Nanotechnology and the Treatment of HIV Infection

Suboptimal adherence, toxicity, drug resistance and viral reservoirs make the lifelong treatment of HIV infection challenging. The emerging field of nanotechnology may play an important role in addressing these challenges by creating drugs that possess pharmacological advantages arising out of unique phenomena that occur at the “nano” scale. At these dimensions, particles have physicochemical properties that are distinct from those of bulk materials or single molecules or atoms. In this review, basic concepts and terms in nanotechnology are defined, and examples are provided of how nanopharmaceuticals such as nanocrystals, nanocapsules, nanoparticles, solid lipid nanoparticles, nanocarriers, micelles, liposomes and dendrimers have been investigated as potential anti-HIV therapies. Such drugs may, for example, be used to optimize the pharmacological characteristics of known antiretrovirals, deliver anti-HIV nucleic acids into infected cells or achieve targeted delivery of antivirals to the immune system, brain or latent reservoirs. Also, nanopharmaceuticals themselves may possess anti-HIV activity. However several hurdles remain, including toxicity, unwanted biological interactions and the difficulty and cost of large-scale synthesis of nanopharmaceuticals

High-Frequency Dynamics of Ocean pH: A Multi-Ecosystem Comparison

The effect of Ocean Acidification (OA) on marine biota is quasi-predictable at best. While perturbation studies, in the form of incubations under elevated pCO2, reveal sensitivities and responses of individual species, one missing link in the OA story results from a chronic lack of pH data specific to a given species' natural habitat. Here, we present a compilation of continuous, high-resolution time series of upper ocean pH, collected using autonomous sensors, over a variety of ecosystems ranging from polar to tropical, open-ocean to coastal, kelp forest to coral reef. These observations reveal a continuum of month-long pH variability with standard deviations from 0.004 to 0.277 and ranges spanning 0.024 to 1.430 pH units. The nature of the observed variability was also highly site-dependent, with characteristic diel, semi-diurnal, and stochastic patterns of varying amplitudes. These biome-specific pH signatures disclose current levels of exposure to both high and low dissolved CO2, often demonstrating that resident organisms are already experiencing pH regimes that are not predicted until 2100. Our data provide a first step toward crystallizing the biophysical link between environmental history of pH exposure and physiological resilience of marine organisms to fluctuations in seawater CO2. Knowledge of this spatial and temporal variation in seawater chemistry allows us to improve the design of OA experiments: we can test organisms with a priori expectations of their tolerance guardrails, based on their natural range of exposure. Such hypothesis-testing will provide a deeper understanding of the effects of OA. Both intuitively simple to understand and powerfully informative, these and similar comparative time series can help guide management efforts to identify areas of marine habitat that can serve as refugia to acidification as well as areas that are particularly vulnerable to future ocean change

Estimating value-at-risk using a multivariate copula-based volatility model: Evidence from European banks

This paper proposes a multivariate copula-based volatility model for estimating Value-at-Risk (VaR) in the banking sector of selected European countries by combining dynamic conditional correlation (DCC) multivariate GARCH (M-GARCH) volatility model and copula functions. Non-normality in multivariate models is associated with the joint probability of the univariate models' marginal probabilities –the joint probability of large market movements, referred to as tail dependence. In this paper, we use copula functions to model the tail dependence of large market movements and test the validity of our results by performing back-testing techniques. The results show that the copula-based approach provides better estimates than the common methods currently used and captures VaR reasonably well based on the differences in the numbers of exceptions produced during different observation periods at the same confidence level

Refining value-at-risk estimates using a Bayesian Markov-switching GJR-GARCH copula-EVT model

In this paper, we propose a model for forecasting Value-at-Risk (VaR) using a Bayesian Markov-switching GJR-GARCH(1,1) model with skewed Student’s-t innovation, copula functions and extreme value theory. A Bayesian Markov-switching GJR-GARCH(1,1) model that identifies non-constant volatility over time and allows the GARCH parameters to vary over time following a Markov process, is combined with copula functions and EVT to formulate the Bayesian Markov-switching GJR-GARCH(1,1) copula-EVT VaR model, which is then used to forecast the level of risk on financial asset returns. We further propose a new method for threshold selection in EVT analysis, which we term the hybrid method. Empirical and back-testing results show that the proposed VaR models capture VaR reasonably well in periods of calm and in periods of crisis

Ectoparasite activity during incubation increases microbial growth on avian eggs

We thank Estefanía López for lab work, and Tomás Pérez-Contreras and Emilio Pagani-Núñez for facilitating collection of some of the flies used in manipulations. We also thank Ángela Martínez-García for help with management of ARISA data and Natalia Juárez and Deseada Parejo for the pictures of owls and roller clutches, respectively. We appreciate the comments provided by Dr. Adèle Mennerat and five anonymous referees on earlier versions of the manuscript.All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.While direct detrimental effects of parasites on hosts are relatively well documented, other more subtle but potentially important effects of parasitism are yet unexplored. Biological activity of ectoparasites, apart from skin injuries and blood-feeding, often results in blood remains, or parasite faeces that accumulate and modify the host environment. In this way, ectoparasite activities and remains may increase nutrient availability that may favour colonization and growth of microorganisms including potential pathogens. Here, by the experimental addition of hematophagous flies (Carnus hemapterus, a common ectoparasite of birds) to nests of spotless starlings Sturnus unicolor during incubation, we explore this possible side effect of parasitism which has rarely, if ever, been investigated. Results show that faeces and blood remains from parasitic flies on spotless starling eggshells at the end of incubation were more abundant in experimental than in control nests. Moreover, eggshell bacterial loads of different groups of cultivable bacteria including potential pathogens, as well as species richness of bacteria in terms of Operational Taxonomic Units (OTUs), were also higher in experimental nests. Finally, we also found evidence of a link between eggshell bacterial loads and increased embryo mortality, which provides indirect support for a bacterial-mediated negative effect of ectoparasitism on host offspring. Trans-shell bacterial infection might be one of the main causes of embryo death and, consequently, this hitherto unnoticed indirect effect of ectoparasitism might be widespread in nature and could affect our understanding of ecology and evolution of host-parasite interactionsFinancial support was provided by Spanish Ministerio de Economía y Competitividad and FEDER (CGL2013-48193-C3-1-P, CGL2013-48193-C3-2-P), by JAE programme to DMG and MRR, and by Juan de la Cierva and Ramón y Cajal programmes to GT. All procedures were conducted under licence from the Environmental Department of the Regional Government of Andalucía, Spain (reference SGYB/FOA/AFR)

An acute bout of swimming increases post-exercise energy intake in young healthy men and women

Single bouts of land-based exercise (for example, walking, running, cycling) do not typically alter post-exercise energy intake on the day of exercise. However, anecdotal and preliminary empirical evidence suggests that swimming may increase appetite and energy intake. This study compared the acute effects of swimming on appetite, energy intake, and food preference and reward, versus exertion-matched cycling and a resting control. Thirty-two men (n=17; mean ± SD age 24 ± 2 years, body mass index [BMI] 25.0 ± 2.6 kg/m2) and women (n=15; age 22 ± 3 years, BMI 22.8 ± 2.3 kg/m2) completed three experimental trials (swimming, cycling, control) in a randomised, crossover design. The exercise trials involved 60-min of ‘hard’ exercise (self-selected rating of perceived exertion: 15) performed 90-min after a standardised breakfast. Food preference and reward were assessed via the Leeds Food Preference Questionnaire 15-min after exercise, whilst ad libitum energy intake was determined 30-min after exercise. The control trial involved identical procedures except no exercise was performed. Compared with control (3259 ± 1265 kJ), swimming increased ad libitum energy intake (3857 ± 1611 kJ; ES=0.47, 95% CI of the mean difference between trials 185, 1010 kJ, P=0.005); the magnitude of increase was smaller after cycling (3652 ± 1619 kJ; ES=0.31, 95% CI -21, 805 kJ, P=0.062). Ad libitum energy intake was similar between swimming and cycling (ES=0.16, 95% CI -207, 618 kJ, P=0.324). This effect was consistent across sexes and unrelated to food preference and reward which were similar after swimming and cycling compared with control. This study has identified an orexigenic effect of swimming. Further research is needed to identify the responsible mechanism(s), including the relevance of water immersion and water temperature per se

THE \u27MESSENGER TEXTS\u27 OF THE THIRD UR DYNASTY

Abstract not availabl

THE \u27MESSENGER TEXTS\u27 OF THE THIRD UR DYNASTY

Abstract not availabl