115 research outputs found

    Is \u27community\u27 important for Community Information Systems?

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    Community information systems have the power to transform communities. However, without fully understanding the pre-requisite factors affecting community information system viability, and the complex relationships between these factors, communities struggle to manage such projects in a way that leads to viable systems that deliver real benefits. This paper develops and presents a Model of Community Information System Viability Pre-requisite Factors, based on both existing literature and the study of three community information system projects. This Model represents the generic factors that inform viability (i.e. leadership, active membership, funding, awareness, and system design and functionality), and also considers the impact of community context. This study argues that the viability of a Community Information System cannot be considered in isolation. All factors are directly impacted by the value of the Community Information System to the community. Management can also heavily impact on the success of a Community Information System

    CRP Enhances the Innate Killing Mechanisms Phagocytosis and ROS Formation in a Conformation and Complement-Dependent Manner

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    Phagocytosis and the formation of reactive oxygen species (ROS) in phagocytic leukocytes are an effective killing mechanism of the innate host defense. These cellular processes of innate immunity function in a complex interplay with humoral factors. C-reactive protein (CRP) in its activated, monomeric isoform (mCRP) has been shown to activate immune cells via the classical complement pathway. We investigated the complement-dependent effects of monomeric CRP (mCRP) on neutrophils and monocyte subtypes using complement-specific inhibitors by both flow cytometry and confocal fluorescence microscopy. We demonstrate that CRP-induced ROS generation is a conformation-specific and complement-dependent process in leukocyte subsets with classical monocytes as the primary source of ROS amongst human monocyte subsets. Elucidation of this complex interplay of CRP and complement in inflammation pathophysiology might help to improve anti-inflammatory therapeutic strategies

    When who and how matter: explaining the success of referendums in Europe

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    This article aims to identify the institutional factors that make a referendum successful. This comparative analysis seeks to explain the success of top-down referendums organized in Europe between 2001 and 2013. It argues and tests for the main effect of three institutional factors (popularity of the initiator, size of parliamentary majority, and political cues during referendum campaigns) and controls for the type of referendum and voter turnout. The analysis uses data collected from referendums and electoral databases, public opinion surveys, and newspaper articles. Results show that referendums proposed by a large parliamentary majority or with clear messages from political parties during campaign are likely to be successful

    Increasing impacts of land use on biodiversity and carbon sequestration driven by population and economic growth

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    Biodiversity and ecosystem service losses driven by land-use change are expected to intensify as a growing and more affluent global population requires more agricultural and forestry products, and teleconnections in the global economy lead to increasing remote environmental responsibility. By combining global biophysical and economic models, we show that, between the years 2000 and 2011, overall population and economic growth resulted in increasing total impacts on bird diversity and carbon sequestration globally, despite a reduction of land-use impacts per unit of gross domestic product (GDP). The exceptions were North America and Western Europe, where there was a reduction of forestry and agriculture impacts on nature accentuated by the 2007-2008 financial crisis. Biodiversity losses occurred predominantly in Central and Southern America, Africa and Asia with international trade an important and growing driver. In 2011, 33% of Central and Southern America and 26% of Africa's biodiversity impacts were driven by consumption in other world regions. Overall, cattle farming is the major driver of biodiversity loss, but oil seed production showed the largest increases in biodiversity impacts. Forestry activities exerted the highest impact on carbon sequestration, and also showed the largest increase in the 2000-2011 period. Our results suggest that to address the biodiversity crisis, governments should take an equitable approach recognizing remote responsibility, and promote a shift of economic development towards activities with low biodiversity impacts

    Rituximab and obinutuzumab differentially hijack the B-cell receptor and NOTCH1 signaling pathways

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    The anti-CD20 monoclonal antibodies rituximab and obinutuzumab differ in their mechanisms of action, with obinutuzumab evoking greater direct B-cell death. To characterize the signaling processes responsible for improved B-cell killing by obinutuzumab, we undertook a phosphoproteomics approach and demonstrate that rituximab and obinutuzumab differentially activate pathways downstream of the B-cell receptor. While both antibodies induce strong ERK and MYC activation sufficient to promote cell cycle arrest and B-cell death, obinutuzumab exceeds rituximab in supporting apoptosis induction by means of aberrant SYK phosphorylation. In contrast, rituximab elicits stronger anti-apoptotic signals by activating AKT, impairing pro-apoptotic BAD, and by releasing membrane-bound NOTCH1 to up-regulate pro-survival target genes. As a consequence, rituximab appears to reinforce BCL2-mediated apoptosis resistance. The unexpected complexity and differences by which rituximab and obinutuzumab interfere with signaling pathways essential for lymphoma pathogenesis and treatment provide important impetus to optimize and personalize the application of different anti-CD20 treatments

    GRIPS - Gamma-Ray Imaging, Polarimetry and Spectroscopy

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    We propose to perform a continuously scanning all-sky survey from 200 keV to 80 MeV achieving a sensitivity which is better by a factor of 40 or more compared to the previous missions in this energy range. The Gamma-Ray Imaging, Polarimetry and Spectroscopy (GRIPS) mission addresses fundamental questions in ESA's Cosmic Vision plan. Among the major themes of the strategic plan, GRIPS has its focus on the evolving, violent Universe, exploring a unique energy window. We propose to investigate γ\gamma-ray bursts and blazars, the mechanisms behind supernova explosions, nucleosynthesis and spallation, the enigmatic origin of positrons in our Galaxy, and the nature of radiation processes and particle acceleration in extreme cosmic sources including pulsars and magnetars. The natural energy scale for these non-thermal processes is of the order of MeV. Although they can be partially and indirectly studied using other methods, only the proposed GRIPS measurements will provide direct access to their primary photons. GRIPS will be a driver for the study of transient sources in the era of neutrino and gravitational wave observatories such as IceCUBE and LISA, establishing a new type of diagnostics in relativistic and nuclear astrophysics. This will support extrapolations to investigate star formation, galaxy evolution, and black hole formation at high redshifts.Comment: to appear in Exp. Astron., special vol. on M3-Call of ESA's Cosmic Vision 2010; 25 p., 25 figs; see also www.grips-mission.e

    A database of naturally occurring human urinary peptides and proteins for use in clinical applications

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    Owing to its availability, ease of collection and correlation with (patho-) physiology, urine is an attractive source for clinical proteomics. However, the lack of comparable datasets from large cohorts has greatly hindered development in this field. Here we report the establishment of a high resolution proteome database of naturally occurring human urinary peptides and proteins - ranging from 800-17,000 Da - from over 3,600 individual samples using capillary electrophoresis coupled to mass spectrometry, yielding an average of 1,500 peptides per sample. All processed data were deposited in an SQL database, currently containing 5,010 relevant unique urinary peptides that serve as classifiers for diagnosis and monitoring of diseases, including kidney and vascular diseases. Of these, 352 have been sequenced to date. To demonstrate the applicability of this database, two examples of disease diagnosis were provided: For renal damage diagnosis, patients with a specific renal disease were identified with high specificity and sensitivity in a blinded cohort of 131 individuals. We further show definition of biomarkers specific for immunosuppression and complications after transplantation (Kaposi's sarcoma). Due to its high information content, this database will be a powerful tool for the validation of biomarkers for both renal and non-renal diseases

    CD40L Deficiency Attenuates Diet-Induced Adipose Tissue Inflammation by Impairing Immune Cell Accumulation and Production of Pathogenic IgG-Antibodies

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    BACKGROUND: Adipose tissue inflammation fuels the metabolic syndrome. We recently reported that CD40L--an established marker and mediator of cardiovascular disease--induces inflammatory cytokine production in adipose cells in vitro. Here, we tested the hypothesis that CD40L deficiency modulates adipose tissue inflammation in vivo. METHODOLOGY/PRINCIPAL FINDINGS: WT or CD40L(-/-) mice consumed a high fat diet (HFD) for 20 weeks. Inflammatory cell recruitment was impaired in mice lacking CD40L as shown by a decrease of adipose tissue macrophages, B-cells, and an increase in protective T-regulatory cells. Mechanistically, CD40L-deficient mice expressed significantly lower levels of the pro-inflammatory chemokine MCP-1 both, locally in adipose tissue and systemically in plasma. Moreover, levels of pro-inflammatory IgG-antibodies against oxidized lipids were reduced in CD40L(-/-) mice. Also, circulating low-density lipoproteins and insulin levels were lower in CD40L(-/-) mice. However, CD40L(-/-) mice consuming HFD were not protected from the onset of diet-induced obesity (DIO), insulin resistance, and hepatic steatosis, suggesting that CD40L selectively limits the inflammatory features of diet-induced obesity rather than its metabolic phenotype. Interestingly, CD40L(-/-) mice consuming a low fat diet (LFD) showed both, a favorable inflammatory and metabolic phenotype characterized by diminished weight gain, improved insulin tolerance, and attenuated plasma adipokine levels. CONCLUSION: We present the novel finding that CD40L deficiency limits adipose tissue inflammation in vivo. These findings identify CD40L as a potential mediator at the interface of cardiovascular and metabolic disease
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