170 research outputs found

    A single-column model intercomparison of a heavily drizzling stratocumulus-topped boundary layer

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    This study presents an intercomparison of single-column model simulations of a nocturnal heavily drizzling marine stratocumulus-topped boundary layer. Initial conditions and forcings are based on nocturnal flight observations off the coast of California during the DYCOMS-II field experiment. Differences in turbulent and microphysical parameterizations between models were isolated by slightly idealizing and standardizing the specification of surface and radiative fluxes. For most participating models, the case was run at both typical operational vertical resolution of about 100 m and also at high vertical resolution of about 10 m. As in prior stratocumulus intercomparisons, the simulations quickly develop considerable scatter in liquid water path (LWP) between models. However, the simulated dependence of cloud base drizzle fluxes on LWP in most models is broadly consistent with recent observations. Sensitivity tests with drizzle turned off show that drizzle substantially decreases LWP for many models. The sensitivity of entrainment rate to drizzle is more muted. Simulated LWP and entrainment are also sensitive to the inclusion of cloud droplet sedimentation. Many models underestimate the fraction of drizzle that evaporates below cloud base, which may distort the simulated feedbacks of drizzle on turbulence, entrainment, and LWP

    Astrometric Methods and Instrumentation to Identify and Characterize Extrasolar Planets: A Review

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    I present a review of astrometric techniques and instrumentation utilized to search for, detect, and characterize extra-solar planets. First, I briefly summarize the properties of the present-day sample of extrasolar planets, in connection with predictions from theoretical models of planet formation and evolution. Next, the generic approach to planet detection with astrometry is described, with significant discussion of a variety of technical, statistical, and astrophysical issues to be faced by future ground-based as well as space-borne efforts in order to achieve the required degree of measurement precision. After a brief summary of past and present efforts to detect planets via milli-arcsecond astrometry, I then discuss the planet-finding capabilities of future astrometric observatories aiming at micro-arcsecond precision. Lastly, I outline a number experiments that can be conducted by means of high-precision astrometry during the next decade, to illustrate its potential for important contributions to planetary science, in comparison with other indirect and direct methods for the detection and characterization of planetary systems.Comment: 61 pages, 8 figures, PASP, accepted (October 2005 issue

    Manipulation of Costimulatory Molecules by Intracellular Pathogens: Veni, Vidi, Vici!!

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    Some of the most successful pathogens of human, such as Mycobacterium tuberculosis (Mtb), HIV, and Leishmania donovani not only establish chronic infections but also remain a grave global threat. These pathogens have developed innovative strategies to evade immune responses such as antigenic shift and drift, interference with antigen processing/presentation, subversion of phagocytosis, induction of immune regulatory pathways, and manipulation of the costimulatory molecules. Costimulatory molecules expressed on the surface of various cells play a decisive role in the initiation and sustenance of immunity. Exploitation of the “code of conduct” of costimulation pathways provides evolutionary incentive to the pathogens and thereby abates the functioning of the immune system. Here we review how Mtb, HIV, Leishmania sp., and other pathogens manipulate costimulatory molecules to establish chronic infection. Impairment by pathogens in the signaling events delivered by costimulatory molecules may be responsible for defective T-cell responses; consequently organisms grow unhindered in the host cells. This review summarizes the convergent devices that pathogens employ to tune and tame the immune system using costimulatory molecules. Studying host-pathogen interaction in context with costimulatory signals may unveil the molecular mechanism that will help in understanding the survival/death of the pathogens. We emphasize that the very same pathways can potentially be exploited to develop immunotherapeutic strategies to eliminate intracellular pathogens

    A History of Drug Discovery for Treatment of Nausea and Vomiting and the Implications for Future Research.

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    The origins of the major classes of current anti-emetics are examined. Serendipity is a recurrent theme in discovery of their anti-emetic properties and repurposing from one indication to another is a continuing trend. Notably, the discoveries have occurred against a background of company mergers and changing anti-emetic requirements. Major drug classes include: (i) Muscarinic receptor antagonists-originated from historical accounts of plant extracts containing atropine and hyoscine with development stimulated by the need to prevent sea-sickness among soldiers during beach landings; (ii) Histamine receptor antagonists-searching for replacements for the anti-malaria drug quinine, in short supply because of wartime shipping blockade, facilitated the discovery of histamine (H1) antagonists (e.g., dimenhydrinate), followed by serendipitous discovery of anti-emetic activity against motion sickness in a patient undergoing treatment for urticaria; (iii) Phenothiazines and dopamine receptor antagonists-investigations of their pharmacology as "sedatives" (e.g., chlorpromazine) implicated dopamine receptors in emesis, leading to development of selective dopamine (D2) receptor antagonists (e.g., domperidone with poor ability to penetrate the blood-brain barrier) as anti-emetics in chemotherapy and surgery; (iv) Metoclopramide and selective 5-hydroxytryptamine3(5-HT3) receptor antagonists-metoclopramide was initially assumed to act only via D2 receptor antagonism but subsequently its gastric motility stimulant effect (proposed to contribute to the anti-emetic action) was shown to be due to 5-hydroxytryptamine4 receptor agonism. Pre-clinical studies showed that anti-emetic efficacy against the newly-introduced, highly emetic, chemotherapeutic agent cisplatin was due to antagonism at 5-HT3 receptors. The latter led to identification of selective 5-HT3 receptor antagonists (e.g., granisetron), a major breakthrough in treatment of chemotherapy-induced emesis; (v) Neurokinin1receptor antagonists-antagonists of the actions of substance P were developed as analgesics but pre-clinical studies identified broad-spectrum anti-emetic effects; clinical studies showed particular efficacy in the delayed phase of chemotherapy-induced emesis. Finally, the repurposing of different drugs for treatment of nausea and vomiting is examined, particularly during palliative care, and also the challenges in identifying novel anti-emetic drugs, particularly for treatment of nausea as compared to vomiting. We consider the lessons from the past for the future and ask why there has not been a major breakthrough in the last 20 years
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