On the Critical Behavior of D1-brane Theories

We study renormalization-group flow patterns in theories arising on D1-branes in various supersymmetry-breaking backgrounds. We argue that the theory of N D1-branes transverse to an orbifold space can be fine-tuned to flow to the corresponding orbifold conformal field theory in the infrared, for particular values of the couplings and theta angles which we determine using the discrete symmetries of the model. By calculating various nonplanar contributions to the scalar potential in the worldvolume theory, we show that fine-tuning is in fact required at finite N, as would be generically expected. We further comment on the presence of singular conformal field theories (such as those whose target space includes a ``throat'' described by an exactly solvable CFT) in the non-supersymmetric context. Throughout the analysis two applications are considered: to gauge theory/gravity duality and to linear sigma model techniques for studying worldsheet string theory.Comment: 23 pages in harvmac big, 8 figure

Dual targeting of MIR-208 and MIR-499 in the treatment of cardiac disorders

The present invention provides a method of treating or preventing cardiac disorders in a subject in need thereof by inhibiting the expression or function of both miR-499 and miR-208 in the heart cells of the subject. In particular, specific protocols for administering inhibitors of the two miRNAs that achieve efficient, long-term suppression are disclosed. In addition, the invention provides a method for treating or preventing musculoskeletal disorders in a subject in need thereof by increasing the expression or activity of both miR-208 and miR-499 in skeletal muscle cells of the subject.Board of Regents, University of Texas Syste

Function estimation with locally adaptive dynamic models

We present a nonparametric Bayesian method for fitting unsmooth and highly oscillating functions, which is based on a locally adaptive hierarchical extension of standard dynamic or state space models. The main idea is to introduce locally varying variances in the state equations and to add a further smoothness prior for this variance function. Estimation is fully Bayesian and carried out by recent MCMC techniques. The whole approach can be understood as an alternative to other nonparametric function estimators, such as local or penalized regression with variable bandwidth or smoothing parameter selection. Performance is illustrated with simulated data, including unsmooth examples constructed for wavelet shrinkage, and by an application to sales data. Although the approach is developed for classical Gaussian nonparametric regression, it can be extended to more complex regression problems

Cyanoacetylene in IC 342: An Evolving Dense Gas Component with Starburst Age

We present the first images of the J=5-4 and J=16-15 lines of the dense gas tracer, cyanoacetylene, HC_3N, in an external galaxy. The central 200 pc of the nearby star-forming spiral galaxy, IC 342, was mapped using the VLA and the Plateau de Bure Interferometer. HC_3N(5-4) line emission is found across the nuclear mini-spiral, but is very weak towards the starburst site, the location of the strongest mid-IR and radio emission. The J=16-15 and 10-9 lines are also faint near the large HII region complex, but are brighter relative to the 5-4 line, consistent with higher excitation. The brightest HC_3N emission is located in the northern arm of the nuclear minispiral, 100 pc away from the radio/IR source to the southwest of the nucleus. This location appears less affected by ultraviolet radiation, and may represent a more embedded, earlier stage of star formation. HC_3N excitation temperatures are consistent with those determined from C^{18}O; the gas is dense, 10^{4-5}/cc, and cool, T_K ~< 40 K. So as to not violate limits on the total H_2 mass determined from C^{18}O, at least two dense components are required to model IC 342's giant molecular clouds. These observations suggest that HC_3N(5-4) is an excellent probe of the dense, quiescent gas in galaxies. The high excitation combined with faint emission towards the dense molecular gas at the starburst indicates that it currently lacks large masses of very dense gas. We propose a scenario where the starburst is being caught in the act of dispersing or destroying its dense gas in the presence of the large HII region. This explains the high star formation efficiency seen in the dense component. The little remaining dense gas appears to be in pressure equilibrium with the starburst HII region.Comment: Accepted, AJ. 12 pages, 5 figure

Comparative Analysis Of Zebrafish And Planarian Model Systems For Developmental Neurotoxicity Screens Using An 87-Compound Library

There is a clear need to establish and validate new methodologies to more quickly and efficiently screen chemicals for potential toxic effects, particularly on development. The emergence of alternative animal systems for rapid toxicology screens presents valuable opportunities to evaluate how systems complement each other. In this article, we compare a chemical library of 87-compounds in two such systems, developing zebrafish and freshwater planarians, by screening for developmental neurotoxic effects. We show that the systems’ toxicological profiles are complementary to each other, with zebrafish yielding more detailed morphological endpoints and planarians more behavioral endpoints. Overall, zebrafish was more sensitive to this chemical library, yielding 86/87 hits, compared to 50/87 hits in planarians. The difference in sensitivity could not be attributed to molecular weight, Log Kow or the bioconcentration factor. Of the 87 chemicals, 28 had previously been evaluated in mammalian developmental neuro- (DNT), neuro- or developmental toxicity studies. Of the 28, 20 were hits in the planarian, and 27 were hits in zebrafish. Eighteen of the 28 had previously been identified as DNT hits in mammals and were highly associated with activity in zebrafish and planarian behavioral assays in this study. Only 1 chemical (out of 28) was a false negative in both zebrafish and planarian systems. Differences in endpoint coverage and system sensitivity illustrate the value of a dual systems approach to rapidly query a large chemical-bioactivity space and provide weight-of-evidence for prioritization of chemicals for further testing

Acute vigabatrin-phenobarbitone-interaction on exploratory behaviour of rats

Vigabatrin (gamma-vinyl GABA) is an irreversible inh:bitor of the enzyme GABA-transaminase (GABA-T) which is responsible for the catabolism of the major inhibitory neurotransmitter gamma- aminobutyric acid (GABA) in the brain. Vigabatrin causes a several fold increase in the levels of brain GABA. The current study investigated further the effects of acute treatment with vigabatrin (100 mgl kg, i.p.) & phenobarbitone sodium (20 mg/kg, i.p.)f alone and in combination, in two rat behavioural models of exploratory activity: the elevated plus-maze model of anxiety and the open field test of locomotor activity. A single injection of vigabatrin or phenobarbitone alone, produced anxiolytic effects in the elevated plus-maze test and increased locomotor activity in the open field test. In contrast, after the concomitant administration of both drugs, the anxiolytic effects were no longer produced in the elevated plus-maze. The increased locomotor activity was also diminished in both tests of exploratory behaviour. These results shed light on the GABA hypothesis of anxiety, insofar as the increased availability of GABA, resulting from either GABA-T inhibition (vigabatrin) or facilitation of GABA-mediated chloride channels (phenobarbitone), seems to result in an increased emotional reactivity which, however, subsequently disappears during combined treatment.peer-reviewe

Multi-Behavioral Endpoint Testing Of An 87-Chemical Compound Library In Freshwater Planarians

There is an increased recognition in the field of toxicology of the value of medium-to-high-throughput screening methods using in vitro and alternative animal models. We have previously introduced the asexual freshwater planarian Dugesia japonica as a new alternative animal model and proposed that it is particularly well-suited for the study of developmental neurotoxicology. In this paper, we discuss how we have expanded and automated our screening methodology to allow for fast screening of multiple behavioral endpoints, developmental toxicity, and mortality. Using an 87-compound library provided by the National Toxicology Program (NTP), consisting of known and suspected neurotoxicants, including drugs, flame retardants, industrial chemicals, polycyclic aromatic hydrocarbons (PAHs), pesticides and presumptive negative controls, we further evaluate the benefits and limitations of the system for medium-throughput screening, focusing on the technical aspects of the system. We show that, in the context of this library, planarians are the most sensitive to pesticides with 16/16 compounds causing toxicity and the least sensitive to PAHs, with only 5/17 causing toxicity. Furthermore, while none of the presumptive negative controls were bioactive in adult planarians, 2/5, acetaminophen and acetylsalicylic acid, were bioactive in regenerating worms. Notably, these compounds were previously reported as developmentally toxic in mammalian studies. Through parallel screening of adults and developing animals, planarians are thus a useful model to detect such developmental-specific effects, which was observed for 13 chemicals in this library. We use the data and experience gained from this screen to propose guidelines for best practices when using planarians for toxicology screens

‘Going implicit’: using implicit measures in organizations

Implicit tests are increasingly being used and discussed in the field of Industrial-Organizational psychology. Despite their growing popularity, little is known about the types of implicit tests that exist, how they operationalize constructs, and how to improve their usefulness to predict relevant organizational behavior. We provide a timely contribution to practitioners and scholars who are considering adopting implicit measures in their organizations. By drawing on dual-processing theory, we reviewed the most prevalent implicit tests (Implicit Association Test, Picture Story Exercise, and Conditional Reasoning Test), and evaluated each against the following criteria: how they work, application areas, psychometric properties, perceptions of fairness, and faking potential. Based on prior empirical evidence, we provide ideas to improve these measures, how they may be applied in practice, and which avenues deserve future research. Together, these recommendations may enhance the value of implicit measures in organizations