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I analyze the components of Mumford's megamachine and align key concerns in two pivotal works that characterize the impact of collective capacities on society: Bruno Latour's Pasteurization of France (1988) and Elias Canetti's Crowds and Power (1962). As I create a model of collective capacities in the sociotechnical according to the parameters of Mumford's megamachine, I rehabilitate two established ideas about the behavior of crowds and about the undue influence of technological systems on human behavior. I depart from Mumford's tactics and those of Canetti and Latour and propose a novel focus for STS on "sociotechnical crowds" as a meaningful unit of social measure. I make clear that Mumford's critique of the sociotechnical status quo still informs the conditions for innovation today.
Using mixed mode qualitative methods in two types of empirical field studies, I then investigate how a focus on the characteristics and components of collective human capacities in sociotechnical systems can affect the design and performance of TA. I propose a new model of TA, Emergent Technology Assessment (ETA), which includes greater public participation and recognizes the interrelationship among experience, affect and the material in mediating the innovation process. The resulting model -- the "soft" megamachine --introduces new strategies to build capacity for responsible innovation in society.
This study draws from three phases of research set in the context of urban development, where images of the future are generated by architects and circulated by built environment professionals to affect client and public decision-making. I begin with a systematic review of professional design literature to identify norms related to visualization. I then conduct in-depth interviews with expert architects to draw out how visualization technologies are used to influence client decision-making. I dive into how different tools manage the future and generate different forms of certainty, uncertainty, persuasion, and risk. Complementing the review and interviews is a case study on ASU at Mesa City Center, a development project aimed at revitalizing downtown Mesa, Arizona. Analysis highlights how project-specific visual tools affect decision-making and the role that client imagination and inference play in understanding and preference. This research unpacks the social, technical, and emotional knowledge embedded in visualization technologies and reveals how they affect decision-making. Information about the future is uniquely mediated by each technology with decision-making bound up in larger sociopolitical processes aimed at reducing uncertainty, building trust, and managing expectations. This suggests that the visual tools we use to depict the future are much more dynamic and influential than they are given credit for.
Bacterial lipopolysaccharides (LPS) are structural components of the outer membranes of Gram-negative bacteria and also are potent inducers of inflammation in mammals. Higher vertebrates are extremely sensitive to LPS, but lower vertebrates, like fish, are resistant to their systemic toxic effects. However, the effects of LPS on the fish intestinal mucosa remain unknown. Edwardsiella ictaluri is a primitive member of the Enterobacteriaceae family that causes enteric septicemia in channel catfish (Ictalurus punctatus). E. ictaluri infects and colonizes deep lymphoid tissues upon oral or immersion infection. Both gut and olfactory organs are the primary sites of invasion. At the systemic level, E. ictaluri pathogenesis is relatively well characterized, but our knowledge about E. ictaluri intestinal interaction is limited. Recently, we observed that E. ictaluri oligo-polysaccharide (O-PS) LPS mutants have differential effects on the intestinal epithelia of orally inoculated catfish. Here we evaluate the effects of E. ictaluri O-PS LPS mutants by using a novel catfish intestinal loop model and compare it to the rabbit ileal loop model inoculated with Salmonella enterica serovar Typhimurium LPS. We found evident differences in rabbit ileal loop and catfish ileal loop responses to E. ictaluri and S. Typhimurium LPS. We determined that catfish respond to E. ictaluri LPS but not to S. Typhimurium LPS. We also determined that E. ictaluri inhibits cytokine production and induces disruption of the intestinal fish epithelia in an O-PS-dependent fashion. The E. ictaluri wild type and ΔwibT LPS mutant caused intestinal tissue damage and inhibited proinflammatory cytokine synthesis, in contrast to E. ictaluri Δgne and Δugd LPS mutants. We concluded that the E. ictaluri O-PS subunits play a major role during pathogenesis, since they influence the recognition of the LPS by the intestinal mucosal immune system of the catfish. The LPS structure of E. ictaluri mutants is needed to understand the mechanism of interaction.
Contemporary vaccine development relies less on empirical methods of vaccine construction, and now employs a powerful array of precise engineering strategies to construct immunogenic live vaccines. In this review, we will survey various engineering techniques used to create attenuated vaccines, with an emphasis on recent advances and insights. We will further explore the adaptation of attenuated strains to create multivalent vaccine platforms for immunization against multiple unrelated pathogens. These carrier vaccines are engineered to deliver sufficient levels of protective antigens to appropriate lymphoid inductive sites to elicit both carrier-specific and foreign antigen-specific immunity. Although many of these technologies were originally developed for use in Salmonella vaccines, application of the essential logic of these approaches will be extended to development of other enteric vaccines where possible. A central theme driving our discussion will stress that the ultimate success of an engineered vaccine rests on achieving the proper balance between attenuation and immunogenicity. Achieving this balance will avoid over-activation of inflammatory responses, which results in unacceptable reactogenicity, but will retain sufficient metabolic fitness to enable the live vaccine to reach deep tissue inductive sites and trigger protective immunity. The breadth of examples presented herein will clearly demonstrate that genetic engineering offers the potential for rapidly propelling vaccine development forward into novel applications and therapies which will significantly expand the role of vaccines in public health.
Background: To be effective, orally administered live Salmonella vaccines must first survive their encounter with the low pH environment of the stomach. To enhance survival, an antacid is often given to neutralize the acidic environment of the stomach just prior to or concomitant with administration of the vaccine. One drawback of this approach, from the perspective of the clinical trial volunteer, is that the taste of a bicarbonate-based acid neutralization system can be unpleasant. Thus, we explored an alternative method that would be at least as effective as bicarbonate and with a potentially more acceptable taste. Because ingestion of protein can rapidly buffer stomach pH, we examined the possibility that the protein-rich Ensure® Nutrition shakes would be effective alternatives to bicarbonate.
Results: We tested one Salmonella enterica serovar Typhimurium and three Salmonella Typhi vaccine strains and found that all strains survived equally well when incubated in either Ensure® or bicarbonate. In a low gastric pH mouse model, Ensure® worked as well or better than bicarbonate to enhance survival through the intestinal tract, although neither agent enhanced the survival of the S. Typhi test strain possessing a rpoS mutation.
Conclusions: Our data show that a protein-rich drink such as Ensure® Nutrition shakes can serve as an alternative to bicarbonate for reducing gastric pH prior to administration of a live Salmonella vaccine.