665 research outputs found

    The VVV Templates Project. Towards an Automated Classification of VVV Light-Curves. I. Building a database of stellar variability in the near-infrared

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    Context. The Vista Variables in the V\'ia L\'actea (VVV) ESO Public Survey is a variability survey of the Milky Way bulge and an adjacent section of the disk carried out from 2010 on ESO Visible and Infrared Survey Telescope for Astronomy (VISTA). VVV will eventually deliver a deep near-IR atlas with photometry and positions in five passbands (ZYJHK_S) and a catalogue of 1-10 million variable point sources - mostly unknown - which require classifications. Aims. The main goal of the VVV Templates Project, that we introduce in this work, is to develop and test the machine-learning algorithms for the automated classification of the VVV light-curves. As VVV is the first massive, multi-epoch survey of stellar variability in the near-infrared, the template light-curves that are required for training the classification algorithms are not available. In the first paper of the series we describe the construction of this comprehensive database of infrared stellar variability. Methods. First we performed a systematic search in the literature and public data archives, second, we coordinated a worldwide observational campaign, and third we exploited the VVV variability database itself on (optically) well-known stars to gather high-quality infrared light-curves of several hundreds of variable stars. Results. We have now collected a significant (and still increasing) number of infrared template light-curves. This database will be used as a training-set for the machine-learning algorithms that will automatically classify the light-curves produced by VVV. The results of such an automated classification will be covered in forthcoming papers of the series.Comment: 12 pages, 16 figures, 3 tables, accepted for publication in A&A. Most of the data are now accessible through http://www.vvvtemplates.org

    Adenosine receptors are the on-and-off switch of astrocytic cannabinoid type 1 (CB1) receptor effect upon synaptic plasticity in the medial prefrontal cortex

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    The medial prefrontal cortex (mPFC) is involved in cognitive functions such as working memory. Astrocytic cannabinoid type 1 receptor (CB1R) induces cytosolic calcium (Ca) concentration changes with an impact on neuronal function. mPFC astrocytes also express adenosine A and A receptors (AR, AR), being unknown the crosstalk between CB1R and adenosine receptors in these cells. We show here that a further level of regulation of astrocyte Ca signaling occurs through CB1R-AR or CB1R-AR heteromers that ultimately impact mPFC synaptic plasticity. CB1R-mediated Ca transients increased and decreased when AR and AR were activated, respectively, unveiling adenosine receptors as modulators of astrocytic CB1R. CB1R activation leads to an enhancement of long-term potentiation (LTP) in the mPFC, under the control of AR but not of AR. Notably, in IP3R2KO mice, that do not show astrocytic Ca level elevations, CB1R activation decreases LTP, which is not modified by AR or AR. The present work suggests that CB1R has a homeostatic role on mPFC LTP, under the control of AR, probably due to physical crosstalk between these receptors in astrocytes that ultimately alters CB1R Ca signaling.This work was supported by the Fundaçao para a Ciência e para a Tecnologia (FCT) (grant PTDC/MED-FAR/30933/2017 to AMS, PD/BD/150342/2019 to JG-R and SFRH/BD/147277/2019 to SC-P), by the International Society for Neurochemistry (Carer DevelopmentGrant 2021 to SHV), the European Union (H2020-WIDESPREAD-05-2017-Twinning (EpiEpinet), grant agreement 952455, to AMS and SHV), the Spanish Ministry for Science, Innovation and Universities (MCIN/ AEI/10.13039/501100011033) and the “ERDF A way of making Europe” (grant PID2021-122586NB-I00 to MN and PID2021-126600OB-I00 to RF), and the Fundación Tatiana Pérez de Guzmán el Bueno (PhD grant to JSR). We would also like to acknowledge the Rodent Facility of Instituto de Medicina Molecular Joao Lobo Antunes, Faculdade de Medicina (Universidade de Lisboa) for their technical support. We would like to acknowledge Dr. Tiago Costa-Coelho and Dr. Daniela M. Magalhaes (iMM, FMUL, Universidade de Lisboa) for their discussion on figure layout design

    Air and wet bulb temperature lapse rates and their impact on snowmaking in a Pyrenean ski resort

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    A set of 17 air temperature and relative humidity sensors were used to analyze the temporal variability of surface air temperature (Tair), wet bulb temperature (Twb), and daily snowmaking hours (SM, number of hours per day with Twb < − 2 °C), lapse rates, and the occurrence of thermal inversions at the Formigal ski resort (Spanish Pyrenees) from December to March during three consecutive ski seasons (2012–2013, 2013–2014, and 2014–2015). The Tair and Twb lapse rates showed strong hourly and daily variability, with both exhibiting almost identical temporal fluctuations. The Twb exhibited average lapse rates that were slightly steeper (− 5.2 °C/km) than those observed for Tair (− 4.9 °C/km). The less steep lapse rates and most thermal inversions were observed in December. Days having less (more) steep Tair and Twb lapse rates were observed under low (high) wind speeds and high (low) relative humidity and air pressure. The temporal dynamics of the SM lapse rates was more complex, as this involved consideration of the average Tair in the ski resort, in addition to the driving factors of the spatio-temporal variability of Twb. Thus, on a number of cold (warm) days, snowmaking was feasible at all elevations at the ski resort, independently of the slopes of the lapse rates. The SM exhibited an average daily lapse rate of 8.2 h/km, with a progressive trend of increase from December to March. Weather types over the Iberian Peninsula tightly control the driving factors of the Tair, Twb, and SM lapse rates (wind speed, relative humidity, and Tair), so the slopes of the lapse rates and the frequency of inversions in relation to elevation for the three variables are very dependent on the occurrence of specific weather types. The less steep lapse rates occurred associated with advections from the southeast, although low lapse rates also occurred during advections from the east and south, and under anticyclonic conditions. The steepest Tair and Twb lapse rates were observed during north and northwest advections, while the steepest rates for SM were observed during days of cyclonic circulation and advections from the northeast.This study was funded by the research project CGL2014-52599-P "Estudio del manto de nieve en la montaña española y su respuesta a la variabilidad y cambio climatico" (Ministry of Economy and Development, MINECO)

    Report of a new mutation in CYBB gene in two patients with X linked chronic granulomatous disease

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    Background: The X-linked form of chronic granulomatous disease (CGD) is a primary immunodeficiency that affects phagocytes of the innate immune system and is characterized by an increased susceptibility to severe bacterial and fungal infections. It is caused by mutations in the CYBB gene, which encodes the 91-kD subunit of phagocyte NADPH oxidase. Aim: To identify the mutation in the CYBB gene in two unrelated patients from Chile with, the diagnosis of X-linked CGD and their families. Patients and methods: The molecular genetic defects of two unrelated patients from Chile with X-linked CGD caused by defects in the CYBB gene were investigated. The underlying mutation was investigated by single strand conformation polymorphism (SSCP) analysis of PCR-amplified genomic DNA and by sequencing of the affected gene region. Results: We found an insertion c.1267_1268insA in exon 10 leading to a frameshift mutation. This mutation is a novel report. We also identified a splice site mutation in the other patient, that presented a c.1326 +1 G > A substitution in intron 10. The mutation was also detectable in his heterozygous mother. Conclusions: This is the first report of the clinical and molecular characterization of Chilean patients with mutations in CYBB gene (Rev Med Chile 2006; 134: 965-72).134896597

    Lifetimes of excited states in P-, As- and Sb-

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    Radiative lifetimes of three elements of the nitrogen group have been experimentally investigated at the Double ElectroStatic Ion Ring Experiment (DESIREE) facility at Stockholm University. The experiments were performed through selective laser photodetachment of excited states of P^-, As^- and Sb^- ions stored in a cryogenic storage ring. The experimental results were compared with theoretically predicted lifetimes, yielding a mixture of very good agreements in some cases and large discrepancies in others. These results are part of our efforts to map out the lifetimes of all excited states in negative ions. This data can be used to benchmark atomic theories, in particularly with respect to the degree of electron correlation that is incorporated in various theoretical models

    Economic impact of infections and antibiotics

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    In this chapter, we review several aspects with respect to the burden of infectious diseases, its impact in morbidity and mortality, and its economic burden. Furthermore, we referenced the actual situation with relation to the use of antimicrobial, the resistance problem and misuse of antibiotic, and the economic impact in the health systems

    Downregulation of hepatic lipopolysaccharide binding protein improves lipogenesis-induced liver lipid accumulation

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    Circulating lipopolysaccharide-binding protein (LBP) is increased in individuals with liver steatosis. We aimed to evaluate the possible impact of liver LBP downregulation using lipid nanoparticle-containing chemically modified LBP small interfering RNA (siRNA) (LNP-Lbp UNA-siRNA) on the development of fatty liver. Weekly LNP-Lbp UNA-siRNA was administered to mice fed a standard chow diet, a high-fat and high-sucrose diet, and a methionine- and choline-deficient diet (MCD). In mice fed a high-fat and high-sucrose diet, which displayed induced liver lipogenesis, LBP downregulation led to reduced liver lipid accumulation, lipogenesis (mainly stearoyl-coenzyme A desaturase 1 [Scd1]) and lipid peroxidation-associated oxidative stress markers. LNP-Lbp UNA-siRNA also resulted in significantly decreased blood glucose levels during an insulin tolerance test. In mice fed a standard chow diet or an MCD, in which liver lipogenesis was not induced or was inhibited (especially Scd1 mRNA), liver LBP downregulation did not impact on liver steatosis. The link between hepatocyte LBP and lipogenesis was further confirmed in palmitate-treated Hepa1-6 cells, in primary human hepatocytes, and in subjects with morbid obesity. Altogether, these data indicate that siRNA against liver Lbp mRNA constitutes a potential target therapy for obesity-associated fatty liver through the modulation of hepatic Scd1

    Lead Optimization of 3,5-Disubstituted-7-Azaindoles for the Treatment of Human African Trypanosomiasis

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    Neglected tropical diseases such as human African trypanosomiasis (HAT) are prevalent primarily in tropical climates and among populations living in poverty. Historically, the lack of economic incentive to develop new treatments for these diseases has meant that existing therapeutics have serious shortcomings in terms of safety, efficacy, and administration, and better therapeutics are needed. We now report a series of 3,5-disubstituted-7-azaindoles identified as growth inhibitors of Trypanosoma brucei, the parasite that causes HAT, through a high-throughput screen. We describe the hit-to-lead optimization of this series and the development and preclinical investigation of 29d, a potent antitrypanosomal compound with promising pharmacokinetic (PK) parameters. This compound was ultimately not progressed beyond in vivo PK studies due to its inability to penetrate the blood-brain barrier (BBB), critical for stage 2 HAT treatments

    Potassium Starvation in Yeast: Mechanisms of Homeostasis Revealed by Mathematical Modeling

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    The intrinsic ability of cells to adapt to a wide range of environmental conditions is a fundamental process required for survival. Potassium is the most abundant cation in living cells and is required for essential cellular processes, including the regulation of cell volume, pH and protein synthesis. Yeast cells can grow from low micromolar to molar potassium concentrations and utilize sophisticated control mechanisms to keep the internal potassium concentration in a viable range. We developed a mathematical model for Saccharomyces cerevisiae to explore the complex interplay between biophysical forces and molecular regulation facilitating potassium homeostasis. By using a novel inference method (“the reverse tracking algorithm”) we predicted and then verified experimentally that the main regulators under conditions of potassium starvation are proton fluxes responding to changes of potassium concentrations. In contrast to the prevailing view, we show that regulation of the main potassium transport systems (Trk1,2 and Nha1) in the plasma membrane is not sufficient to achieve homeostasis
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