Mechanism of active K + secretion by flounder urinary bladder

We investigated the mechanism of active K + transport by the urinary bladder of the winter flounder by measuring transepithelial properties in Ussing Chambers and by determining the cellular electrical potential profile using conventional microelectrodes. In the absence of transmural electrochemical potential gradients isolated bladders can exhibit a serosa-to-mucosa short circuit which is due entirely to net K + secretion. The properties of transcellular K + movement can be adequately described by a model which provides for active K + uptake across the basolateral membrane via an electrogenic Na/K ATPase and K + exit from the cell across the apical membrane down an electrochemical potential gradient via K + channels which are blocked by mucosal barium. The conductance of the apical membranes of the transporting cells appears to be due almost solely to K + while that of the basolateral membrane may be due largely to Cl − .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47455/1/424_2004_Article_BF00585048.pd

Subanesthetic ketamine treatment promotes abnormal interactions between neural subsystems and alters the properties of functional brain networks

Acute treatment with subanesthetic ketamine, a non-competitive N-methyl-D-aspartic acid (NMDA) receptor antagonist, is widely utilized as a translational model for schizophrenia. However, how acute NMDA receptor blockade impacts on brain functioning at a systems level, to elicit translationally relevant symptomatology and behavioral deficits, has not yet been determined. Here, for the first time, we apply established and recently validated topological measures from network science to brain imaging data gained from ketamine-treated mice to elucidate how acute NMDA receptor blockade impacts on the properties of functional brain networks. We show that the effects of acute ketamine treatment on the global properties of these networks are divergent from those widely reported in schizophrenia. Where acute NMDA receptor blockade promotes hyperconnectivity in functional brain networks, pronounced dysconnectivity is found in schizophrenia. We also show that acute ketamine treatment increases the connectivity and importance of prefrontal and thalamic brain regions in brain networks, a finding also divergent to alterations seen in schizophrenia. In addition, we characterize how ketamine impacts on bipartite functional interactions between neural subsystems. A key feature includes the enhancement of prefrontal cortex (PFC)-neuromodulatory subsystem connectivity in ketamine-treated animals, a finding consistent with the known effects of ketamine on PFC neurotransmitter levels. Overall, our data suggest that, at a systems level, acute ketamine-induced alterations in brain network connectivity do not parallel those seen in chronic schizophrenia. Hence, the mechanisms through which acute ketamine treatment induces translationally relevant symptomatology may differ from those in chronic schizophrenia. Future effort should therefore be dedicated to resolve the conflicting observations between this putative translational model and schizophrenia

High Bandwidth GaN-Based Micro-LEDs for Multi-Gb/s Visible Light Communications

Gallium-nitride (GaN) based light-emitting diodes (LEDs) are highly-efficient sources for general purpose illumination. Furthermore, being semiconductor-based light sources, they are readily compatible with intelligent drive electronics. Visible light communications (VLC) is a technology which leverages these advantageous properties of GaN LEDs and can supplement existing wireless communications by offering a large, licence-free spectral bandwidth. Here we report on progress in the development of micro-scale GaN LEDs (micro-LEDs), optimised for VLC. These blue-emitting micro-LEDs are shown to have very high electrical-to-optical modulation bandwidths, exceeding 800~MHz. The data transmission capabilities of the micro-LEDs are illustrated by demonstrations using on-off-keying (OOK), pulse-amplitude modulation (PAM) and orthogonal frequency division multiplexing (OFDM) modulation schemes to transmit data over free space at rates of 1.7, 3.4 and 5 Gb/s, respectively

The "Artificial Mathematician" Objection: Exploring the (Im)possibility of Automating Mathematical Understanding

Reuben Hersh confided to us that, about forty years ago, the late Paul Cohen predicted to him that at some unspecified point in the future, mathematicians would be replaced by computers. Rather than focus on computers replacing mathematicians, however, our aim is to consider the (im)possibility of human mathematicians being joined by “artificial mathematicians” in the proving practice—not just as a method of inquiry but as a fellow inquirer

Diffusion and drift of graphene flake on graphite surface

Diffusion and drift of a graphene flake on a graphite surface are analyzed. A potential energy relief of the graphene flake is computed using ab initio and empirical calculations. Based on the analysis of this relief, different mechanisms of diffusion and drift of the graphene flake on the graphite surface are considered. A new mechanism of diffusion and drift of the flake is proposed. According to the proposed mechanism, rotational transition of the flake from commensurate to incommensurate state takes place with subsequent simultaneous rotation and translational motion until a commensurate state is reached again, and so on. Analytic expressions for the diffusion coefficient and mobility of the flake corresponding to different mechanisms are derived in wide ranges of temperatures and sizes of the flake. The molecular dynamics simulations and estimates based on ab initio and empirical calculations demonstrate that the proposed mechanism can be dominant under certain conditions. The influence of structural defects on the diffusion of the flake is examined on the basis of calculations of the potential energy relief and molecular dynamics simulations. The methods of control over the diffusion and drift of graphene components in nanoelectromechanical systems are discussed. The possibility to experimentally determine the barriers to relative motion of graphene layers based on the study of diffusion of a graphene flake is considered. The results obtained can be also applied to polycyclic aromatic molecules on graphene and should be qualitatively valid for a set of commensurate adsorbate-adsorbent systems.Comment: 42 pages, 7 figure

A comparison of missing data methods for hypothesis tests of the treatment effect in substance abuse clinical trials: a Monte-Carlo simulation study

<p>Abstract</p> <p>Background</p> <p>Missing data due to attrition are rampant in substance abuse clinical trials. However, missing data are often ignored in the presentation of substance abuse clinical trials. This paper demonstrates missing data methods which may be used for hypothesis testing.</p> <p>Methods</p> <p>Methods involving stratifying and weighting individuals based on missing data pattern are shown to produce tests that are robust to missing data mechanisms in terms of Type I error and power. In this article, we describe several methods of combining data that may be used for testing hypotheses of the treatment effect. Furthermore, illustrations of each test's Type I error and power under different missing data percentages and mechanisms are quantified using a Monte-Carlo simulation study.</p> <p>Results</p> <p>Type I error rates were similar for each method, while powers depended on missing data assumptions. Specifically, power was greatest for the weighted, compared to un-weighted methods, especially for greater missing data percentages.</p> <p>Conclusion</p> <p>Results of this study as well as extant literature demonstrate the need for standards of design and analysis specific to substance abuse clinical trials. Given the known substantial attrition rates and concern for the missing data mechanism in substance abuse clinical trials, investigators need to incorporate missing data methods a priori. That is, missing data methods should be specified at the outset of the study and not after the data have been collected.</p

Passive cation permeability of turtle colon: Evidence for a negative interaction between intracellular sodium and apical sodium permeability

The role of intracellular sodium in the regulation of apical sodium permeability was investigated in an electrically “tight” epithelium, the turtle colon. In the presence of low mucosal sodium (3 mM) and serosal ouabain, an inhibitor of the basolateral sodium pump, the apical membrane retained a substantial amiloride-sensitive, sodium conductance and the basolateral membrane exhibited a barium-sensitive potassium conductance in parallel with a significant sodium (and lithium) conductance. In the presence of a high mucosal sodium concentration (114 mM), however, inhibition of active sodium absorption by ouabain led to a disappearance of the amiloride-sensitive, transepithelial conductance that was due, at least in part, to a virtual abolition of the apical sodium permeability. Two lines of evidence indicate that this permeability decrease was dependent upon an increase in intracellular sodium content. First, raising the mucosal sodium concentration from 3–114 mM in the presence of ouabain reversibly inhibited the amiloride-sensitive conductance. The time course of the decline in conductance paralleled the apparent intracellular accumulation of sodium in exchange for potassium, which was monitored as a transient deflection in the amiloride-sensitive, short-circuit current. Second, the inhibitory effect of mucosal sodium-addition was markedly attenuated by serosal barium, which prevented the accumulation of sodium by blocking the electrically coupled, basolateral potassium exit. These results support the notion of a “negative feedback” effect of intracellular sodium on the apical sodium permeability.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47451/1/424_2004_Article_BF00583286.pd

Mapping gene associations in human mitochondria using clinical disease phenotypes

Nuclear genes encode most mitochondrial proteins, and their mutations cause diverse and debilitating clinical disorders. To date, 1,200 of these mitochondrial genes have been recorded, while no standardized catalog exists of the associated clinical phenotypes. Such a catalog would be useful to develop methods to analyze human phenotypic data, to determine genotype-phenotype relations among many genes and diseases, and to support the clinical diagnosis of mitochondrial disorders. Here we establish a clinical phenotype catalog of 174 mitochondrial disease genes and study associations of diseases and genes. Phenotypic features such as clinical signs and symptoms were manually annotated from full-text medical articles and classified based on the hierarchical MeSH ontology. This classification of phenotypic features of each gene allowed for the comparison of diseases between different genes. In turn, we were then able to measure the phenotypic associations of disease genes for which we calculated a quantitative value that is based on their shared phenotypic features. The results showed that genes sharing more similar phenotypes have a stronger tendency for functional interactions, proving the usefulness of phenotype similarity values in disease gene network analysis. We then constructed a functional network of mitochondrial genes and discovered a higher connectivity for non-disease than for disease genes, and a tendency of disease genes to interact with each other. Utilizing these differences, we propose 168 candidate genes that resemble the characteristic interaction patterns of mitochondrial disease genes. Through their network associations, the candidates are further prioritized for the study of specific disorders such as optic neuropathies and Parkinson disease. Most mitochondrial disease phenotypes involve several clinical categories including neurologic, metabolic, and gastrointestinal disorders, which might indicate the effects of gene defects within the mitochondrial system. The accompanying knowledgebase (http://www.mitophenome.org/) supports the study of clinical diseases and associated genes

Are recovery stories helpful for women with eating disorders? A pilot study and commentary on future research

Background: Anecdotally it is well known that eating disorder memoirs are popular with people with anorexia nervosa and recovery stories are readily available online. However, no research to date has empirically explored whether such stories are helpful for current sufferers. The aim of the current pilot study was to explore the efficacy of recovery narratives as a means of improving motivation and self-efficacy and to qualitatively explore patient perspectives of such stories. Method: Fifty-seven women with anorexia nervosa and subclinical anorexia nervosa participated in this online study. Participants were randomised to either receive recovery stories or to a wait-list control group. After completing baseline measures, participants read five stories about recovery, and completed post-intervention measures two weeks later. Results: The quantitative results indicated that reading stories of recovery had no effect on motivation and self-efficacy over a two-week period. In contrast, the qualitative results showed that the stories generated thoughts about the possibility of recovery and the majority indicated they would recommend them to others. Conclusions: This study adds to a growing body of research exploring the integration of voices of lived experience into treatment approaches. Future research should focus on 1) identifying for whom and at which stage of illness recovery stories might be helpful; 2) the mechanism via which they might operate; and 3) the most helpful way of presenting such stories