2 resultados para Huygens, Christiaan (1629-1695) -- Biographies

em QSpace: Queen's University - Canada


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Thrombin-activatable fibrinolysis inhibitor (TAFI) is a human plasma zymogen that acts as a molecular link between the coagulation and fibrinolytic cascades. TAFI can be activated by thrombin and plasmin but the reaction is enhanced significantly when thrombin is in a complex with the endothelial cofactor thrombomodulin (TM). The in vitro properties of TAFI have been extensively characterized. Activated TAFI (TAFIa) is a thermally unstable enzyme that attenuates fibrinolysis by catalyzing the removal of basic residues from partially degraded fibrin. The in vivo role of the TAFI pathway, however, is poorly defined and very little is known about the role of different activators in regulating the TAFI pathway. In the present study, we have constructed and characterized various TAFI mutants that are resistant to activation by specific activators. Based on peptide sequence studies, these mutants were constructed by altering key amino acid residues surrounding the scissile R92-A93 bond. We measured the thermal stabilities of all our mutants and found them to be similar to wild type TAFI. We have identified that the TAFI mutants P91S, R92K, and S90P are impaired in activation by thrombin or thrombin-TM, thrombin alone, and thrombin alone or plasmin, respectively. The TAFI mutants A93V and S94V were predicted to be resistant to activation by plasmin but this was not observed. The triple mutant, DVV was not activated by any of the aforementioned activators. Finally, we have used in vitro fibrin clot lysis assays to evaluate the antifibrinolytic potential of our variants and were able to correlate their effectiveness with their respective activation kinetics. In summary, we have developed activation resistant TAFI variants that can potentially be used to explore the role of the TAFI pathway in vivo.

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“Red coats and wild birds: military culture and ornithology across the nineteenth-century British Empire” investigates the intersections between British military culture and the practices and ideas of ornithology, with a particular focus on the British Mediterranean. Considering that British officers often occupied several imperial sites over the course of their military careers, to what extent did their movements shape their ornithological knowledge and identities at “home” and abroad? How did British military naturalists perceive different local cultures (with different attitudes to hunting, birds, field science, etc.) and different local natures (different sets of birds and environments)? How can trans-imperial careers be written using not only textual sources (for example, biographies and personal correspondence) but also traces of material culture? In answering these questions, I centre my work on the Mediterranean region as a “colonial sea” in the production of hybrid identities and cultural practices, and the mingling of people, ideas, commodities, and migratory birds. I focus on the life geographies of four military officers: Thomas Wright Blakiston, Andrew Leith Adams, L. Howard Lloyd Irby, and Philip Savile Grey Reid. By the mid-nineteenth century, the Mediterranean region emerged as a crucial site for the security of the British “empire route” to India and South Asia, especially with the opening of the Suez Canal in 1869. Military stations served as trans-imperial sites, connecting Britain to India through the flow of military manpower, commodities, information, and bodily experiences across the empire. By using a “critical historical geopolitics of empire” to examine the material remnants of the “avian imperial archive,” I demonstrate how the practices and performances of British military field ornithology helped to: materialize the British Mediterranean as a moral “semi-tropical” place for the physical and cultural acclimatization of British officers en route to and from India; reinforce imperial presence in the region; and make “visible in new ways” the connectivity of North Africa to Europe through the geographical distribution of birds. I also highlight the ways in which the production of ornithological knowledge by army officers was entwined with forms of temperate martial masculinity.