108 research outputs found

    Cascade oxime formation, cyclization to a nitrone, and intermolecular dipolar cycloaddition.

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    Simple haloaldehydes, including enolisable aldehydes, were found to be suitable for the formation of cyclic products by cascade (domino) condensation, cyclisation, dipolar cycloaddition chemistry. This multi-component reaction approach to heterocyclic compounds was explored by using hydroxylamine, a selection of aldehydes, and a selection of activated dipolarophiles. Initial condensation gives intermediate oximes that undergo cyclisation with displacement of halide to give intermediate nitrones; these nitrones undergo in situ intermolecular dipolar cycloaddition reactions to give isoxazolidines. The cycloadducts from using dimethyl fumarate were treated with zinc/acetic acid to give lactam products and this provides an easy way to prepare pyrrolizinones, indolizinones, and pyrrolo[2,1-a]isoquinolinones. The chemistry is illustrated with a very short synthesis of the pyrrolizidine alkaloid macronecine and a formal synthesis of petasinecine

    Sigma-2 receptor ligands potentiate conventional chemotherapies and improve survival in models of pancreatic adenocarcinoma

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    <p>Abstract</p> <p>Background</p> <p>We have previously reported that the sigma-2 receptor is highly expressed in pancreas cancer. Furthermore, we have demonstrated that sigma-2 receptor specific ligands induce apoptosis in a dose-dependent fashion. Here, we examined whether sigma-2 receptor ligands potentiate conventional chemotherapies such as gemcitabine and paclitaxel.</p> <p>Methods</p> <p>Mouse (Panc-02) and human (CFPAC-1, Panc-1, AsPC-1) pancreas cancer cell lines were used in this study. Apoptosis was determined by FACS or immunohistochemical analysis after TUNEL and Caspase-3 staining. Combination therapy with the sigma-2 ligand SV119 and the conventional chemotherapies gemcitabine and paclitaxel was evaluated in an allogenic animal model of pancreas cancer.</p> <p>Results</p> <p>SV119, gemcitabine, and paclitaxel induced apoptosis in a dose-dependent fashion in all pancreas cancer cell lines tested. Combinations demonstrated increases in apoptosis. Mice were treated with SV119 (1 mg/day) which was administered in combination with paclitaxel (300 μg/day) over 7 days to mice with established tumors. A survival benefit was observed with combination therapy (p = 0.0002). Every other day treatment of SV119 (1 mg/day) in combination with weekly treatment of gemcitabine (1.5 mg/week) for 2 weeks also showed a survival benefit (p = 0.046). Animals tolerated the combination therapy and no gross toxicity was noted in serum biochemistry data or on necropsy.</p> <p>Conclusion</p> <p>SV119 augments tumoricidal activity of paclitaxel and gemcitabine without major side effects. These results highlight the potential utility of the sigma-2 ligand as an adjuvant treatment in pancreas cancer.</p

    "What Do They Want Me To Say?" The hidden curriculum at work in the medical school selection process: a qualitative study

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    <p>Abstract</p> <p>Background</p> <p>There has been little study of the role of the essay question in selection for medical school. The purpose of this study was to obtain a better understanding of how applicants approached the essay questions used in selection at our medical school in 2007.</p> <p>Methods</p> <p>The authors conducted a qualitative analysis of 210 essays written as part of the medical school admissions process, and developed a conceptual framework to describe the relationships, ideas and concepts observed in the data.</p> <p>Results</p> <p>Findings of this analysis were confirmed in interviews with applicants and assessors. Analysis revealed a tension between "genuine" and "expected" responses that we believe applicants experience when choosing how to answer questions in the admissions process. A theory named "What do they want me to say?" was developed to describe the ways in which applicants modulate their responses to conform to their expectations of the selection process; the elements of this theory were confirmed in interviews with applicants and assessors.</p> <p>Conclusions</p> <p>This work suggests the existence of a "hidden curriculum of admissions" and demonstrates that the process of selection has a strong influence on applicant response. This paper suggests ways that selection might be modified to address this effect. Studies such as this can help us to appreciate the unintended consequences of admissions processes and can identify ways to make the selection process more consistent, transparent and fair.</p

    The Inclusiveness and Emptiness of <i>Gong Qi</i>: A Non-Anglophone Perspective on Ethics from a Sino-Japanese Corporation

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    This article introduces a non-Anglophone concept of gong qi(communal vessel, 公器) as a metaphor for ‘corporation’. It contributes an endogenous perspective from a Sino-Japanese organizational context that enriches mainstream business ethics literature, otherwise heavily reliant on Western traditions. We translate the multi-layered meanings of gong qi based on analysis of its ideograms, its references into classical philosophies, and contemporary application in this Japanese multinational corporation in China. Gong qi contributes a perspective that sees a corporation as an inclusive and virtuous social entity, and also addresses the elusive, implicit, and forever evolving nature of organizational life that is rarely noticed. We propose gong qi can be applied in other organizations and wider cultural contexts to show a new way of seeing and understanding business ethics and organization. Rather than considering virtue as a list of definable individual qualities, we suggest that the metaphor of gong qi reveals how virtue can be experienced as indeterminate, yet immanently present, like the substance of emptiness. This, then allows us to see the virtue of immanence, the beauty of implicitness, and hence, the efficacy of gong qi

    Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

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    A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements
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