6,955 research outputs found

    Toarcian oceanic anoxic event: An assessment of global causes using belemnite C isotope records

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    Two hypotheses have been proposed to explain simultaneous large negative excursions (up to 7% PeeDee belemnite) in bulk carbonate (delta(13)C(carb)) and organic carbon isotope records (delta(13)C(org)) from black shales marking the Toarcian oceanic anoxic event (T-OAE). The first explanation envisions recycling of dissolved inorganic carbon (DIC) with a light isotopic signature into the photic zone from the lower levels of a salinity-stratified water mass, essentially requiring a regional paleoceanographic driver of the carbon cycle. The second involves the rapid and massive dissociation of methane from gas hydrates that effectively renders the T-OAE a global perturbation of the carbon cycle. We present C isotope records from belemnites (delta(13)C(bel)) sampled from two localities, calibrated with high-resolution ammonite biostratigraphy and Sr isotope stratigraphy, in Yorkshire (England) and Dotternhausen (Germany), that can be used to assess which model best explains the observed changes in carbon isotopes. Our records of the delta(13)C composition of belemnite calcite do not show the large negative C isotope excursions shown by coeval records of delta(13)C in sedimentary organic matter or bulk sedimentary carbonate. It follows that isotopically light carbon cannot have dominated the ocean-atmosphere carbon reservoir during the Toarcian OAE, as would be required were the methane release hypothesis correct. On the basis of an evaluation of available carbon isotope records we discuss a model in which the recycling of DIC from the deeper levels of a stratified water body, and shallowing of anoxic conditions into the photic zone, can explain all isotopic profiles. In particular, the model accounts for the higher C isotope values of belemnites that are characteristic of open ocean, well-mixed conditions, and the lower C isotope values of neritic phytoplankton communities that recorded the degree of density stratification and shallowing of anoxia in the photic zone

    Budget-restricted utility games with ordered strategic decisions

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    We introduce the concept of budget games. Players choose a set of tasks and each task has a certain demand on every resource in the game. Each resource has a budget. If the budget is not enough to satisfy the sum of all demands, it has to be shared between the tasks. We study strategic budget games, where the budget is shared proportionally. We also consider a variant in which the order of the strategic decisions influences the distribution of the budgets. The complexity of the optimal solution as well as existence, complexity and quality of equilibria are analyzed. Finally, we show that the time an ordered budget game needs to convergence towards an equilibrium may be exponential

    The Heme Protein P450 from Adrenal Cortex: Its Reactivities in Ferric and Ferrous Forms

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    In the course of this reaction cycle the heme protein undergoes a series of changes of its coordination around the Fe (on reduction to its »unliganded~ Fe2+ state, on binding of the 0 2 molecule, and upon introduction of the second reducing equivalent, as the heme protein returns to its original Fe3+ state}. Steroid substrates, inhibitors, and a variety of agents bind to the heme protein P450(Fe3+), isolated in a S = 1/2 form from bovine adrenal glands, with high affinities at sites near the heme group, but do not as a rule enter the coordination sphere of the Fe. This leads to perturbations of the electronic structure which can be followed by spectroscopic techniques (optical absorption, EPR spectroscopy) in combination with suitable chemical methods. Direct replacement of a ligand can also be achieved. The ferrous heme protein P450(Fe2+), in its unliganded and liganded forms, was also investigated. P450(Fe2•) combines readily with small ligands such as 0 2 (418 nm), CO (448 nm), and nitric oxide. Larger lipophilic molecules (e. g. pyridine derivatives, other heterocyclic compounds, haloalkanes, or hydroperoxides) also bind readily to P450(Fe2+), often with high affinities. They tend to enter the coordination sphere of the Fe and form stable complexes often with distinct optical absorption (440-470 nm); additional unspecific binding is frequently observed. Representative examples of the results for the various cases of interactions are presented and are discussed in relation to a hypothetical structure of P450(Fe3• ), S = 1/2, as a protoheme IX complex, with a thiol-group and a N-containing group as axial ligands; the observations are further related to the required changes in coordination in the course of the hydroxylation reaction

    The Heme Protein P450 from Adrenal Cortex: Its Reactivities in Ferric and Ferrous Forms

    Get PDF
    In the course of this reaction cycle the heme protein undergoes a series of changes of its coordination around the Fe (on reduction to its »unliganded~ Fe2+ state, on binding of the 0 2 molecule, and upon introduction of the second reducing equivalent, as the heme protein returns to its original Fe3+ state}. Steroid substrates, inhibitors, and a variety of agents bind to the heme protein P450(Fe3+), isolated in a S = 1/2 form from bovine adrenal glands, with high affinities at sites near the heme group, but do not as a rule enter the coordination sphere of the Fe. This leads to perturbations of the electronic structure which can be followed by spectroscopic techniques (optical absorption, EPR spectroscopy) in combination with suitable chemical methods. Direct replacement of a ligand can also be achieved. The ferrous heme protein P450(Fe2+), in its unliganded and liganded forms, was also investigated. P450(Fe2•) combines readily with small ligands such as 0 2 (418 nm), CO (448 nm), and nitric oxide. Larger lipophilic molecules (e. g. pyridine derivatives, other heterocyclic compounds, haloalkanes, or hydroperoxides) also bind readily to P450(Fe2+), often with high affinities. They tend to enter the coordination sphere of the Fe and form stable complexes often with distinct optical absorption (440-470 nm); additional unspecific binding is frequently observed. Representative examples of the results for the various cases of interactions are presented and are discussed in relation to a hypothetical structure of P450(Fe3• ), S = 1/2, as a protoheme IX complex, with a thiol-group and a N-containing group as axial ligands; the observations are further related to the required changes in coordination in the course of the hydroxylation reaction

    The Internet Addiction Test in a Young Adult U.S. Population

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    Internet use has increased rapidly over the past 20 years, accompanied by a growing number of individuals whose Internet use has adverse effects on their lives. Yet no study to date has administered the Young\u27s Internet Addiction Test (IAT) in the United States, nor has the reliability been assessed in a U.S. population. Thus, we aimed to: (a) assess the reliability of the instrument and (b) examine sociodemographic characteristics associated with the Internet addiction score. Participants included young adults 21–28 years of age, the third generation of a 50-year longitudinal cohort, the New England Family Study. The mean weighted kappa across all 20 items of the instrument was 0.45 and the median was 0.46. To examine correlates of the addiction score, we examined age, gender, race/ethnicity, education, partnership status, employment, social support, and depression diagnosis. In the fully adjusted model, those with social support had −3.96 (95% CI: −6.52 to −1.41) lower Internet addiction scores on average compared to those without social support. Also, those with a depression diagnosis had 3.28 (95% confidence interval [CI]: 1.03–5.84) higher Internet addiction scores on average compared to those without a depression diagnosis. Study findings suggest that Young\u27s IAT had good reliability in a U.S. young adult population. Therefore, this measure can be a useful tool to measure Internet addiction in young adult populations in the United States. Future studies should examine the potential benefits of social support and depression treatment in Internet addiction among young adults in the United States

    In silico and in vitro drug screening identifies new therapeutic approaches for Ewing sarcoma.

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    The long-term overall survival of Ewing sarcoma (EWS) patients remains poor; less than 30% of patients with metastatic or recurrent disease survive despite aggressive combinations of chemotherapy, radiation and surgery. To identify new therapeutic options, we employed a multi-pronged approach using in silico predictions of drug activity via an integrated bioinformatics approach in parallel with an in vitro screen of FDA-approved drugs. Twenty-seven drugs and forty-six drugs were identified, respectively, to have anti-proliferative effects for EWS, including several classes of drugs in both screening approaches. Among these drugs, 30 were extensively validated as mono-therapeutic agents and 9 in 14 various combinations in vitro. Two drugs, auranofin, a thioredoxin reductase inhibitor, and ganetespib, an HSP90 inhibitor, were predicted to have anti-cancer activities in silico and were confirmed active across a panel of genetically diverse EWS cells. When given in combination, the survival rate in vivo was superior compared to auranofin or ganetespib alone. Importantly, extensive formulations, dose tolerance, and pharmacokinetics studies demonstrated that auranofin requires alternative delivery routes to achieve therapeutically effective levels of the gold compound. These combined screening approaches provide a rapid means to identify new treatment options for patients with a rare and often-fatal disease
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