Optimization of Roadway Electrification Integrating Wireless Power Transfer: TechnoEconomic Assessment and Lifecycle Analysis

Electric vehicles are the main technology currently being pursued to reduce dependence on fossil fuels in the transportation sector. These vehicles provide both reduced greenhouse gas emissions and decreased operating costs when compared to conventional internal combustion vehicles, while providing the flexibility to use both renewable and fossil energy. However, these vehicles have seen limited consumer adoption due to their large purchase prices and limited driving range. Both purchase price and driving range are related to the large onboard battery systems required for electric vehicle travel. One solution to decrease dependence on large battery systems has focused on charging vehicles in-motion using wireless power transfer. In-motion charging of electric vehicles would allow for longer range travel with smaller onboard battery systems which would lead to cheaper vehicles and, in turn, greater consumer acceptance. Wireless power transfer is commonly used for small electronics (i.e. cell phones), but has seen limited use on large scale projects. Therefore, limited work has been done to understand the feasibility of in-motion charging of electric vehicles using wireless power transfer. The goal of this thesis is to better understand the economic feasibility, environmental benefit, and infrastructure requirements of a wirelessly charged electric vehicle fleet for transportation in the United States

QM/MM simulations as an assay for carbapenemase activity in class A β-lactamases

Carbapenemases are distinguished from carbapenem-inhibited β-lactamases with a protocol involving QM/MM free energy simulations of acyl–enzyme deacylation, requiring only the enzyme 3D structure as input.</p

Which older people decline participation in a primary care trial of physical activity and why: insights from a mixed methods approach

This article is available through the Brunel Open Access Publishing Fund. Copyright 2014 Rogers et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background: Physical activity is of vital importance to older peoples’ health. Physical activity intervention studies with older people often have low recruitment, yet little is known about non-participants. Methods: Patients aged 60–74 years from three UK general practices were invited to participate in a nurse-supported pedometer-based walking intervention. Demographic characteristics of 298 participants and 690 non-participants were compared. Health status and physical activity of 298 participants and 183 non-participants who completed a survey were compared using age, sex adjusted odds ratios (OR) (95% confidence intervals). 15 non-participants were interviewed to explore perceived barriers to participation. Results: Recruitment was 30% (298/988). Participants were more likely than non-participants to be female (54% v 47%; p = 0.04) and to live in affluent postcodes (73% v 62% in top quintile; p < 0.001). Participants were more likely than non-participants who completed the survey to have an occupational pension OR 2.06 (1.35-3.13), a limiting longstanding illness OR 1.72 (1.05-2.79) and less likely to report being active OR 0.55 (0.33-0.93) or walking fast OR 0.56 (0.37-0.84). Interviewees supported general practice-based physical activity studies, particularly walking, but barriers to participation included: already sufficiently active, reluctance to walk alone or at night, physical symptoms, depression, time constraints, trial equipment and duration. Conclusion: Gender and deprivation differences suggest some selection bias. However, trial participants reported more health problems and lower activity than non-participants who completed the survey, suggesting appropriate trial selection in a general practice population. Non-participant interviewees indicated that shorter interventions, addressing physical symptoms and promoting confidence in pursuing physical activity, might increase trial recruitment and uptake of practice-based physical activity endeavours.The National Institute for Health Research (NIHR) under its Research for Patient Benefit Programme (Grant Reference Number PB-PG-0909-20055)

Should Research Ethics Encourage the Production of Cost-Effective Interventions?

This project considers whether and how research ethics can contribute to the provision of cost-effective medical interventions. Clinical research ethics represents an underexplored context for the promotion of cost-effectiveness. In particular, although scholars have recently argued that research on less-expensive, less-effective interventions can be ethical, there has been little or no discussion of whether ethical considerations justify curtailing research on more expensive, more effective interventions. Yet considering cost-effectiveness at the research stage can help ensure that scarce resources such as tissue samples or limited subject popula- tions are employed where they do the most good; can support parallel efforts by providers and insurers to promote cost-effectiveness; and can ensure that research has social value and benefits subjects. I discuss and rebut potential objections to the consideration of cost-effectiveness in research, including the difficulty of predicting effectiveness and cost at the research stage, concerns about limitations in cost-effectiveness analysis, and worries about overly limiting researchers’ freedom. I then consider the advantages and disadvantages of having certain participants in the research enterprise, including IRBs, advisory committees, sponsors, investigators, and subjects, consider cost-effectiveness. The project concludes by qualifiedly endorsing the consideration of cost-effectiveness at the research stage. While incorporating cost-effectiveness considerations into the ethical evaluation of human subjects research will not on its own ensure that the health care system realizes cost-effectiveness goals, doing so nonetheless represents an important part of a broader effort to control rising medical costs

Novel role for the innate immune receptor toll-like receptor 4 (TLR4) in the regulation of the wnt signaling pathway and photoreceptor apoptosis

Recent evidence has implicated innate immunity in regulating neuronal survival in the brain during stroke and other neurodegenerations. Photoreceptors are specialized light-detecting neurons in the retina that are essential for vision. In this study, we investigated the role of the innate immunity receptor TLR4 in photoreceptors. TLR4 activation by lipopolysaccharide (LPS) significantly reduced the survival of cultured mouse photoreceptors exposed to oxidative stress. With respect to mechanism, TLR4 suppressed Wnt signaling, decreased phosphorylation and activation of the Wnt receptor LRP6, and blocked the protective effect of the Wnt3a ligand. Paradoxically, TLR4 activation prior to oxidative injury protected photoreceptors, in a phenomenon known as preconditioning. Expression of TNFα and its receptors TNFR1 and TNFR2 decreased during preconditioning, and preconditioning was mimicked by TNFα antagonists, but was independent of Wnt signaling. Therefore, TLR4 is a novel regulator of photoreceptor survival that acts through the Wnt and TNFα pathways. © 2012 Yi et al

UNCLES: Method for the identification of genes differentially consistently co-expressed in a specific subset of datasets

Background: Collective analysis of the increasingly emerging gene expression datasets are required. The recently proposed binarisation of consensus partition matrices (Bi-CoPaM) method can combine clustering results from multiple datasets to identify the subsets of genes which are consistently co-expressed in all of the provided datasets in a tuneable manner. However, results validation and parameter setting are issues that complicate the design of such methods. Moreover, although it is a common practice to test methods by application to synthetic datasets, the mathematical models used to synthesise such datasets are usually based on approximations which may not always be sufficiently representative of real datasets. Results: Here, we propose an unsupervised method for the unification of clustering results from multiple datasets using external specifications (UNCLES). This method has the ability to identify the subsets of genes consistently co-expressed in a subset of datasets while being poorly co-expressed in another subset of datasets, and to identify the subsets of genes consistently co-expressed in all given datasets. We also propose the M-N scatter plots validation technique and adopt it to set the parameters of UNCLES, such as the number of clusters, automatically. Additionally, we propose an approach for the synthesis of gene expression datasets using real data profiles in a way which combines the ground-truth-knowledge of synthetic data and the realistic expression values of real data, and therefore overcomes the problem of faithfulness of synthetic expression data modelling. By application to those datasets, we validate UNCLES while comparing it with other conventional clustering methods, and of particular relevance, biclustering methods. We further validate UNCLES by application to a set of 14 real genome-wide yeast datasets as it produces focused clusters that conform well to known biological facts. Furthermore, in-silico-based hypotheses regarding the function of a few previously unknown genes in those focused clusters are drawn. Conclusions: The UNCLES method, the M-N scatter plots technique, and the expression data synthesis approach will have wide application for the comprehensive analysis of genomic and other sources of multiple complex biological datasets. Moreover, the derived in-silico-based biological hypotheses represent subjects for future functional studies.The National Institute for Health Research (NIHR) under its Programme Grants for Applied Research Programme (Grant Reference Number RP-PG-0310-1004)

Transport and binding of tumor necrosis factor-α in articular cartilage depend on its quaternary structure

The effect of tumor necrosis factor-α (TNFα) on cartilage matrix degradation is mediated by its transport and binding within the extracellular matrix (ECM) of the tissue, which mediates availability to cell receptors. Since the bioactive form of TNFα is a homotrimer of monomeric subunits, conversion between trimeric and monomeric forms during intratissue transport may affect binding to ECM and, thereby, bioactivity within cartilage. We studied the transport and binding of TNFα in cartilage, considering the quaternary structure of this cytokine. Competitive binding assays showed significant binding of TNFα in cartilage tissue, leading to an enhanced uptake. However, studies in which TNFα was cross-linked to remain in the trimeric form revealed that the binding of trimeric TNFα was negligible. Thus, binding of TNFα to ECM was associated with the monomeric form. Binding of TNFα was not disrupted by pre-treating cartilage tissue with trypsin, which removes proteoglycans and glycoproteins but leaves the collagen network intact. Therefore, proteoglycan loss during osteoarthritis should only alter the passive diffusion of TNFα but not its binding interaction with the remaining matrix. Our results suggest that matrix binding and trimer–monomer conversion of TNFα both play crucial roles in regulating the accessibility of bioactive TNFα within cartilage.National Institute of Arthritis and Musculoskeletal and Skin Diseases (U.S.) (Grant AR45779)National Institute of Arthritis and Musculoskeletal and Skin Diseases (U.S.) (Grant AR60331

PACE-UP (Pedometer and consultation evaluation--UP)--a pedometer-based walking intervention with and without practice nurse support in primary care patients aged 45-75 years: study protocol for a randomised controlled trial.

BACKGROUND: Most adults do not achieve the 150 minutes weekly of at least moderate intensity activity recommended for health. Adults' most common physical activity (PA) is walking, light intensity if strolling, moderate if brisker. Pedometers can increase walking; however, most trials have been short-term, have combined pedometer and support effects, and have not reported PA intensity. This trial will investigate whether pedometers, with or without nurse support, can help less active 45-75 year olds to increase their PA over 12 months. METHODS/DESIGN: DESIGN: Primary care-based 3-arm randomized controlled trial with 12-month follow-up and health economic and qualitative evaluations. PARTICIPANTS: Less active 45-75 year olds (n = 993) will be recruited by post from six South West London general practices, maximum of two per household and households randomised into three groups. Step-count and time spent at different PA intensities will be assessed for 7 days at baseline, 3 and 12 months by accelerometer. Questionnaires and anthropometric assessments will be completed. INTERVENTION: The pedometer-alone group will be posted a pedometer (Yamax Digi-Walker SW-200), handbook and diary detailing a 12-week pedometer-based walking programme, using targets from their baseline assessment. The pedometer-plus-support group will additionally receive three practice nurse PA consultations. The handbook, diary and consultations include behaviour change techniques (e.g., self-monitoring, goal-setting, relapse prevention planning). The control group will receive usual care. OUTCOMES: Changes in average daily step-count (primary outcome), time spent sedentary and in at least moderate intensity PA weekly at 12 months, measured by accelerometry. Other outcomes include change in body mass index, body fat, self-reported PA, quality of life, mood and adverse events. Cost-effectiveness will be assessed by the incremental cost of the intervention to the National Health Service and incremental cost per change in step-count and per quality adjusted life year. Qualitative evaluations will explore reasons for trial non-participation and the interventions' acceptability. DISCUSSION: The PACE-UP trial will determine the effectiveness and cost-effectiveness of a pedometer-based walking intervention delivered by post or practice nurse to less active primary care patients aged 45-75 years old. Approaches to minimise bias and challenges anticipated in delivery will be discussed

Galectins and their involvement in ocular disease and development

Galectins are carbohydrate binding proteins with high affinity to ß-galactoside containing glycoconjugates. Understanding of the functions of galectins has grown steadily over the past decade, as a result of substantial advancements in the field of glycobiology. Galectins have been shown to be versatile molecules that participate in a range of important biological systems, including inflammation, neovascularisation and fibrosis. These processes are of particular importance in ocular tissues, where a major theme of recent research has been to divert diseases away from pathways which result in loss of function into pathways of repair and regeneration. This review summarises our current understanding galectins in the context important ocular diseases, followed by an update on current clinical studies and future directions

Feasibility of wireless power transfer for electrification of transportation: Techno-economics and life cycle assessment

Integration of wireless power transfer (WPT) systems in roadways and vehicles represents a promising alternative to traditional internal combustion transportation systems. The economic feasibility and environmental impact of WPT applied to the transportation system is evaluated through the development of engineering system models. For a 20% penetration of the WPT technology in vehicles, results show a 20% reduction in air pollutants, 10% reduction in energy use and CO2 emissions and a societal level payback (defined as total cost of ownership savings compared to a traditional vehicle equal to roadway infrastructure) of 3 years. The modeled system covers 86% of all traffic in the US, impacts 40% of all roadways and shifts $180 billion per year from oil production to jobs in local power generation and development, construction, and maintenance of electrified roadways and new electric vehicles. Results on model sensitivity to energy prices, payback as a function of penetration, and trucking vs light duty use are presented