een goede bodemstructuur en een gezonde bodem zijn belangrijk in de biologische landbouw. Bodemverdichting is vaak direct te zien aan een biologisch gewas. Daarom maken biologische ondernemers gebruik van vaste mest, groenbemesters, rijpaden, GPS besturing en mechanisatie die niet zwaarder is dan noodzakelijk. Ook niet kerende grondbewerking (NKG) kan een positieve invloed op de bodemstructuur hebben

Optimal sequencing of a set of positive numbers with the variance of the sequence's partial sums maximized

We consider the problem of sequencing a set of positive numbers. We try to find the optimal sequence to maximize the variance of its partial sums. The optimal sequence is shown to have a beautiful structure. It is interesting to note that the symmetric problem which aims at minimizing the variance of the same partial sums is proved to be NP-complete in the literature.Comment: 12 pages;Accepted for publication in Optimization Lette

Outstanding Issues in Solar Dynamo Theory

The magnetic activity of the Sun, as manifested in the sunspot cycle, originates deep within its convection zone through a dynamo mechanism which involves non-trivial interactions between the plasma and magnetic field in the solar interior. Recent advances in magnetohydrodynamic dynamo theory have led us closer towards a better understanding of the physics of the solar magnetic cycle. In conjunction, helioseismic observations of large-scale flows in the solar interior has now made it possible to constrain some of the parameters used in models of the solar cycle. In the first part of this review, I briefly describe this current state of understanding of the solar cycle. In the second part, I highlight some of the outstanding issues in solar dynamo theory related to the the nature of the dynamo $\alpha$-effect, magnetic buoyancy and the origin of Maunder-like minima in activity. I also discuss how poor constraints on key physical processes such as turbulent diffusion, meridional circulation and turbulent flux pumping confuse the relative roles of these vis-a-vis magnetic flux transport. I argue that unless some of these issues are addressed, no model of the solar cycle can claim to be ``the standard model'', nor can any predictions from such models be trusted; in other words, we are still not there yet.Comment: To appear in "Magnetic Coupling between the Interior and the Atmosphere of the Sun", eds. S.S. Hasan and R.J. Rutten, Astrophysics and Space Science Proceedings, Springer-Verlag, Heidelberg, Berlin, 200