Concentrative nucleoside transporter 1 (hCNT1) promotes phenotypic changes relevant to tumor biology in a translocation independent manner

Nucleoside transporters (NTs) mediate the uptake of nucleosides and nucleobases across the plasma membrane, mostly for salvage purposes. The canonical NTs belong to two gene families, SLC29 and SLC28. The former encode equilibrative nucleoside transporter proteins (ENTs), which mediate the facilitative diffusion of natural nucleosides with broad selectivity, whereas the latter encode concentrative nucleoside transporters (CNTs), which are sodium-coupled and show high affinity for substrates with variable selectivity. These proteins are expressed in most cell types, exhibiting apparent functional redundancy. This might indicate that CNTs play specific roles in the physiology of the cell beyond nucleoside salvage. Here, we addressed this possibility using adenoviral vectors to restore tumor cell expression of hCNT1 or a polymorphic variant (hCNT1S546P) lacking nucleoside translocation ability. We found that hCNT1 restoration in pancreatic cancer cells significantly altered cell-cycle progression and phosphorylation status of key signal-transducing kinases, promoted poly-(ADP ribose) polymerase hyperactivation and cell death, and reduced tumor growth and cell migration. Importantly, the translocation-defective transporter triggered these same effects on cell physiology. These data predict a novel and totally unexpected biological role for the nucleoside transporter protein hCNT1 that appears to be independent of its role as mediator of nucleoside uptake by cells, thereby suggesting a transceptor function. Cell Death & Disease Anastasis Stephanou Receiving Editor Cell Death & Disease 19th Apr 2013 Dr Perez-Torras Av/ Diagonal 643. Edif. Prevosti, Pl -1 Barcelona 08028 Spain RE: Manuscript CDDIS-13-0136R, 'CDDIS-13-0136R' Dear Dr Perez-Torras, It is a pleasure to inform you that your manuscript has been evaluated at the editorial level and has now been officially accepted for publication in Cell Death & Disease, pending you meet the following editorial requirements: 1) the list of the abbreviations is missing please include Could you send us the revised text as word file via e-mail and we will proceed and transfer the paper onto our typesetters. Please download, print, sign, and return the Licence to Publish Form using the link below. This must be returned via FAX to ++ 39 06 7259 6977 before your manuscript can be published:

What young people with spina bifida want to know about sex and are not being told.

OBJECTIVE: The aim of this paper was to examine sexual knowledge, concerns and needs of youth with spina bifida (SB) to inform the medical community on ways to better support their sexual health. METHODS: As part of the Video Intervention/Prevention Assessment (VIA) - transitions, a prospective cohort study, 309 h of video data were collected from 14 participants (13-28 years old) with SB. Participants were loaned a video camcorder for 8-12 weeks to shoot visual narratives about any aspects of their lives. V/A visual narratives were analysed with grounded theory using NVivo. RESULTS: Out of 14 participants, 11 (six women) addressed issues surrounding romantic relationships and sexuality in their video clips. Analysis revealed shared concerns, questions and challenges regarding sexuality gathered under four main themes: romantic relationships, sexuality, fertility and parenthood, and need for more talk on sexuality. CONCLUSIONS: Youth with SB reported difficulties in finding answers to questions regarding their sexuality, romantic relationships and fertility. This study revealed a need for help from the medical community to inform and empower youth with SB in the area of sexual health. Through sexual and reproductive health education with patients and parents starting at an early age, medical providers can further encourage healthy emotional and physical development in adolescents transitioning into adulthood.

Analysis of the feeding behaviour of the mosquito Culex pipiens L. (Diptera: Culicidae) in relation to West Nile virus

The goal ofthis literature review is to inform the reader on several aspects of West Nile Virus (WNV) transmission by its mosquito vector, Culex pipiens and to elucidate how Cx. pipiens and WNV are intertwined. The first few sections of the literature review describe the life cycle and blood feeding behaviours ofmosquitoes so that baseline data ofmosquito biology are established. In addition to explaining how and why a mosquito blood feeds, the section on "Blood Meal Analysis" describes the different methods for determining the vertebrate source of mosquito blood meals and a brief history of these testing methods. Since this thesis looks at the feeding behaviour of Cx. pipiens, it is important to know how to determine what they are feeding upon. Discussion on other mosquito-borne diseases related to WNV gives a broader perspective to the thesis, and examines other diseases that have occurred in Ontario in the past. This is followed by background information on WNV and theories on how this virus came to North America and how it relates to Cx. pipiens. The final sections discuss Cx. pipiens and give background information to how this species of mosquito exists and behaves within North America.

APPLICATION OF GEOMATICS TECHNOLOGIES TO CHARACTERIZE SPATIAL VARIABILITY AT STRATUS VINEYARDS

Vineyards vary over space and time, making geomatics technologies ideally suited to study terroir. This study applied geomatics technologies - GPS, remote sensing and GIS - to characterize the spatial variability at Stratus Vineyards in the Niagara Region. The concept of spatial terroir was used to visualize, monitor and analyze the spatial and temporal variability of variables that influence grape quality. Spatial interpolation and spatial autocorrelation were used to measure the pattern demonstrated by soil moisture, leaf water potential, vine vigour, soil composition and grape composition on two Cabernet Franc blocks and one Chardonnay block. All variables demonstrated some spatial variability within and between the vineyard block and over time. Soil moisture exhibited the most significant spatial clustering and was temporally stable. Geomatics technologies provided valuable spatial information related to the natural spatial variability at Stratus Vineyards and can be used to inform and influence vineyard management decisions.

Priming the Governance System for Climate Change Adaptation: The Application of a Social Ecological Inventory (SEI) to Engage Actors in Niagara, Canada

Adaptive systems of governance are increasingly gaining attention in respect to complex and uncertain social-ecological systems. Adaptive co-management is one strategy to make adaptive governance operational and holds promise with respect to community climate change adaptation as it facilitates participation and learning across scales and fosters adaptive capacity and resilience. Developing tools which hasten the realization of such approaches are growing in importance. This paper describes explores the Social Ecological Inventory (SEI) as a tool to 'prime' a regional climate change adaptation network. The SEI tool draws upon the social-ecological systems approach in which social and ecological systems are considered linked. SEIs bridge the gap between conventional stakeholder analysis and biological inventories and take place through a six phase process. A case study describes the results of applying an SEI to prime an adaptive governance network for climate change adaptation in the Niagara Region of Canada. Lessons learned from the case study are discussed and highlight how the SEI catalyzed the adaptive co-management process in the case. Future avenues for SEIs in relation to climate change adaptation emerge from this exploratory work and offer opportunities to inform research and adaptation planning.

Letter to Mr. Steers from Samuel D. Woodruff regarding Lot 30

Letter to Mr. Steers from Samuel D. Woodruff regarding Lot 30, Concession 2 in Enniskillen (1 double sided page). Mr. Woodruff is asking Mr. Steers to inform him if he will attest to the claim of Mr. Clement. This letter is written in pencil and is quite faded but the text is still legible, April 18, 1848.

Introduction to graphic arts history

An introductory 1 hour lecture given in wk2 to x50 year 1 Graphic Arts students at Winchester School of Art. The aims of the lecture are: 1. Explore how to use historical sources appropriately 
to inform design practice
 2. Make connections between contemporary 
designs and the past

Modeling and Mapping Golden-winged Warbler Abundance to Improve Regional Conservation Strategies

Conservation planning requires identifying pertinent habitat factors and locating geographic locations where land management may improve habitat conditions for high priority species. I derived habitat models and mapped predicted abundance for the Golden-winged Warbler (Vermivora chrysoptera), a species of high conservation concern, using bird counts, environmental variables, and hierarchical models applied at multiple spatial scales. My aim was to understand habitat associations at multiple spatial scales and create a predictive abundance map for purposes of conservation planning for the Golden-winged Warbler. My models indicated a substantial influence of landscape conditions, including strong positive associations with total forest composition within the landscape. However, many of the associations I observed were counter to reported associations at finer spatial extents; for instance, I found Golden-winged Warblers negatively associated with several measures of edge habitat. No single spatial scale dominated, indicating that this species is responding to factors at multiple spatial scales. I found Golden-winged Warbler abundance was negatively related with Blue-winged Warbler (Vermivora cyanoptera) abundance. I also observed a north-south spatial trend suggestive of a regional climate effect that was not previously noted for this species. The map of predicted abundance indicated a large area of concentrated abundance in west-central Wisconsin, with smaller areas of high abundance along the northern periphery of the Prairie Hardwood Transition. This map of predicted abundance compared favorably with independent evaluation data sets and can thus be used to inform regional planning efforts devoted to conserving this species.

Flight initiation distances of nesting Piping Plovers (Charadrius melodus) in response to human disturbance

Birds frequently interact with people when they occur in coupled human-ecological or anthropogenic environments, which makes the protection of legally protected species a challenge. Flight initiation distances (FIDs) are often used to inform development of appropriate buffer distances required for human exclusion zones used to protect birds nesting in anthropogenic landscapes. Piping Plovers (Charadrius melodus) are protected by the Endangered Species Act in the United States and often nest in areas used by humans. Studies evaluating Piping Plover FIDs are limited and implementation of exclusion zones has been inconsistent across the species’ range. We measured Piping Plover response and FIDs to naturally occurring stimuli on public beaches at Lake McConaughy, Nebraska, USA. Piping Plover FIDs differed most by stimulus class (vehicle, human, dog, human with dog), Julian day, and hour of day. Piping Plover FIDs were greatest for dog and human with dog compared to humans and vehicles. For all types of stimuli, Piping Plover FIDs decreased over time during the nesting season and increased slightly during each day. In the majority of instances in which Piping Plovers left their nests, return times to the nest were relatively short (less than three minutes). These results suggest Piping Plovers become habituated to the presence of human-related stimuli over the course of a nesting season, but other explanations such as parental investment and risk allocation cannot be excluded. Additional research and improved guidance regarding the implementation of exclusion zones is needed so managers can implement effective protection programs in anthropogenic landscapes.

What is the new medicines use review ‘patient survey’ attempting to capture in the context of existing patient satisfaction with pharmacy questionnaires and a new conceptual framework?

The community pharmacy service medicines use review (MUR) was introduced in 2005 ‘to improve patient knowledge, concordance and use of medicines’ through a private patient–pharmacist consultation. The MUR presents a fundamental change in community pharmacy service provision. While traditionally pharmacists are dispensers of medicines and providers of medicines advice, and patients as recipients, the MUR considers pharmacists providing consultation-type activities and patients as active participants. The MUR facilitates a two-way discussion about medicines use. Traditional patient–pharmacist behaviours transform into a new set of behaviours involving the booking of appointments, consultation processes and form completion, and the physical environment of the patient–pharmacist interaction moves from the traditional setting of the dispensary and medicines counter to a private consultation room. Thus, the new service challenges traditional identities and behaviours of the patient and the pharmacist as well as the environment in which the interaction takes place. In 2008, the UK government concluded there is at present too much emphasis on the quantity of MURs rather than on their quality.[1] A number of plans to remedy the perceived imbalance included a suggestion to reward ‘health outcomes’ achieved, with calls for a more focussed and scientific approach to the evaluation of pharmacy services using outcomes research. Specifically, the UK government set out the main principal research areas for the evaluation of pharmacy services to include ‘patient and public perceptions and satisfaction’as well as ‘impact on care and outcomes’. A limited number of ‘patient satisfaction with pharmacy services’ type questionnaires are available, of varying quality, measuring dimensions relating to pharmacists’ technical competence, behavioural impressions and general satisfaction. For example, an often cited paper by Larson[2] uses two factors to measure satisfaction, namely ‘friendly explanation’ and ‘managing therapy’; the factors are highly interrelated and the questions somewhat awkwardly phrased, but more importantly, we believe the questionnaire excludes some specific domains unique to the MUR. By conducting patient interviews with recent MUR recipients, we have been working to identify relevant concepts and develop a conceptual framework to inform item development for a Patient Reported Outcome Measure questionnaire bespoke to the MUR. We note with interest the recent launch of a multidisciplinary audit template by the Royal Pharmaceutical Society of Great Britain (RPSGB) in an attempt to review the effectiveness of MURs and improve their quality.[3] This template includes an MUR ‘patient survey’. We will discuss this ‘patient survey’ in light of our work and existing patient satisfaction with pharmacy questionnaires, outlining a new conceptual framework as a basis for measuring patient satisfaction with the MUR. Ethical approval for the study was obtained from the NHS Surrey Research Ethics Committee on 2 June 2008. References 1. Department of Health (2008). Pharmacy in England: Building on Strengths – Delivering the Future. London: HMSO. www. official-documents.gov.uk/document/cm73/7341/7341.pdf (accessed 29 September 2009). 2. Larson LN et al. Patient satisfaction with pharmaceutical care: update of a validated instrument. JAmPharmAssoc 2002; 42: 44–50. 3. Royal Pharmaceutical Society of Great Britain (2009). Pharmacy Medicines Use Review – Patient Audit. London: RPSGB. http:// qi4pd.org.uk/index.php/Medicines-Use-Review-Patient-Audit. html (accessed 29 September 2009).

Application of one-list capture-recapture models to scrapie surveillance data in Great Britain

In this paper, we apply one-list capture-recapture models to estimate the number of scrapie-affected holdings in Great Britain. We applied this technique to the Compulsory Scrapie Flocks Scheme dataset where cases from all the surveillance sources monitoring the presence of scrapie in Great Britain, the abattoir survey, the fallen stock survey and the statutory reporting of clinical cases, are gathered. Consequently, the estimates of prevalence obtained from this scheme should be comprehensive and cover all the different presentations of the disease captured individually by the surveillance sources. Two estimators were applied under the one-list approach: the Zelterman estimator and Chao's lower bound estimator. Our results could only inform with confidence the scrapie-affected holding population with clinical disease; this moved around the figure of 350 holdings in Great Britain for the period under study, April 2005-April 2006. Our models allowed the stratification by surveillance source and the input of covariate information, holding size and country of origin. None of the covariates appear to inform the model significantly. Crown Copyright (C) 2008 Published by Elsevier B.V. All rights reserved.

Theory and practice in value management: a reply to Ellis et al (2005)

The constructivist model of 'soft' value management (VM) is contrasted with the VM discourse appropriated by cost consultants who operate from within UK quantity surveying (QS) practices. The enactment of VM by cost consultants is shaped by the institutional context within which they operate and is not necessarily representative of VM practice per se. Opportunities to perform VM during the formative stages of design are further constrained by the positivistic rhetoric that such practitioners use to conceptualize and promote their services. The complex interplay between VM theory and practice is highlighted and analysed from a non-deterministic perspective. Codified models of 'best practice' are seen to be socially constructed and legitimized through human interaction in the context of interorganizational networks. Published methodologies are seen to inform practice in only a loose and indirect manner, with extensive scope for localized improvization. New insights into the relationship between VM theory and practice are derived from the dramaturgical metaphor. The social reality of VM is seen to be constituted through scripts and performances, both of which are continuously contested across organizational arenas. It is concluded that VM defies universal definition and is conceptualized and enacted differently across different localized contexts.

Physiological expression of human thermal comfort to indoor operative temperature in the non-HVAC environment

A physiological experiment was carried out in a naturally ventilated, non-HVAC indoor environment of a spacious experimental room. More than 300 healthy university students volunteered for this study. The purpose of the study was to investigate the human physiological indicators which could be used to characterise the indoor operative temperature changes in a building and their impact on human thermal comfort based on the different climatic characteristics people would experience in Chongqing, China. The study found that sensory nerve conduction velocity (SCV) could objectively provide a good indicator for assessment of the human response to changes in indoor operative temperatures in a naturally ventilated situation. The results showed that with the changes in the indoor operative temperatures, the changing trend in the nerve conduction velocity was basically the same as that of the skin temperature at the sensory nerve measuring segment (Tskin(scv)). There was good coherent consistency among the factors: indoor operative temperature, SCV and Tskin(scv) in a certain indoor operative temperature range. Through self-adaptation and self-feedback regulation, the human physiological indicators would produce certain adaptive changes to deal with the changes in indoor operative temperature. The findings of this study should provide the baseline data to inform guidelines for the development of thermal environment-related standards that could contribute to efficient use of energy in buildings in China.

Quantifying the response of the ORAC aerosol optical depth retrieval for MSG SEVIRI to aerosol model assumptions

We test the response of the Oxford-RAL Aerosol and Cloud (ORAC) retrieval algorithm for MSG SEVIRI to changes in the aerosol properties used in the dust aerosol model, using data from the Dust Outflow and Deposition to the Ocean (DODO) flight campaign in August 2006. We find that using the observed DODO free tropospheric aerosol size distribution and refractive index increases simulated top of the atmosphere radiance at 0.55 µm assuming a fixed erosol optical depth of 0.5 by 10–15 %, reaching a maximum difference at low solar zenith angles. We test the sensitivity of the retrieval to the vertical distribution f the aerosol and find that this is unimportant in determining simulated radiance at 0.55 µm. We also test the ability of the ORAC retrieval when used to produce the GlobAerosol dataset to correctly identify continental aerosol outflow from the African continent and we find that it poorly constrains aerosol speciation. We develop spatially and temporally resolved prior distributions of aerosols to inform the retrieval which incorporates five aerosol models: desert dust, maritime, biomass burning, urban and continental. We use a Saharan Dust Index and the GEOS-Chem chemistry transport model to describe dust and biomass burning aerosol outflow, and compare AOD using our speciation against the GlobAerosol retrieval during January and July 2006. We find AOD discrepancies of 0.2–1 over regions of intense biomass burning outflow, where AOD from our aerosol speciation and GlobAerosol speciation can differ by as much as 50 - 70 %.

Effective communication to improve udder health: can social science help?

Improved udder health requires consistent application of appropriate management practices by those involved in managing dairy herds and the milking process. Designing effective communication requires that we understand why dairy herd managers behave in the way they do and also how the means of communication can be used both to inform and to influence. Social sciences- ranging from economics to anthropology - have been used to shed light on the behaviour of those who manage farm animals. Communication science tells us that influencing behaviour is not simply a question of „getting the message across‟ but of addressing the complex of factors that influence an individual‟s behavioural decisions. A review of recent studies in the animal health literature shows that different social science frameworks and methodologies offer complementary insights into livestock managers‟ behaviour but that the diversity of conceptual and methodological frameworks presents a challenge for animal health practitioners and policy makers who seek to make sense of the findings – and for researchers looking for helpful starting points. Data from a recent study in England illustrate the potential of „home-made‟ conceptual frameworks to help unravel the complexity of farmer behaviour. At the same time, though, the data indicate the difficulties facing those designing communication strategies in a context where farmers believe strongly that they are already doing all they can reasonably be expected to do to minimise animal health risks.