2,578 research outputs found

    Peacemaking Embodied: Dance as a Connecting Thread Weaving Senegalese Ethnicities

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    Senegal remains one of the more peaceful, stable countries in Sub-Saharan Africa with little to no ethnic conflict or racial tension. Numerous social factors are credited with promoting this peace, ranging from political decisions to friendly jokes between different ethnic groups. Some artists claim that dance promotes positive relations between ethnicities; however, little to no academic literature reflects this social dynamic. Thus I have used formal interviews, informal interviews, observation, and participant observation to explore if Senegalese dance serves to promote peace between ethnic groups and, if so, why it has the power to serve this purpose. Through connecting the ideas of participants with observations of dances, I discerned that traditional Senegalese dance promotes peaceful relationships between ethnicities. This is due to widely-held associations with traditional dance, themes that emphasize commonality in humanity, and the effects of directly articulating dance as a peacebuilding art form

    Firearm Contagion: A New Look At History

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    The relative roles of CO2 and palaeogeography in determining Late Miocene climate: results from a terrestrial model-data comparison

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    The Late Miocene (∼11.6–5.3 Ma) palaeorecord provides evidence for a warmer and wetter climate than that of today and there is uncertainty in the palaeo-CO2 record of at least 150 ppmv. We present results from fully coupled atmosphere-ocean-vegetation simulations for the Late Miocene that examine the relative roles of palaeogeography (topography and ice sheet geometry) and CO2 concentration in the determination of Late Miocene climate through comprehensive terrestrial model-data comparisons. Assuming that the data accurately reflects the Late Miocene climate, and that the Late Miocene palaeogeographic reconstruction used in the model is robust, then results indicate that the proxy-derived precipitation differences between the Late Miocene and modern can be largely accounted for by the palaeogeographic changes alone. However, the proxy-derived temperatures differences between the Late Miocene and modern can only begin to be accounted for if we assume a palaeo-CO2 concentration towards the higher end of the range of estimates

    Identification of the Amino Acids 300–600 of IRS-2 as 14-3-3 Binding Region with the Importance of IGF-1/Insulin-Regulated Phosphorylation of Ser-573

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    Phosphorylation of insulin receptor substrate (IRS)-2 on tyrosine residues is a key event in IGF-1/insulin signaling and leads to activation of the PI 3-kinase and the Ras/MAPK pathway. Furthermore, phosphorylated serine/threonine residues on IRS-2 can induce 14-3-3 binding. In this study we searched IRS-2 for novel phosphorylation sites and investigated the interaction between IRS-2 and 14-3-3. Mass spectrometry identified a total of 24 serine/threonine residues on IRS-2 with 12 sites unique for IRS-2 while the other residues are conserved in IRS-1 and IRS-2. IGF-1 stimulation led to increased binding of 14-3-3 to IRS-2 in transfected HEK293 cells and this binding was prevented by inhibition of the PI 3-kinase pathway and an Akt/PKB inhibitor. Insulin-stimulated interaction between endogenous IRS-2 and 14-3-3 was observed in rat hepatoma cells and in mice liver after an acute insulin stimulus and refeeding. Using different IRS-2 fragments enabled localization of the IGF-1-dependent 14-3-3 binding region spanning amino acids 300–600. The 24 identified residues on IRS-2 included several 14-3-3 binding candidates in the region 300–600. Single alanine mutants of these candidates led to the identification of serine 573 as 14-3-3 binding site. A phospho-site specific antibody was generated to further characterize serine 573. IGF-1-dependent phosphorylation of serine 573 was reduced by inhibition of PI 3-kinase and Akt/PKB. A negative role of this phosphorylation site was implicated by the alanine mutant of serine 573 which led to enhanced phosphorylation of Akt/PKB in an IGF-1 time course experiment. To conclude, our data suggest a physiologically relevant role for IGF-1/insulin-dependent 14-3-3 binding to IRS-2 involving serine 573

    Hydrodynamic guiding for addressing subsets of immobilized cells and molecules in microfluidic systems

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    BACKGROUND: The interest in microfluidics and surface patterning is increasing as the use of these technologies in diverse biomedical applications is substantiated. Controlled molecular and cellular surface patterning is a costly and time-consuming process. Methods for keeping multiple separate experimental conditions on a patterned area are, therefore, needed to amplify the amount of biological information that can be retrieved from a patterned surface area. We describe, in three examples of biomedical applications, how this can be achieved in an open microfluidic system, by hydrodynamically guiding sample fluid over biological molecules and living cells immobilized on a surface. RESULTS: A microfluidic format of a standard assay for cell-membrane integrity showed a fast and dose-dependent toxicity of saponin on mammalian cells. A model of the interactions of human mononuclear leukocytes and endothelial cells was established. By contrast to static adhesion assays, cell-cell adhesion in this dynamic model depended on cytokine-mediated activation of both endothelial and blood cells. The microfluidic system allowed the use of unprocessed blood as sample material, and a specific and fast immunoassay for measuring the concentration of C-reactive protein in whole blood was demonstrated. CONCLUSION: The use of hydrodynamic guiding made multiple and dynamic experimental conditions on a small surface area possible. The ability to change the direction of flow and produce two-dimensional grids can increase the number of reactions per surface area even further. The described microfluidic system is widely applicable, and can take advantage of surfaces produced by current and future techniques for patterning in the micro- and nanometer scale

    Mapping a waste disposal site using Tellus airborne geophysical data

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    Leakage of fluids from unregulated and/or poorly engineered waste disposal sites poses a significant direct risk to groundwater quality. Characterisation and monitoring of waste disposal sites and potentially associated groundwater contaminant plumes are generally invasive, time-consuming and expensive, particularly when the extent of the plume is unknown. This study examines the value of incorporating of Tellus and Tellus Border airborne electromagnetic (AEM) data into current assessment protocols for the characterisation and monitoring of contaminant sources and subsurface contaminant plumes. The findings demonstrate the feasibility of using airborne and ground-based non-invasive geophysical data as part of existing tiered assessment protocols for prioritising suspected sites and for guiding targeted intrusive investigations and subsequent remediation efforts

    A mathematical model of glutathione metabolism

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    <p>Abstract</p> <p>Background</p> <p>Glutathione (GSH) plays an important role in anti-oxidant defense and detoxification reactions. It is primarily synthesized in the liver by the transsulfuration pathway and exported to provide precursors for in situ GSH synthesis by other tissues. Deficits in glutathione have been implicated in aging and a host of diseases including Alzheimer's disease, Parkinson's disease, cardiovascular disease, cancer, Down syndrome and autism.</p> <p>Approach</p> <p>We explore the properties of glutathione metabolism in the liver by experimenting with a mathematical model of one-carbon metabolism, the transsulfuration pathway, and glutathione synthesis, transport, and breakdown. The model is based on known properties of the enzymes and the regulation of those enzymes by oxidative stress. We explore the half-life of glutathione, the regulation of glutathione synthesis, and its sensitivity to fluctuations in amino acid input. We use the model to simulate the metabolic profiles previously observed in Down syndrome and autism and compare the model results to clinical data.</p> <p>Conclusion</p> <p>We show that the glutathione pools in hepatic cells and in the blood are quite insensitive to fluctuations in amino acid input and offer an explanation based on model predictions. In contrast, we show that hepatic glutathione pools are highly sensitive to the level of oxidative stress. The model shows that overexpression of genes on chromosome 21 and an increase in oxidative stress can explain the metabolic profile of Down syndrome. The model also correctly simulates the metabolic profile of autism when oxidative stress is substantially increased and the adenosine concentration is raised. Finally, we discuss how individual variation arises and its consequences for one-carbon and glutathione metabolism.</p

    Combined bezafibrate and medroxyprogesterone acetate: potential novel therapy for acute myeloid leukaemia

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    Background: The majority of acute myeloid leukaemia (AML) patients are over sixty years of age. With current treatment regimens, survival rates amongst these, and also those younger patients who relapse, remain dismal and novel therapies are urgently required. In particular, therapies that have anti-leukaemic activity but that, unlike conventional chemotherapy, do not impair normal haemopoiesis. Principal Findings: Here we demonstrate the potent anti-leukaemic activity of the combination of the lipid-regulating drug bezafibrate (BEZ) and the sex hormone medroxyprogesterone acetate (MPA) against AML cell lines and primary AML cells. The combined activity of BEZ and MPA (B/M) converged upon the increased synthesis and reduced metabolism of prostaglandin D2 (PGD2) resulting in elevated levels of the downstream highly bioactive, anti-neoplastic prostaglandin 15-deoxy Δ12,14 PGJ2 (15d-PGJ2). BEZ increased PGD2 synthesis via the generation of reactive oxygen species (ROS) and activation of the lipid peroxidation pathway. MPA directed prostaglandin synthesis towards 15d-PGJ2 by inhibiting the PGD2 11β -ketoreductase activity of the aldo-keto reductase AKR1C3, which metabolises PGD2 to 9α11β-PGF2α. B/M treatment resulted in growth arrest, apoptosis and cell differentiation in both AML cell lines and primary AML cells and these actions were recapitulated by treatment with 15d-PGJ2. Importantly, the actions of B/M had little effect on the survival of normal adult myeloid progenitors. Significance: Collectively our data demonstrate that B/M treatment of AML cells elevated ROS and delivered the anti-neoplastic actions of 15d-PGJ2. These observations provide the mechanistic rationale for the redeployment of B/M in elderly and relapsed AML

    Significant Factors in the Inkjet Manufacture of Frequency Selective Surfaces

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    Additive fabrication of electromagnetic structures by inkjet printing technology is both cost effective and compatible with a wide range environmentally-friendly substrates, enabling fabrication of frequency selective surface arrays with line dimensions less than 0.1 mm; difficult to achieve with conventional subtractive techniques. Several approaches have been investigated in order to produce low-cost frequency selective panels with acceptable level of isolation, such as savings in ink by depositing it at the edges of dipole elements where the surface current tends to maximize. The FSS transmission characteristics were improved by jetting multiple ink layers on the whole elements and at the edges. The electrical resistance of various arrays have been measured and analysed and has been used to assess the performances of the FSS

    Need for Cognition and its relation to academic achievement in different learning environments

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    The present study investigates how Need for Cognition (NFC), an individual's tendency to engage in and enjoy thinking, relates to academic achievement in 9th grade students (N = 3.355) attending different school tracks to understand whether school track moderates this relation when controlling for student background variables. Using structural regression analyses, our findings revealed small and significant positive relations between NFC and academic achievement in German, French and Math. Relations were strongest in the highest and weakest in the lowest track. No significant track difference between the highest and the intermediary track could be identified; significant differences of small effect size between the intermediary and the lowest track were found in favor of the intermediary track in the relation between NFC and academic achievement in German and Math. These findings underpin the importance of NFC in academic settings, while highlighting that the relation between NFC and achievement varies with the characteristics of different learning environments
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