Tauroursodeoxycholic acid exerts anticholestatic effects by a cooperative cPKC alpha-/PKA-dependent mechanism in rat liver.

Objective: Ursodeoxycholic acid (UDCA) exerts anticholestatic effects in part by protein kinase C (PKC)-dependent mechanisms. Its taurine conjugate, TUDCA, is a cPKCa agonist. We tested whether protein kinase A (PKA) might contribute to the anticholestatic action of TUDCA via cooperative cPKCa-/PKA-dependent mechanisms in taurolithocholic acid (TLCA)-induced cholestasis. Methods: In perfused rat liver, bile flow was determined gravimetrically, organic anion secretion spectrophotometrically, lactate dehydrogenase (LDH) release enzymatically, cAMP response-element binding protein (CREB) phosphorylation by immunoblotting, and cAMP by immunoassay. PKC/PKA inhibitors were tested radiochemically. In vitro phosphorylation of the conjugate export pump, Mrp2/Abcc2, was studied in rat hepatocytes and human Hep-G2 hepatoma cells. Results: In livers treated with TLCA (10 mmol/l)+TUDCA (25 mmol/l), combined inhibition of cPKC by the cPKCselective inhibitor Go¨6976 (100 nmol/l) or the nonselective PKC inhibitor staurosporine (10 nmol/l) and of PKA by H89 (100 nmol/l) reduced bile flow by 36% (p,0.05) and 48% (p,0.01), and secretion of the Mrp2/ Abcc2 substrate, 2,4-dinitrophenyl-S-glutathione, by 31% (p,0.05) and 41% (p,0.01), respectively; bile flow was unaffected in control livers or livers treated with TUDCA only or TLCA+taurocholic acid. Inhibition of cPKC or PKA alone did not affect the anticholestatic action of TUDCA. Hepatic cAMP levels and CREB phosphorylation as readout of PKA activity were unaffected by the bile acids tested, suggesting a permissive effect of PKA for the anticholestatic action of TUDCA. Rat and human hepatocellular Mrp2 were phosphorylated by phorbol ester pretreatment and recombinant cPKCa, nPKCe, and PKA, respectively, in a staurosporine-sensitive manner. Conclusion: UDCA conjugates exert their anticholestatic action in bile acid-induced cholestasis in part via cooperative post-translational cPKCa-/PKA-dependent mechanisms. Hepatocellular Mrp2 may be one target of bile acid-induced kinase activation

Coherent motion of stereocilia assures the concerted gating of hair-cell transduction channels

The hair cell's mechanoreceptive organelle, the hair bundle, is highly sensitive because its transduction channels open over a very narrow range of displacements. The synchronous gating of transduction channels also underlies the active hair-bundle motility that amplifies and tunes responsiveness. The extent to which the gating of independent transduction channels is coordinated depends on how tightly individual stereocilia are constrained to move as a unit. Using dual-beam interferometry in the bullfrog's sacculus, we found that thermal movements of stereocilia located as far apart as a bundle's opposite edges display high coherence and negligible phase lag. Because the mechanical degrees of freedom of stereocilia are strongly constrained, a force applied anywhere in the hair bundle deflects the structure as a unit. This feature assures the concerted gating of transduction channels that maximizes the sensitivity of mechanoelectrical transduction and enhances the hair bundle's capacity to amplify its inputs.Comment: 24 pages, including 6 figures, published in 200

Bounded H_\infty-calculus for pseudodifferential Douglis-Nirenberg systems of mild regularity

Parameter-ellipticity with respect to a closed subsector of the complex plane for pseudodifferential Douglis-Nirenberg systems is discussed and shown to imply the existence of a bounded H_\infty-calculus in suitable scales of Sobolev, Besov, and Hoelder spaces. We also admit non pseudodifferential perturbations. Applications concern systems with coefficients of mild Hoelder regularity and the generalized thermoelastic plate equations.Comment: 22 page

Applications of Information Theory to Analysis of Neural Data

Information theory is a practical and theoretical framework developed for the study of communication over noisy channels. Its probabilistic basis and capacity to relate statistical structure to function make it ideally suited for studying information flow in the nervous system. It has a number of useful properties: it is a general measure sensitive to any relationship, not only linear effects; it has meaningful units which in many cases allow direct comparison between different experiments; and it can be used to study how much information can be gained by observing neural responses in single trials, rather than in averages over multiple trials. A variety of information theoretic quantities are commonly used in neuroscience - (see entry "Definitions of Information-Theoretic Quantities"). In this entry we review some applications of information theory in neuroscience to study encoding of information in both single neurons and neuronal populations.Comment: 8 pages, 2 figure

Control of a SiC 2.5 MHz resonant full-bridge inverter for inductively driven plasma

The electronic ballast of an inductively driven plasma faces a mostly inductive, variable load impedance. The SiC full-bridge inverter uses the inductive behavior to achieve zero-voltage-switching and a switching frequency of 2.5 MHz, at 3.9 kVA and 764W in the plasma. The control is realized on a modern, small TI Piccolo microcontroller with a high-resolution PWM module and compensates for the variable load impedance. We present design and experimental results of a 2.5 MHz inverter for inductively driven plasma without the need for a large FPGA controller

Lebesgue regularity for differential difference equations with fractional damping

We provide necessary and sufficient conditions for the existence and unique-ness of solutions belonging to the vector-valued space of sequences �(Z, X) forequations that can be modeled in the formΔu(n)+Δu(n)=Au(n)+G(u)(n)+ (n), n ∈ Z,,>0,≥0,where X is a Banach space, ∈ �(Z, X), A is a closed linear operatorwith domain D(A) defined on X,andG is a nonlinear function. The oper-ator Δdenotes the fractional difference operator of order >0inthesense of Grünwald-Letnikov. Our class of models includes the discrete timeKlein-Gordon, telegraph, and Basset equations, among other differential differ-ence equations of interest. We prove a simple criterion that shows the existenceof solutions assuming that f is small and that G is a nonlinear term

ScanImage: Flexible software for operating laser scanning microscopes

BACKGROUND: Laser scanning microscopy is a powerful tool for analyzing the structure and function of biological specimens. Although numerous commercial laser scanning microscopes exist, some of the more interesting and challenging applications demand custom design. A major impediment to custom design is the difficulty of building custom data acquisition hardware and writing the complex software required to run the laser scanning microscope. RESULTS: We describe a simple, software-based approach to operating a laser scanning microscope without the need for custom data acquisition hardware. Data acquisition and control of laser scanning are achieved through standard data acquisition boards. The entire burden of signal integration and image processing is placed on the CPU of the computer. We quantitate the effectiveness of our data acquisition and signal conditioning algorithm under a variety of conditions. We implement our approach in an open source software package (ScanImage) and describe its functionality. CONCLUSIONS: We present ScanImage, software to run a flexible laser scanning microscope that allows easy custom design

Full oxide heterostructure combining a high-Tc diluted ferromagnet with a high-mobility conductor

We report on the growth of heterostructures composed of layers of the high-Curie temperature ferromagnet Co-doped (La,Sr)TiO3 (Co-LSTO) with high-mobility SrTiO3 (STO) substrates processed at low oxygen pressure. While perpendicular spin-dependent transport measurements in STO//Co-LSTO/LAO/Co tunnel junctions demonstrate the existence of a large spin polarization in Co-LSTO, planar magnetotransport experiments on STO//Co-LSTO samples evidence electronic mobilities as high as 10000 cm2/Vs at T = 10 K. At high enough applied fields and low enough temperatures (H < 60 kOe, T < 4 K) Shubnikov-de Haas oscillations are also observed. We present an extensive analysis of these quantum oscillations and relate them with the electronic properties of STO, for which we find large scattering rates up to ~ 10 ps. Thus, this work opens up the possibility to inject a spin-polarized current from a high-Curie temperature diluted oxide into an isostructural system with high-mobility and a large spin diffusion length.Comment: to appear in Phys. Rev.

Characterization of Turing diffusion-driven instability on evolving domains

In this paper we establish a general theoretical framework for Turing diffusion-driven instability for reaction-diffusion systems on time-dependent evolving domains. The main result is that Turing diffusion-driven instability for reaction-diffusion systems on evolving domains is characterised by Lyapunov exponents of the evolution family associated with the linearised system (obtained by linearising the original system along a spatially independent solution). This framework allows for the inclusion of the analysis of the long-time behavior of the solutions of reaction-diffusion systems. Applications to two special types of evolving domains are considered: (i) time-dependent domains which evolve to a final limiting fixed domain and (ii) time-dependent domains which are eventually time periodic. Reaction-diffusion systems have been widely proposed as plausible mechanisms for pattern formation in morphogenesis