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

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

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

Perturbation theory of the space-time non-commutative real scalar field theories

The perturbative framework of the space-time non-commutative real scalar field theory is formulated, based on the unitary S-matrix. Unitarity of the S-matrix is explicitly checked order by order using the Heisenberg picture of Lagrangian formalism of the second quantized operators, with the emphasis of the so-called minimal realization of the time-ordering step function and of the importance of the $\star$-time ordering. The Feynman rule is established and is presented using $\phi^4$ scalar field theory. It is shown that the divergence structure of space-time non-commutative theory is the same as the one of space-space non-commutative theory, while there is no UV-IR mixing problem in this space-time non-commutative theory.Comment: Latex 26 pages, notations modified, add reference

How to understand Pakistan’s hybrid regime: the importance of a multidimensional continuum

Pakistan has had a chequered democratic history but elections in 2013 marked a second turnover in power, and the first transition in Pakistan’s history from one freely elected government to another. How do we best categorize (and therefore understand) political developments in Pakistan? Is it now safe to categorize it as an electoral democracy or is it still a hybrid case of democracy? Using the Pakistani case as an example, this article argues that hybrid regimes deserve consideration as a separate case (rather than as a diminished sub type of democracy or authoritarianism), but must be categorised along a multidimensional continuum to understand the dynamics of power within the political system

Labeling the human skeleton with 41Ca to assess changes in bone calcium metabolism

Bone research is limited by the methods available for detecting changes in bone metabolism. While dual X-ray absorptiometry is rather insensitive, biochemical markers are subject to significant intra-individual variation. In the study presented here, we evaluated the isotopic labeling of bone using 41Ca, a long-lived radiotracer, as an alternative approach. After successful labeling of the skeleton, changes in the systematics of urinary 41Ca excretion are expected to directly reflect changes in bone Ca metabolism. A minute amount of 41Ca (100nCi) was administered orally to 22 postmenopausal women. Kinetics of tracer excretion were assessed by monitoring changes in urinary 41Ca/40Ca isotope ratios up to 700days post-dosing using accelerator mass spectrometry and resonance ionization mass spectrometry. Isotopic labeling of the skeleton was evaluated by two different approaches: (i) urinary 41Ca data were fitted to an established function consisting of an exponential term and a power law term for each individual; (ii) 41Ca data were analyzed by population pharmacokinetic (NONMEM) analysis to identify a compartmental model that describes urinary 41Ca tracer kinetics. A linear three-compartment model with a central compartment and two sequential peripheral compartments was found to best fit the 41Ca data. Fits based on the use of the combined exponential/power law function describing urinary tracer excretion showed substantially higher deviations between predicted and measured values than fits based on the compartmental modeling approach. By establishing the urinary 41Ca excretion pattern using data points up to day 500 and extrapolating these curves up to day 700, it was found that the calculated 41Ca/40Ca isotope ratios in urine were significantly lower than the observed 41Ca/40Ca isotope ratios for both techniques. Compartmental analysis can overcome this limitation. By identifying relative changes in transfer rates between compartments in response to an intervention, inaccuracies in the underlying model cancel out. Changes in tracer distribution between compartments were modeled based on identified kinetic parameters. While changes in bone formation and resorption can, in principle, be assessed by monitoring urinary 41Ca excretion over the first few weeks post-dosing, assessment of an intervention effect is more reliable ∼150days post-dosing when excreted tracer originates mainly from bon

The quest for companions to post-common envelope binaries. II. NSVS14256825 and HS0705+6700

We report new mid-eclipse times of the two close binaries NSVS14256825 and HS0705+6700, harboring an sdB primary and a low-mass main-sequence secondary. Both objects display clear variations in the measured orbital period, which can be explained by the action of a third object orbiting the binary. If this interpretation is correct, the third object in NSVS14256825 is a giant planet with a mass of roughly 12 M_Jup. For HS0705+6700, we provide evidence that strengthens the case for the suggested periodic nature of the eclipse time variation and reduces the uncertainties in the parameters of the brown dwarf implied by that model. The derived period is 8.4 yr and the mass is 31 M_Jup, if the orbit is coplanar with the binary. This research is part of the PlanetFinders project, an ongoing collaboration between professional astronomers and student groups at high schools.Comment: Accepted by Astron. and Astrophy

Optimum Small Optical Beam Displacement Measurement

We derive the quantum noise limit for the optical beam displacement of a TEM00 mode. Using a multimodal analysis, we show that the conventional split detection scheme for measuring beam displacement is non-optimal with 80% efficiency. We propose a new displacement measurement scheme that is optimal for small beam displacement. This scheme utilises a homodyne detection setup that has a TEM10 mode local oscillator. We show that although the quantum noise limit to displacement measurement can be surpassed using squeezed light in appropriate spatial modes for both schemes, the TEM10 homodyning scheme out-performs split detection for all values of squeezing.Comment: 13 pages, 7 figure

Nano-displacement measurements using spatially multimode squeezed light

We demonstrate the possibility of surpassing the quantum noise limit for simultaneous multi-axis spatial displacement measurements that have zero mean values. The requisite resources for these measurements are squeezed light beams with exotic transverse mode profiles. We show that, in principle, lossless combination of these modes can be achieved using the non-degenerate Gouy phase shift of optical resonators. When the combined squeezed beams are measured with quadrant detectors, we experimentally demonstrate a simultaneous reduction in the transverse x- and y- displacement fluctuations of 2.2 dB and 3.1 dB below the quantum noise limit.Comment: 21 pages, 9 figures, submitted to "Special Issue on Fluctuations & Noise in Photonics & Quantum Optics" of J. Opt.

Non-autonomous stochastic evolution equations and applications to stochastic partial differential equations

In this paper we study the following non-autonomous stochastic evolution equation on a UMD Banach space $E$ with type 2, {equation}\label{eq:SEab}\tag{SE} {{aligned} dU(t) & = (A(t)U(t) + F(t,U(t))) dt + B(t,U(t)) dW_H(t), \quad t\in [0,T], U(0) & = u_0. {aligned}. {equation} Here $(A(t))_{t\in [0,T]}$ are unbounded operators with domains $(D(A(t)))_{t\in [0,T]}$ which may be time dependent. We assume that $(A(t))_{t\in [0,T]}$ satisfies the conditions of Acquistapace and Terreni. The functions $F$ and $B$ are nonlinear functions defined on certain interpolation spaces and $u_0\in E$ is the initial value. $W_H$ is a cylindrical Brownian motion on a separable Hilbert space $H$. Under Lipschitz and linear growth conditions we show that there exists a unique mild solution of \eqref{eq:SEab}. Under assumptions on the interpolation spaces we extend the factorization method of Da Prato, Kwapie\'n, and Zabczyk, to obtain space-time regularity results for the solution $U$ of \eqref{eq:SEab}. For Hilbert spaces $E$ we obtain a maximal regularity result. The results improve several previous results from the literature. The theory is applied to a second order stochastic partial differential equation which has been studied by Sanz-Sol\'e and Vuillermot. This leads to several improvements of their result.Comment: Accepted for publication in Journal of Evolution Equation