947 resultados para Knox Church (Dunedin, N.Z.)


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Modern scientific world-view has undermined traditional myths, the functional survival of which seems to depend today in the West on a positivist justification. This would place them in the field of real History, through their study and revitalization by pseudoscientific disciplines such as the Atlantis and the ancient astronaut hypotheses. These have inspired new epic poems in (regular) verse that combine classic and/or biblical myths with a (pseudo)scientific modern world-view. For example, the critical rewriting of Noah’s myth by using the ancient astronaut hypothesis as a fictional device to produce a contemporary kind of plausibility allowed Abel Montagut to renew epic poetry, updating it also by adopting science fiction chronotopes in order to structure his fictional construction and to generate a high ethical sense for our time. Thus, his Poemo de Utnoa (1993) / La gesta d’Utnoa (1996), which has become a major classic of the literature in Esperanto thanks to its original version in this language, is a landmark of both science fiction and neo-biblical epics. This poem is written from a secular and purely literary perspective.

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PURPOSE: Poly(ADP-ribose) polymerase (PARP) plays an important role in DNA repair, and PARP inhibitors can enhance the activity of DNA-damaging agents in vitro and in vivo. AG014699 is a potent PARP inhibitor in phase II clinical development. However, the range of therapeutics with which AG014699 could interact via a DNA-repair based mechanism is limited. We aimed to investigate a novel, vascular-based activity of AG014699, underlying in vivo chemosensitization, which could widen its clinical application. EXPERIMENTAL DESIGN: Temozolomide response was analyzed in vitro and in vivo. Vessel dynamics were monitored using "mismatch" following the administration of perfusion markers and real-time analysis of fluorescently labeled albumin uptake in to tumors established in dorsal window chambers. Further mechanistic investigations used ex vivo assays of vascular smooth muscle relaxation, gut motility, and myosin light chain kinase (MLCK) inhibition. RESULTS: AG014699 failed to sensitize SW620 cells to temozolomide in vitro but induced pronounced enhancement in vivo. AG014699 (1 mg/kg) improved tumor perfusion comparably with the control agents nicotinamide (1 g/kg) and AG14361 (forerunner to AG014699; 10 mg/kg). AG014699 and AG14361 relaxed preconstricted vascular smooth muscle more potently than the standard agent, hydralazine, with no impact on gut motility. AG014699 inhibited MLCK at concentrations that relaxed isolated arteries, whereas AG14361 had no effect. CONCLUSION: Increased vessel perfusion elicited by AG014699 could increase tumor drug accumulation and therapeutic response. Vasoactive concentrations of AG014699 do not cause detrimental side effects to gut motility and may increase the range of therapeutics with which AG014699 could be combined with for clinical benefi