724 research outputs found

    Rules of the Laboratory of the Maine State College of Agriculture and the Mechanic Arts

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    A scan of the published rules for the scientific laboratory on the campus of Maine State College in 1871

    Promoting differentiation of cultured myoblasts using biomimetic surfaces that present alpha-laminin-2 peptides.

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    Traditionally, muscle cell lines are cultured on glass coverslips and differentiated to investigate myoblast fusion and differentiation. Efficient differentiation of myoblasts produces a dense network of myotubes with the correct organisation for contraction. Here we have tested the ability of artificially generated, precisely controlled peptide surfaces to enhance the efficiency of myoblast differentiation. We focused on specific short peptides from α-laminin-2 (IKVSV, VQLRNGFPYFSY and GLLFYMARINHA) as well as residues 15–155 from FGF1. We tested if these peptides in isolation, and/or in combination promoted muscle differentiation in culture, by promoting fusion and/or by improving sarcomere organisation. The majority of these peptides promoted fusion and differentiation in two different mouse myogenic cell lines and in primary human myoblasts. The additive effects of all four peptides gave the best results for both mouse cell lines tested, while primary human cell cultures differentiated equally well on most peptide surfaces tested. These data show that a mixture of short biomimetic peptides can reliably promote differentiation in mouse and human myoblasts

    What is bitumen?

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/32618/1/0000761.pd

    Decentralisation and performance: Autonomy and incentives in Local Health Economies

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    This project will examine the inter-relationship between governance mechanisms, autonomy and incentives in local health economies (LHEs). This interaction shapes decentralisation policies in the NHS and is thought to shape LHE performance. Recently, English health policy has been implementing new forms of decentralisation (eg. earned autonomy, Foundation Trusts) by altering the mix of governance mechanisms (command, collaboration and competition) and making explicit use of autonomy and incentives, thereby aiming to improve NHS performance. Local contextual factors might also shape performance outcomes. The project involves a synergy between the multi-disciplinary teams involved in 2 previous NCC-SDO funded studies. The aim is to investigate the inter-relationship between decentralisation and performance in LHEs. The project has 5 objectives: a. To examine the impact of decentralisation upon performance through analysis of selected 'tracers (as examples of current priorities) in 3 case-studies; b. To describe the local interaction of governance mechanisms; c. To evaluate the degree of autonomy available to local health-care organisations; d. To assess the (financial and non-financial) incentives associated with different policy initiatives; e. To provide lessons for policy-makers and managers at all levels in implementing decentralisation, managing the implications of autonomy and incentives, and addressing performance management through incentives. The study will use mixed methods. First, analysis of policy and performance data will generate the broad pattern of decentralisation and performance across England. Analysis of these data will aid selection of case-studies and 'tracers (examples within case-studies). Second, three case-studies will be selected which represent a maximum variety of pre-defined criteria. Longitudinal, comparative case-study methods include (a) 'mapping LHE performance and organisational characteristics (using local performance and activity data, and published reports); (b) a survey of senior staff in 3 LHEs (n=c.180) to provide their perceptions of current LHE issues and constraints (especially relating to tracer examples); (c) interviews with a sample of stakeholders (n=c.120) will identify the strengths and effects of organisational relationships across the LHE (such as the impact of service developments in the tracer examples); (d) observation of local planning meetings. Parts (a) and (b) will be conducted in year 1, parts (c) and (d) in years 2 and 3. Quantitative analysis will provide descriptive statistics of broad patterns and association. Qualitative analysis will provide thematic comparisons by LHE, organisational type and tracer example. Analysis will identify the pathways by which governance, autonomy and incentives can facilitate improved performance and also the conditions under which the optimal balance of these may be achieved in different contexts. The study will also consider conceptual frameworks (including 'decision space , resource dependency and principal-agent) to improve understanding of the inter-relationships within LHE and the intersection of national/vertical and local/horizontal pressures affecting performance. The study will engage decision-makers at all stages (via data collection, formative and summative feedback and as members of an Advisory Group). Formative feedback to LHEs (and NCC-SDO) will help validate emergent findings and sharpen subsequent fieldwork. Final dissemination will include such (oral and written) feedback, NCC-SDO report, presentations and publications to practitioner and research communities

    Excessive ENaC-mediated sodium influx drives NLRP3 inflammasome-dependent autoinflammation in cystic fibrosis

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    Cystic Fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and results in defective CFTR-mediated chloride transport, dysregulation of epithelial sodium channels (ENaC) and exaggerated innate immune responses. We tested the hypothesis that upregulation of ENaC drives autoinflammation in this complex monogenic disease.We show that monocytes from patients with CF exhibit a systemic proinflammatory cytokine signature, with associated anti-inflammatory M2-type macrophage deficiency. Cells harboring CF mutations are hyperresponsive to NLRP3 stimulation, as evidenced by increased IL-18, IL-1ÎČ, ASC-specks levels in serum and caspase-1 activity in monocytes, and by increased IL-18 production and caspase-1 activity in human bronchial epithelial cells (HBECs). In both cell types there is an associated shift to glycolytic metabolism with succinate release, in response to increased energy requirements. Inhibition of amiloride-sensitive sodium channels partially reverses the NLRP3-dependent inflammation and metabolic shift in these cells. Overexpression of ÎČ-ENaC, in the absence of CFTR dysfunction, increases NLRP3-dependent inflammation, indicating a CFTR-independent ENaC axis in CF pathophysiology. Sodium channel modulation provides an important therapeutic strategy to combat lung inflammation in CF.</jats:p

    Estimation of productivity in pine and oak forests in northern Portugal using Biome-BGC

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    Studies about the productivity of forest ecosystems help to quantify sequestered carbon and provide data that are used in forest management. Forests in northern Portugal are an important economic resource, but their productivity in scenarios of future climate change is not yetwell understood. The objectives of this study were to evaluate and compare simulated net primary production (NPP) andNPPbased onmeasured data of twotree species located in the Vila Real district forests, pine (Pinus pinaster Aiton) and oak (Quercus pyrenaica Willd.) and assess their simulatedNPPin diverse climate conditions, including future climate scenariosandincreasing atmospheric CO2 concentrations. An ecosystem process model, Biome-BGC, which simulates carbon, nitrogen and water cycles of forest ecosystems close to equilibrium conditions, was used to examine the importance of site and ecophysiological factors on the productivity of these forests. Climate change scenarios and increased CO2 concentrations were tested to explore potential responses of the studied species. The model provided good estimates of NPP. There was a strong correlation between the simulated and measured NPP values in the pine (15) and oak (15) stands. The NPP of these forests are predicted to increase in the future with a CO2 increase whereas in a climate with higher temperature and lower soil moisture, the NPP will decrease. These results confirm that precipitation is a very important climate variable to growth and productivity in the Mediterranean forest ecosystems. This study also demonstrated the ability of Biome-BGC to accurately simulate forest ecosystems behaviour and encourages the application of model simulations in Portugalinfo:eu-repo/semantics/publishedVersio

    A different appetite for sovereignty? Independence movements in subnational island jurisdictions

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    Local autonomy in a subnational jurisdiction is more likely to be gained, secured or enhanced where there are palpable movements or political parties agitating for independence in these smaller territories. A closer look at the fortunes, operations and dynamics of independence parties from subnational island jurisdictions can offer some interesting insights on the appetite for sovereignty and independence, but also the lack thereof, in the twenty-first century.peer-reviewe

    The impact of Cochrane Systematic Reviews : a mixed method evaluation of outputs from Cochrane Review Groups supported by the UK National Institute for Health Research

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    © 2014 Bunn 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/4.0), 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: There has been a growing emphasis on evidence-informed decision making in health care. Systematic reviews, such as those produced by the Cochrane Collaboration, have been a key component of this movement. The UK National Institute for Health Research (NIHR) Systematic Review Programme currently supports 20 Cochrane Review Groups (CRGs). The aim of this study was to identify the impacts of Cochrane reviews published by NIHR funded CRGs during the years 2007-11. Methods: We sent questionnaires to CRGs and review authors, interviewed guideline developers and used bibliometrics and documentary review to get an overview of CRG impact and to evaluate the impact of a sample of 60 Cochrane reviews. We used a framework with four categories (knowledge production, research targeting, informing policy development, and impact on practice/services). Results: A total of 1502 new and updated reviews were produced by the 20 NIHR funded CRGs between 2007-11. The clearest impacts were on policy with a total of 483 systematic reviews cited in 247 sets of guidance; 62 were international, 175 national (87 from the UK) and 10 local. Review authors and CRGs provided some examples of impact on practice or services, for example safer use of medication, the identification of new effective drugs or treatments and potential economic benefits through the reduction in the use of unproven or unnecessary procedures. However, such impacts are difficult to objectively document and the majority of reviewers were unsure if their review had produced specific impacts. Qualitative data suggested that Cochrane reviews often play an instrumental role in informing guidance although a poor fit with guideline scope or methods, reviews being out of date and a lack of communication between CRGs and guideline developers were barriers to their use. Conclusions: Health and economic impacts of research are generally difficult to measure. We found that to be the case with this evaluation. Impacts on knowledge production and clinical guidance were easier to identify and substantiate than those on clinical practice. Questions remain about how we define and measure impact and more work is needed to develop suitable methods for impact analysis.Peer reviewe

    Analyzing the impact of course structure on electronic textbook use in blended introductory physics courses

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    We investigate how elements of course structure (i.e., the frequency of assessments as well as the sequencing and weight of course resources) influence the usage patterns of electronic textbooks (e-texts) in introductory physics courses. Specifically, we analyze the access logs of courses at Michigan State University and the Massachusetts Institute of Technology, each of which deploy e-texts as primary or secondary texts in combination with different formative assessments (e.g., embedded reading questions) and different summative assessment (exam) schedules. As such studies are frequently marred by arguments over what constitutes a “meaningful” interaction with a particular page (usually judged by how long the page remains on the screen), we consider a set of different definitions of “meaningful” interactions. We find that course structure has a strong influence on how much of the e-texts students actually read, and when they do so. In particular, courses that deviate strongly from traditional structures, most notably by more frequent exams, show consistently high usage of the materials with far less “cramming” before exams.National Science Foundation (U.S.) (Grant DUE-1044294)Google (Firm
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