7,907 research outputs found

    From Heisenberg matrix mechanics to EBK quantization: theory and first applications

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    Despite the seminal connection between classical multiply-periodic motion and Heisenberg matrix mechanics and the massive amount of work done on the associated problem of semiclassical (EBK) quantization of bound states, we show that there are, nevertheless, a number of previously unexploited aspects of this relationship that bear on the quantum-classical correspondence. In particular, we emphasize a quantum variational principle that implies the classical variational principle for invariant tori. We also expose the more indirect connection between commutation relations and quantization of action variables. With the help of several standard models with one or two degrees of freedom, we then illustrate how the methods of Heisenberg matrix mechanics described in this paper may be used to obtain quantum solutions with a modest increase in effort compared to semiclassical calculations. We also describe and apply a method for obtaining leading quantum corrections to EBK results. Finally, we suggest several new or modified applications of EBK quantization.Comment: 37 pages including 3 poscript figures, submitted to Phys. Rev.

    Structural and compositional properties of brown dwarf disks: the case of 2MASS J04442713+2512164

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    In order to improve our understanding of substellar formation, we have performed a compositional and structural study of a brown dwarf disk. We present the result of photometric, spectroscopic and imaging observations of 2MASS J04442713+2512164, a young brown dwarf (M7.25) member of the Taurus association. Our dataset, combined with results from the literature, provides a complete coverage of the spectral energy distribution from the optical to the millimeter including the first photometric measurement of a brown dwarf disk at 3.7mm, and allows us to perform a detailed analysis of the disk properties. The target was known to have a disk. High resolution optical spectroscopy shows that it is intensely accreting, and powers a jet and an outflow. The disk structure is similar to that observed for more massive TTauri stars. Spectral decomposition models of Spitzer/IRS spectra suggest that the mid-infrared emission from the optically thin disk layers is dominated by grains with intermediate sizes (1.5micron). Crystalline silicates are significantly more abondant in the outer part and/or deeper layers of the disk, implying very efficient mixing and/or additional annealing processes. Sub-millimeter and millimeter data indicate that most of the disk mass is in large grains (>1mm)Comment: 17 pages, 10 figures, 7 tables, accepted for A&

    A Feasibility Study of Quantifying Longitudinal Brain Changes in Herpes Simplex Virus (HSV) Encephalitis Using Magnetic Resonance Imaging (MRI) and Stereology.

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    OBJECTIVES: To assess whether it is feasible to quantify acute change in temporal lobe volume and total oedema volumes in herpes simplex virus (HSV) encephalitis as a preliminary to a trial of corticosteroid therapy. METHODS: The study analysed serially acquired magnetic resonance images (MRI), of patients with acute HSV encephalitis who had neuroimaging repeated within four weeks of the first scan. We performed volumetric measurements of the left and right temporal lobes and of cerebral oedema visible on T2 weighted Fluid Attenuated Inversion Recovery (FLAIR) images using stereology in conjunction with point counting. RESULTS: Temporal lobe volumes increased on average by 1.6% (standard deviation (SD 11%) in five patients who had not received corticosteroid therapy and decreased in two patients who had received corticosteroids by 8.5%. FLAIR hyperintensity volumes increased by 9% in patients not receiving treatment with corticosteroids and decreased by 29% in the two patients that had received corticosteroids. CONCLUSIONS: This study has shown it is feasible to quantify acute change in temporal lobe and total oedema volumes in HSV encephalitis and suggests a potential resolution of swelling in response to corticosteroid therapy. These techniques could be used as part of a randomized control trial to investigate the efficacy of corticosteroids for treating HSV encephalitis in conjunction with assessing clinical outcomes and could be of potential value in helping to predict the clinical outcomes of patients with HSV encephalitis

    A Randomized Trial to Assess Anti-HIV Activity in Female Genital Tract Secretions and Soluble Mucosal Immunity Following Application of 1% Tenofovir Gel

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    Preclinical and early phase clinical microbicide studies have not consistently predicted the outcome of efficacy trials. To address this gap, candidate biomarkers of microbicide pharmacodynamics and safety were evaluated in a double-blind, placebo-controlled trial of tenofovir gel, the first microbicide to demonstrate significant protection against HIV acquisition.30 women were randomized to apply a single daily dose of tenofovir or placebo gel for 14 consecutive days. Anti-HIV activity was measured in cervicovaginal lavage (CVL) on Days 0, 3, 7, 14 and 21 by luciferase assay as a surrogate marker of pharmacodynamics. Endogenous activity against E. coli and HSV-2 and concentrations of immune mediators were quantified in CVL as candidate biomarkers of safety. Tenofovir levels were measured in CVL and blood.A significant increase in anti-HIV activity was detected in CVL from women who applied tenofovir gel compared to their endogenous anti-HIV activity in genital tract secretions on Day 0 and compared to activity in CVL from women in the placebo group. The activity correlated significantly with CVL concentration of tenofovir (r = 0.6, p<0.001) and fit a sigmoid E(max) pharmacodynamic model. Anti-HIV activity in CVL from women who applied tenofovir persisted when virus was introduced in semen, whereas endogenous anti-HIV activity decreased. Tenofovir did not trigger an inflammatory response or induce sustained loss in endogenous antimicrobial activity or immune mediators.Tenofovir gel had no deleterious impact on soluble mucosal immunity. The increased anti-HIV activity in CVL, which persisted in the presence of semen and correlated with tenofovir concentration, is consistent with the efficacy observed in a recent clinical trial. These results promote quantified CVL anti-HIV activity as a surrogate of tissue pharmacodynamics and as a potential biomarker of adherence to product. This simple, feasible and inexpensive bioassay may promote the development of models more predictive of microbicide efficacy.ClinicalTrials.gov NCT00594373

    Appraisal of progenitor markers in the context of molecular classification of breast cancers

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    Clinical management of breast cancer relies on case stratification, which increasingly employs molecular markers. The motivation behind delineating breast epithelial differentiation is to better target cancer cases through innate sensitivities bequeathed to the cancer from its normal progenitor state. A combination of histopathological and molecular classification of breast cancer cases suggests a role for progenitors in particular breast cancer cases. Although a remarkable fraction of the real tissue repertoire is maintained within a population of independent cell line cultures, some steps that are closer to the terminal differentiation state and that form a majority of primary human breast tissues are missing in the cell line cultures. This raises concerns about current breast cancer models

    GASPS observations of Herbig Ae/Be stars with PACS/Herschel. The atomic and molecular content of their protoplanetary discs

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    We observed a sample of 20 representative Herbig Ae/Be stars and five A-type debris discs with PACS onboard of Herschel. The observations were done in spectroscopic mode, and cover far-IR lines of [OI], [CII], CO, CH+, H2O and OH. We have a [OI]63 micron detection rate of 100% for the Herbig Ae/Be and 0% for the debris discs. [OI]145 micron is only detected in 25%, CO J=18-17 in 45% (and less for higher J transitions) of the Herbig Ae/Be stars and for [CII] 157 micron, we often found spatially variable background contamination. We show the first detection of water in a Herbig Ae disc, HD 163296, which has a settled disc. Hydroxyl is detected as well in this disc. CH+, first seen in HD 100546, is now detected for the second time in a Herbig Ae star, HD 97048. We report fluxes for each line and use the observations as line diagnostics of the gas properties. Furthermore, we look for correlations between the strength of the emission lines and stellar or disc parameters, such as stellar luminosity, UV and X-ray flux, accretion rate, PAH band strength, and flaring. We find that the stellar UV flux is the dominant excitation mechanism of [OI]63 micron, with the highest line fluxes found in those objects with a large amount of flaring and greatest PAH strength. Neither the amount of accretion nor the X-ray luminosity has an influence on the line strength. We find correlations between the line flux of [OI]63 micron and [OI]145 micron, CO J = 18-17 and [OI]6300 \AA, and between the continuum flux at 63 micron and at 1.3 mm, while we find weak correlations between the line flux of [OI]63 micron and the PAH luminosity, the line flux of CO J = 3-2, the continuum flux at 63 micron, the stellar effective temperature and the Brgamma luminosity. (Abbreviated version)Comment: 20 pages, 29 figures, accepted by Astronomy and Astrophysic

    Caspase-8 binding to cardiolipin in giant unilamellar vesicles provides a functional docking platform for bid

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    Caspase-8 is involved in death receptor-mediated apoptosis in type II cells, the proapoptotic programme of which is triggered by truncated Bid. Indeed, caspase-8 and Bid are the known intermediates of this signalling pathway. Cardiolipin has been shown to provide an anchor and an essential activating platform for caspase-8 at the mitochondrial membrane surface. Destabilisation of this platform alters receptor-mediated apoptosis in diseases such as Barth Syndrome, which is characterised by the presence of immature cardiolipin which does not allow caspase-8 binding. We used a simplified in vitro system that mimics contact sites and/or cardiolipin-enriched microdomains at the outer mitochondrial surface in which the platform consisting of caspase-8, Bid and cardiolipin was reconstituted in giant unilamellar vesicles. We analysed these vesicles by flow cytometry and confirm previous results that demonstrate the requirement for intact mature cardiolipin for caspase-8 activation and Bid binding and cleavage. We also used confocal microscopy to visualise the rupture of the vesicles and their revesiculation at smaller sizes due to alteration of the curvature following caspase-8 and Bid binding. Biophysical approaches, including Laurdan fluorescence and rupture/tension measurements, were used to determine the ability of these three components (cardiolipin, caspase-8 and Bid) to fulfil the minimal requirements for the formation and function of the platform at the mitochondrial membrane. Our results shed light on the active functional role of cardiolipin, bridging the gap between death receptors and mitochondria

    Striatal interneurons in dissociated cell culture

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    In addition to the well-characterized direct and indirect projection neurons there are four major interneuron types in the striatum. Three contain GABA and either parvalbumin, calretinin or NOS/NPY/somatostatin. The fourth is cholinergic. It might be assumed that dissociated cell cultures of striatum (typically from embryonic day E18.5 in rat and E14.5 for mouse) contain each of these neuronal types. However, in dissociated rat striatal (caudate/putamen, CPu) cultures arguably the most important interneuron, the giant aspiny cholinergic neuron, is not present. When dissociated striatal neurons from E14.5 Sprague–Dawley rats were mixed with those from E18.5 rats, combined cultures from these two gestational periods yielded surviving cholinergic interneurons and representative populations of the other interneuron types at 5 weeks in vitro. Neurons from E12.5 CD-1 mice were combined with CPu neurons from E14.5 mice and the characteristics of striatal interneurons after 5 weeks in vitro were determined. All four major classes of interneurons were identified in these cultures as well as rare tyrosine hydroxylase positive interneurons. However, E14.5 mouse CPu cultures contained relatively few cholinergic interneurons rather than the nearly total absence seen in the rat. A later dissection day (E16.5) was required to obtain mouse CPu cultures totally lacking the cholinergic interneuron. We show that these cultures generated from two gestational age cells have much more nearly normal proportions of interneurons than the more common organotypic cultures of striatum. Interneurons are generated from both ages of embryos except for the cholinergic interneurons that originate from the medial ganglionic eminence of younger embryos. Study of these cultures should more accurately reflect neuronal processing as it occurs in the striatum in vivo. Furthermore, these results reveal a procedure for parallel culture of striatum and cholinergic depleted striatum that can be used to examine the function of the cholinergic interneuron in striatal networks

    Advances in ab-initio theory of Multiferroics. Materials and mechanisms: modelling and understanding

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    Within the broad class of multiferroics (compounds showing a coexistence of magnetism and ferroelectricity), we focus on the subclass of "improper electronic ferroelectrics", i.e. correlated materials where electronic degrees of freedom (such as spin, charge or orbital) drive ferroelectricity. In particular, in spin-induced ferroelectrics, there is not only a {\em coexistence} of the two intriguing magnetic and dipolar orders; rather, there is such an intimate link that one drives the other, suggesting a giant magnetoelectric coupling. Via first-principles approaches based on density functional theory, we review the microscopic mechanisms at the basis of multiferroicity in several compounds, ranging from transition metal oxides to organic multiferroics (MFs) to organic-inorganic hybrids (i.e. metal-organic frameworks, MOFs)Comment: 22 pages, 9 figure
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