Penrose limits, supergravity and brane dynamics

We investigate the Penrose limits of classical string and M-theory backgrounds. We prove that the number of (super)symmetries of a supergravity background never decreases in the limit. We classify all the possible Penrose limits of AdS x S spacetimes and of supergravity brane solutions. We also present the Penrose limits of various other solutions: intersecting branes, supersymmetric black holes and strings in diverse dimensions, and cosmological models. We explore the Penrose limit of an isometrically embedded spacetime and find a generalisation to spaces with more than one time. Finally, we show that the Penrose limit is a large tension limit for all branes including those with fields of Born--Infeld type.Comment: 67 page

Homogeneity and plane-wave limits

We explore the plane-wave limit of homogeneous spacetimes. For plane-wave limits along homogeneous geodesics the limit is known to be homogeneous and we exhibit the limiting metric in terms of Lie algebraic data. This simplifies many calculations and we illustrate this with several examples. We also investigate the behaviour of (reductive) homogeneous structures under the plane-wave limit.Comment: In memory of Stanley Hobert, 33 pages. Minor corrections and some simplification of Section 4.3.

Darboux Transformations for Supersymmetric Korteweg - de Vries Equations

\hspace{.2in}We consider the Darboux type transformations for the spectral problems of supersymmetric KdV systems. The supersymmetric analogies of Darboux and Darboux-Levi transformations are established for the spectral problems of Manin-Radul-Mathieu sKdV and Manin-Radul sKdV. Several B\"acklund transformations are derived for the MRM sKdV and MR sKdV systems.Comment: Latex, 8 pages AS-ITP-94-4

HSF-1, HIF-1and HSP90 expression on recombinant Pichia pastoris under fed-batch fermentation

Pichia pastoris is a methylotrophic yeast used as an efficient expression system for heterologous protein production as compared to other expression systems. Considering that every cell must respond to environmental changes to survive and differentiate, determination of endogenous protein related to heat stress responses and hypoxia, it would necessary to establish the temperature and methanol concentration conditions for optimal growth. The aim of this study is characterize the culture conditions through the putative biomarkers in different conditions of temperature and methanol concentration. Three yeast cultures were performed: 3X = 3% methanol -10 °C, 4X = 3% methanol -30 °C, and 5X = 1% methanol -10 °C. The expression level of HIF-1α, HSF-1, HSP-70 and HSP-90 biomarkers were measured by Western blot and in situ detection was performed by immunocytochemistry. The western blot results of HIF-1α and HSP-90 did not indicate statistically significant in the culture conditions studied. Respect to biomarkers location, HIF-1α and HSP-90 presented differences between cultures. In conclusion, the results suggest the cultures in a hypoxic condition produce a high density and yeast cells smaller. Beside the high density would not necessary related with a high production of recombinant proteins in modified-genetically P. pastoris

Supersymmetric Gauge Theories, Vortices and Equivariant Cohomology

We construct actions for (p,0)- and (p,1)- supersymmetric, 1 <= p <= 4, two-dimensional gauge theories coupled to non-linear sigma model matter with a Wess-Zumino term. We derive the scalar potential for a large class of these models. We then show that the Euclidean actions of the (2,0) and (4,0)-supersymmetric models without Wess-Zumino terms are bounded by topological charges which involve the equivariant extensions of the Kahler forms of the sigma model target spaces evaluated on the two-dimensional spacetime. We give similar bounds for Euclidean actions of appropriate gauge theories coupled to non-linear sigma model matter in higher spacetime dimensions which now involve the equivariant extensions of the Kahler forms of the sigma model target spaces and the second Chern character of gauge fields. The BPS configurations are generalisations of abelian and non-abelian vortices.Comment: 45 pages, Late

Heterotic Black Horizons

We show that the supersymmetric near horizon geometry of heterotic black holes is either an AdS_3 fibration over a 7-dimensional manifold which admits a G_2 structure compatible with a connection with skew-symmetric torsion, or it is a product R^{1,1} * S^8, where S^8 is a holonomy Spin(7) manifold, preserving 2 and 1 supersymmetries respectively. Moreover, we demonstrate that the AdS_3 class of heterotic horizons can preserve 4, 6 and 8 supersymmetries provided that the geometry of the base space is further restricted. Similarly R^{1,1} * S^8 horizons with extended supersymmetry are products of R^{1,1} with special holonomy manifolds. We have also found that the heterotic horizons with 8 supersymmetries are locally isometric to AdS_3 * S^3 * T^4, AdS_3 * S^3 * K_3 or R^{1,1} * T^4 * K_3, where the radii of AdS_3 and S^3 are equal and the dilaton is constant.Comment: 35 pages, latex. Minor alterations to equation (3.11) and section 4.1, the conclusions are not affecte

Liver Enzyme Abnormalities and Associated Risk Factors in HIV Patients on Efavirenz-Based HAART with or without Tuberculosis Co-Infection in Tanzania.

To investigate the timing, incidence, clinical presentation, pharmacokinetics and pharmacogenetic predictors for antiretroviral and anti-tuberculosis drug induced liver injury (DILI) in HIV patients with or without TB co-infection. A total of 473 treatment naïve HIV patients (253 HIV only and 220 with HIV-TB co-infection) were enrolled prospectively. Plasma efavirenz concentration and CYP2B6*6, CYP3A5*3, *6 and *7, ABCB1 3435C/T and SLCO1B1 genotypes were determined. Demographic, clinical and laboratory data were collected at baseline and up to 48 weeks of antiretroviral therapy. DILI case definition was according to Council for International Organizations of Medical Sciences (CIOMS). Incidence of DILI and identification of predictors was evaluated using Cox Proportional Hazards Model. The overall incidence of DILI was 7.8% (8.3 per 1000 person-week), being non-significantly higher among patients receiving concomitant anti-TB and HAART (10.0%, 10.7 per 1000 person-week) than those receiving HAART alone (5.9%, 6.3 per 1000 person-week). Frequency of CYP2B6*6 allele (p = 0.03) and CYP2B6*6/*6 genotype (p = 0.06) was significantly higher in patients with DILI than those without. Multivariate cox regression model indicated that CYP2B6*6/*6 genotype and anti-HCV IgG antibody positive as significant predictors of DILI. Median time to DILI was 2 weeks after HAART initiation and no DILI onset was observed after 12 weeks. No severe DILI was seen and the gain in CD4 was similar in patients with or without DILI. Antiretroviral and anti-tuberculosis DILI does occur in our setting, presenting early following HAART initiation. DILI seen is mild, transient and may not require treatment interruption. There is good tolerance to HAART and anti-TB with similar immunological outcomes. Genetic make-up mainly CYP2B6 genotype influences the development of efavirenz based HAART liver injury in Tanzanians

Stress-Induced Reinstatement of Drug Seeking: 20 Years of Progress

In human addicts, drug relapse and craving are often provoked by stress. Since 1995, this clinical scenario has been studied using a rat model of stress-induced reinstatement of drug seeking. Here, we first discuss the generality of stress-induced reinstatement to different drugs of abuse, different stressors, and different behavioral procedures. We also discuss neuropharmacological mechanisms, and brain areas and circuits controlling stress-induced reinstatement of drug seeking. We conclude by discussing results from translational human laboratory studies and clinical trials that were inspired by results from rat studies on stress-induced reinstatement. Our main conclusions are (1) The phenomenon of stress-induced reinstatement, first shown with an intermittent footshock stressor in rats trained to self-administer heroin, generalizes to other abused drugs, including cocaine, methamphetamine, nicotine, and alcohol, and is also observed in the conditioned place preference model in rats and mice. This phenomenon, however, is stressor specific and not all stressors induce reinstatement of drug seeking. (2) Neuropharmacological studies indicate the involvement of corticotropin-releasing factor (CRF), noradrenaline, dopamine, glutamate, kappa/dynorphin, and several other peptide and neurotransmitter systems in stress-induced reinstatement. Neuropharmacology and circuitry studies indicate the involvement of CRF and noradrenaline transmission in bed nucleus of stria terminalis and central amygdala, and dopamine, CRF, kappa/dynorphin, and glutamate transmission in other components of the mesocorticolimbic dopamine system (ventral tegmental area, medial prefrontal cortex, orbitofrontal cortex, and nucleus accumbens). (3) Translational human laboratory studies and a recent clinical trial study show the efficacy of alpha-2 adrenoceptor agonists in decreasing stress-induced drug craving and stress-induced initial heroin lapse