Differential metabolism of alprazolam by liver and brain cytochrome (P4503A) to pharmacologically active metabolite

Cytochrome P450 (P450) is a superfamily of enzymes which mediates metabolism of xenobiotics including drugs. Alprazolam, an anti-anxiety agent, is metabolized in rat and human liver by P4503A1 and P4503A4 respectively, to 4-hydroxy alprazolam (4-OHALP, pharmacologically less active) and α-hydroxy alprazolam (α-OHALP, pharmacologically more active). We examined P450 mediated metabolism of alprazolam by rat and human brain microsomes and observed that the relative amount of α-OHALP formed in brain was higher than liver. This biotransformation was mediated by a P450 isoform belonging to P4503A subfamily, which is constitutively expressed in neuronal cells in rat and human brain. The formation of larger amounts of α-OHALP in neurons points to local modulation of pharmacological activity in brain, at the site of action of the anti-anxiety drug. Since hydroxy metabolites of alprazolam are hydrophilic and not easily cleared through blood-CSF barrier, α-OHALP would potentially have a longer half-life in brain

Quasinormal Spectrum and Quantization of Charged Black Holes

Black-hole quasinormal modes have been the subject of much recent attention, with the hope that these oscillation frequencies may shed some light on the elusive theory of quantum gravity. We study {\it analytically} the asymptotic quasinormal spectrum of a {\it charged} scalar field in the (charged) Reissner-Nordstr\"om spacetime. We find an analytic expression for these black-hole resonances in terms of the black-hole physical parameters: its Bekenstein-Hawking temperature $T_{BH}$, and its electric potential $\Phi$. We discuss the applicability of the results in the context of black-hole quantization. In particular, we show that according to Bohr's correspondence principle, the asymptotic resonance corresponds to a fundamental area unit $\Delta A=4\hbar\ln2$.Comment: 4 page

Terahertz magneto-optical spectroscopy of two-dimensional hole and electron systems

We have used terahertz (THz) magneto-optical spectroscopy to investigate the cyclotron resonance in high mobility two-dimensional electron and hole systems. Our experiments reveal long-lived (~20 ps) coherent oscillations in the measured signal in the presence of a perpendicular magnetic field. The cyclotron frequency extracted from the oscillations varies linearly with magnetic field for a two-dimensional electron gas (2DEG), as expected. However, we find that the complex non-parabolic valence band structure in a two-dimensional hole gas (2DHG) causes the cyclotron frequency and effective mass to vary nonlinearly with the magnetic field, as verified by multiband Landau level calculations. This is the first time that THz magneto-optical spectroscopy has been used to study 2DHG, and we expect that these results will motivate further studies of these unique 2D nanosystems.Comment: 11 pages, 7 figure

Perturbative calculation of quasi-normal modes of Schwarzschild black holes

We discuss a systematic method of analytically calculating the asymptotic form of quasi-normal frequencies of a four-dimensional Schwarzschild black hole by expanding around the zeroth-order approximation to the wave equation proposed by Motl and Neitzke. We obtain an explicit expression for the first-order correction and arbitrary spin. Our results are in agreement with the results from WKB and numerical analyses in the case of gravitational waves.Comment: 11 pages; references added and a sign error corrected; to appear in CQ

Observations with the High Altitude GAmma-Ray (HAGAR) telescope array in the Indian Himalayas

The High Altitude GAmma-Ray (HAGAR) array is a wavefront sampling array of 7 telescopes, set-up at Hanle, at 4270 m amsl, in the Ladakh region of the Himalayas (Northern India). It constitutes the first phase of the HImalayan Gamma-Ray Observatory (HIGRO) project. HAGAR is the first array of atmospheric Cherenkov telescopes established at a so high altitude, and was designed to reach a relatively low threshold (currently around 200 GeV) with quite a low mirror area (31 m2). Regular source observations are running since September 2008. Estimation of the sensitivity of the experiment is undergoing using several hours of data from the direction of Crab nebula, the standard candle source of TeV gamma-ray astronomy, and from dark regions. Data were acquired using the On-source/Off-source tracking mode, and by comparing these sky regions the strength of the gamma-ray signal could be estimated. Gamma-ray events arrive close to telescope axis direction while the cosmic-ray background events arrive from the whole field of view. We discuss our analysis procedures for the estimate of arrival direction, estimate of gamma ray flux from Crab nebula, and the sensitivity of the HAGAR system, in this paper

Introduction: reconsidering the region in India: mobilities, actors and development politics

In this introduction to a special issue on ‘Reconsidering the Region in India’, we aim to develop a synthetic and theoretically nuanced account of the multifarious ways in which the idea of region has been imbricated in diverse spatial, political, cultural and socio-economic configurations. We draw from various bodies of anthropological, geographic and historical literature to elaborate on three themes that we believe are central to understanding contemporary processes of region-making in India: trans-regional mobilities and connections; the actors who produce and perform regional imaginaries; and changing regional politics of development.IS

Parametric Study of CPT Resonance in Rubidium Vapor Cell for Application in Atomic Clock

The performance of Coherent Population Trapping (CPT) based atomic clocks primarily depends on the characteristics of CPT resonance. We have performed experiments to study and optimize the characteristics of CPT resonance in 87Rb atoms by measuring its contrast and full-width-at-half maximum (FWHM) as function of laser excitation and temperature of atomic vapor cells with different dimensions. A four-level atomic model is used to simulate CPT resonance characteristics along the length of atomic vapor cell. The model incorporates scaling law to understand collision dynamics in cells with different radius for a range of laser excitation intensities and the results are compared with experimental data. The quality figure, calculated from the measured values of FWHM and contrast, decreases with increase in laser intensity and improves in cells with higher dimension (radius). The optimum temperature corresponding to maximum quality figure varies with laser excitation intensity as well as cell dimension. The underlying collision dynamics and density effects that are responsible for the observed resonance characteristics are discussed

Direct Observation of Dimerization between Different CREB1 Isoforms in a Living Cell

Cyclic AMP-responsive element binding protein 1 (CREB1) plays multiple functions as a transcription factor in gene regulation. CREB1 proteins are also known to be expressed in several spliced isoforms that act as transcriptional activators or repressors. The activator isoforms, possessing the functional domains for kinase induction and for interaction with other transcriptional regulators, act as transcriptional activators. On the other hand, some isoforms, lacking those functional domains, are reported to be repressors that make heterodimers with activator isoforms. The complex and ingenious function for CREB1 arises in part from the variation in their spliced isoforms, which allows them to interact with each other. To date, however, the dimerization between the activator and repressor isoforms has not yet been proved directly in living cells. In this study, we applied fluorescence cross-correlation spectroscopy (FCCS) to demonstrate direct observation of dimerization between CREB1 activator and repressor. The FCCS is a well established spectroscopic method to determine the interaction between the different fluorescent molecules in the aqueous condition. Using differently labeled CREB1 isoforms, we successfully observed the interaction of CREB1 activator and repressor via dimerization in the nuclei of cultured cells. As a result, we confirmed the formation of heterodimer between CREB1 activator and repressor isoforms in living cells