Evidence for involvement of both IKCa and SKCa channels in hyperpolarizing responses of the rat middle cerebral artery

Endothelium-derived hyperpolarizing factor responses in the rat middle cerebral artery are blocked by inhibiting IKCa channels alone, contrasting with peripheral vessels where block of both IKCa and SKCa is required. As the contribution of IKCa and SKCa to endothelium-dependent hyperpolarization differs in peripheral arteries, depending on the level of arterial constriction, we investigated the possibility that SKCa might contribute to equivalent hyperpolarization in cerebral arteries under certain conditions. METHODS: Rat middle cerebral arteries (approximately 175 microm) were mounted in a wire myograph. The effect of KCa channel blockers on endothelium-dependent responses to the protease-activated receptor 2 agonist, SLIGRL (20 micromol/L), were then assessed as simultaneous changes in tension and membrane potential. These data were correlated with the distribution of arterial KCa channels revealed with immunohistochemistry. RESULTS: SLIGRL hyperpolarized and relaxed cerebral arteries undergoing variable levels of stretch-induced tone. The relaxation was unaffected by specific inhibitors of IKCa (TRAM-34, 1 micromol/L) or SKCa (apamin, 50 nmol/L) alone or in combination. In contrast, the associated smooth-muscle hyperpolarization was inhibited, but only with these blockers in combination. Blocking nitric oxide synthase (NOS) or guanylyl cyclase evoked smooth-muscle depolarization and constriction, with both hyperpolarization and relaxation to SLIGRL being abolished by TRAM-34 alone, whereas apamin had no effect. Immunolabeling showed SKCa and IKCa within the endothelium. CONCLUSIONS: In the absence of NO, IKCa underpins endothelium-dependent hyperpolarization and relaxation in cerebral arteries. However, when NOS is active SKCa contributes to hyperpolarization, whatever the extent of background contraction. These changes may have relevance in vascular disease states where NO release is compromised and when the levels of SKCa expression may be altered

Hypergraphic LP Relaxations for Steiner Trees

We investigate hypergraphic LP relaxations for the Steiner tree problem, primarily the partition LP relaxation introduced by Koenemann et al. [Math. Programming, 2009]. Specifically, we are interested in proving upper bounds on the integrality gap of this LP, and studying its relation to other linear relaxations. Our results are the following. Structural results: We extend the technique of uncrossing, usually applied to families of sets, to families of partitions. As a consequence we show that any basic feasible solution to the partition LP formulation has sparse support. Although the number of variables could be exponential, the number of positive variables is at most the number of terminals. Relations with other relaxations: We show the equivalence of the partition LP relaxation with other known hypergraphic relaxations. We also show that these hypergraphic relaxations are equivalent to the well studied bidirected cut relaxation, if the instance is quasibipartite. Integrality gap upper bounds: We show an upper bound of sqrt(3) ~ 1.729 on the integrality gap of these hypergraph relaxations in general graphs. In the special case of uniformly quasibipartite instances, we show an improved upper bound of 73/60 ~ 1.216. By our equivalence theorem, the latter result implies an improved upper bound for the bidirected cut relaxation as well.Comment: Revised full version; a shorter version will appear at IPCO 2010

ROCnReg: An R Package for Receiver Operating Characteristic Curve Inference With and Without Covariates

This paper introduces the package ROCnReg that allows estimating the pooled ROC curve, the covariate-specific ROC curve, and the covariate-adjusted ROC curve by different methods, both from (semi) parametric and nonparametric perspectives and within Bayesian and frequentist paradigms. From the estimated ROC curve (pooled, covariate-specific, or covariate-adjusted), several summary measures of discriminatory accuracy, such as the (partial) area under the ROC curve and the Youden index, can be obtained. The package also provides functions to obtain ROC-based optimal threshold values using several criteria, namely, the Youden index criterion and the criterion that sets a target value for the false positive fraction. For the Bayesian methods, we provide tools for assessing model fit via posterior predictive checks, while the model choice can be carried out via several information criteria. Numerical and graphical outputs are provided for all methods. This is the only package implementing Bayesian procedures for ROC curves

Web-based expert systems:benefits and challenges

Convergence of technologies in the Internet and the field of expert systems have offered new ways of sharing and distributing knowledge. However, there has been a general lack of research in the area of web-based expert systems (ES). This paper addresses the issues associated with the design, development, and use of web-based ES from a standpoint of the benefits and challenges of developing and using them. The original theory and concepts in conventional ES were reviewed and a knowledge engineering framework for developing them was revisited. The study considered three web-based ES: WITS-advisor - for e-business strategy development, Fish-Expert - for fish disease diagnosis, and IMIS - to promote intelligent interviews. The benefits and challenges in developing and using ES are discussed by comparing them with traditional standalone systems from development and application perspectives. © 2004 Elsevier B.V. All rights reserved

Scalar diagrammatic rules for Born amplitudes in QCD

We show that all Born amplitudes in QCD can be calculated from scalar propagators and a set of three- and four-valent vertices. In particular, our approach includes amplitudes with any number of quark pairs. The quarks may be massless or massive. The proof of the formalism is given entirely within quantum field theory.Comment: 20 pages, references adde

Improved Algorithm for Degree Bounded Survivable Network Design Problem

We consider the Degree-Bounded Survivable Network Design Problem: the objective is to find a minimum cost subgraph satisfying the given connectivity requirements as well as the degree bounds on the vertices. If we denote the upper bound on the degree of a vertex v by b(v), then we present an algorithm that finds a solution whose cost is at most twice the cost of the optimal solution while the degree of a degree constrained vertex v is at most 2b(v) + 2. This improves upon the results of Lau and Singh and that of Lau, Naor, Salavatipour and Singh

Proton and non-proton activation of ASIC channels.

The Acid-Sensing Ion Channels (ASIC) exhibit a fast desensitizing current when activated by pH values below 7.0. By contrast, non-proton ligands are able to trigger sustained ASIC currents at physiological pHs. To analyze the functional basis of the ASIC desensitizing and sustained currents, we have used ASIC1a and ASIC2a mutants with a cysteine in the pore vestibule for covalent binding of different sulfhydryl reagents. We found that ASIC1a and ASIC2a exhibit two distinct currents, a proton-induced desensitizing current and a sustained current triggered by sulfhydryl reagents. These currents differ in their pH dependency, their sensitivity to the sulfhydryl reagents, their ionic selectivity and their relative magnitude. We propose a model for ASIC1 and ASIC2 activity where the channels can function in two distinct modes, a desensitizing mode and a sustained mode depending on the activating ligands. The pore vestibule of the channel represents a functional site for binding non-proton ligands to activate ASIC1 and ASIC2 at neutral pH and to prevent channel desensitization

The role of the principal, teachers and students in restoring the culture of learning, teaching and service (COLT) in black secondary schools in the Pretoria region

Political and social instability over many years has led to a crisis in the South African education system. One of the crucial changes and challenges that the new democracy faces is to reconstruct a society and an education system that will be able to establish a culture conducive to learning, teaching and services in schools (COLT). This article examines factors that have led to a loss of the culture of learning and teaching (COLT) in South African schools, and the characteristics of a positive culture expected by principals, teachers and students. Results indicate that although principals are attempting to influence this culture, there is little support for such changes from teachers and students. (South African Journal of Education: 2001 21(4): 311-316