Elucidation of xenobiotic metabolism pathways in human skin and human skin models by proteomic profiling

Human skin has the capacity to metabolise foreign chemicals (xenobiotics), but knowledge of the various enzymes involved is incomplete. A broad-based unbiased proteomics approach was used to describe the profile of xenobiotic metabolising enzymes present in human skin and hence indicate principal routes of metabolism of xenobiotic compounds. Several in vitro models of human skin have been developed for the purpose of safety assessment of chemicals. The suitability of these epidermal models for studies involving biotransformation was assessed by comparing their profiles of xenobiotic metabolising enzymes with those of human skin

Drivers and uncertainties of future global marine primary production in marine ecosystem models

Past model studies have projected a global decrease in marine net primary production (NPP) over the 21st century, but these studies focused on the multi-model mean rather than on the large inter-model differences. Here, we analyze model-simulated changes in NPP for the 21st century under IPCC's high-emission scenario RCP8.5. We use a suite of nine coupled carbon–climate Earth system models with embedded marine ecosystem models and focus on the spread between the different models and the underlying reasons. Globally, NPP decreases in five out of the nine models over the course of the 21st century, while three show no significant trend and one even simulates an increase. The largest model spread occurs in the low latitudes (between 30° S and 30° N), with individual models simulating relative changes between −25 and +40 %. Of the seven models diagnosing a net decrease in NPP in the low latitudes, only three simulate this to be a consequence of the classical interpretation, i.e., a stronger nutrient limitation due to increased stratification leading to reduced phytoplankton growth. In the other four, warming-induced increases in phytoplankton growth outbalance the stronger nutrient limitation. However, temperature-driven increases in grazing and other loss processes cause a net decrease in phytoplankton biomass and reduce NPP despite higher growth rates. One model projects a strong increase in NPP in the low latitudes, caused by an intensification of the microbial loop, while NPP in the remaining model changes by less than 0.5 %. While models consistently project increases NPP in the Southern Ocean, the regional inter-model range is also very substantial. In most models, this increase in NPP is driven by temperature, but it is also modulated by changes in light, macronutrients and iron as well as grazing. Overall, current projections of future changes in global marine NPP are subject to large uncertainties and necessitate a dedicated and sustained effort to improve the models and the concepts and data that guide their developmen

On the thermal footsteps of Neutralino relic gases

Current literature suggests that neutralinos are the dominant cold dark matter particle species. Assuming the microcanonical definition of entropy, we examine the local entropy per particle produced between the ``freeze out'' era to the present. An ``entropy consistency'' criterion emerges by comparing this entropy with the entropy per particle of actual galactic structures given in terms of dynamical halo variables. We apply this criterion to the cases when neutralinos are mosly b-inos and mostly higgsinos, in conjunction with the usual ``abundance'' criterion requiring that present neutralino relic density complies with 0.1 < \Omega_{\chic{\tilde\chi^0_1}} < 0.3 for $h\simeq 0.65$. The joint application of both criteria reveals that a better fitting occurs for the b-ino channels, hence the latter seem to be favoured over the higgsino channels. The suggested methodology can be applied to test other annihilation channels of the neutralino, as well as other particle candidates of thermal gases relics.Comment: LaTex AIP style, 8 pages including 1 figure. Final version to appear in Proceedings of the Mexican School of Astrophysics (EMA), Guanajuato, M\'exico, July 31 - August 7, 200

Lower nappe aeration in smooth channels: experimental data and numerical simulation

Bed aerators designed to increase air void ratio are used to prevent cavitation and related damages in spillways. Air entrained in spillway discharges also increases the dissolved oxygen concentration of the water, which can be important for the downstream fishery. This study considers results from a systematic series of measurements along the jet formed by a bed aerator, involving concentration profiles, pressure profiles, velocity fields and corresponding air discharges. The experimental results are, then, compared, with results of computational fluid dynamics (CFD) simulations with the aim of predicting the air discharge numerically. Comparisons with jet lengths and the air entrainment coefficients from the literature are also made. It is shown that numerical predictive tools furnish air discharges comparable to measured values. However, if more detailed predictions are desired, verification experiments are still necessary.Aeradores de fundo projetados para aumentar a concentração de ar são utilizados para previnir a cavitação e danos dela derivados em vertedouros. O oxigênio contido na água também é um parâmetro relevante para garantir alta qualidade das águas a jusante do vertedouro, com reflexos na qualidade ambiental. Equações e critérios de projeto existentes ainda são considerados aproximados, mostrando a necessidade de mais estudos para elucidar os mecanismos que governam o carreamento de ar. Este trabalho apresenta resultados de uma série sistemática de medidas de concentração de ar ao longo da superfície inferior do jato de um aerador de fundo, juntamente com medidas pertinentes de descargas de ar e campos de velocidade da água. Foram feitas comparações com resultados da literatura, considerando perfis de concentração ao longo do jato do aerador até a região de jusante. As medições sob condições controladas forneceram informações necessárias para testar resultados numéricos de aeração obtidos em simulações desses escoamentos, utilizando mecânica dos fluidos computacional (CFD). Mostra-se que ferramentas numéricas preditivas fornecem vazões de ar comparáveis aos valores medidos. Também é concluído que, se detalhes são necessários, experimentos são ainda úteis.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Sequential group trial to determine gastrointestinal site of absorption and systemic exposure of azathioprine

Azathioprine (AZA) is used in the treatment of patients with refractory inflammatory bowel disease; however, its use is limited because of systemic toxicity associated with long-term use. Ileocecal delivery of AZA might be advantageous if local intestinal therapeutic effects could be provided with decreased systemic side effects. Decreased cecal systemic absorption would allow higher dosages of AZA to be administered. A two-phase study was performed to compare the systemic exposure of AZA and 6-mercaptopurine (6-MP) following administration of AZA into the stomach, jejunum, and cecum and to compare the systemic exposure to AZA and 6-MP following administration of three different dosages of AZA into the cecum. In phase I, six healthy male volunteers received three 50 mg sequential doses of AZA via an oral tube directly placed into the stomach, jejunum, and cecum, respectively. In phase II, six healthy male volunteers received three different dosages (50, 300, 600 mg of AZA) into the cecum. Plasma concentrations of AZA and 6-MP at various times were quantified and area under the plasma concentration-time curve (AUC) and mean residence time (MRT) were determined. No significant differences in the AUC of AZA were seen at the different sites. The AUC of 6-MP following administration of AZA into the jejunum (67.0 ± 30.1 ng × hr/ml) was higher compared to the stomach (39.9 ± 38.1 ng/hr/ml) and cecum (29.2 ± 10.9 ng × hr/ml). Jejunal absorption was 68% higher than absorption from the stomach and 129% higher than that of the cecum. Gastric absorption was 27% higher than that of the cecum. Increased dosages given into the cecum resulted in increased AUCs of AZA and 6-MP. The AUCs of AZA following 50, 300, and 600 mg dosages were 16.9 ± 7.4, 52.3 ± 67.2, and 132 ± 151 ng × hr/ml, respectively, and the AUCs of 6-MP were 22.2 ± 14.9, 63.4 ± 50.6, and 104 ± 115 ng × hr/ml, respectively. Systemic exposure to 6-MP is reduced following administration of AZA into the cecum, most likely secondary to reduced absorption of 6-MP from the colon. Higher dosages of AZA presented to the cecum do result in increased systemic absorption, but may still allow more drug to be administered with less toxicity than the same dose received orally

The Atacama Cosmology Telescope: The LABOCA/ACT Survey of Clusters at All Redshifts

We present a multi-wavelength analysis of eleven Sunyaev Zel'dovich effect (SZE)-selected galaxy clusters (ten with new data) from the Atacama Cosmology Telescope (ACT) southern survey. We have obtained new imaging from the Large APEX Bolometer Camera (345GHz; LABOCA) on the Atacama Pathfinder EXperiment (APEX) telescope, the Australia Telescope Compact Array (2.1GHz; ATCA), and the Spectral and Photometric Imaging Receiver (250, 350, and $500\,\rm\mu m$; SPIRE) on the Herschel Space Observatory. Spatially-resolved 345GHz SZE increments with integrated S/N > 5 are found in six clusters. We compute 2.1GHz number counts as a function of cluster-centric radius and find significant enhancements in the counts of bright sources at projected radii $\theta < \theta_{2500}$. By extrapolating in frequency, we predict that the combined signals from 2.1GHz-selected radio sources and 345GHz-selected SMGs contaminate the 148GHz SZE decrement signal by ~5% and the 345GHz SZE increment by ~18%. After removing radio source and SMG emission from the SZE signals, we use ACT, LABOCA, and (in some cases) new Herschel SPIRE imaging to place constraints on the clusters' peculiar velocities. The sample's average peculiar velocity relative to the cosmic microwave background is $153\pm 383\,\rm km\,s^{-1}$.Comment: 19 pages, 11 figures, Accepted for Publication in The Astrophysical Journa

Bone healing response in cyclically loaded implants : comparing zero, one, and two loading sessions per day

When bone implants are loaded, they are inevitably subjected to displacement relative to bone. Such micromotion generates stress/strain states at the interface that can cause beneficial or detrimental sequels. The objective of this study is to better understand the mechanobiology of bone healing at the tissue-implant interface during repeated loading. Machined screw shaped Ti implants were placed in rat tibiae in a hole slightly bigger than the implant diameter. Implants were held stable by a specially-designed bone plate that permits controlled loading. Three loading regimens were applied, (a) zero loading, (b) one daily loading session of 60 cycles with an axial force of 1.5 N/cycle for 7 days, and (c) two such daily sessions with the same axial force also for 7 days. Finite element analysis was used to characterize the mechanobiological conditions produced by the loading sessions. After 7 days, the implants with surrounding interfacial tissue were harvested and processed for histological, histomorphometric and DNA microarray analyses. Histomorphometric analyses revealed that the group subjected to repeated loading sessions exhibited a significant decrease in bone-implant contact and increase in bone-implant distance, as compared to unloaded implants and those subjected to only one loading session. Gene expression profiles differed during osseointegration between all groups mainly with respect to inflammatory and unidentified gene categories. The results indicate that increasing the daily cyclic loading of implants induces deleterious changes in the bone healing response, most likely due to the accumulation of tissue damage and associated inflammatory reaction at the bone-implant interface

Could the cosmic acceleration be transient? A cosmographic evaluation

A possible slowing down of the cosmic expansion is investigated through a cosmographic approach. By expanding the luminosity distance to fourth order and fitting the SN Ia data from the most recent compilations (Union, Constitution and Union 2), the marginal likelihood distributions for the deceleration parameter today suggest a recent reduction of the cosmic acceleration and indicate that there is a considerable probability for $q_0>0$. Also in contrast to the prediction of the $\Lambda$CDM model, the cosmographic $q(z)$ reconstruction permits a cosmic expansion history where the cosmic acceleration could already have peaked and be presently slowing down, which would imply that the recent accelerated expansion of the Universe is a transient phenomenon. It is also shown that to describe a transient acceleration the luminosity distance needs to be expanded at least to fourth order. The present cosmographic results depend neither on the validity of general relativity nor on the matter-energy contents of the Universe.Comment: 11 pages, 4 figures. Accepted for publication in Classical and Quantum Gravit

Another exact inflationary solution

A new closed-form inflationary solution is given for a hyperbolic interaction potential. The method used to arrive at this solution is outlined as it appears possible to generate additional sets of equations which satisfy the model. In addition a new form of decaying cosmological constant is presented.Comment: 10 pages, 0 figure

Application of mathematical modelling for investigating oxygen transfer energy requirement and process design of an aerobic continuous stirred tank fermenter

Fermentation kinetic and oxygen transfer modelling coupled with energy analysis was applied to investigate how key input design variables influenced fermenter size, feed substrate requirement, wasted substrate and aeration system electrical energy requirement. The study showed that trade-offs and compromises are required to select the values of key input variables that can produce superior process designs in terms of the output variables. For example, reducing steady-state oxygen concentration reduced aeration system energy requirements and associated carbon footprint but increased fermenter size and associated cost. Mathematical modelling can assist in more precisely zoning in quantitatively on the selection of design input variable values that can produce a best compromise between conflicting design output variables. Mathematical modelling can also highlight design sensitivities. For example, if the steady-state sugar concentration is reduced below a certain value, then this can lead to an exponential increase in fermenter volume and associated cost, thus it is prudent to operate on the conservative side of this value