131 research outputs found

    CHEMICAL ENGINEERING DIVISION BURNUP, CROSS SECTIONS, AND DOSIMETRY SEMIANNUAL REPORT, JANUARY--JUNE 1972.

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    Research and development efforts of the burnup, cross sections and dosimetry programs in the Chemical Engineering Division of Argonne National Laboratory are reported for the period January to June 1972. Work is reported in the following areas: (1) development of an X-ray spectrometric method for the determination of the rare-earth fission products and application of this method to the determinations of burnup in nuclear fuels; (2) determination of fast ·fission yields of bum up monitors and other fission products; (3) a search for a spon~aneously fissioning isomer of {sup 241}Pu; (4) measurements of the tritium and alpha particle yields in fast-neutron fission of {sup 235}U and {sup 239}Pu; (5) evaluations of available data on the differential cross sections for the {sup 56}Fe(n,p){sup 56}Mn and {sup 32}S(n,p){sup 32}P reactions; and (6) measurements of both fission rates by solid-state track recorders and reaction rates by foil activation, in the Coupled Fast Reactivity Measurement Facility

    Towards an integrated set of surface meteorological observations for climate science and applications

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    Observations are the foundation for understanding the climate system. Yet, currently available land meteorological data are highly fractured into various global, regional and national holdings for different variables and timescales, from a variety of sources, and in a mixture of formats. Added to this, many data are still inaccessible for analysis and usage. To meet modern scientific and societal demands as well as emerging needs such as the provision of climate services, it is essential that we improve the management and curation of available land-based meteorological holdings. We need a comprehensive global set of data holdings, of known provenance, that is truly integrated both across Essential Climate Variables (ECVs) and across timescales to meet the broad range of stakeholder needs. These holdings must be easily discoverable, made available in accessible formats, and backed up by multi-tiered user support. The present paper provides a high level overview, based upon broad community input, of the steps that are required to bring about this integration. The significant challenge is to find a sustained means to realize this vision. This requires a long-term international program. The database that results will transform our collective ability to provide societally relevant research, analysis and predictions in many weather and climate related application areas across much of the globe

    Quantitaton of rate of gastrointestinal and buccal absorption of acidic and basic drugs based on extraction theory

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    Equations have been derived which quantitatively describe the rate of gastrointestinal and buccal absorption of acidic and basic drugs as a function of pH of aqueous lumenal contents and time. The equations have been used to fit observed data in the literature, and the estimated parameters are reported. An equation which describes the renal clearance of an acidic or basic drug as a function of urinary pH is also derived. In essence, the equations quantitate the pH-partition hypothesis and explain most, if not all, related observed data in the literature. The results suggest that the aqueous diffusion layer may not rate-limit absorption of monomeric drug molecules but that absorption is rate-limited by transfer of drug out of the membrane in vivo.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45024/1/10928_2005_Article_BF01060026.pd

    Cancer stem cell drugs target K-ras signaling in a stemness context

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    Cancer stem cells (CSCs) are considered to be responsible for treatment relapse and have therefore become a major target in cancer research. Salinomycin is the most established CSC inhibitor. However, its primary mechanistic target is still unclear, impeding the discovery of compounds with similar anti-CSC activity. Here, we show that salinomycin very specifically interferes with the activity of K-ras4B, but not H-ras, by disrupting its nanoscale membrane organization. We found that caveolae negatively regulate the sensitivity to this drug. On the basis of this novel mechanistic insight, we defined a K-ras-associated and stem cell-derived gene expression signature that predicts the drug response of cancer cells to salinomycin. Consistent with therapy resistance of CSC, 8% of tumor samples in the TCGA-database displayed our signature and were associated with a significantly higher mortality. Using our K-ras-specific screening platform, we identified several new candidate CSC drugs. Two of these, ophiobolin A and conglobatin A, possessed a similar or higher potency than salinomycin. Finally, we established that the most potent compound, ophiobolin A, exerts its K-ras4B-specific activity through inactivation of calmodulin. Our data suggest that specific interference with the K-ras4B/calmodulin interaction selectively inhibits CSC.Peer reviewe

    Do pharmacokinetic polymorphisms explain treatment failure in high-risk patients with neuroblastoma?

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