Photometry of supernovae in an image series : methods and application to the Supernova Legacy Survey (SNLS)

We present a technique to measure lightcurves of time-variable point sources on a spatially structured background from imaging data. The technique was developed to measure light curves of SNLS supernovae in order to infer their distances. This photometry technique performs simultaneous PSF photometry at the same sky position on an image series. We describe two implementations of the method: one that resamples images before measuring fluxes, and one which does not. In both instances, we sketch the key algorithms involved and present the validation using semi-artificial sources introduced in real images in order to assess the accuracy of the supernova flux measurements relative to that of surrounding stars. We describe the methods required to anchor these PSF fluxes to calibrated aperture catalogs, in order to derive SN magnitudes. We find a marginally significant bias of 2 mmag of the after-resampling method, and no bias at the mmag accuracy for the non-resampling method. Given surrounding star magnitudes, we determine the systematic uncertainty of SN magnitudes to be less than 1.5 mmag, which represents about one third of the current photometric calibration uncertainty affecting SN measurements. The SN photometry delivers several by-products: bright star PSF flux mea- surements which have a repeatability of about 0.6%, as for aperture measurements; we measure relative astrometric positions with a noise floor of 2.4 mas for a single-image bright star measurement; we show that in all bands of the MegaCam instrument, stars exhibit a profile linearly broadening with flux by about 0.5% over the whole brightness range.Comment: Accepted for publication in A&A. 20 page

Morphine Enhances HIV-1SF162-Mediated Neuron Death and Delays Recovery of Injured Neurites

HIV-1 enters the CNS soon after initial systemic infection; within the CNS parenchyma infected and/or activated perivascular macrophages, microglia and astrocytes release viral and cellular toxins that drive secondary toxicity in neurons and other cell types. Our previous work has largely modeled HIV-neuropathology using the individual viral proteins Tat or gp120, with murine striatal neurons as targets. To model disease processes more closely, the current study uses supernatant from HIV-1-infected cells. Supernatant from HIV-1SF162-infected differentiated-U937 cells (HIV+sup) was collected and p24 level was measured by ELISA to assess the infection. Injection drug abuse is a significant risk factor for HIV-infection, and opiate drug abusers show increased HIV-neuropathology, even with anti-retroviral treatments. We therefore assessed HIV+sup effects on neuronal survival and neurite growth/pruning with or without concurrent exposure to morphine, an opiate that preferentially acts through µ-opioid receptors. Effects of HIV+sup ± morphine were assessed on neuronal populations, and also by time-lapse imaging of individual cells. HIV+sup caused dose-dependent toxicity over a range of p24 levels (10–500 pg/ml). Significant interactions occurred with morphine at lower p24 levels (10 and 25 pg/ml), and GSK3β was implicated as a point of convergence. In the presence of glia, selective neurotoxic measures were significantly enhanced and interactions with morphine were also augmented, perhaps related to a decreased level of BDNF. Importantly, the arrest of neurite growth that occurred with exposure to HIV+sup was reversible unless neurons were continuously exposed to morphine. Thus, while reducing HIV-infection levels may be protective, ongoing exposure to opiates may limit recovery. Opiate interactions observed in this HIV-infective environment were similar, though not entirely concordant, with Tat/gp120 interactions reported previously, suggesting unique interactions with virions or other viral or cellular proteins released by infected and/or activated cells

Exploration of bivalent ligands targeting putative mu opioid receptor and chemokine receptor CCR5 dimerization

Modern antiretroviral therapies have provided HIV-1 infected patients longer lifespans and better quality of life. However, several neurological complications are now being seen in these patients due to HIV-1 associated injury of neurons by infected microglia and astrocytes. In addition, these effects can be further exacerbated with opiate use and abuse. One possible mechanism for such potentiation effects of opiates is the interaction of the mu opioid receptor (MOR) with the chemokine receptor CCR5 (CCR5), a known HIV-1 co-receptor, to form MOR-CCR5 heterodimer. In an attempt to understand this putative interaction and its relevance to neuroAIDS, we designed and synthesized a series of bivalent ligands targeting the putative CCR5-MOR heterodimer. To understand how these bivalent ligands may interact with the heterodimer, biological studies including calcium mobilization inhibition, binding affinity, HIV-1 invasion, and cell fusion assays were applied. In particular, HIV-1 infection assays using human peripheral blood mononuclear cells, macrophages, and astrocytes revealed a notable synergy in activity for one particular bivalent ligand. Further, a molecular model of the putative CCR5-MOR heterodimer was constructed, docked with the bivalent ligand, and molecular dynamics simulations of the complex was performed in a membrane-water system to help understand the biological observation

The effect of completeness of revascularization during CABG with single versus multiple arterial grafts

IntroductionIncomplete coronary revascularization is associated with suboptimal outcomes. We investigated the longâ term effects of Incomplete, Complete, and Supraâ complete revascularization and whether these effects differed in the setting of singleâ arterial and multiâ arterial coronary artery bypass graft (CABG).MethodsWe analyzed 15â year mortality in 7157 CABG patients (64.1â ±â 10.5 years; 30% women). All patients received a left internal thoracic artery to left anterior descending coronary artery graft with additional venous grafts only (singleâ arterial) or with at least one additional arterial graft (multiâ arterial) and were grouped based on a completeness of revascularization index (CRIâ =â number of grafts minus the number of diseased principal coronary arteries): Incomplete (CRIâ â ¤â â 1 [Nâ =â 320;4.5%]); Complete (CRIâ =â 0 [Nâ =â 2882;40.3%]; reference group); and two Supraâ complete categories (CRIâ =â +1[Nâ =â 3050; 42.6%]; CRIâ â ¥â +â 2 [Nâ =â 905; 12.6%]). Riskâ adjusted mortality hazard ratios (AHR) were calculated using comprehensive propensity score adjustment by Cox regression.ResultsIncomplete revascularization was rare (4.5%) but associated with increased mortality in all patients (AHR [95% confidence interval]â =â 1.53 [1.29â 1.80]), those undergoing singleâ arterial CABG (AHRâ =â 1.27 [1.04â 1.54]) and multiâ arterial CABG (AHRâ =â 2.18 [1.60â 2.99]), as well as in patients with 3â Vessel (AHRâ =â 1.37 [1.16â 1.62]) and, to a lesser degree, with 2â Vessel (AHRâ =â 1.67 [0.53â 5.23]) coronary disease. Supraâ complete revascularization was generally associated with incrementally decreased mortality in all patients (AHR [CRIâ =â +1]â =â 0.94 [0.87â 1.03]); AHR [CRIâ â ¥â +2]â =â 0.74 [0.64â 0.85]), and was driven by a significantly decreased mortality risk in singleâ arterial CABG (AHR [CRIâ =â +1]â =â 0.90 [0.81â 0.99]; AHR [CRIâ â ¥â +2]â =â 0.64 [0.53â 0.78]); and 3â Vessel disease patients (AHR [CRIâ =â +1]â =â 0.94 [0.86â 1.04]; and AHR [CRIâ â ¥â +2]â =â 0.75 [0.63â 0.88]) with no impact in multiâ arterial CABG (AHR [CRIâ =â +1]â =â 1.07 [0.91â 1.26]; AHR [CRIâ â ¥â +2]â =â 0.93 [0.73â 1.17]).ConclusionsIncomplete revascularization is associated with decreased late survival, irrespective of grafting strategy. Alternatively, supraâ complete revascularization is associated with improved survival in patients with 3â Vessel CAD, and in singleâ arterial but not multiâ arterial CABG.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146364/1/jocs13810.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146364/2/jocs13810_am.pd

Quasiparticle tunnel electroresistance in superconducting junctions

The term tunnel electroresistance (TER) denotes a fast, non-volatile, reversible resistance switching triggered by voltage pulses in ferroelectric tunnel junctions. It is explained by subtle mechanisms connected to the voltage-induced reversal of the ferroelectric polarization. Here we demonstrate that effects functionally indistinguishable from the TER can be produced in a simpler junction scheme-a direct contact between a metal and an oxide-through a different mechanism: a reversible redox reaction that modifies the oxide's ground-state. This is shown in junctions based on a cuprate superconductor, whose ground-state is sensitive to the oxygen stoichiometry and can be tracked in operando via changes in the conductance spectra. Furthermore, we find that electrochemistry is the governing mechanism even if a ferroelectric is placed between the metal and the oxide. Finally, we extend the concept of electroresistance to the tunnelling of superconducting quasiparticles, for which the switching effects are much stronger than for normal electrons. Besides providing crucial understanding, our results provide a basis for non-volatile Josephson memory devices. The non-volatile switching of tunnel electroresistance in ferroelectric junctions provides the basis for memory and neuromorphic computing devices. Rouco et al. show tunnel electroresistance in superconductor-based junctions that arises from a redox rather than ferroelectric mechanism and is enhanced by superconductivity

Enhanced insulin sensitivity associated with provision of mono and polyunsaturated fatty acids in skeletal muscle cells involves counter modulation of PP2A

International audienceAims/Hypothesis: Reduced skeletal muscle insulin sensitivity is a feature associated with sustained exposure to excess saturated fatty acids (SFA), whereas mono and polyunsaturated fatty acids (MUFA and PUFA) not only improve insulin sensitivity but blunt SFA-induced insulin resistance. The mechanisms by which MUFAs and PUFAs institute these favourable changes remain unclear, but may involve stimulating insulin signalling by counter-modulation/repression of protein phosphatase 2A (PP2A). This study investigated the effects of oleic acid (OA; a MUFA), linoleic acid (LOA; a PUFA) and palmitate (PA; a SFA) in cultured myotubes and determined whether changes in insulin signalling can be attributed to PP2A regulation. Principal Findings: We treated cultured skeletal myotubes with unsaturated and saturated fatty acids and evaluated insulin signalling, phosphorylation and methylation status of the catalytic subunit of PP2A. Unlike PA, sustained incubation of rat or human myotubes with OA or LOA significantly enhanced Akt-and ERK1/2-directed insulin signalling. This was not due to heightened upstream IRS1 or PI3K signalling nor to changes in expression of proteins involved in proximal insulin signalling, but was associated with reduced dephosphorylation/inactivation of Akt and ERK1/2. Consistent with this, PA reduced PP2Ac demethylation and tyrosine 307 phosphorylation-events associated with PP2A activation. In contrast, OA and LOA strongly opposed these PA-induced changes in PP2Ac thus exerting a repressive effect on PP2A.Conclusions/Interpretation: Beneficial gains in insulin sensitivity and the ability of unsaturated fatty acids to oppose palmitate-induced insulin resistance in muscle cells may partly be accounted for by counter-modulation of PP2A