Positive autoregulation of GDNF levels in the ventral tegmental area mediates long-lasting inhibition of excessive alcohol consumption.

Glial cell line-derived neurotrophic factor (GDNF) is an essential growth factor for the survival and maintenance of the midbrain dopaminergic (DA-ergic) neurons. Activation of the GDNF pathway in the ventral tegmental area (VTA), where the GDNF receptors are expressed, produces a long-lasting suppression of excessive alcohol consumption in rats. Previous studies conducted in the DA-ergic-like cells, SHSY5Y, revealed that GDNF positively regulates its own expression, leading to a long-lasting activation of the GDNF signaling pathway. Here we determined whether GDNF activates a positive autoregulatory feedback loop in vivo within the VTA, and if so, whether this mechanism underlies the long-lasting suppressive effects of the growth factor on excessive alcohol consumption. We found that a single infusion of recombinant GDNF (rGDNF; 10 μg) into the VTA induces a long-lasting local increase in GDNF mRNA and protein levels, which depends upon de novo transcription and translation of the polypeptide. Importantly, we report that the GDNF-mediated positive autoregulatory feedback loop accounts for the long-lasting inhibitory actions of GDNF in the VTA on excessive alcohol consumption. Specifically, the long-lasting suppressive effects of a single rGDNF infusion into the VTA on excessive alcohol consumption were prevented when protein synthesis was inhibited, as well as when the upregulation of GDNF expression was prevented using short hairpin RNA to focally knock down GDNF mRNA in the VTA. Our results could have implications for the development of long-lasting treatments for disorders in which GDNF has a beneficial role, including drug addiction, chronic stress and Parkinson's disease

Direct Numerical Simulations of the Kraichnan Model: Scaling Exponents and Fusion Rules

We present results from direct numerical simulations of the Kraichnan model for passive scalar advection by a rapidly-varying random scaling velocity field for intermediate values of the velocity scaling exponent. These results are compared with the scaling exponents predicted for this model by Kraichnan. Further, we test the recently proposed fusion rules which govern the scaling properties of multi-point correlations, and present results on the linearity of the conditional statistics of the Laplacian operator on the scalar field.Comment: PRL, submitted, 4 pages, 5 figures (not included). Online (HTML) version and PS source of the paper with figures available at http://lvov.weizmann.ac.il/onlinelist.htm

The critical region of strong-coupling lattice QCD in different large-N limits

We study the critical behavior at nonzero temperature phase transitions of an effective Hamiltonian derived from lattice QCD in the strong-coupling expansion. Following studies of related quantum spin systems that have a similar Hamiltonian, we show that for large $N_c$ and fixed $g^2N_c$, mean field scaling is not expected, and that the critical region has a finite width at $N_c=\infty$. A different behavior rises for $N_f\to \infty$ and fixed $N_c$ and $g^2/N_f$, which we study in two spatial dimensions and for $N_c=1$. We find that the width of the critical region is suppressed by $1/N_f^p$ with $p=1/2$, and argue that a generalization to $N_c>1$ and to three dimensions will change this only in detail (e.g. the value of $p>0$), but not in principle. We conclude by stating under what conditions this suppression is expected, and remark on possible realizations of this phenomenon in lattice gauge theories in the continuum.Comment: 24 pages, 6 figures. New version includes: a more extensive discussion of strong-coupling expansions and their region of validity. Accordingly I have reworded the descriptions of the investigated limits. Removed typos and misprint

Cost-Benefit Analysis of a Redundant System with Server having Refreshment Facility Subject to Inspection

In this paper two units cold standby system has been discussed with the facility that server inspect the failed unit before repair/replacement of the unit and server may allow to take refreshment whenever needed. The operative unit may fail directly from normal mode and the cold standby unit may be failed owing to remain unused for a longer period of time. There is single server who serves the dual purpose of inspection and repair immediately whenever required. Also, after having refreshment the server may eventually perform the better service efficiently. The time to take refreshment and repair activity follows negative exponential distribution whereas the distributions of unit failure and server failure are taken as arbitrary with different probability density functions. The expressions of various stochastic measures are analyzed in steady state using semi-Markov process and regenerative point technique. The graphs are sketched for arbitrary values of the parameters to delineate the behavior of some important performance measures to check the efficacy of the system model under such situations

Secret-Sharing for NP

A computational secret-sharing scheme is a method that enables a dealer, that has a secret, to distribute this secret among a set of parties such that a "qualified" subset of parties can efficiently reconstruct the secret while any "unqualified" subset of parties cannot efficiently learn anything about the secret. The collection of "qualified" subsets is defined by a Boolean function. It has been a major open problem to understand which (monotone) functions can be realized by a computational secret-sharing schemes. Yao suggested a method for secret-sharing for any function that has a polynomial-size monotone circuit (a class which is strictly smaller than the class of monotone functions in P). Around 1990 Rudich raised the possibility of obtaining secret-sharing for all monotone functions in NP: In order to reconstruct the secret a set of parties must be "qualified" and provide a witness attesting to this fact. Recently, Garg et al. (STOC 2013) put forward the concept of witness encryption, where the goal is to encrypt a message relative to a statement "x in L" for a language L in NP such that anyone holding a witness to the statement can decrypt the message, however, if x is not in L, then it is computationally hard to decrypt. Garg et al. showed how to construct several cryptographic primitives from witness encryption and gave a candidate construction. One can show that computational secret-sharing implies witness encryption for the same language. Our main result is the converse: we give a construction of a computational secret-sharing scheme for any monotone function in NP assuming witness encryption for NP and one-way functions. As a consequence we get a completeness theorem for secret-sharing: computational secret-sharing scheme for any single monotone NP-complete function implies a computational secret-sharing scheme for every monotone function in NP

Post-ISCO Ringdown Amplitudes in Extreme Mass Ratio Inspiral

An extreme mass ratio inspiral consists of two parts: adiabatic inspiral and plunge. The plunge trajectory from the innermost stable circular orbit (ISCO) is special (somewhat independent of initial conditions). We write an expression for its solution in closed-form and for the emitted waveform. In particular we extract an expression for the associated black-hole ringdown amplitudes, and evaluate them numerically.Comment: 21 pages, 5 figures. v4: added section with numerical evaluation of the ringdown amplitude

Industrial Clustering and the Returns to Inventive Activity Canadian Biotechnology Firms, 1991-2000

We examine how industrial clustering affects biotechnology firms’ innovativeness, contrasting similar firms not located in clusters or located in clusters that are or are not focused on the firm’s technological specialization. Using detailed firm level data, we find clustered firms are eight times more innovative than geographically remote firms, with largest effects for firms located in clusters strong in their own specialization. For firms located in a cluster strong in their specialization we also find that R&D productivity is enhanced by a firm’s own R&D alliances and also by the R&D alliances of other colocated firms.Biotechnology, industrial clustering, knowledge spillovers, R&D productivity, strategic alliances

Fixed Scalars and Suppression of Hawking Evaporation

For an extreme charged black hole some scalars take on a fixed value at the horizon determined by the charges alone. We call them fixed scalars. We find the absorption cross section for a low frequency wave of a fixed scalar to be proportional to the square of the frequency. This implies a strong suppression of the Hawking radiation near extremality. We compute the coefficient of proportionality for a specific model.Comment: 10 pages, late

Secure self-calibrating quantum random bit generator

Random bit generators (RBGs) are key components of a variety of information processing applications ranging from simulations to cryptography. In particular, cryptographic systems require "strong" RBGs that produce high-entropy bit sequences, but traditional software pseudo-RBGs have very low entropy content and therefore are relatively weak for cryptography. Hardware RBGs yield entropy from chaotic or quantum physical systems and therefore are expected to exhibit high entropy, but in current implementations their exact entropy content is unknown. Here we report a quantum random bit generator (QRBG) that harvests entropy by measuring single-photon and entangled two-photon polarization states. We introduce and implement a quantum tomographic method to measure a lower bound on the "min-entropy" of the system, and we employ this value to distill a truly random bit sequence. This approach is secure: even if an attacker takes control of the source of optical states, a secure random sequence can be distilled.Comment: 5 pages, 2 figure