Effect of oxidative stress on ABC transporters: contribution to epilepsy pharmacoresistance

Epilepsy is a neurological disorder affecting around 1%-2% of population worldwide and its treatment includes use of antiepileptic drugs to control seizures. Failure to respond to antiepileptic drug therapy is a major clinical problem and over expression of ATP-binding cassette transporters is considered one of the major reasons for pharmacoresistance. In this review, we have summarized the regulation of ABC transporters in response to oxidative stress due to disease and antiepileptic drugs. Further, ketogenic diet and antioxidants were examined for their role in pharmacoresistance. The understanding of signalling pathways and mechanism involved may help in identifying potential therapeutic targets and improving drug response

NUMERICAL TRANSIENT HEAT TRANSFER ANALYSIS OF REACTOR FOR MAGNESIUM BASED ALLOY FOR HYDROGEN STORAGE APPLICATION

Metal hydrides are potential hydrogen storage media. They release hydrogen at moderate temperatures and pressures. Magnesium hydride is a promising approach for stationary power system application, due to high hydrogen storage capacity by weight. Magnesium hydride based reactor design is more complex due to high thermal energy release and absorption during hydriding reaction and dehydriding reaction, respectively. In this study, results of a numerical modeling study are presented for a 1.5 kg Magnesium alloy based hydriding reactor. Temperature profile in the reactor is computed by FEM analysis using ANSYS software for hydriding and dehydriding reaction. FEM analysis indicates that the reactor temperature is raised from 200 C to 422 ºC in 20 minutes during the hydriding process. Hence, a “cooling system” is required for maintaining temperature during the hydriding process. During the dehydriding process, maximum temperature drop occurs from 350 C to 189 ºC in 20 minutes. Therefore, an external heat source of 2 kW is required for maintaining the temperature during dehydriding. Details are presented

Transnational reflections on transnational research projects on men, boys and gender relations

This article reflects on the research project, ‘Engaging South African and Finnish youth towards new traditions of non-violence, equality and social well-being’, funded by the Finnish and South African national research councils, in the context of wider debates on research, projects and transnational processes. The project is located within a broader analysis of research projects and projectization (the reduction of research to separate projects), and the increasing tendencies for research to be framed within and as projects, with their own specific temporal and organizational characteristics. This approach is developed further in terms of different understandings of research across borders: international, comparative, multinational and transnational. Special attention is given to differences between research projects that are in the Europe and the EU, and projects that are between the global North and the global South. The theoretical, political and practical challenges of the North-South research project are discussed

Development of a self-report measure of capability wellbeing for adults: the ICECAP-A

Purpose The benefits of health and social care are not confined to patient health alone and therefore broader measures of wellbeing may be useful for economic evaluation.\ud This paper reports the development of a simple measure of capability wellbeing for adults (ICECAP-A).\ud Methods In-depth, informant-led, interviews to identify the attributes of capability wellbeing were conducted with 36 adults in the UK. Eighteen semi-structured, repeat interviews were carried out to develop a capability-based descriptive system for the measure. Informants were purposively selected to ensure variation in socio-economic status, age, sex, ethnicity and health. Data analysis was carried out inductively and iteratively alongside interviews, and findings were used to shape the questions in later interviews.\ud Results Five over-arching attributes of capability wellbeing were identified for the measure: ‘‘stability’’,‘‘attachment’’, ‘‘achievement’’, ‘‘autonomy’’ and ‘‘enjoyment’’. One item, with four response categories, was developed for each attribute for the ICECAP-A descriptive system.\ud Conclusions The ICECAP-A capability measure represents a departure from traditional health economics outcome measures, by treating health status as an influence over broader attributes of capability wellbeing. Further work is required to value and validate the attributes and test the sensitivity of the ICECAP-A to healthcare interventions

Entanglement and purity of two-mode Gaussian states in noisy channels

We study the evolution of purity, entanglement and total correlations of general two--mode Gaussian states of continuous variable systems in arbitrary uncorrelated Gaussian environments. The time evolution of purity, Von Neumann entropy, logarithmic negativity and mutual information is analyzed for a wide range of initial conditions. In general, we find that a local squeezing of the bath leads to a faster degradation of purity and entanglement, while it can help to preserve the mutual information between the modes.Comment: 10 pages, 8 figure

Control of human endometrial stromal cell motility by PDGF-BB, HB-EGF and trophoblast-secreted factors

Human implantation involves extensive tissue remodeling at the fetal-maternal interface. It is becoming increasingly evident that not only trophoblast, but also decidualizing endometrial stromal cells are inherently motile and invasive, and likely contribute to the highly dynamic processes at the implantation site. The present study was undertaken to further characterize the mechanisms involved in the regulation of endometrial stromal cell motility and to identify trophoblast-derived factors that modulate migration. Among local growth factors known to be present at the time of implantation, heparin-binding epidermal growth factor-like growth factor (HB-EGF) triggered chemotaxis (directed locomotion), whereas platelet-derived growth factor (PDGF)-BB elicited both chemotaxis and chemokinesis (non-directed locomotion) of endometrial stromal cells. Supernatants of the trophoblast cell line AC-1M88 and of first trimester villous explant cultures stimulated chemotaxis but not chemokinesis. Proteome profiling for cytokines and angiogenesis factors revealed neither PDGF-BB nor HB-EGF in conditioned media from trophoblast cells or villous explants, while placental growth factor, vascular endothelial growth factor and PDGF-AA were identified as prominent secretory products. Among these, only PDGF-AA triggered endometrial stromal cell chemotaxis. Neutralization of PDGF-AA in trophoblast conditioned media, however, did not diminish chemoattractant activity, suggesting the presence of additional trophoblast-derived chemotactic factors. Pathway inhibitor studies revealed ERK1/2, PI3 kinase/Akt and p38 signaling as relevant for chemotactic motility, whereas chemokinesis depended primarily on PI3 kinase/Akt activation. Both chemotaxis and chemokinesis were stimulated upon inhibition of Rho-associated, coiled-coil containing protein kinase. The chemotactic response to trophoblast secretions was not blunted by inhibition of isolated signaling cascades, indicating activation of overlapping pathways in trophoblast-endometrial communication. In conclusion, trophoblast signals attract endometrial stromal cells, while PDGF-BB and HB-EGF, although not identified as trophoblast-derived, are local growth factors that may serve to fine-tune directed and non-directed migration at the implantation site

Neighbourhood, Route and Workplace-Related Environmental Characteristics Predict Adults' Mode of Travel to Work

Commuting provides opportunities for regular physical activity which can reduce the risk of chronic disease. Commuters' mode of travel may be shaped by their environment, but understanding of which specific environmental characteristics are most important and might form targets for intervention is limited. This study investigated associations between mode choice and a range of objectively assessed environmental characteristics.Participants in the Commuting and Health in Cambridge study reported where they lived and worked, their usual mode of travel to work and a variety of socio-demographic characteristics. Using geographic information system (GIS) software, 30 exposure variables were produced capturing characteristics of areas around participants' homes and workplaces and their shortest modelled routes to work. Associations between usual mode of travel to work and personal and environmental characteristics were investigated using multinomial logistic regression.Of the 1124 respondents, 50% reported cycling or walking as their usual mode of travel to work. In adjusted analyses, home-work distance was strongly associated with mode choice, particularly for walking. Lower odds of walking or cycling rather than driving were associated with a less frequent bus service (highest versus lowest tertile: walking OR 0.61 [95% CI 0.20–1.85]; cycling OR 0.43 [95% CI 0.23–0.83]), low street connectivity (OR 0.22, [0.07–0.67]; OR 0.48 [0.26–0.90]) and free car parking at work (OR 0.24 [0.10–0.59]; OR 0.55 [0.32–0.95]). Participants were less likely to cycle if they had access to fewer destinations (leisure facilities, shops and schools) close to work (OR 0.36 [0.21–0.62]) and a railway station further from home (OR 0.53 [0.30–0.93]). Covariates strongly predicted travel mode (pseudo r-squared 0.74).Potentially modifiable environmental characteristics, including workplace car parking, street connectivity and access to public transport, are associated with travel mode choice, and could be addressed as part of transport policy and infrastructural interventions to promote active commuting

The blue channel of the Keck low-resolution imaging spectrometer

This paper summarizes the optical, mechanical, electrical, and software design of LRIS-B, the blue channel of the Keck Low Resolution and Imaging Spectrograph. The LRIS-B project will shortly be completing the existing LRIS instrument through the addition of dichroic beamsplitters, grisms to disperse light on the blue channel, broad-band u, B, and V photometric filters, a blue and near-UV transmitting camera lens, and a large format blue-sensitive CCD detector. LRIS-B will also introduce piezoelectric xy-actuation of the CCD detector inside its Dewar, in order to compensate for flexure in the existing instrument; ultimately the red-side CCD detector will be similarly equipped, its PZT xy-stage being independently programmed. The optical design of the LRIS-B camera uses only fused silica and calcium fluoride elements, and includes a decentered meniscus element to compensate for coma introduced by the LRIS off-axis paraboloid collimator. The design of the blue channel grisms have been optimized for maximum blaze efficiency, the highest dispersion grism having a groove density of 1200 gr/mm. Optical elements not in use at any given time will be stowed in carousels externally mounted to the instrument sidewalls. The entire instrument is designed to permit remote operation

Speeding-Up Expensive Evaluations in High-Level Synthesis Using Solution Modeling and Fitness Inheritance

High-Level Synthesis (HLS) is the process of developing digital circuits from behavioral specifications. It involves three interdependent and NP-complete optimization problems: (i) the operation scheduling, (ii) the resource allocation, and (iii) the controller synthesis. Evolutionary Algorithms have been already effectively applied to HLS to find good solution in presence of conflicting design objectives. In this paper, we present an evolutionary approach to HLS that extends previous works in three respects: (i) we exploit the NSGA-II, a multi-objective genetic algorithm, to fully automate the design space exploration without the need of any human intervention, (ii) we replace the expensive evaluation process of candidate solutions with a quite accurate regression model, and (iii) we reduce the number of evaluations with a fitness inheritance scheme. We tested our approach on several benchmark problems. Our results suggest that all the enhancements introduced improve the overall performance of the evolutionary search

Social presence and dishonesty in retail

Self-service checkouts (SCOs) in retail can benefit consumers and retailers, providing control and autonomy to shoppers independent from staff, together with reduced queuing times. Recent research indicates that the absence of staff may provide the opportunity for consumers to behave dishonestly, consistent with a perceived lack of social presence. This study examined whether a social presence in the form of various instantiations of embodied, visual, humanlike SCO interface agents had an effect on opportunistic behaviour. Using a simulated SCO scenario, participants experienced various dilemmas in which they could financially benefit themselves undeservedly. We hypothesised that a humanlike social presence integrated within the checkout screen would receive more attention and result in fewer instances of dishonesty compared to a less humanlike agent. This was partially supported by the results. The findings contribute to the theoretical framework in social presence research. We concluded that companies adopting self-service technology may consider the implementation of social presence in technology applications to support ethical consumer behaviour, but that more research is required to explore the mixed findings in the current study.<br/