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Description

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

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.

ContributorsSantander, Javier (Author) / Kilbourne, Jacquelyn (Author) / Park, Jie Yeun (Author) / Martin, Taylor (Author) / Loh, Amanda (Author) / Diaz, Ignacia (Author) / Rojas, Robert (Author) / Segovia, Cristopher (Author) / DeNardo, Dale (Author) / Curtiss, Roy (Author) / ASU Biodesign Center Immunotherapy, Vaccines and Virotherapy (Contributor) / Biodesign Institute (Contributor)
Created2014-08-01
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Description

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

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.

Created2014-07-31
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Description

We report the results of an ethnographic study of a natural food cooperative in which we found an inherent tension in its mission between idealism and pragmatism, and we explore the dynamics through which that tension was managed and engaged in day-to-day governance and activities. Insights from participant observation, archival

We report the results of an ethnographic study of a natural food cooperative in which we found an inherent tension in its mission between idealism and pragmatism, and we explore the dynamics through which that tension was managed and engaged in day-to-day governance and activities. Insights from participant observation, archival data, semi-structured interviews, and surveys provide a detailed and holistic account of the intergroup and intragroup processes through which the co-op negotiated its dualistic nature, as embodied in its hybrid organizational identity. The findings suggest that the value of each side of the duality was recognized at both the individual and organizational levels. Members’ discomfort with the duality, however, led them to split the mission in two and identify with one part, while projecting their less-favored part on others, creating an identity foil (an antithesis). This splitting resulted in ingroups and outgroups and heated intergroup conflict over realizing cooperative ideals vs. running a viable business. Ingroup members favoring one part of the mission nonetheless identified with the outgroup favoring the other because it embodied a side of themselves they continued to value. Individuals who exemplified their ingroup’s most extreme attributes were seen by the outgroup as prototypical, thus serving as “lightning rods” for intergroup conflict; this dynamic paradoxically enabled other ingroup members to work more effectively with moderate members of the outgroup. The idealist–pragmatist duality was kept continually in play over time through oscillating decisions and actions that shifted power from one group to the other, coupled with ongoing rituals to repair and maintain relationships disrupted by the messiness of the process. Thus ostensible dysfunctionality at the group level fostered functionality at the organizational level.

ContributorsAshforth, Blake (Author) / Reingen, J. (Author) / W.P. Carey School of Business (Contributor)
Created2014-09-01
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Description

Deposits of dark material appear on Vesta’s surface as features of relatively low-albedo in the visible wavelength range of Dawn’s camera and spectrometer. Mixed with the regolith and partially excavated by younger impacts, the material is exposed as individual layered outcrops in crater walls or ejecta patches, having been uncovered

Deposits of dark material appear on Vesta’s surface as features of relatively low-albedo in the visible wavelength range of Dawn’s camera and spectrometer. Mixed with the regolith and partially excavated by younger impacts, the material is exposed as individual layered outcrops in crater walls or ejecta patches, having been uncovered and broken up by the impact. Dark fans on crater walls and dark deposits on crater floors are the result of gravity-driven mass wasting triggered by steep slopes and impact seismicity. The fact that dark material is mixed with impact ejecta indicates that it has been processed together with the ejected material. Some small craters display continuous dark ejecta similar to lunar dark-halo impact craters, indicating that the impact excavated the material from beneath a higher-albedo surface. The asymmetric distribution of dark material in impact craters and ejecta suggests non-continuous distribution in the local subsurface. Some positive-relief dark edifices appear to be impact-sculpted hills with dark material distributed over the hill slopes.

Dark features inside and outside of craters are in some places arranged as linear outcrops along scarps or as dark streaks perpendicular to the local topography. The spectral characteristics of the dark material resemble that of Vesta’s regolith. Dark material is distributed unevenly across Vesta’s surface with clusters of all types of dark material exposures. On a local scale, some craters expose or are associated with dark material, while others in the immediate vicinity do not show evidence for dark material. While the variety of surface exposures of dark material and their different geological correlations with surface features, as well as their uneven distribution, indicate a globally inhomogeneous distribution in the subsurface, the dark material seems to be correlated with the rim and ejecta of the older Veneneia south polar basin structure. The origin of the dark material is still being debated, however, the geological analysis suggests that it is exogenic, from carbon-rich low-velocity impactors, rather than endogenic, from freshly exposed mafic material or melt, exposed or created by impacts.

ContributorsJaumann, R. (Author) / Nass, A. (Author) / Otto, K. (Author) / Krohn, K. (Author) / Stephan, K. (Author) / McCord, T. B. (Author) / Williams, David (Author) / Raymond, C. A. (Author) / Blewett, D. T. (Author) / Hiesinger, H. (Author) / Yingst, R. A. (Author) / De Sanctis, M. C. (Author) / Palomba, E. (Author) / Roatsch, T. (Author) / Matz, K-D. (Author) / Preusker, F. (Author) / Scholten, F. (Author) / Russell, C. T. (Author) / College of Liberal Arts and Sciences (Contributor)
Created2014-09-15
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Description

Mobile applications markets with app stores have introduced a new approach to define and sell software applications with access to a large body of heterogeneous consumer population. This research examines key seller- and app-level characteristics that impact success in an app store market. We tracked individual apps and their presence

Mobile applications markets with app stores have introduced a new approach to define and sell software applications with access to a large body of heterogeneous consumer population. This research examines key seller- and app-level characteristics that impact success in an app store market. We tracked individual apps and their presence in the top-grossing 300 chart in Apple's App Store and examined how factors at different levels affect the apps' survival in the top 300 chart. We used a generalized hierarchical modeling approach to measure sales performance, and confirmed the results with the use of a hazard model and a count regression model. We find that broadening app offerings across multiple categories is a key determinant that contributes to a higher probability of survival in the top charts. App-level attributes such as free app offers, high initial ranks, investment in less-popular (less-competitive) categories, continuous quality updates, and high-volume and high-user review scores have positive effects on apps' sustainability. In general, each diversification decision across a category results in an approximately 15 percent increase in the presence of an app in the top charts. Survival rates for free apps are up to two times more than that for paid apps. Quality (feature) updates to apps can contribute up to a threefold improvement in survival rate as well. A key implication of the results of this study is that sellers must utilize the natural segmentation in consumer tastes offered by the different categories to improve sales performance.

ContributorsLee, Gun-woong (Author) / Santanam, Raghu (Author) / W.P. Carey School of Business (Contributor)
Created2013-11-30
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Description

Evolutionary dynamical models for cyclic competitions of three species (e.g., rock, paper, and scissors, or RPS) provide a paradigm, at the microscopic level of individual interactions, to address many issues in coexistence and biodiversity. Real ecosystems often involve competitions among more than three species. By extending the RPS game model

Evolutionary dynamical models for cyclic competitions of three species (e.g., rock, paper, and scissors, or RPS) provide a paradigm, at the microscopic level of individual interactions, to address many issues in coexistence and biodiversity. Real ecosystems often involve competitions among more than three species. By extending the RPS game model to five (rock-paper-scissors-lizard-Spock, or RPSLS) mobile species, we uncover a fundamental type of mesoscopic interactions among subgroups of species. In particular, competitions at the microscopic level lead to the emergence of various local groups in different regions of the space, each involving three species. It is the interactions among the groups that fundamentally determine how many species can coexist. In fact, as the mobility is increased from zero, two transitions can occur: one from a five- to a three-species coexistence state and another from the latter to a uniform, single-species state. We develop a mean-field theory to show that, in order to understand the first transition, group interactions at the mesoscopic scale must be taken into account. Our findings suggest, more broadly, the importance of mesoscopic interactions in coexistence of great many species.

ContributorsCheng, Hongyan (Author) / Yao, Nan (Author) / Huang, Zi-Gang (Author) / Park, Junpyo (Author) / Do, Younghae (Author) / Lai, Ying-Cheng (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2014-12-15
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Description

The current research examines how the price of a medication influences consumers’ beliefs about their own disease risk—a critical question with new laws mandating greater price transparency for health care goods and services. Four studies reveal that consumers believe that lifesaving health goods are priced according to perceived need (i.e.,

The current research examines how the price of a medication influences consumers’ beliefs about their own disease risk—a critical question with new laws mandating greater price transparency for health care goods and services. Four studies reveal that consumers believe that lifesaving health goods are priced according to perceived need (i.e., communal-sharing principles) and that price consequently influences risk perceptions and intentions to consume care. Specifically, consumers believe that lower medication prices signal greater accessibility to anyone in need, and such accessibility thus makes them feel that their own self-risk is elevated, increasing consumption. The reverse is true for higher prices. Importantly, these effects are limited to self-relevant health threats and reveal that consumers make inconsistent assumptions about risk, prevalence, and need with price exposure. These findings suggest that while greater price transparency may indeed reduce consumption of higher-priced goods, it may do so for both necessary and unnecessary care.

ContributorsSamper, Adriana (Author) / Schwartz, Janet A. (Author) / W.P. Carey School of Business (Contributor)
Created2012-11-14
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Description

Consumers often face situations in which their feelings of personal control are threatened. In such contexts, what role should products play in helping consumers pursue their goals (e.g., losing weight, maintaining a clean home)? Across five studies, we challenge the traditional view that low control is detrimental to effort and

Consumers often face situations in which their feelings of personal control are threatened. In such contexts, what role should products play in helping consumers pursue their goals (e.g., losing weight, maintaining a clean home)? Across five studies, we challenge the traditional view that low control is detrimental to effort and demonstrate that consumers prefer products that require them to engage in hard work when feelings of control are low. Such high-effort products reassure individuals that desired outcomes are possible while also enabling them to feel as if they have driven their own outcomes. We also identify important boundary conditions, finding that both the nature of individuals' thoughts about control and their perceived rate of progress toward goals are important factors in the desire to exert increased effort.

ContributorsCutright, Keisha M. (Author) / Samper, Adriana (Author) / W.P. Carey School of Business (Contributor)
Created2014-10-01
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Description

This paper studies an infinite-horizon repeated moral hazard problem where a single principal employs several agents. We assume that the principal cannot observe the agents' effort choices; however, agents can observe each other and can be contractually required to make observation reports to the principal. Observation reports, if truthful, can

This paper studies an infinite-horizon repeated moral hazard problem where a single principal employs several agents. We assume that the principal cannot observe the agents' effort choices; however, agents can observe each other and can be contractually required to make observation reports to the principal. Observation reports, if truthful, can serve as a monitoring instrument to discipline the agents. However, reports are cheap talk so that it is also possible for agents to collude, i.e., where they shirk, earn rents, and report otherwise to the principal. The main result of the paper constructs a class of collusion-proof contracts with two properties. First, equilibrium payoffs to both the principal and the agents approach their first-best benchmarks as the discount factor tends to unity. These payoff bounds apply to all subgame perfect equilibria in the game induced by the contract. Second, while equilibria themselves depend on the discount factor, the contract that induces these equilibria is independent of the discount factor.

ContributorsChandrasekher, Madhav (Author) / W.P. Carey School of Business (Contributor)
Created2015-01-01
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Description

The impacts of information technology (IT) on total factor productivity (TFP) are assessed through an integrative framework of IT-induced externalities and IT-leveraged innovations. Based on network externalities and endogenous growth theory, our study aims to reconcile the seeming discrepancy between the recent observed evidence and the prediction by neoclassical growth

The impacts of information technology (IT) on total factor productivity (TFP) are assessed through an integrative framework of IT-induced externalities and IT-leveraged innovations. Based on network externalities and endogenous growth theory, our study aims to reconcile the seeming discrepancy between the recent observed evidence and the prediction by neoclassical growth theory. We argue that computerization has reshaped the competitive landscape into a network economy with IT-induced externalities that benefit not only IT purchasers but also other stakeholders. Moreover, IT is a platform technology that can leverage innovations to enhance the technological level of production process. Consequently, these two factors of IT-induced externalities and IT-leveraged innovations exert positive impacts on TFP, suggesting IT plays a more pivotal role than input consumption and accumulation that neoclassical growth theory assumes for IT. We use panel data from 30 Organization of Economic Cooperation and Development (OECD) countries over the period of 2000–2009 to empirically test hypotheses on this IT-TFP link. Implications are drawn from our findings for future research to measure IT׳s contributions at the macro level more accurately, and policymakers are urged to cultivate IT׳s positive impacts on TFP to help sustain long-term economic growth.

ContributorsChou, Yen-Chun (Author) / Chuang, Howard Hao-Chun (Author) / Shao, Benjamin (Author) / W.P. Carey School of Business (Contributor)
Created2014-12-01