Voltage-dependent Ca2+ Fluxes in Skeletal Myotubes Determined Using a Removal Model Analysis

The purpose of this study was to quantify the Ca2+ fluxes underlying Ca2+ transients and their voltage dependence in myotubes by using the “removal model fit” approach. Myotubes obtained from the mouse C2C12 muscle cell line were voltage-clamped and loaded with a solution containing the fluorescent indicator dye fura-2 (200 μM) and a high concentration of EGTA (15 mM). Ca2+ inward currents and intracellular ratiometric fluorescence transients were recorded in parallel. The decaying phases of Ca2+-dependent fluorescence signals after repolarization were fitted by theoretical curves obtained from a model that included the indicator dye, a slow Ca2+ buffer (to represent EGTA), and a sequestration mechanism as Ca2+ removal components. For each cell, the rate constants of slow buffer and transport and the off rate constant of fura-2 were determined in the fit. The resulting characterization of the removal properties was used to extract the Ca2+ input fluxes from the measured Ca2+ transients during depolarizing pulses. In most experiments, intracellular Ca2+ release dominated the Ca2+ input flux. In these experiments, the Ca2+ flux was characterized by an initial peak followed by a lower tonic phase. The voltage dependence of peak and tonic phase could be described by sigmoidal curves that reached half-maximal activation at −16 and −20 mV, respectively, compared with −2 mV for the activation of Ca2+ conductance. The ratio of the peak to tonic phase (flux ratio) showed a gradual increase with voltage as in rat muscle fibers indicating the similarity to EC coupling in mature mammalian muscle. In a subgroup of myotubes exhibiting small fluorescence signals and in cells treated with 30 μM of the SERCA pump inhibitor cyclopiazonic acid (CPA) and 10 mM caffeine, the calculated Ca2+ input flux closely resembled the L-type Ca2+ current, consistent with the absence of SR Ca2+ release under these conditions and in support of a valid determination of the time course of myoplasmic Ca2+ input flux based on the optical indicator measurements

Self consistent theory of unipolar charge-carrier injection in metal/insulator/metal systems

A consistent device model to describe current-voltage characteristics of metal/insulator/metal systems is developed. In this model the insulator and the metal electrodes are described within the same theoretical framework by using density of states distributions. This approach leads to differential equations for the electric field which have to be solved in a self consistent manner by considering the continuity of the electric displacement and the electrochemical potential in the complete system. The model is capable of describing the current-voltage characteristics of the metal/insulator/metal system in forward and reverse bias for arbitrary values of the metal/ insulator injection barriers. In the case of high injection barriers, approximations are provided offering a tool for comparison with experiments. Numerical calculations are performed exemplary using a simplified model of an organic semiconductor.Comment: 21 pages, 8 figure

Associations between socioeconomic status and environmental toxicant concentrations in adults in the USA: NHANES 2001-2010

This is the final version, also available from Elsevier via the DOI in this record.Low level chronic exposure to toxicants is associated with a range of adverse health effects. Understanding the various factors that influence the chemical burden of an individual is of critical importance to public health strategies. We investigated the relationships between socioeconomic status (SES) and bio-monitored chemical concentration in five cross-sectional waves of the U.S. National Health and Nutrition Examination Survey (NHANES).We utilised adjusted linear regression models to investigate the association between 179 toxicants and the poverty income ratio (PIR) for five NHANES waves. We then selected a subset of chemicals associated with PIR in 3 or more NHANES waves and investigated potential mediating factors using structural equation modelling.PIR was associated with 18 chemicals in 3 or more NHANES waves. Higher SES individuals had higher burdens of serum and urinary mercury, arsenic, caesium, thallium, perfluorooctanoic acid, perfluorononanoic acid, mono(carboxyoctyl) phthalate and benzophenone-3. Inverse associations were noted between PIR and serum and urinary lead and cadmium, antimony, bisphenol A and three phthalates (mono-benzyl, mono-isobutyl, mono-n-butyl). Key mediators included fish and shellfish consumption for the PIR, mercury, arsenic, thallium and perfluorononanoic acid associations. Sunscreen use was an important mediator in the benzophenone-3/PIR relationship. The association between PIR and cadmium or lead was partially mediated by smoking, occupation and diet.These results provide a comprehensive analysis of exposure patterns as a function of socioeconomic status in US adults, providing important information to guide future public health remediation measures to decrease toxicant and disease burdens within society. © 2013 Elsevier Ltd.University of ExeterEuropean Social Fund Convergence Programme for Cornwall and the Isles of ScillyEuropean Regional Development Fund Programme 2007 to 201

Heavy Scalar Top Quark Decays in the Complex MSSM: A Full One-Loop Analysis

We evaluate all two-body decay modes of the heavy scalar top quark in the Minimal Supersymmetric Standard Model with complex parameters (cMSSM) and no generation mixing. The evaluation is based on a full one-loop calculation of all decay channels, also including hard QED and QCD radiation. The renormalization of the complex parameters is described in detail. The dependence of the heavy scalar top quark decay on the relevant cMSSM parameters is analyzed numerically, including also the decay to Higgs bosons and another scalar quark or to a top quark and the lightest neutralino. We find sizable contributions to many partial decay widths and branching ratios. They are roughly of O(10%) of the tree-level results, but can go up to 30% or higher. These contributions are important for the correct interpretation of scalar top quark decays at the LHC and, if kinematically allowed, at the ILC. The evaluation of the branching ratios of the heavy scalar top quark will be implemented into the Fortran code FeynHiggs.Comment: 86 pages, 38 figures; minor changes, version published as Phys. Rev. D86 (2012) 03501

Integrated Display and Environmental Awareness System - System Architecture Definition

The Integrated Display and Environmental Awareness System (IDEAS) is an interdisciplinary team project focusing on the development of a wearable computer and Head Mounted Display (HMD) based on Commercial-Off-The-Shelf (COTS) components for the specific application and needs of NASA technicians, engineers and astronauts. Wearable computers are on the verge of utilization trials in daily life as well as industrial environments. The first civil and COTS wearable head mounted display systems were introduced just a few years ago and they probed not only technology readiness in terms of performance, endurance, miniaturization, operability and usefulness but also maturity of practice in perspective of a socio-technical context. Although the main technical hurdles such as mass and power were addressed as improvements on the technical side, the usefulness, practicality and social acceptance were often noted on the side of a broad variety of humans' operations. In other words, although the technology made a giant leap, its use and efficiency still looks for the sweet spot. The first IDEAS project started in January 2015 and was concluded in January 2017. The project identified current COTS systems' capability at minimum cost and maximum applicability and brought about important strategic concepts that will serve further IDEAS-like system development

A highly flexible and compact magnetoresistive analytic device

A grand vision of realization of smart and compact multifunctional microfluidic devices for wearable health monitoring, environment sensing and point-of-care tests emerged with the fast development of flexible electronics. As a vital component towards this vision, magnetic functionality in flexible fluidics is still missing although demanded by the broad utility of magnetic nanoparticles in medicine and biology. Here, we demonstrate the first flexible microfluidic analytic device with integrated high-performance giant magnetoresistive (GMR) sensors. This device can be bent to a radius of 2 mm while still retaining its full performance. Various dimensions of magnetic emulsion droplets can be probed with high precision using a limit of detection of 0.5 pl, providing broad applicability in high-throughput droplet screening, flow cytometry and drug development. The flexible feature of this analytic device holds great promise in the realization of wearable, implantable multifunctional platforms for biomedical, pharmaceutical and chemical applications

Treatment of tuberculosis in a region with high drug resistance: Outcomes, drug resistance amplification and re-infection

Introduction: Emerging antituberculosis drug resistance is a serious threat for tuberculosis (TB) control, especially in Eastern European countries. Methods: We combined drug susceptibility results and molecular strain typing data with treatment outcome reports to assess the influence of drug resistance on TB treatment outcomes in a prospective cohort of patients from Abkhazia (Georgia). Patients received individualized treatment regimens based on drug susceptibility testing (DST) results. Definitions for antituberculosis drug resistance and treatment outcomes were in line with current WHO recommendations. First and second line DST, and molecular typing were performed in a supranational laboratory for Mycobacterium tuberculosis (MTB) strains from consecutive sputum smear-positive TB patients at baseline and during treatment. Results: At baseline, MTB strains were fully drug-susceptible in 189/326 (58.0%) of patients. Resistance to at least H or R (PDR-TB) and multidrug-resistance (MDR-TB) were found in 69/326 (21.2%) and 68/326 (20.9%) of strains, respectively. Three MDR-TB strains were also extensively resistant (XDR-TB). During treatment, 3/189 (1.6%) fully susceptible patients at baseline were re-infected with a MDR-TB strain and 2/58 (3.4%) PDR-TB patients became MDR-TB due to resistance amplification. 5/ 47 (10.6%) MDR- patients became XDR-TB during treatment. Treatment success was observed in 161/189 (85.2%), 54/69 (78.3%) and 22/68 (32.3%) of patients with fully drug susceptible, PDR- and MDR-TB, respectively. Development of ofloxacin resistance was significantly associated with a negative treatment outcome. Conclusion: In Abkhazia, a region with high prevalence of drug resistant TB, the use of individualized MDR-TB treatment regimens resulted in poor treatment outcomes and XDR-TB amplification. Nosocomial transmission of MDR-TB emphasizes the importance of infection control in hospitals

Self-consistent analytical solution of a problem of charge-carrier injection at a conductor/insulator interface

We present a closed description of the charge carrier injection process from a conductor into an insulator. Common injection models are based on single electron descriptions, being problematic especially once the amount of charge-carriers injected is large. Accordingly, we developed a model, which incorporates space charge effects in the description of the injection process. The challenge of this task is the problem of self-consistency. The amount of charge-carriers injected per unit time strongly depends on the energy barrier emerging at the contact, while at the same time the electrostatic potential generated by the injected charge- carriers modifies the height of this injection barrier itself. In our model, self-consistency is obtained by assuming continuity of the electric displacement and the electrochemical potential all over the conductor/insulator system. The conductor and the insulator are properly taken into account by means of their respective density of state distributions. The electric field distributions are obtained in a closed analytical form and the resulting current-voltage characteristics show that the theory embraces injection-limited as well as bulk-limited charge-carrier transport. Analytical approximations of these limits are given, revealing physical mechanisms responsible for the particular current-voltage behavior. In addition, the model exhibits the crossover between the two limiting cases and determines the validity of respective approximations. The consequences resulting from our exactly solvable model are discussed on the basis of a simplified indium tin oxide/organic semiconductor system.Comment: 23 pages, 6 figures, accepted to Phys.Rev.

Detecting Generalized Synchronization Between Chaotic Signals: A Kernel-based Approach

A unified framework for analyzing generalized synchronization in coupled chaotic systems from data is proposed. The key of the proposed approach is the use of the kernel methods recently developed in the field of machine learning. Several successful applications are presented, which show the capability of the kernel-based approach for detecting generalized synchronization. It is also shown that the dynamical change of the coupling coefficient between two chaotic systems can be captured by the proposed approach.Comment: 20 pages, 15 figures. massively revised as a full paper; issues on the choice of parameters by cross validation, tests by surrogated data, etc. are added as well as additional examples and figure

Charge carrier injection into insulating media: single-particle versus mean-field approach

Self-consistent, mean-field description of charge injection into a dielectric medium is modified to account for discreteness of charge carriers. The improved scheme includes both the Schottky barrier lowering due to the individual image charge and the barrier change due to the field penetration into the injecting electrode that ensures validity of the model at both high and low injection rates including the barrier dominated and the space-charge dominated regimes. Comparison of the theory with experiment on an unipolar ITO/PPV/Au-device is presented.Comment: 32 pages, 9 figures; revised version accepted to PR