305 research outputs found

    Fluid effects in model granular flows

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    Pore fluid plays a crucial role in many granular flows, especially those in geophysical settings. However, the transition in behaviour between dry flows and fully saturated flows and the underlying physics that relate to this are poorly understood. In this paper, we report the results of small-scale flume experiments using monodisperse granular particles with varying water content and volume in which the basal pore pressure, total pressure, flow height and velocity profile were measured at a section. We compare the results with theoretical profiles for granular flow and with flow regimes based on dimensional analysis. The runout and the centre of mass were also calculated from the deposit surface profiles. As the initial water content by mass was increased from zero to around 10%, we first observed a drop in mobility by approximately 50%, as surface tension caused cohesive behaviour due to matric suction. As the water content was further increased up to 45%, the mobility also increased dramatically, with increased flow velocity up to 50%, increased runout distance up to 240% and reduced travel angle by up to 10° compared to the dry case. These effects can be directly related to the basal pore pressure, with both negative pressures and positive pore pressures being measured relative to atmospheric during the unsteady flow. We find that the initial flow volume plays a role in the development of relative pore pressure, such that, at a fixed relative water content, larger flows exhibit greater positive pore pressures, greater velocities and greater relative runout distances. This aligns with many other granular experiments and field observations. Our findings suggest that the fundamental role of the pore fluid is to reduce frictional contact forces between grains thus increasing flow velocity and bulk mobility. While this can occur by the development of excess pore pressure, it can also occur where the positive pore pressure is not in excess of hydrostatic, as shown here, since buoyancy and lubrication alone will reduce frictional forces

    Measurement of matric suction using tensiometric and axis translation techniques

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    Experimental equipment for the measurement of matric suction in unsaturated soils using hydraulic tensiometers and the axis translation technique share a common working principle; that is, the measurement of a pressure differential across a high air entry porous ceramic. In this paper, the current state of the art in these two suction measurement techniques is presented and discussed together with the underlying physics thereby giving the reader the necessary basis to use and interpret the results obtained from those two techniques

    The Importance of Partnership in the Rollout of Triple-Drug Therapy to Eliminate Lymphatic Filariasis in the Pacific

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    We discuss the experience of some Pacific island countries in introducing the new WHO-recommended treatment protocol for lymphatic filariasis—a triple-drug therapy composed of ivermectin, diethylcarbamazine, and albendazole. The successful rollout of the new treatment protocol was dependent on strong partnerships among these countries’ ministries of health, WHO, and other stakeholders. Effective communication among these partners allowed for lessons learned to cross borders and have a positive impact on the experiences of other countries. We also describe various challenges confronted during this process and the ways these countries overcame them

    ‘Forgotten Europeans’: transnational minority activism in the age of European integration

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    YesThis article examines transnational activism by coalitions of national minorities in Europe from the early 20th century to the present, setting this within the broader ‘security versus democracy dilemma’ that continues to surround international discussions on minority rights. Specifically, we analyse two organisations – the European Nationalities Congress (1925–1938) and the Federal Union of European Nationalities (1949–) – which, while linked, have never been subject to a detailed comparison based on primary sources. In so far as comparisons do exist, they present these bodies in highly negative terms, as mere fronts for inherently particularistic nationalisms that threaten political stability, state integrity and peace. Our more in‐depth analysis provides a fresh and more nuanced perspective: it shows that, in both cases, concepts of European integration and ‘unity in diversity’ have provided the motivating goals and frameworks for transnational movements advocating common rights for all minorities and seeking positive interaction with the interstate world

    Role of the p53/p21 system in the response of human colon carcinoma cells to Doxorubicin

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    BACKGROUND: Colon adenocarcinomas are refractory to a number of widely used anticancer agents. Multifactorial mechanisms have been implicated in this intrinsically resistant phenotype, including deregulation of cell death pathways. In this regard, the p53 protein has a well established role in the control of tumor cell response to DNA damaging agents; however, the relationship between p53-driven genes and drug sensitivity remains controversial. The present study investigates the role of the p53/p21 system in the response of human colon carcinoma cells to treatment with the cytotoxic agent doxorubicin (DOX) and the possibility to modify the therapeutic index of DOX by modulation of p53 and/or p21 protein levels. METHODS: The relationship between p53 and p21 protein levels and the cytotoxic effect of DOX was investigated, by MTT assay and western blot analysis, in HCT116 (p53-positive) and HT29 (p53-negative) colon cancer cells. We then assessed the effects of DOX in two isogenic cell lines derived from HCT116 by abrogating the expression and/or function of p53 and p21 (HCT116-E6 and HCT116 p21-/-, respectively). Finally, we evaluated the effect of pre-treatment with the piperidine nitroxide Tempol (TPL), an agent that was reported to induce p21 expression irrespective of p53 status, on the cytotoxicity of DOX in the four cell lines. Comparisons of IC50 values and apoptotic cell percentages were performed by ANOVA and Bonferroni's test for independent samples. C.I. calculations were performed by the combination Index method. RESULTS: Our results indicate that, in the colon carcinoma cell lines tested, sensitivity to DOX is associated with p21 upregulation upon drug exposure, and DOX cytotoxicity is potentiated by pre-treatment with TPL, but only in those cell lines in which p21 can be upregulated. CONCLUSIONS: p21 induction may significantly contribute to the response of colon adenocarcinomas cells to DOX treatment; and small molecules that can exploit p53-independent pathways for p21 induction, such as TPL, may find a place in chemotherapeutic protocols for the clinical management of colorectal cancer, where p53 function is often lost, due to genetic or epigenetic defects or to post-transcriptional inactivating mechanisms
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