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

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

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

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

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

Economic impact of infections and antibiotics

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

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

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

Defining Multiple Characteristic Raman Bands of α-Amino Acids as Biomarkers for Planetary Missions Using a Statistical Method

Biomarker molecules, such as amino acids, are key to discovering whether life exists elsewhere in the Solar System. Raman spectroscopy, a technique capable of detecting biomarkers, will be on board future planetary missions including the ExoMars rover. Generally, the position of the strongest band in the spectra of amino acids is reported as the identifying band. However, for an unknown sample, it is desirable to define multiple characteristic bands for molecules to avoid any ambiguous identification. To date, there has been no definition of multiple characteristic bands for amino acids of interest to astrobiology. This study examinedL-alanine, L-aspartic acid, L-cysteine, L-glutamine and glycine and defined several Raman bands per molecule for reference as characteristic identifiers. Per amino acid, 240 spectra were recorded and compared using established statistical tests including ANOVA. The number of characteristic bands defined were 10, 12, 12, 14 and 19 for L-alanine (strongest intensity band: 832 cm-1), L-aspartic acid (938 cm-1), L-cysteine (679 cm-1),L-glutamine (1090 cm−1) and glycine (875 cm-1), respectively. The intensity of bands differed by up to six times when several points on the crystal sample were rotated through 360 °; to reduce this effect when defining characteristic bands for other molecules, we find that spectra should be recorded at a statistically significant number of points per sample to remove the effect of sample rotation. It is crucial that sets of characteristic Raman bands are defined for biomarkers that are targets for future planetary missions to ensure a positive identification can be made

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

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

The VVV Templates Project Towards an automated classification of VVV light-curves: I. Building a database of stellar variability in the near-infrared

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