2,922 research outputs found

    A desalination guide for South African municipal engineers

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    Municipalities need to develop Water Services Development Plans (WSDPs) as a first requirement in their budgetary process, and need to be made aware of the options that are available to provide more than basic services. While 25./personEd has been set as the minimum basic water supply and while many consumers receive far in excess of this amount, there are areas of the country where water of acceptable quality is not available for household use. However, in many areas adequate quantities of saline water may be, or are, readily available. This is especially the case for coastal cities and towns.The cost of treating water is only part of the total cost of making drinking water available to the consumer. This together with the fact that membrane technology is becoming more affordable and that energy can be recovered, makes the desalination of water viable for domestic purposes.A desk study, funded by the Department Water Affairs and Forestry and managed by the Water Research Commission, was undertaken to identify treatment options for desalinating seawater from both the Indian and Atlantic oceans or brackish water from boreholes. The specific objectives of the project were to compile a Guide on the technologies that can be implemented in South Africa to treat saline water to drinking water standards, to identify the pretreatment that is necessary, and to present guidelines on operational, maintenance, management and environmental aspects relevant to the selection and use of these technologies. An important aspect was also to quantify the capital and operating costs for planning purposes of the different components needed to successfully bring the water to the accepted standards for potable and domestic use.Of particular importance for the South African application was to identify the level of skills required for daily operation of the desalination plants, the level of skills required to provide technical back-up and advice, and to identify and advise on the competencies, training needs and capacity building required at operator and management levels. Lastly, the relevant local environmental legislations governing desalination were also identified

    Dasatinib inhibits CXCR4 signaling in chronic lymphocytic leukaemia cells and impairs migration towards CXCL12

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    Chemokines and their ligands play a critical role in enabling chronic lymphocytic leukaemia (CLL) cells access to protective microenvironmental niches within tissues, ultimately resulting in chemoresistance and relapse: disruption of these signaling pathways has become a novel therapeutic approach in CLL. The tyrosine kinase inhibitor dasatinib inhibits migration of several cell lines from solid-organ tumours, but effects on CLL cells have not been reported. We studied the effect of clinically achievable concentrations of dasatinib on signaling induced by the chemokine CXCL12 through its' receptor CXCR4, which is highly expressed on CLL cells. Dasatinib pre-treatment inhibited Akt and ERK phosphorylation in CLL cells upon stimulation with CXCL12. Dasatinib also significantly diminished the rapid increase in actin polymerisation observed in CLL cells following CXCL12 stimulation. Moreover, the drug significantly inhibited chemotaxis in a transwell assay, and reduced the percentage of cells able to migrate beneath a CXCL12-expressing murine stromal cell line. Dasatinib also abrogated the anti-apoptotic effect of prolonged CXCL12 stimulation on cultured CLL cells. These data suggest that dasatinib, akin to other small molecule kinase inhibitors targeting the B-cell receptor signaling pathway, may redistribute CLL cells from protective tissue niches to the peripheral blood, and support the investigation of dasatinib in combination strategies

    Evolutionary history of the Nesophontidae, the last unplaced Recent mammal family

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    The mammalian evolutionary tree has lost several major clades through recent human-caused extinctions. This process of historical biodiversity loss has particularly affected tropical island regions such as the Caribbean, an area of great evolutionary diversification but poor molecular preservation. The most enigmatic of the recently extinct endemic Caribbean mammals are the Nesophontidae, a family of morphologically plesiomorphic lipotyphlan insectivores with no consensus on their evolutionary affinities, and which constitute the only major recent mammal clade to lack any molecular information on their phylogenetic placement. Here, we use a palaeogenomic approach to place Nesophontidae within the phylogeny of recent Lipotyphla. We recovered the near-complete mitochondrial genome and sequences for 17 nuclear genes from a ∼750-year-old Hispaniolan Nesophontes specimen, and identify a divergence from their closest living relatives, the Solenodontidae, more than 40 million years ago. Nesophontidae is thus an older distinct lineage than many extant mammalian orders, highlighting not only the role of island systems as “museums” of diversity that preserve ancient lineages, but also the major human-caused loss of evolutionary history

    The PI3-kinase delta inhibitor idelalisib (GS-1101) targets integrin-mediated adhesion of chronic lymphocytic leukemia (CLL) cell to endothelial and marrow stromal cells

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    CLL cell trafficking between blood and tissue compartments is an integral part of the disease process. Idelalisib, a phosphoinositide 3-kinase delta (PI3K\u3b4) inhibitor causes rapid lymph node shrinkage, along with an increase in lymphocytosis, prior to inducing objective responses in CLL patients. This characteristic activity presumably is due to CLL cell redistribution from tissues into the blood, but the underlying mechanisms are not fully understood. We therefore analyzed idelalisib effects on CLL cell adhesion to endothelial and bone marrow stromal cells (EC, BMSC). We found that idelalisib inhibited CLL cell adhesion to EC and BMSC under static and shear flow conditions. TNF\u3b1-induced VCAM-1 (CD106) expression in supporting layers increased CLL cell adhesion and accentuated the inhibitory effect of idelalisib. Co-culture with EC and BMSC also protected CLL from undergoing apoptosis, and this EC- and BMSC-mediated protection was antagonized by idelalisib. Furthermore, we demonstrate that CLL cell adhesion to EC and VLA-4 (CD49d) resulted in the phosphorylation of Akt, which was sensitive to inhibition by idelalisib. These findings demonstrate that idelalisib interferes with integrin-mediated CLL cell adhesion to EC and BMSC, providing a novel mechanism to explain idelalisib-induced redistribution of CLL cells from tissues into the blood

    Conveying Audience Emotions through Humanoid Robot Gestures to an Orchestra during a Live Musical Exhibition

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    In the last twenty years, robotics have been applied in many heterogeneous contexts. Among them, the use of humanoid robots during musical concerts have been proposed and investigated by many authors. In this paper, we propose a contribution in the area of robotics application in music, consisting of a system for conveying audience emotions during a live musical exhibition, by means of a humanoid robot. In particular, we provide all spectators with a mobile app, by means of which they can select a specific color while listening to a piece of music (act). Each color is mapped to an emotion, and the audience preferences are then processed in order to select the next act to be played. This decision, based on the overall emotion felt by the audience, is then communicated by the robot through body gestures to the orchestra. Our first results show that spectators enjoy such kind of interactive musical performance, and are encouraging for further investigations

    Uncertainty quantification for kinetic models in socio-economic and life sciences

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    Kinetic equations play a major rule in modeling large systems of interacting particles. Recently the legacy of classical kinetic theory found novel applications in socio-economic and life sciences, where processes characterized by large groups of agents exhibit spontaneous emergence of social structures. Well-known examples are the formation of clusters in opinion dynamics, the appearance of inequalities in wealth distributions, flocking and milling behaviors in swarming models, synchronization phenomena in biological systems and lane formation in pedestrian traffic. The construction of kinetic models describing the above processes, however, has to face the difficulty of the lack of fundamental principles since physical forces are replaced by empirical social forces. These empirical forces are typically constructed with the aim to reproduce qualitatively the observed system behaviors, like the emergence of social structures, and are at best known in terms of statistical information of the modeling parameters. For this reason the presence of random inputs characterizing the parameters uncertainty should be considered as an essential feature in the modeling process. In this survey we introduce several examples of such kinetic models, that are mathematically described by nonlinear Vlasov and Fokker--Planck equations, and present different numerical approaches for uncertainty quantification which preserve the main features of the kinetic solution.Comment: To appear in "Uncertainty Quantification for Hyperbolic and Kinetic Equations

    Stereotypical Chronic Lymphocytic Leukemia B-Cell Receptors Recognize Survival Promoting Antigens on Stromal Cells

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    Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world. Survival of CLL cells depends on their close contact with stromal cells in lymphatic tissues, bone marrow and blood. This microenvironmental regulation of CLL cell survival involves the stromal secretion of chemo- and cytokines as well as the expression of adhesion molecules. Since CLL survival may also be driven by antigenic stimulation through the B-cell antigen receptor (BCR), we explored the hypothesis that these processes may be linked to each other. We tested if stromal cells could serve as an antigen reservoir for CLL cells, thus promoting CLL cell survival by stimulation through the BCR. As a proof of principle, we found that two CLL BCRs with a common stereotyped heavy chain complementarity-determining region 3 (previously characterized as “subset 1”) recognize antigens highly expressed in stromal cells – vimentin and calreticulin. Both antigens are well-documented targets of autoantibodies in autoimmune disorders. We demonstrated that vimentin is displayed on the surface of viable stromal cells and that it is present and bound by the stereotyped CLL BCR in CLL-stroma co-culture supernatant. Blocking the vimentin antigen by recombinant soluble CLL BCR under CLL-stromal cell co-culture conditions reduces stroma-mediated anti-apoptotic effects by 20–45%. We therefore conclude that CLL BCR stimulation by stroma-derived antigens can contribute to the protective effect that the stroma exerts on CLL cells. This finding sheds a new light on the understanding of the pathobiology of this so far mostly incurable disease

    Mathematical imaging methods for mitosis analysis in live-cell phase contrast microscopy

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    In this paper we propose a workflow to detect and track mitotic cells in time-lapse microscopy image sequences. In order to avoid the requirement for cell lines expressing fluorescent markers and the associated phototoxicity, phase contrast microscopy is often preferred over fluorescence microscopy in live-cell imaging. However, common specific image characteristics complicate image processing and impede use of standard methods. Nevertheless, automated analysis is desirable due to manual analysis being subjective, biased and extremely time-consuming for large data sets. Here, we present the following workflow based on mathematical imaging methods. In the first step, mitosis detection is performed by means of the circular Hough transform. The obtained circular contour subsequently serves as an initialisation for the tracking algorithm based on variational methods. It is sub-divided into two parts: in order to determine the beginning of the whole mitosis cycle, a backwards tracking procedure is performed. After that, the cell is tracked forwards in time until the end of mitosis. As a result, the average of mitosis duration and ratios of different cell fates (cell death, no division, division into two or more daughter cells) can be measured and statistics on cell morphologies can be obtained. All of the tools are featured in the user-friendly MATLAB®Graphical User Interface MitosisAnalyser.JSG acknowledges support by the NIHR Cambridge Biomedical Research Centre and would like to thank Hendrik Dirks, Fjedor Gaede [45] and Jonas Geiping [46] for fruitful discussions in the context of a practical course at WWU Münster in 2014 and significant speed-up and GPU implementation of earlier versions of the code. JSG and MB would like to thank Michael Möller for providing the basic tracking code and acknowledge support by ERC via Grant EU FP 7 - ERC Consolidator Grant 615216 LifeInverse. MB acknowledges further support by the German Science Foundation DFG via Cells-in-Motion Cluster of Excellence. CBS acknowledges support from the EPSRC grant Nr. EP/M00483X/1, from the Leverhulme grant “Breaking the non-convexity barrier”, from the EPSRC Centre for Mathematical And Statistical Analysis Of Multimodal Clinical Imaging grant Nr. EP/N014588/1, and the Cantab Capital Institute for the Mathematics of Information. JAH, SBK, JAP, AS and SR were funded by Cancer Research UK, The University of Cambridge and Hutchison Whampoa Ltd. SBK also received funding from Pancreatic Cancer UK
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