347 research outputs found

    WAT-A-GAME: sharing water and policies in your own basin

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    40th Annual Conference, Int. Simulation And Gaming Association, Singapour, SGP, 29-/06/2009 - 03/07/2009International audienceAfter having designed and used various games for learning and supporting water management and governance, many similarities appear. However, the components, topologies, and social and political setting of the basins are different. Therefore we have started designing andvalidating a new generic game platform, WAT-A-GAME, alias AMANZI. This new game aims at facilitating exploration and transformation of water management and water use at the small catchment scale. It gives a simple but enlightening view of the various consequences of individual and collective choices, including regulation policies. After comparing it with some previous games, we discuss its main rationales and features. We show how it can be adapted to very different settings, how players can usefully contribute to designing an instance, and how it can especially address dialogue between multi-level stakeholders. We describe an application in South-Africa, in the Inkomati basin and the preliminary results of this instance

    Investigation on the thermal gelation of Chitosan/\u3b2-Glycerophosphate solutions

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    This work deals with the effect of temperature on the thermal-gelation process of water solutions containing chitosan \u3b2-glycerolphosphate disodium salt hydrate. In particular, the attention is focused on the role played by temperature on the gel final properties, a very important aspect in the frame of drug delivery systems. The study was performed by combining rheology and low field nuclear magnetic resonance, two approaches that revealed to be highly synergic as they can detect different aspects of the developing polymeric network. This study indicates that 30 \ub0C represent a sort of threshold for both the gelation kinetics and the gel final properties. Indeed, above this temperature, gelation kinetics was rapid and yielded to a strong gel. On the contrary, a slow kinetics and a final weak gel occurred below 30 \ub0C. Finally, rheology and low field NMR allowed, independently, evaluating the time evolution of the network mesh size upon gelation

    Drug Nanocrystals: Theoretical Background of Solubility Increase and Dissolution Rate Enhancement

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    The peculiar higher solubility of drug nanocrystals compared to macrocrystals appeals to the pharmaceutical field. Indeed, until now, about 70 % of the potential drug candidates are discarded due to low bioavailability related with poor solubility in water. Since a modern and efficient design strategy for nanocrystal-based delivery systems requires the knowledge of the theoretical relation between nanocrystal size and solubility, the aim of this paper is to build up a physically-oriented thermodynamic model relating to nanocrystal dimensions with their melting temperature, enthalpy, solubility and dissolution rate. In particular, the developed model will be applied to vinpocetine, a poorly soluble drug used in the treatment of various types of cerebrovascular circulatory disorders

    Drug Nanocrystals: Theoretical Background of Solubility Increase and Dissolution Rate Enhancement

    Get PDF
    The peculiar higher solubility of drug nanocrystals compared to macrocrystals appeals to the pharmaceutical field. Indeed, until now, about 70 % of the potential drug candidates are discarded due to low bioavailability related with poor solubility in water. Since a modern and efficient design strategy for nanocrystal-based delivery systems requires the knowledge of the theoretical relation between nanocrystal size and solubility, the aim of this paper is to build up a physically-oriented thermodynamic model relating to nanocrystal dimensions with their melting temperature, enthalpy, solubility and dissolution rate. In particular, the developed model will be applied to vinpocetine, a poorly soluble drug used in the treatment of various types of cerebrovascular circulatory disorders

    Endocytosis of the Anthrax Toxin Is Mediated by Clathrin, Actin and Unconventional Adaptors

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    The anthrax toxin is a tripartite toxin, where the two enzymatic subunits require the third subunit, the protective antigen (PA), to interact with cells and be escorted to their cytoplasmic targets. PA binds to cells via one of two receptors, TEM8 and CMG2. Interestingly, the toxin times and triggers its own endocytosis, in particular through the heptamerization of PA. Here we show that PA triggers the ubiquitination of its receptors in a β-arrestin-dependent manner and that this step is required for clathrin-mediated endocytosis. In addition, we find that endocytosis is dependent on the heterotetrameric adaptor AP-1 but not the more conventional AP-2. Finally, we show that endocytosis of PA is strongly dependent on actin. Unexpectedly, actin was also found to be essential for efficient heptamerization of PA, but only when bound to one of its 2 receptors, TEM8, due to the active organization of TEM8 into actin-dependent domains. Endocytic pathways are highly modular systems. Here we identify some of the key players that allow efficient heptamerization of PA and subsequent ubiquitin-dependent, clathrin-mediated endocytosis of the anthrax toxin

    Designed Azolopyridinium Salts Block Protective Antigen Pores In Vitro and Protect Cells from Anthrax Toxin

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    Background:Several intracellular acting bacterial protein toxins of the AB-type, which are known to enter cells by endocytosis, are shown to produce channels. This holds true for protective antigen (PA), the binding component of the tripartite anthrax-toxin of Bacillus anthracis. Evidence has been presented that translocation of the enzymatic components of anthrax-toxin across the endosomal membrane of target cells and channel formation by the heptameric/octameric PA63 binding/translocation component are related phenomena. Chloroquine and some 4-aminoquinolones, known as potent drugs against Plasmodium falciparium infection of humans, block efficiently the PA63-channel in a dose dependent way.Methodology/Principal Findings:Here we demonstrate that related positively charged heterocyclic azolopyridinium salts block the PA63-channel in the μM range, when both, inhibitor and PA63 are added to the same side of the membrane, the cis-side, which corresponds to the lumen of acidified endosomal vesicles of target cells. Noise-analysis allowed the study of the kinetics of the plug formation by the heterocycles. In vivo experiments using J774A.1 macrophages demonstrated that the inhibitors of PA63-channel function also efficiently block intoxication of the cells by the combination lethal factor and PA63 in the same concentration range as they block the channels in vitro.Conclusions/Significance:These results strongly argue in favor of a transport of lethal factor through the PA63-channel and suggest that the heterocycles used in this study could represent attractive candidates for development of novel therapeutic strategies against anthrax. © 2013 Beitzinger et al

    Pressure-induced reconstructive phase transition in Cd3As2

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    Cadmium arsenide Cd3As2 hosts massless Dirac electrons in its ambient-conditions tetragonal phase. We report X-ray diffraction and electrical resistivity measurements of Cd3As2 upon cycling pressure beyond the critical pressure of the tetragonal phase and back to ambient conditions. We find that at room temperature the transition between the low- and high-pressure phases results in large microstrain and reduced crystallite size both on rising and falling pressure. This leads to non-reversible electronic properties including self-doping associated with defects and a reduction of the electron mobility by an order of magnitude due to increased scattering. Our study indicates that the structural transformation is sluggish and shows a sizable hysteresis of over 1 GPa. Therefore, we conclude that the transition is first-order reconstructive, with chemical bonds being broken and rearranged in the high-pressure phase. Using the diffraction measurements we demonstrate that annealing at ~200 deg. C greatly improves the crystallinity of the high-pressure phase. We show that its Bragg peaks can be indexed as a primitive orthorhombic lattice with a_HP = 8.68 Ă…, b_HP = 17.15 Ă… and c_HP = 18.58 Ă…. The diffraction study indicates that during the structural transformation a new phase with another primitive orthorhombic structure may be also stabilized by deviatoric stress, providing an additional venue for tuning the unconventional electronic states in Cd3As2

    Rheological Study on Crosslinking and Gelation of Amidated Carboxymethylcellulose Solutions

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    Viscosupplementation is an intra-articular symptomatic treatment of mild osteoarthritis in synovial joints. It normally consists of single or repeated injections of hyaluronan- based fluids, aimed to restore desirable viscoelastic behavior of the synovial fluid and thus recreate the intra-articular joint homeostasis. Recently, a novel viscosupplement based on amidated carboxymethylcellulose has been developed by blending the soluble polymer (CMCAp) with its crosslinked derivative (CMCAg) in appropriate proportions and concentrations in order to ensure an optimal combination of flow behavior and viscoelastic properties. The present work is concerned with the rheological monitoring of the crosslinking reaction performed at 25 °C by starting from aqueous CMCAp solutions in order to describe the time evolution of the linear viscoelastic moduli occurring along the whole gelation process and to individuate how the polymer concentration affects the mechanical response at the sol-gel transition and the fractal dimension of the incipient polymeric network
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