8,257 research outputs found

    Challenges in the Pharmacotherapy of Urogenital Disorders

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    Collisional Formation and Modeling of Asteroid Families

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    In the last decade, thanks to the development of sophisticated numerical codes, major breakthroughs have been achieved in our understanding of the formation of asteroid families by catastrophic disruption of large parent bodies. In this review, we describe numerical simulations of asteroid collisions that reproduced the main properties of families, accounting for both the fragmentation of an asteroid at the time of impact and the subsequent gravitational interactions of the generated fragments. The simulations demonstrate that the catastrophic disruption of bodies larger than a few hundred meters in diameter leads to the formation of large aggregates due to gravitational reaccumulation of smaller fragments, which helps explain the presence of large members within asteroid families. Thus, for the first time, numerical simulations successfully reproduced the sizes and ejection velocities of members of representative families. Moreover, the simulations provide constraints on the family dynamical histories and on the possible internal structure of family members and their parent bodies.Comment: Chapter to appear in the (University of Arizona Press) Space Science Series Book: Asteroids I

    Fragment properties at the catastrophic disruption threshold: The effect of the parent body's internal structure

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    Numerical simulations of asteroid break-ups, including both the fragmentation of the parent body and the gravitational interactions between the fragments, have allowed us to reproduce successfully the main properties of asteroid families formed in different regimes of impact energy, starting from a non-porous parent body. In this paper, using the same approach, we concentrate on a single regime of impact energy, the so-called catastrophic threshold usually designated by Q*D, which results in the escape of half of the target's mass. Thanks to our recent implementation of a model of fragmentation of porous materials, we can characterize Q*D for both porous and non-porous targets with a wide range of diameters. We can then analyze the potential influence of porosity on the value of Q*D, and by computing the gravitational phase of the collision in the gravity regime, we can characterize the collisional outcome in terms of the fragment size and ejection speed distributions, which are the main outcome properties used by collisional models to study the evolutions of the different populations of small bodies. We also check the dependency of Q*D on the impact speed of the projectile. In the strength regime, which corresponds to target sizes below a few hundreds of meters, we find that porous targets are more difficult to disrupt than non-porous ones. In the gravity regime, the outcome is controlled purely by gravity and porosity in the case of porous targets. In the case of non-porous targets, the outcome also depends on strength. We then propose some power-law relationships between Q*D and both target's size and impact speed that can be used in collisional evolution models.Comment: 18 pages, 19 Figures. Accepted for publication in Icaru

    A Comprehensive Review of the Pharmacodynamics, Pharmacokinetics, and Clinical Effects of the Neutral Endopeptidase Inhibitor Racecadotril

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    Racecadotril, via its active metabolite thiorphan, is an inhibitor of the enzyme neutral endopeptidase (NEP, EC 3.4.24.11), thereby increasing exposure to NEP substrates including enkephalins and atrial natriuretic peptide (ANP). Upon oral administration racecadotril is rapidly and effectively converted into the active metabolite thiorphan, which does not cross the blood–brain-barrier. Racecadotril has mainly been tested in animal models and patients of three therapeutic areas. As an analgesic the effects of racecadotril across animal models were inconsistent. In cardiovascular diseases such as hypertension or congestive heart failure results from animal studies were promising, probably related to increased exposure to ANP, but clinical results have not shown substantial therapeutic benefit over existing treatment options in cardiovascular disease. In contrast, racecadotril was consistently effective in animal models and patients with various forms of acute diarrhea by inhibiting pathologic (but not basal) secretion from the gut without changing gastro-intestinal transit time or motility. This included studies in both adults and children. In direct comparative studies with loperamide in adults and children, racecadotril was at least as effective but exhibited fewer adverse events in most studies, particularly less rebound constipation. Several guidelines recommend the use of racecadotril as addition to oral rehydration treatment in children with acute diarrhea

    Human Urinary Bladder Strip Relaxation by the β-Adrenoceptor Agonist Isoprenaline: Methodological Considerations and Effects of Gender and Age

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    The present study was primarily designed to explore various methodological aspects related to organ bath experiments evaluating human detrusor relaxation by the β-adrenoceptor agonist isoprenaline. Data are based upon a series of 30 consecutive patients, and this cohort was also used to explore possible effects of gender and age. KCl-induced contraction was related to strip length but not weight or cross-sectional area, indicating that the former is most suitable for data normalization. Storage of detrusor strips in cold buffer for up to 2 days did not affect contractile responses to KCl or efficacy of isoprenaline to cause relaxation but significantly affected the isoprenaline potency. No such alterations were observed with up to 1 day of cold storage. The type (KCl vs. passive tension) or strength of contractile stimulus had only minor effects on isoprenaline responses although these differences reached statistical significance in some cases. Similarly, gender and age had only minor if any effects on KCl-induced contraction or isoprenaline-induced relaxation, but the current data are too limited for robust conclusions. In summary we have evaluated experimental conditions for the testing of human detrusor strip contraction and relaxation which should be useful for future larger studies

    Topographical coloured plasmonic coins

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    The use of metal nanostructures for colourization has attracted a great deal of interest with the recent developments in plasmonics. However, the current top-down colourization methods based on plasmonic concepts are tedious and time consuming, and thus unviable for large-scale industrial applications. Here we show a bottom-up approach where, upon picosecond laser exposure, a full colour palette independent of viewing angle can be created on noble metals. We show that colours are related to a single laser processing parameter, the total accumulated fluence, which makes this process suitable for high throughput industrial applications. Statistical image analyses of the laser irradiated surfaces reveal various distributions of nanoparticle sizes which control colour. Quantitative comparisons between experiments and large-scale finite-difference time-domain computations, demonstrate that colours are produced by selective absorption phenomena in heterogeneous nanoclusters. Plasmonic cluster resonances are thus found to play the key role in colour formation.Comment: 9 pages, 5 figure

    Discovering novel enzymes by functional screening of plurigenomic libraries from alga-associated <i>Flavobacteriia</i> and <i>Gammaproteobacteria</i>

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    Alga-associated microorganisms, in the context of their numerous interactions with the host and the complexity of the marine environment, are known to produce diverse hydrolytic enzymes with original biochemistry. We recently isolated several macroalgal-polysaccharide-degrading bacteria from the surface of the brown alga Ascophyllum nodosum. These active isolates belong to two classes: the Flavobacteriia and the Gammaproteobacteria. In the present study, we constructed two “plurigenomic” (with multiple bacterial genomes) libraries with the 5 most interesting isolates (regarding their phylogeny and their enzymatic activities) of each class (Fv and Gm libraries). Both libraries were screened for diverse hydrolytic activities. Five activities, out of the 48 previously identified in the natural polysaccharolytic isolates, were recovered by functional screening: a xylanase (GmXyl7), a beta-glucosidase (GmBg1), an esterase (GmEst7) and two iota-carrageenases (Fvi2.5 and Gmi1.3). We discuss here the potential role of the used host-cell, the average DNA insert-sizes and the used restriction enzymes on the divergent screening yields obtained for both libraries and get deeper inside the “great screen anomaly”. Interestingly, the discovered esterase probably stands for a novel family of homoserine o-acetyltransferase-like-esterases, while the two iota-carrageenases represent new members of the poorly known GH82 family (containing only 19 proteins since its description in 2000). These original results demonstrate the efficiency of our uncommon “plurigenomic” library approach and the underexplored potential of alga-associated cultivable microbiota for the identification of novel and algal-specific enzymes
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