Polyphenolic C-glucosidic ellagitannins present in oak-aged wine inhibit HIV-1 nucleocapsid protein

HIV-1 nucleocapsid protein (NC) is a nucleic acid chaperone implicated in several steps of the virus replication cycle and an attractive new target for drug development. In reverse transcription, NC destabilizes nucleic acid secondary structures and catalyzes the annealing of HIV-1 TAR RNA to its DNA copy (cTAR) to form the heteroduplex TAR/cTAR. A screening program led to the identification of the plant polyphenols acutissimins A and B as potent inhibitors of NC in different assays. These two flavano-ellagitannins, which are found in wine aged in oak barrels, exhibited different mechanisms of protein inhibition and higher potency relatively to their epimers, epiacutissimins A and B, and to simpler structures notably representing hydrolytic fragments and metabolites therefrom

An ensemble approach to assess hydrological models’ contribution to uncertainties in the analysis of climate change impact on water resources

Over the recent years, several research efforts investigated the impact of climate change on water resources for different regions of the world. The projection of future river flows is affected by different sources of uncertainty in the hydro-climatic modelling chain. One of the aims of the QBic3 5 project (Que´bec-Bavarian International Collaboration on Climate Change) is to assess the contribution to uncertainty of hydrological models by using an ensemble of hydrological models presenting a diversity of structural complexity (i.e. lumped, semi distributed and distributed models). The study investigates two humid, mid-latitude catchments with natural flow conditions; one located in 10 Southern Que´bec (Canada) and one in Southern Bavaria (Germany). Daily flow is simulated with four different hydrological models, forced by outputs from regional climate models driven by a given number of GCMs’ members over a reference (1971–2000) and a future (2041–2070) periods. The results show that the choice of the hydrological model does strongly affect the climate change response of selected hydrological indicators, especially those related to low flows. Indicators related to high flows seem less sensitive on the choice of the hydrological model. Therefore, the computationally less demanding models (usually simple, lumped and conceptual) give a significant level of trust for high and overall mean flows

On the need for bias correction in regional climate scenarios to assess climate change impacts on river runoff

In climate change impact research, the assessment of future river runoff as well as the catchment scale water balance is impeded by different sources of modeling uncertainty. Some research has already been done in order to quantify the uncertainty of climate 5 projections originating from the climate models and the downscaling techniques as well as from the internal variability evaluated from climate model member ensembles. Yet, the use of hydrological models adds another layer of incertitude. Within the QBic3 project (Qu´ebec-Bavaria International Collaboration on Climate Change) the relative contributions to the overall uncertainty from the whole model chain (from global climate 10 models to water management models) are investigated using an ensemble of multiple climate and hydrological models. Although there are many options to downscale global climate projections to the regional scale, recent impact studies tend to use Regional Climate Models (RCMs). One reason for that is that the physical coherence between atmospheric and land-surface 15 variables is preserved. The coherence between temperature and precipitation is of particular interest in hydrology. However, the regional climate model outputs often are biased compared to the observed climatology of a given region. Therefore, biases in those outputs are often corrected to reproduce historic runoff conditions from hydrological models using them, even if those corrections alter the relationship between temperature and precipitation. So, as bias correction may affect the consistency between RCM output variables, the use of correction techniques and even the use of (biased) climate model data itself is sometimes disputed among scientists. For those reasons, the effect of bias correction on simulated runoff regimes and the relative change in selected runoff indicators is explored. If it affects the conclusion of climate change analysis in 25 hydrology, we should consider it as a source of uncertainty. If not, the application of bias correction methods is either unnecessary in hydro-climatic projections, or safe to use as it does not alter the change signal of river runoff. The results of the present paper highlight the analysis of daily runoff simulated with four different hydrological models in two natural-flow catchments, driven by different regional climate models for a reference and a future period. As expected, bias correction of climate model outputs is important for the reproduction of the runoff regime of the 5 past regardless of the hydrological model used. Then again, its impact on the relative change of flow indicators between reference and future period is weak for most indicators with the exception of the timing of the spring flood peak. Still, our results indicate that the impact of bias correction on runoff indicators increases with bias in the climate simulations

Deep Learning for Vanishing Point Detection Using an Inverse Gnomonic Projection

We present a novel approach for vanishing point detection from uncalibrated monocular images. In contrast to state-of-the-art, we make no a priori assumptions about the observed scene. Our method is based on a convolutional neural network (CNN) which does not use natural images, but a Gaussian sphere representation arising from an inverse gnomonic projection of lines detected in an image. This allows us to rely on synthetic data for training, eliminating the need for labelled images. Our method achieves competitive performance on three horizon estimation benchmark datasets. We further highlight some additional use cases for which our vanishing point detection algorithm can be used.Comment: Accepted for publication at German Conference on Pattern Recognition (GCPR) 2017. This research was supported by German Research Foundation DFG within Priority Research Programme 1894 "Volunteered Geographic Information: Interpretation, Visualisation and Social Computing

Concepts and Principles of Photodynamic Therapy as an Alternative Antifungal Discovery Platform

Opportunistic fungal pathogens may cause superficial or serious invasive infections, especially in immunocompromised and debilitated patients. Invasive mycoses represent an exponentially growing threat for human health due to a combination of slow diagnosis and the existence of relatively few classes of available and effective antifungal drugs. Therefore systemic fungal infections result in high attributable mortality. There is an urgent need to pursue and deploy novel and effective alternative antifungal countermeasures. Photodynamic therapy (PDT) was established as a successful modality for malignancies and age-related macular degeneration but photodynamic inactivation has only recently been intensively investigated as an alternative antimicrobial discovery and development platform. The concept of photodynamic inactivation requires microbial exposure to either exogenous or endogenous photosensitizer molecules, followed by visible light energy, typically wavelengths in the red/near infrared region that cause the excitation of the photosensitizers resulting in the production of singlet oxygen and other reactive oxygen species that react with intracellular components, and consequently produce cell inactivation and death. Antifungal PDT is an area of increasing interest, as research is advancing (i) to identify the photochemical and photophysical mechanisms involved in photoinactivation; (ii) to develop potent and clinically compatible photosensitizers; (iii) to understand how photoinactivation is affected by key microbial phenotypic elements multidrug resistance and efflux, virulence and pathogenesis determinants, and formation of biofilms; (iv) to explore novel photosensitizer delivery platforms; and (v) to identify photoinactivation applications beyond the clinical setting such as environmental disinfectants

Adapting SAM for CDF

The CDF and D0 experiments probe the high-energy frontier and as they do so have accumulated hundreds of Terabytes of data on the way to petabytes of data over the next two years. The experiments have made a commitment to use the developing Grid based on the SAM system to handle these data. The D0 SAM has been extended for use in CDF as common patterns of design emerged to meet the similar requirements of these experiments. The process by which the merger was achieved is explained with particular emphasis on lessons learned concerning the database design patterns plus realization of the use cases.Comment: Talk from the 2003 Computing in High Energy and Nuclear Physics (CHEP03), La Jolla, Ca, USA, March 2003, 4 pages, pdf format, TUAT00

Heavy Flavours in Collider Experiments

Current issues in the studies of Heavy Flavours in colliders are described with particular emphasis on experiments in which the UK is involved. Results on charm production at HERA are examined and compared to those at the Tevatron. B production rates at the Tevatron as well as the status of B lifetimes and mixing in the LEP collaborations and at the Tevatron are highlighted. The measurement of sin2beta from CDF is described as well as the most recent results on top physics at the Tevatron

An ensemble approach to assess hydrological models' contribution to uncertainties in the analysis of climate change impact on water resources

Over the recent years, several research efforts investigated the impact of climate change on water resources for different regions of the world. The projection of future river flows is affected by different sources of uncertainty in the hydro-climatic modelling chain. One of the aims of the QBic<sup>3</sup> project (Québec-Bavarian International Collaboration on Climate Change) is to assess the contribution to uncertainty of hydrological models by using an ensemble of hydrological models presenting a diversity of structural complexity (i.e., lumped, semi distributed and distributed models). The study investigates two humid, mid-latitude catchments with natural flow conditions; one located in Southern Québec (Canada) and one in Southern Bavaria (Germany). Daily flow is simulated with four different hydrological models, forced by outputs from regional climate models driven by global climate models over a reference (1971–2000) and a future (2041–2070) period. The results show that, for our hydrological model ensemble, the choice of model strongly affects the climate change response of selected hydrological indicators, especially those related to low flows. Indicators related to high flows seem less sensitive on the choice of the hydrological model

Autonomous multi-platform observations during the Salinity Processes in the Upper-ocean Regional Study

Author Posting. © The Oceanography Society, 2017. This article is posted here by permission of The Oceanography Society for personal use, not for redistribution. The definitive version was published in Oceanography 30, no. 2 (2017): 38–48, doi:10.5670/oceanog.2017.218.The Salinity Processes in the Upper-ocean Regional Study (SPURS) aims to understand the patterns and variability of sea surface salinity. In order to capture the wide range of spatial and temporal scales associated with processes controlling salinity in the upper ocean, research vessels delivered autonomous instruments to remote sites, one in the North Atlantic and one in the Eastern Pacific. Instruments sampled for one complete annual cycle at each of these two sites, which are subject to contrasting atmospheric forcing. The SPURS field programs coordinated sampling from many different platforms, using a mix of Lagrangian and Eulerian approaches. This article discusses the motivations, implementation, and first results of the SPURS-1 and SPURS-2 programs.SPURS is supported by multiple NASA grants, with important additional contributions from the US National Science Foundation, NOAA, and the Office of Naval Research, as well as international agencies. SVP drifters are deployed with support from NASA and the NOAA funded Global Drifter Program at the Lagrangian Drifter Laboratory of the Scripps Institution of Oceanography. SVP-S2 drifters are provided by NOAA-AOML and NASA. PRAWLER mooring development is supported by NOAA’s Office of Oceanic and Atmospheric Research, Ocean Observing and Monitoring Division, and by NOAA/PMEL

Comparative study of the stability of bimatoprost 0.03% and latanoprost 0.005%: A patient-use study

<p>Abstract</p> <p>Background</p> <p>The stability of ophthalmic preparations in multidose containers is influenced by the preservative as well as the stability of the active ingredient. Unstable drugs may require refrigeration to preserve their active ingredient level and they are more likely to degrade over time, therefore becoming more susceptible to degradation based on patient mishandling. The purpose of this study was to determine the degree of molecular degradation that occurs in bimatoprost and latanoprost in a patient-use setting.</p> <p>Methods</p> <p>This was an open-label, laboratory evaluation of the relative stability of bimatoprost and latanoprost. Patients presently using bimatoprost (n = 31) or latanoprost (n = 34) were identified at 2 clinical sites in Brazil. Patients were instructed to use and store their drops as usual and return all used medication bottles between day 28 and day 34 after opening.</p> <p>Results</p> <p>Bimatoprost demonstrated no degradation, but latanoprost degraded at various levels. The mean age of bimatoprost was 43.0 ± 3.4 days and the mean age of latanoprost was 43.9 ± 2.8 days (P = .072). The mean percentage of labeled concentration was 103.7% in the bimatoprost bottles and 88.1% in the latanoprost bottles (P < 001).</p> <p>Conclusion</p> <p>This study showed that bimatoprost maintained ≥100% concentration throughout the study period while latanoprost did not.</p