527 research outputs found

    Generic model of an atom laser

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    We present a generic model of an atom laser by including a pump and loss term in the Gross-Pitaevskii equation. We show that there exists a threshold for the pump above which the mean matter field assumes a non-vanishing value in steady-state. We study the transient regime of this atom laser and find oscillations around the stationary solution even in the presence of a loss term. These oscillations are damped away when we introduce a position dependent loss term. For this case we present a modified Thomas-Fermi solution that takes into account the pump and loss. Our generic model of an atom laser is analogous to the semi-classical theory of the laser.Comment: 15 pages, including 5 figures, submitted to Phys. Rev. A, revised manuscript, file also available at http://www.physik.uni-ulm.de/quan/users/kne

    Gas Accretion and Star Formation Rates

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    Cosmological numerical simulations of galaxy evolution show that accretion of metal-poor gas from the cosmic web drives the star formation in galaxy disks. Unfortunately, the observational support for this theoretical prediction is still indirect, and modeling and analysis are required to identify hints as actual signs of star-formation feeding from metal-poor gas accretion. Thus, a meticulous interpretation of the observations is crucial, and this observational review begins with a simple theoretical description of the physical process and the key ingredients it involves, including the properties of the accreted gas and of the star-formation that it induces. A number of observations pointing out the connection between metal-poor gas accretion and star-formation are analyzed, specifically, the short gas consumption time-scale compared to the age of the stellar populations, the fundamental metallicity relationship, the relationship between disk morphology and gas metallicity, the existence of metallicity drops in starbursts of star-forming galaxies, the so-called G dwarf problem, the existence of a minimum metallicity for the star-forming gas in the local universe, the origin of the alpha-enhanced gas forming stars in the local universe, the metallicity of the quiescent BCDs, and the direct measurements of gas accretion onto galaxies. A final section discusses intrinsic difficulties to obtain direct observational evidence, and points out alternative observational pathways to further consolidate the current ideas.Comment: Invited review to appear in Gas Accretion onto Galaxies, Astrophysics and Space Science Library, eds. A. J. Fox & R. Dav\'e, to be published by Springe

    Patient-centric trials for therapeutic development in precision oncology

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    An enhanced understanding of the molecular pathology of disease gained from genomic studies is facilitating the development of treatments that target discrete molecular subclasses of tumours. Considerable associated challenges include how to advance and implement targeted drug-development strategies. Precision medicine centres on delivering the most appropriate therapy to a patient on the basis of clinical and molecular features of their disease. The development of therapeutic agents that target molecular mechanisms is driving innovation in clinical-trial strategies. Although progress has been made, modifications to existing core paradigms in oncology drug development will be required to realize fully the promise of precision medicine

    Surrogate endpoints for overall survival in digestive oncology trials: which candidates? A questionnaires survey among clinicians and methodologists

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    <p>Abstract</p> <p>Background</p> <p>Overall survival (OS) is the gold standard for the demonstration of a clinical benefit in cancer trials. Replacement of OS by a surrogate endpoint allows to reduce trial duration. To date, few surrogate endpoints have been validated in digestive oncology. The aim of this study was to draw up an ordered list of potential surrogate endpoints for OS in digestive cancer trials, by way of a survey among clinicians and methodologists. Secondary objective was to obtain their opinion on surrogacy and quality of life (QoL).</p> <p>Methods</p> <p>In 2007 and 2008, self administered sequential questionnaires were sent to a panel of French clinicians and methodologists involved in the conduct of cancer clinical trials. In the first questionnaire, panellists were asked to choose the most important characteristics defining a surrogate among six proposals, to give advantages and drawbacks of the surrogates, and to answer questions about their validation and use. Then they had to suggest potential surrogate endpoints for OS in each of the following tumour sites: oesophagus, stomach, liver, pancreas, biliary tract, lymphoma, colon, rectum, and anus. They finally gave their opinion on QoL as surrogate endpoint. In the second questionnaire, they had to classify the previously proposed candidate surrogates from the most (position #1) to the least relevant in their opinion.</p> <p>Frequency at which the endpoints were chosen as first, second or third most relevant surrogates was calculated and served as final ranking.</p> <p>Results</p> <p>Response rate was 30% (24/80) in the first round and 20% (16/80) in the second one. Participants highlighted key points concerning surrogacy. In particular, they reminded that a surrogate endpoint is expected to predict clinical benefit in a well-defined therapeutic situation. Half of them thought it was not relevant to study QoL as surrogate for OS.</p> <p>DFS, in the neoadjuvant settings or early stages, and PFS, in the non operable or metastatic settings, were ranked first, with a frequency of more than 69% in 20 out of 22 settings. PFS was proposed in association with QoL in metastatic primary liver and stomach cancers (both 81%). This composite endpoint was ranked second in metastatic oesophageal (69%), colorectal (56%) and anal (56%) cancers, whereas QoL alone was also suggested in most metastatic situations.</p> <p>Other endpoints frequently suggested were R0 resection in the neoadjuvant settings (oesophagus (69%), stomach (56%), pancreas (75%) and biliary tract (63%)) and response. An unexpected endpoint was metastatic PFS in non operable oesophageal (31%) and pancreatic (44%) cancers. Quality and results of surgical procedures like sphincter preservation were also cited as eligible surrogate endpoints in rectal (19%) and anal (50% in case of localized disease) cancers. Except for alpha-FP kinetic in hepatocellular carcinoma (13%) and CA19-9 decline (6%) in pancreas, few endpoints based on biological or tumour markers were proposed.</p> <p>Conclusion</p> <p>The overall results should help prioritise the endpoints to be statistically evaluated as surrogate for OS, so that trialists and clinicians can rely on endpoints that ensure relevant clinical benefit to the patient.</p

    Functional Desaturase Fads1 (Δ5) and Fads2 (Δ6) Orthologues Evolved before the Origin of Jawed Vertebrates

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    Long-chain polyunsaturated fatty acids (LC-PUFAs) such as arachidonic (ARA), eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids are essential components of biomembranes, particularly in neural tissues. Endogenous synthesis of ARA, EPA and DHA occurs from precursor dietary essential fatty acids such as linoleic and α-linolenic acid through elongation and Δ5 and Δ6 desaturations. With respect to desaturation activities some noteworthy differences have been noted in vertebrate classes. In mammals, the Δ5 activity is allocated to the Fads1 gene, while Fads2 is a Δ6 desaturase. In contrast, teleosts show distinct combinations of desaturase activities (e.g. bifunctional or separate Δ5 and Δ6 desaturases) apparently allocated to Fads2-type genes. To determine the timing of Fads1-Δ5 and Fads2-Δ6 evolution in vertebrates we used a combination of comparative and functional genomics with the analysis of key phylogenetic species. Our data show that Fads1 and Fads2 genes with Δ5 and Δ6 activities respectively, evolved before gnathostome radiation, since the catshark Scyliorhinus canicula has functional orthologues of both gene families. Consequently, the loss of Fads1 in teleosts is a secondary episode, while the existence of Δ5 activities in the same group most likely occurred through independent mutations into Fads2 type genes. Unexpectedly, we also establish that events of Fads1 gene expansion have taken place in birds and reptiles. Finally, a fourth Fads gene (Fads4) was found with an exclusive occurrence in mammalian genomes. Our findings enlighten the history of a crucially important gene family in vertebrate fatty acid metabolism and physiology and provide an explanation of how observed lineage-specific gene duplications, losses and diversifications might be linked to habitat-specific food web structures in different environments and over geological timescales
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