Artificially lit surface of Earth at night increasing in radiance and extent

This is the author accepted manuscript. The final version is available from AAAS via the DOI in this record.A central aim of the “lighting revolution” (the transition to solid-state lighting technology) is decreased energy consumption. This could be undermined by a rebound effect of increased use in response to lowered cost of light. We use the first-ever calibrated satellite radiometer designed for night lights to show that from 2012 to 2016, Earth’s artificially lit outdoor area grew by 2.2% per year, with a total radiance growth of 1.8% per year. Continuously lit areas brightened at a rate of 2.2% per year. Large differences in national growth rates were observed, with lighting remaining stable or decreasing in only a few countries. These data are not consistent with global scale energy reductions but rather indicate increased light pollution, with corresponding negative consequences for flora, fauna, and human well-being.This article is based upon work from COST Action ES1204 LoNNe, supported by COST (European Cooperation in Science and Technology). The authors acknowledge the funding received by ERA-PLANET (www.era-planet.eu) funded by the EC as part of H2020 (contract no. 689443). NOAA’s participation was funded by NASA’s VIIRS science program, contract number NNH15AZ01I. ASM’s contribution was funded by ORISON project (H2020-INFRASUPP-2015-2) Cities at Night

Value at Risk models with long memory features and their economic performance

We study alternative dynamics for Value at Risk (VaR) that incorporate a slow moving component and information on recent aggregate returns in established quantile (auto) regression models. These models are compared on their economic performance, and also on metrics of first-order importance such as violation ratios. By better economic performance, we mean that changes in the VaR forecasts should have a lower variance to reduce transaction costs and should lead to lower exceedance sizes without raising the average level of the VaR. We find that, in combination with a targeted estimation strategy, our proposed models lead to improved performance in both statistical and economic terms

Turbulence in a transient channel flow with a wall of pyramid roughness

A direct numerical simulation investigation of a transient flow in a channel with a smooth top wall and a roughened bottom wall made of close-packed pyramids is presented. An initially stationary turbulent flow is accelerated rapidly to a new flow rate and the transient flow behaviour after the acceleration is studied. The equivalent roughness heights of the initial and final flows are $k_{s}^{+}=14.5$k+s=14.5 and 41.5, respectively. Immediately after the acceleration ends, the induced change behaves in a ‘plug-flow’ manner. Above the roughness crests, the additional velocity due to the perturbation flow is uniform; below the crest, it reduces approximately linearly to zero at the bottom of the roughness elements. The interaction of the perturbation flow with the rough wall is characterised by a series of events that resemble those observed in roughness-induced laminar–turbulent transitions. The process has two broad stages. In the first of these, large-scale vortices, comparable in extent to the roughness wavelength, develop around each roughness element and high-speed streaks form along the ridge lines of the elements. After a short time, each vortex splits into two, namely (i) a standing vortex in front of the element and (ii) a counter-rotating hairpin vortex behind it. The former is largely inactive, but the latter advects downstream with increasing strength, and later lifts away from the wall. These hairpin vortices wrap around strong low-speed streaks. The second stage of the overall process is the breakdown of the hairpin vortices into many smaller multi-scale vortices distributed randomly in space, leading eventually to a state of conventional turbulence. Shortly after the beginning of the first stage, the three components of the r.m.s of the velocity fluctuation all increase significantly in the near-wall region as a result of the vortical structures, and their spectra bear strong signatures of the surface topology. During the second stage, the overall turbulence energy in this region varies only slightly, but the spectrum evolves significantly, eventually approaching that of conventional turbulence. The direct effect of roughness on the flow is confined to a region up to approximately three element heights above the roughness crests. Turbulence in the core region does not begin to increase until after the transition near the wall is largely complete. The processes of transition over the smooth and rough walls of the channel are practically independent of each other. The flow over the smooth wall follows a laminar–turbulent transition and, as known from previous work, resembles a free-stream turbulence-induced boundary layer bypass transition

Intercomparison of spectroradiometers and Sun photometers for the determination of the aerosol optical depth during the VELETA-2002 field campaign

[ 1] In July 2002 the VELETA-2002 field campaign was held in Sierra Nevada ( Granada) in the south of Spain. The main objectives of this field campaign were the study of the influence of elevation and atmospheric aerosols on measured UV radiation. In the first stage of the field campaign, a common calibration and intercomparison between Licor-1800 spectroradiometers and Cimel-318 Sun photometers was performed in order to assess the quality of the measurements from the whole campaign. The intercomparison of the Licor spectroradiometers showed, for both direct and global irradiances, that when the comparisons were restricted to the visible part of the spectrum the deviations were within the instruments' nominal accuracies which allows us to rely on these instruments for measuring physical properties of aerosols at the different measurement stations. A simultaneous calibration on AOD data was performed for the Cimel-318 Sun photometers. When a common calibration and methodology was applied, the deviation was lowered to much less than 0.01 for AOD. At the same time an intercomparison has been made between the AOD values given by the spectroradiometers and the Sun photometers, with deviations obtained from 0.01 to 0.03 for the AOD in the visible range, depending on the channel. In the UVA range, the AOD uncertainty was estimated to be around 0.02 and 0.05 for Cimel and Licor respectively. In general the experimental differences were in agreement with this uncertainty estimation. In the UVB range the AOD measurements should not be used due to maximum instrumental uncertainties

Mating skew in Barbary macaque males: the role of female mating synchrony, female behavior, and male–male coalitions

A fundamental question of sexual selection theory concerns the causes and consequences of reproductive skew among males. The priority of access (PoA) model (Altmann, Ann NY Acad Sci 102:338–435, 1962) has been the most influential framework in primates living in permanent, mixed-sex groups, but to date it has only been tested with the appropriate data on female synchrony in a handful of species. In this paper, we used mating data from one large semi-free ranging group of Barbary macaques: (1) to provide the first test of the priority-of-access model in this species, using mating data from 11 sexually active females (including six females that were implanted with a hormonal contraceptive but who showed levels of sexual activity comparable to those of naturally cycling females) and (2) to determine the proximate mechanism(s) underlying male mating skew. Our results show that the fit of the observed distribution of matings with sexually attractive females to predictions of the PoA model was poor, with lower-ranking males mating more than expected. While our work confirms that female mating synchrony sets an upper limit to monopolization by high-ranking individuals, other factors are also important. Coalitionary activity was the main tactic used by males to lower mating skew in the study group. Coalitions were expressed in a strongly age-related fashion and allowed subordinate, post-prime males to increase their mating success by targeting more dominant, prime males. Conversely, females, while mating promiscuously with several males during a given mating cycle, were more likely to initiate their consortships with prime males, thus reducing the overall effectiveness of coalitions. We conclude that high-ranking Barbary macaque males have a limited ability to monopolize mating access, leading to a modest mating skew among them

Nonlinear pharmacokinetics of therapeutic proteins resulting from receptor mediated endocytosis

Receptor mediated endocytosis (RME) plays a major role in the disposition of therapeutic protein drugs in the body. It is suspected to be a major source of nonlinear pharmacokinetic behavior observed in clinical pharmacokinetic data. So far, mostly empirical or semi-mechanistic approaches have been used to represent RME. A thorough understanding of the impact of the properties of the drug and of the receptor system on the resulting nonlinear disposition is still missing, as is how to best represent RME in pharmacokinetic models. In this article, we present a detailed mechanistic model of RME that explicitly takes into account receptor binding and trafficking inside the cell and that is used to derive reduced models of RME which retain a mechanistic interpretation. We find that RME can be described by an extended Michaelis–Menten model that accounts for both the distribution and the elimination aspect of RME. If the amount of drug in the receptor system is negligible a standard Michaelis–Menten model is capable of describing the elimination by RME. Notably, a receptor system can efficiently eliminate drug from the extracellular space even if the total number of receptors is small. We find that drug elimination by RME can result in substantial nonlinear pharmacokinetics. The extent of nonlinearity is higher for drug/receptor systems with higher receptor availability at the membrane, or faster internalization and degradation of extracellular drug. Our approach is exemplified for the epidermal growth factor receptor system

Mucosal Progranulin expression is induced by H. pylori, but independent of Secretory Leukocyte Protease Inhibitor (SLPI) expression

<p>Abstract</p> <p>Background</p> <p>Mucosal levels of Secretory Leukocyte Protease Inhibitor (SLPI) are specifically reduced in relation to <it>H. pylori</it>-induced gastritis. Progranulin is an epithelial growth factor that is proteolytically degraded into fragments by elastase (the main target of SLPI). Considering the role of SLPI for regulating the activity of elastase, we studied whether the <it>H. pylori</it>-induced reduction of SLPI and the resulting increase of elastase-derived activity would reduce the Progranulin protein levels both <it>ex vivo </it>and <it>in vitro</it>.</p> <p>Methods</p> <p>The expression of Progranulin was studied in biopsies of <it>H. pylori</it>-positive, -negative and -eradicated subjects as well as in the gastric tumor cell line AGS by ELISA, immunohistochemistry and real-time RT-PCR.</p> <p>Results</p> <p><it>H. pylori</it>-infected subjects had about 2-fold increased antral Progranulin expression compared to <it>H. pylori</it>-negative and -eradicated subjects (P < 0.05). Overall, no correlations between mucosal Progranulin and SLPI levels were identified. Immunohistochemical analysis confirmed the upregulation of Progranulin in relation to <it>H. pylori </it>infection; both epithelial and infiltrating immune cells contributed to the higher Progranulin expression levels. The <it>H. pylori</it>-induced upregulation of Progranulin was verified in AGS cells infected by <it>H. pylori</it>. The down-regulation of endogenous SLPI expression in AGS cells by siRNA methodology did not affect the Progranulin expression independent of the infection by <it>H. pylori</it>.</p> <p>Conclusions</p> <p>Taken together, Progranulin was identified as novel molecule that is upregulated in context to <it>H. pylori </it>infection. In contrast to other diseases, SLPI seems not to have a regulatory role for Progranulin in <it>H. pylori</it>-mediated gastritis.</p

Inferring serum proteolytic activity from LC-MS/MS data

<p>Abstract</p> <p>Background</p> <p>In this paper we deal with modeling serum proteolysis process from tandem mass spectrometry data. The parameters of peptide degradation process inferred from LC-MS/MS data correspond directly to the activity of specific enzymes present in the serum samples of patients and healthy donors. Our approach integrate the existing knowledge about peptidases' activity stored in MEROPS database with the efficient procedure for estimation the model parameters.</p> <p>Results</p> <p>Taking into account the inherent stochasticity of the process, the proteolytic activity is modeled with the use of Chemical Master Equation (CME). Assuming the stationarity of the Markov process we calculate the expected values of digested peptides in the model. The parameters are fitted to minimize the discrepancy between those expected values and the peptide activities observed in the MS data. Constrained optimization problem is solved by Levenberg-Marquadt algorithm.</p> <p>Conclusions</p> <p>Our results demonstrates the feasibility and potential of high-level analysis for LC-MS proteomic data. The estimated enzyme activities give insights into the molecular pathology of colorectal cancer. Moreover the developed framework is general and can be applied to study proteolytic activity in different systems.</p

Population pharmacokinetics of the humanised monoclonal antibody, HuHMFG1 (AS1402), derived from a phase I study on breast cancer

International audienceBACKGROUND: HuHMFG1 (AS1402) is a humanised monoclonal antibody that has undergone a phase I trial in metastatic breast cancer. The aim of this study was to characterise the pharmacokinetics (PKs) of HuHMFG1 using a population PK model. METHOD: Data were derived from a phase I study of 26 patients receiving HuHMFG1 at doses ranging from 1 to 16 mg kg(-1). Data were analysed using NONMEM software and covariates were included. A limited sampling strategy (LSS) was developed using training and a validation data set. RESULTS: A linear two-compartment model was shown to be adequate to describe data. Covariate analysis indicated that weight was not related to clearance. An LSS was successfully developed on the basis of the model, in which one sample is collected immediately before the start of an infusion and the second is taken at the end of infusion. CONCLUSION: A two-compartment population PK model successfully describes HuHMFG1 behaviour. The model suggests using a fixed dose of HuHMFG1, which would simplify dosing. The model could be used to optimise dose level and dosing schedule if more data on the correlation between exposure and efficacy become available from future studies. The derived LSS could optimise further PK assessment of this antibody