Mitochondrial and plasma membrane potential of cultured cerebellar neurons during glutamate-induced necrosis, apoptosis, and tolerance.

A failure of mitochondrial bioenergetics has been shown to be closely associated with the onset of apoptotic and necrotic neuronal injury. Here, we developed an automated computational model that interprets the single-cell fluorescence for tetramethylrhodamine methyl ester (TMRM) as a consequence of changes in either delta psi(m) or delta psi(p), thus allowing for the characterization of responses for populations of single cells and subsequent statistical analysis. Necrotic injury triggered by prolonged glutamate excitation resulted in a rapid monophasic or biphasic loss of delta psi(m) that was closely associated with a loss of delta psi(p) and a rapid decrease in neuronal NADPH and ATP levels. Delayed apoptotic injury, induced by transient glutamate excitation, resulted in a small, reversible decrease in TMRM fluorescence, followed by a sustained hyperpolarization of delta psi(m) as confirmed using the delta psi(p)-sensitive anionic probe DiBAC2(3). This hyperpolarization of delta psi(m) was closely associated with a significant increase in neuronal glucose uptake, NADPH availability, and ATP levels. Statistical analysis of the changes in delta psi(m) or delta psi(p) at a single-cell level revealed two major correlations; those neurons displaying a more pronounced depolarization of delta psi(p) during the initial phase of glutamate excitation entered apoptosis more rapidly, and neurons that displayed a more pronounced hyperpolarization of delta psi(m) after glutamate excitation survived longer. Indeed, those neurons that were tolerant to transient glutamate excitation (18%) showed the most significant increases in delta psi(m). Our results indicate that a hyperpolarization of delta psi(m) is associated with increased glucose uptake, NADPH availability, and survival responses during excitotoxic injury

Role of CD56-expressing immature biliary epithelial cells in biliary atresia

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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

Exploring young people's and youth workers' experiences of spaces for ‘youth development’: creating cultures of participation

The paper focuses on the emergence of ‘positive youth development’ and its impact on older, more established practices of working with young people, such as youth work. Drawing on ethnographic fieldwork in England between 2004 and 2006, in particular young people's and youth workers' accounts of participating in youth work, the analysis engages with the social spaces in which youth work takes place and asks key questions about why young people might participate in youth spaces, what they get out of participating and how such spaces can promote cultures of participation. The analysis shows that such spaces provide young people and their communities with biographical continuity and time becomes a key component for sustaining such spaces. The argument is made for a more nuanced understanding of what young people get out of their participation in youth spaces, and for an epistemological approach to youth praxis that embraces the messiness and inequalities of lived experience

Understanding English alcohol policy as a neoliberal condemnation of the carnivalesque

Much academic work has argued that alcohol policy in England over the past 25 years can be characterised as neoliberal, particularly in regard to the night-time economy and attempts to address “binge” drinking. Understanding neoliberalism as a particular “mentality of government” that circumscribes the range of policy options considered appropriate and practical for a government to take, this article notes how the particular application of policy can vary by local context. This article argues that the approach of successive governments in relation to alcohol should be seen as based on a fear and condemnation of the carnivalesque, understood as a time when everyday norms and conventions are set aside, and the world is – for a limited period only – turned inside out. This analysis is contrasted with previous interpretations that have characterised government as condemning intoxication and particular forms of pleasure taken in drinking. Although these concepts are useful in such analysis, this article suggests that government concerns are broader and relate to wider cultures surrounding drunkenness. Moreover, there is an ambivalence to policy in relation to alcohol that is better conveyed by the concept of the carnivalesque than imagining simply a condemnation of pleasure or intoxication

Labelling and Family Resemblance in the discrimination of polymorphous categories by pigeons

publication-status: Acceptedtypes: Article© 2011 Springer Verlag. This is a post print version of the article published in Animal Cognition, 2011, 14 (1), pp 21-34. The final publication is available at link.springer.comTwo experiments examined whether pigeons discriminate polymorphous categories on the basis of a single highly predictive feature or overall similarity. In the first experiment, pigeons were trained to discriminate between categories of photographs of complex real objects. Within these pictures, single features had been manipulated to produce a highly salient texture cue. Either the picture or the texture provided a reliable cue for discrimination during training, but in probe tests, the picture and texture cues were put into conflict. Some pigeons showed a significant tendency to discriminate on the basis of the picture cue (overall similarity or family resemblance), whereas others appeared to rely on the manipulated texture cue. The second experiment used artificial polymorphous categories in which one dimension of the stimulus provided a completely reliable cue to category membership, whereas three other dimensions provided cues that were individually unreliable but collectively provided a completely reliable basis for discrimination. Most pigeons came under the control of the reliable cue rather than the unreliable cues. A minority, however, came under the control of single dimensions from the unreliable set. We conclude that cue salience can be more important than cue reliability in determining what features will control behavior when multiple cues are available

Global-scale climate impact functions: the relationship between climate forcing and impact

Although there is a strong policy interest in the impacts of climate change corresponding to different degrees of climate change, there is so far little consistent empirical evidence of the relationship between climate forcing and impact. This is because the vast majority of impact assessments use emissions-based scenarios with associated socio-economic assumptions, and it is not feasible to infer impacts at other temperature changes by interpolation. This paper presents an assessment of the global-scale impacts of climate change in 2050 corresponding to defined increases in global mean temperature, using spatially-explicit impacts models representing impacts in the water resources, river flooding, coastal, agriculture, ecosystem and built environment sectors. Pattern-scaling is used to construct climate scenarios associated with specific changes in global mean surface temperature, and a relationship between temperature and sea level used to construct sea level rise scenarios. Climate scenarios are constructed from 21 climate models to give an indication of the uncertainty between forcing and response. The analysis shows that there is considerable uncertainty in the impacts associated with a given increase in global mean temperature, due largely to uncertainty in the projected regional change in precipitation. This has important policy implications. There is evidence for some sectors of a non-linear relationship between global mean temperature change and impact, due to the changing relative importance of temperature and precipitation change. In the socio-economic sectors considered here, the relationships are reasonably consistent between socio-economic scenarios if impacts are expressed in proportional terms, but there can be large differences in absolute terms. There are a number of caveats with the approach, including the use of pattern-scaling to construct scenarios, the use of one impacts model per sector, and the sensitivity of the shape of the relationships between forcing and response to the definition of the impact indicator

A Long Baseline Neutrino Oscillation Experiment Using J-PARC Neutrino Beam and Hyper-Kamiokande

Document submitted to 18th J-PARC PAC meeting in May 2014. 50 pages, 41 figuresDocument submitted to 18th J-PARC PAC meeting in May 2014. 50 pages, 41 figuresDocument submitted to 18th J-PARC PAC meeting in May 2014. 50 pages, 41 figuresHyper-Kamiokande will be a next generation underground water Cherenkov detector with a total (fiducial) mass of 0.99 (0.56) million metric tons, approximately 20 (25) times larger than that of Super-Kamiokande. One of the main goals of Hyper-Kamiokande is the study of $CP$ asymmetry in the lepton sector using accelerator neutrino and anti-neutrino beams. In this document, the physics potential of a long baseline neutrino experiment using the Hyper-Kamiokande detector and a neutrino beam from the J-PARC proton synchrotron is presented. The analysis has been updated from the previous Letter of Intent [K. Abe et al., arXiv:1109.3262 [hep-ex]], based on the experience gained from the ongoing T2K experiment. With a total exposure of 7.5 MW $\times$ 10$^7$ sec integrated proton beam power (corresponding to $1.56\times10^{22}$ protons on target with a 30 GeV proton beam) to a $2.5$-degree off-axis neutrino beam produced by the J-PARC proton synchrotron, it is expected that the $CP$ phase $\delta_{CP}$ can be determined to better than 19 degrees for all possible values of $\delta_{CP}$, and $CP$ violation can be established with a statistical significance of more than $3\,\sigma$ ($5\,\sigma$) for $76$ ($58$) of the $\delta_{CP}$ parameter space

Social enterprise policy design: Constructing social enterprise in the UK and Korea

Taking the elusive definition of social enterprise as its starting point, this study seeks to understand the impact of government policies on the development of social enterprises in the national contexts of the UK and South Korea. The social construction of target populations is utilised as a theoretical framework in order to identify which factors influence government policy. A comparison of the two countries over a 14-year period from 1997 to 2010 reveals that, despite very different contexts, governments in both countries have taken an instrumental approach to social enterprise. This tendency is more pronounced in Korea however, where government has limited the input of stakeholders and used an approval system to control access to the social enterprise name. The study concludes by recommending a more value-oriented approach to social enterprise

Assessing sustainability in housing LED urban regeneration : insights from a housing association in Northern England

How far do current assessment methods allow the thorough evaluation of sustainable urban regeneration? Would it be useful, to approach the evaluation of the environmental and social impacts of housing regeneration schemes, by making both hidden pitfalls and potentials explicit, and budgeting costs and benefits in the stakeholders’ perspective? The paper aims at answering these questions, by focusing on a case study located in the Manchester area, the City West Housing Trust, a nonprofit housing association. Drawing from extensive fieldwork and including several interviews with key experts from this housing association, the paper first attempts to monetize the environmental and social value of two extant projects – a high-rise housing estate and an environmentally-led program. It then discusses whether and how a stakeholder-oriented approach would allow more engagement of both current and potential funders in the projects at hand. Findings from both the literature and the empirical data that was gathered show how in current housing regeneration processes, room for significant improvements in terms of assessment methods still exist. Findings additionally show that the environmental and social spillovers are largely disregarded because of a gap in the evaluation tools. This may also hinder the potential contributions of further funders in the achievements of higher impacts in terms of sustainability