1,767 research outputs found

    Equality of Participation Online Versus Face to Face: Condensed Analysis of the Community Forum Deliberative Methods Demonstration

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    Online deliberation may provide a more cost-effective and/or less inhibiting environment for public participation than face to face (F2F). But do online methods bias participation toward certain individuals or groups? We compare F2F versus online participation in an experiment affording within-participants and cross-modal comparisons. For English speakers required to have Internet access as a condition of participation, we find no negative effects of online modes on equality of participation (EoP) related to gender, age, or educational level. Asynchronous online discussion appears to improve EoP for gender relative to F2F. Data suggest a dampening effect of online environments on black participants, as well as amplification for whites. Synchronous online voice communication EoP is on par with F2F across individuals. But individual-level EoP is much lower in the online forum, and greater online forum participation predicts greater F2F participation for individuals. Measured rates of participation are compared to self-reported experiences, and other findings are discussed.Comment: 14 pages, 10 tables, to appear in Efthimios Tambouris, Panos Panagiotopoulos, {\O}ystein S{\ae}b{\o}, Konstantinos Tarabanis, Michela Milano, Theresa Pardo, and Maria Wimmer (Editors), Electronic Participation: Proceedings of the 7th IFIP WG 8.5 International Conference, ePart 2015 (Thessaloniki, August 30-September 2), Springer LNCS Vol. 9249, 201

    Deletion of vascular endothelial growth factor in myeloid cells accelerates tumorigenesis.

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    Angiogenesis and the development of a vascular network are required for tumour progression, and they involve the release of angiogenic factors, including vascular endothelial growth factor (VEGF-A), from both malignant and stromal cell types. Infiltration by cells of the myeloid lineage is a hallmark of many tumours, and in many cases the macrophages in these infiltrates express VEGF-A. Here we show that the deletion of inflammatory-cell-derived VEGF-A attenuates the formation of a typical high-density vessel network, thus blocking the angiogenic switch in solid tumours in mice. Vasculature in tumours lacking myeloid-cell-derived VEGF-A was less tortuous, with increased pericyte coverage and decreased vessel length, indicating vascular normalization. In addition, loss of myeloid-derived VEGF-A decreases the phosphorylation of VEGF receptor 2 (VEGFR2) in tumours, even though overall VEGF-A levels in the tumours are unaffected. However, deletion of myeloid-cell VEGF-A resulted in an accelerated tumour progression in multiple subcutaneous isograft models and an autochthonous transgenic model of mammary tumorigenesis, with less overall tumour cell death and decreased tumour hypoxia. Furthermore, loss of myeloid-cell VEGF-A increased the susceptibility of tumours to chemotherapeutic cytotoxicity. This shows that myeloid-derived VEGF-A is essential for the tumorigenic alteration of vasculature and signalling to VEGFR2, and that these changes act to retard, not promote, tumour progression

    Discovery of a hepatitis C target and its pharmacological inhibitors by microfluidic affinity analysis

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    More effective therapies are urgently needed against hepatitis C virus (HCV), a major cause of viral hepatitis. We used in vitro protein expression and microfluidic affinity analysis to study RNA binding by the HCV transmembrane protein NS4B, which plays an essential role in HCV RNA replication. We show that HCV NS4B binds RNA and that this binding is specific for the 3' terminus of the negative strand of the viral genome with a dissociation constant (K(d)) of approximately 3.4 nM. A high-throughput microfluidic screen of a compound library identified 18 compounds that substantially inhibited binding of RNA by NS4B. One of these compounds, clemizole hydrochloride, was found to inhibit HCV RNA replication in cell culture that was mediated by its suppression of NS4B's RNA binding, with little toxicity for the host cell. These results yield new insight into the HCV life cycle and provide a candidate compound for pharmaceutical development

    Civic crowdfunding research: challenges, opportunities, and future agenda

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    Civic crowdfunding is a sub-type of crowdfunding through which citizens, in collaboration with government, fund projects providing a community service. Although in the early stages of development, civic crowdfunding is a promising area for both research and application due to its potential impact on citizen engagement, as well as its influence on the success of a wide range of civic projects ranging from physical structures to amenities and local services. However, the field remains under-addressed in academic research and underdeveloped in terms of the number of civic projects posted to crowdfunding platforms. Acknowledging these issues, we outline the history of civic crowdfunding and describe the current landscape, focusing on online crowdfunding platforms established specifically for the funding of civic projects (Citizinvestor, ioby, Neighbor.ly, Spacehive). The challenges and the opportunities of civic crowdfunding are examined, and its distinguishing characteristics are outlined, including a consideration of the impact of social media and platform features. We then propose a research agenda to help shape the future of this emergent field

    The association between retraction of the torn rotator cuff and increasing expression of hypoxia inducible factor 1α and vascular endothelial growth factor expression: an immunohistological study

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    <p>Abstract</p> <p>Background</p> <p>Differing levels of tendon retraction are found in full-thickness rotator cuff tears. The pathophysiology of tendon degeneration and retraction is unclear. Neoangiogenesis in tendon parenchyma indicates degeneration. Hypoxia inducible factor 1α (HIF) and vascular endothelial growth factor (VEGF) are important inducers of neoangiogenesis. Rotator cuff tendons rupture leads to fatty muscle infiltration (FI) and muscle atrophy (MA). The aim of this study is to clarify the relationship between HIF and VEGF expression, neoangiogenesis, FI, and MA in tendon retraction found in full-thickness rotator cuff tears.</p> <p>Methods</p> <p>Rotator cuff tendon samples of 33 patients with full-thickness medium-sized rotator cuff tears were harvested during reconstructive surgery. The samples were dehydrated and paraffin embedded. For immunohistological determination of VEGF and HIF expression, sample slices were strained with VEGF and HIF antibody dilution. Vessel density and vessel size were determined after Masson-Goldner staining of sample slices. The extent of tendon retraction was determined intraoperatively according to Patte's classification. Patients were assigned to 4 categories based upon Patte tendon retraction grade, including one control group. FI and MA were measured on standardized preoperative shoulder MRI.</p> <p>Results</p> <p>HIF and VEGF expression, FI, and MA were significantly higher in torn cuff samples compared with healthy tissue (p < 0.05). HIF and VEGF expression, and vessel density significantly increased with extent of tendon retraction (p < 0.05). A correlation between HIF/VEGF expression and FI and MA could be found (p < 0.05). There was no significant correlation between HIF/VEGF expression and neovascularity (p > 0.05)</p> <p>Conclusion</p> <p>Tendon retraction in full-thickness medium-sized rotator cuff tears is characterized by neovascularity, increased VEGF/HIF expression, FI, and MA. VEGF expression and neovascularity may be effective monitoring tools to assess tendon degeneration.</p

    Assessing the Effect of Piperacillin/Tazobactam on Hematological Parameters in Patients Admitted with Moderate or Severe Foot Infections

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    Introduction: Piperacillin/tazobactam is a commonly used antibiotic for the empirical treatment of severe diabetic foot infections. One of the most feared complications of this drug is the development of pancytopenia. The aim of this study was to determine whether the use of piperacillin/tazobactam caused any hematological changes in patients admitted with severe diabetes-related foot infections from a specialist multidisciplinary foot clinic. Specifically, looking at whether it caused anemia, leukopenia, neutropenia, or thrombocytopenia. Methods: A 1-year retrospective analysis of patients admitted to a tertiary care center for treatment of diabetes-related foot infection using piperacillin/tazobactam. Hematological indices, urea and electrolytes, and C-reactive protein (CRP) were recorded pretreatment, during treatment, and posttreatment. HbA1c, vitamin B12, folate, thyroid-stimulating hormone, and free thyroxin were also analyzed to exclude any potential confounders as a cause of pancytopenia. Results: A total of 154 patients were admitted between 1 January 2016 and 31 December 2016 who received piperacillin/tazobactam for severe diabetes-related foot infection. On admission, white cell count and CRP were raised and fell significantly within the first 48 h. Other hematological factors did not change. Five patients developed a mild pancytopenia, of which three were unexplained. Conclusion: In this relatively small cohort, pancytopenia did not occur. As such, piperacillin/tazobactam appeared to have a low risk of adverse hematological outcomes and remains the treatment of choice for severe diabetes-related foot infections

    Tinkering Evolution of Post-Transcriptional RNA Regulons: Puf3p in Fungi as an Example

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    Genome-wide studies of post-transcriptional mRNA regulation in model organisms indicate a “post-transcriptional RNA regulon” model, in which a set of functionally related genes is regulated by mRNA–binding RNAs or proteins. One well-studied post-transcriptional regulon by Puf3p functions in mitochondrial biogenesis in budding yeast. The evolution of the Puf3p regulon remains unclear because previous studies have shown functional divergence of Puf3p regulon targets among yeast, fruit fly, and humans. By analyzing evolutionary patterns of Puf3p and its targeted genes in forty-two sequenced fungi, we demonstrated that, although the Puf3p regulon is conserved among all of the studied fungi, the dedicated regulation of mitochondrial biogenesis by Puf3p emerged only in the Saccharomycotina clade. Moreover, the evolution of the Puf3p regulon was coupled with evolution of codon usage bias in down-regulating expression of genes that function in mitochondria in yeast species after genome duplication. Our results provide a scenario for how evolution like a tinker exploits pre-existing materials of a conserved post-transcriptional regulon to regulate gene expression for novel functional roles
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