643 research outputs found

    One potato, two potato: 'Mashed Library' two years in

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    An article aimed at academic librarians about the 'Mashed Library' movement and series of unconferences, which are all about 'bringing together interested people and doing interesting stuff with libraries and technology'

    The virtual Tate

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    development of measures of polyneuropathy impairment in hattr amyloidosis from nis to mnis 7

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    Abstract Hereditary transthyretin-mediated amyloidosis (hATTR amyloidosis) is a rare, life-threatening disease, caused by point mutations in the transthyretin gene. It is a heterogeneous, multisystem disease with rapidly progressing polyneuropathy (including sensory, motor, and autonomic impairments) and cardiac dysfunction. Measures used to assess polyneuropathy in other diseases have been tested as endpoints in hATTR amyloidosis clinical trials (i.e. Neuropathy Impairment Score [NIS], NIS-lower limb, and NIS + 7), yet the unique nature of the polyneuropathy in this disease has necessitated modifications to these scales. In particular, the heterogeneous impairment and the aggressive disease course have been key drivers in developing scales that better capture the disease burden and progression of polyneuropathy in hATTR amyloidosis. The modified NIS + 7 (mNIS + 7) scale was specifically designed to assess polyneuropathy impairment in patients with hATTR amyloidosis, and has been the primary endpoint in two recent, phase III studies in this disease. The mNIS + 7 uses highly standardized, quantitative, and referenced assessments to quantify decreased muscle weakness, muscle stretch reflexes, sensory loss, and autonomic impairment. Physicians using this scale in clinical trials should be specifically trained and monitored to minimize variability. This article discusses the different scales that have been/are being used to assess polyneuropathy in patients with hATTR amyloidosis, their correlation with other disease assessments, and reflects on how and why scales have evolved to the latest iteration of mNIS + 7

    ASSETS AND CONSTRAINTS RELATING TO THE LOCATION DECISIONS OF SMALL MANUFACTURING BUSINESSES IN VERMONT

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    The goal of this research is to identify the assets and constraints that exist specific to small business manufacturers in Vermont. To satisfy this goal, the study examines factors that influence location decisions as well as identifying what obstacles business owners have experienced. The idea for this project originated in response to the troubled economic condition of several Vermont communities, where unemployment rates are unusually high and income unusually low. Understanding what obstacles business faces might enable future ideas on how to solve these problems. Once assets are identified, they can be capitalized on, leading to more successful business operations. Preliminary data was collected through a telephone interview survey with Vermont small business owners. The data was analyzed in order to discover incentives and obstacles that existed for Vermont manufacturers as a whole, as well as in specific industries. Results from the survey suggested that Vermont's largest asset is that it offers an excellent quality of life. However, results alluded to several difficulties that owners are faced with, particularly complying with certain rules and regulations, obtaining adequate finances, a low-skilled workforce, and a weak communication network for small businesses.community development, small business, Community/Rural/Urban Development,

    Dynamic, small-world social network generation through local agent interactions

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    To model agent relationships in agent-based models, it is often necessary to incorporate a social network whose topology is commonly assumed to be “small-world.” This is potentially problematic, as the classification is broad and covers a wide-range of network statistics. Furthermore, real networks are often dynamic, in that edges and nodes can appear or disappear, and spatial, in that connections are influenced by an agent's position within a particular social space. These properties are difficult to achieve in current network formation tools. We have, therefore, developed a novel social network formation model, that creates and dynamically adjusts small-world networks using local spatial interactions, while maintaining tunable global network statistics from across the broad space of possible small-world networks. It is, therefore, a useful tool for multiagent simulations and diffusion processes, particularly those in which agents and edges die or are constrained in their movement within some social space. We also show, using a simple epidemiological diffusion model, that a range of networks can all satisfy the small-world criterion, but behave quite differently. This demonstrates that it is problematic to generalize results across the whole space of small-world networks

    Structural determinants at the M2 muscarinic receptor modulate the RGS4-GIRK response to pilocarpine by impairment of the receptor voltage sensitivity.

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    Membrane potential controls the response of the M2 muscarinic receptor to its ligands. Membrane hyperpolarization increases response to the full agonist acetylcholine (ACh) while decreasing response to the partial agonist pilocarpine. We previously have demonstrated that the regulator of G-protein signaling (RGS) 4 protein discriminates between the voltage-dependent responses of ACh and pilocarpine; however, the underlying mechanism remains unclear. Here we show that RGS4 is involved in the voltage-dependent behavior of the M2 muscarinic receptor-mediated signaling in response to pilocarpine. Additionally we revealed structural determinants on the M2 muscarinic receptor underlying the voltage-dependent response. By electrophysiological recording in Xenopus oocytes expressing M2 muscarinic receptor and G-protein-gated inwardly rectifying K+ channels, we quantified voltage-dependent desensitization of pilocarpine-induced current in the presence or absence of RGS4. Hyperpolarization-induced desensitization of the current required for RGS4, also depended on pilocarpine concentration. Mutations of charged residues in the aspartic acid-arginine-tyrosine motif of the M2 muscarinic receptor, but not intracellular loop 3, significantly impaired the voltage-dependence of RGS4 function. Thus, our results demonstrated that voltage-dependence of RGS4 modulation is derived from the M2 muscarinic receptor. These results provide novel insights into how membrane potential impacts G-protein signaling by modulating GPCR communication with downstream effectors

    Creating an Institutional Repository on the Cheap

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    Digital Commons is a product from bepress™ for creating an open access institutional repository. Butler University Libraries have used Digital Commons to create a repository for Butler theses and faculty research, Selected Works pages to highlight the publications of Butler faculty and staff, and open electronic journal access for a discontinued journal and a continuing print-based journal, both published by Butler. This presentation demonstrate the utility of the Digital Commons product for the development of an open access repository for Butler University and shares the methods we have employed to maximize the use of the resources available to us to implement it
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