ASU Scholarship Showcase

The Florence Statement on Triclosan and Triclocarban documents a consensus of more than 200 scientists and medical professionals on the hazards of and lack of demonstrated benefit from common uses of triclosan and triclocarban. These chemicals may be used in thousands of personal care and consumer products as well as in building materials. Based on extensive peer-reviewed research, this statement concludes that triclosan and triclocarban are environmentally persistent endocrine disruptors that bioaccumulate in and are toxic to aquatic and other organisms. Evidence of other hazards to humans and ecosystems from triclosan and triclocarban is presented along with recommendations intended to prevent future harm from triclosan, triclocarban, and antimicrobial substances with similar properties and effects. Because antimicrobials can have unintended adverse health and environmental impacts, they should only be used when they provide an evidence-based health benefit. Greater transparency is needed in product formulations, and before an antimicrobial is incorporated into a product, the long-term health and ecological impacts should be evaluated.

Salmonella enterica serovar Typhimurium genome encodes 13 fimbrial operons. Most of the fimbriae encoded by these operons are not produced under laboratory conditions but are likely to be synthesized in vivo. We used an in vivo expression technology (IVET) strategy to identify four fimbrial operons, agf, saf, sti, and stc that are expressed in the spleen. When any three of these operons were deleted, the strain retained wild-type virulence. However, when all four operons were deleted, the resulting strain was completely attenuated, indicating that these four fimbriae play functionally redundant roles critical for virulence. In mice, oral doses of as low as 1 × 10[superscript 5] CFU of the strain with four fimbrial operons deleted provided 100% protection against challenge with 1 × 10[superscript 9] CFU of wild-type S. Typhimurium. We also examined the possible effect of these fimbriae on the ability of a Salmonella vaccine strain to deliver a guest antigen. We modified one of our established attenuated vaccine strains, χ9088, to delete three fimbrial operons while the fourth operon was constitutively expressed. Each derivative was modified to express the Streptococcus pneumoniae antigen PspA. Strains that constitutively expressed saf or stc elicited a strong Th1 response with significantly greater levels of anti-PspA serum IgG and greater protective efficacy than strains carrying saf or stc deletions. The isogenic strain in which all four operons were deleted generated the lowest anti-PspA levels and did not protect against challenge with virulent S. pneumoniae. Our results indicate that these fimbriae play important roles, as yet not understood, in Salmonella virulence and immunogenicity.

Antibiotic-resistant bacterial infections are difficult to treat, producing a burden on healthcare and the economy. Extraintestinal pathogenic Escherichia coli (ExPEC) strains frequently carry antibiotic resistance genes, cause infections outside of the intestine, and are causative agents of hospital-acquired infections. Developing a prevention strategy against this pathogen is challenging due to its antibiotic resistance and antigenic diversity. E. coli common pilus (ECP) is frequently found in ExPEC strains and may serve as a common antigen to induce protection against several ExPEC serotypes. In addition, live recombinant attenuated Salmonella vaccine (RASV) strains have been used to prevent Salmonella infection and can also be modified to deliver foreign antigens. Thus, the objective of this study was to design a RASV to produce ECP on its surface and assess its ability to provide protection against ExPEC infections. To constitutively display ECP in a RASV strain, we genetically engineered a vector (pYA4428) containing aspartate-β-semialdehyde dehydrogenase and E. coli ecp genes and introduced it into RASV χ9558. RASV χ9558 containing an empty vector (pYA3337) was used as a control to assess protection conferred by the RASV strain without ECP.

We assessed vaccine efficacy in in vitro bacterial inhibition assays and mouse models of ExPEC-associated human infections. We found that RASV χ9558(pYA4428) synthesized the major pilin (EcpA) and tip pilus adhesin (EcpD) on the bacterial surface. Mice orally vaccinated with RASV χ9558(pYA3337) without ECP or χ9558(pYA4428) with ECP, produced anti-Salmonella LPS and anti-E. coli EcpA and EcpD IgG and IgA antibodies. RASV strains showed protective potential against some E. coli and Salmonella strains as assessed using in vitro assays. In mouse sepsis and urinary tract infection challenge models, both vaccines had significant protection in some internal organs. Overall, this work showed that RASVs can elicit an immune response to E. coli and Salmonella antigens in some mice, provide significant protection in some internal organs during ExPEC challenge, and thus this study is a promising initial step toward developing a vaccine for prevention of ExPEC infections. Future studies should optimize the ExPEC antigens displayed by the RASV strain for a more robust immune response and enhanced protection against ExPEC infection.

Evolutionary games model a common type of interactions in a variety of complex, networked, natural systems and social systems. Given such a system, uncovering the interacting structure of the underlying network is key to understanding its collective dynamics. Based on compressive sensing, we develop an efficient approach to reconstructing complex networks under game-based interactions from small amounts of data. The method is validated by using a variety of model networks and by conducting an actual experiment to reconstruct a social network. While most existing methods in this area assume oscillator networks that generate continuous-time data, our work successfully demonstrates that the extremely challenging problem of reverse engineering of complex networks can also be addressed even when the underlying dynamical processes are governed by realistic, evolutionary-game type of interactions in discrete time.

The Future of Wastewater Sensing workshop is part of a collaboration between Arizona State University Center for Nanotechnology in Society in the School for the Future of Innovation in Society, the Biodesign Institute’s Center for Environmental Security, LC Nano, and the Nano-enabled Water Treatment (NEWT) Systems NSF Engineering Research Center. The Future of Wastewater Sensing workshop explores how technologies for studying, monitoring, and mining wastewater and sewage sludge might develop in the future, and what consequences may ensue for public health, law enforcement, private industry, regulations and society at large. The workshop pays particular attention to how wastewater sensing (and accompanying research, technologies, and applications) can be innovated, regulated, and used to maximize societal benefit and minimize the risk of adverse outcomes, when addressing critical social and environmental challenges.

Controlling complex networks has become a forefront research area in network science and engineering. Recent efforts have led to theoretical frameworks of controllability to fully control a network through steering a minimum set of driver nodes. However, in realistic situations not every node is accessible or can be externally driven, raising the fundamental issue of control efficacy: if driving signals are applied to an arbitrary subset of nodes, how many other nodes can be controlled? We develop a framework to determine the control efficacy for undirected networks of arbitrary topology. Mathematically, based on non-singular transformation, we prove a theorem to determine rigorously the control efficacy of the network and to identify the nodes that can be controlled for any given driver nodes. Physically, we develop the picture of diffusion that views the control process as a signal diffused from input signals to the set of controllable nodes. The combination of mathematical theory and physical reasoning allows us not only to determine the control efficacy for model complex networks and a large number of empirical networks, but also to uncover phenomena in network control, e.g., hub nodes in general possess lower control centrality than an average node in undirected networks.

We designed and evaluated an active sampling device, using as analytical targets a family of pesticides purported to contribute to honeybee colony collapse disorder. Simultaneous sampling of bulk water and pore water was accomplished using a low-flow, multi-channel pump to deliver water to an array of solid-phase extraction cartridges. Analytes were separated using either liquid or gas chromatography, and analysis was performed using tandem mass spectrometry (MS/MS). Achieved recoveries of fipronil and degradates in water spiked to nominal concentrations of 0.1, 1, and 10 ng/L ranged from 77 ± 12 to 110 ± 18%. Method detection limits (MDLs) were as low as 0.040–0.8 ng/L. Extraction and quantitation of total fiproles at a wastewater-receiving wetland yielded concentrations in surface water and pore water ranging from 9.9 ± 4.6 to 18.1 ± 4.6 ng/L and 9.1 ± 3.0 to 12.6 ± 2.1 ng/L, respectively. Detected concentrations were statistically indistinguishable from those determined by conventional, more laborious techniques (p > 0.2 for the three most abundant fiproles). Aside from offering time-averaged sampling capabilities for two phases simultaneously with picogram-per-liter MDLs, the novel methodology eliminates the need for water and sediment transport via in situ solid phase extraction.

A challenging problem in network science is to control complex networks. In existing frameworks of structural or exact controllability, the ability to steer a complex network toward any desired state is measured by the minimum number of required driver nodes. However, if we implement actual control by imposing input signals on the minimum set of driver nodes, an unexpected phenomenon arises: due to computational or experimental error there is a great probability that convergence to the final state cannot be achieved. In fact, the associated control cost can become unbearably large, effectively preventing actual control from being realized physically. The difficulty is particularly severe when the network is deemed controllable with a small number of drivers. Here we develop a physical controllability framework based on the probability of achieving actual control. Using a recently identified fundamental chain structure underlying the control energy, we offer strategies to turn physically uncontrollable networks into physically controllable ones by imposing slightly augmented set of input signals on properly chosen nodes. Our findings indicate that, although full control can be theoretically guaranteed by the prevailing structural controllability theory, it is necessary to balance the number of driver nodes and control cost to achieve physical control.

Outer membrane vesicles (OMVs) isolated from Salmonella Typhimurium are potentially useful for developing subunit vaccines because of high immunogenicity and protective efficacy. However, flagella might remain in OMV pellets following OMV purification, resulting in non-essential immune responses and counteraction of bacterial protective immune responses when developing a vaccine against infection of multiple serotypes Salmonella. In this study, a flagellin-deficient S. Typhimurium mutant was constructed. Lipopolysaccharide profiles, protein profiles and cryo-electron microscopy revealed that there were no significant differences between the wild-type and mutant OMVs, with the exception of a large amount of flagellin in the wild-type OMVs. Neither the wild-type OMVs nor the non-flagellin OMVs were toxic to macrophages. Mice immunized with the non-flagellin OMVs produced high concentrations of IgG. The non-flagellin OMVs elicited strong mucosal antibody responses in mice when administered via the intranasal route in addition to provoking higher cross-reactive immune responses against OMPs isolated from S. Choleraesuis and S. Enteritidis. Both intranasal and intraperitoneal immunization with the non-flagellin OMVs provided efficient protection against heterologous S. Choleraesuis and S. Enteritidis challenge. Our results indicate that the flagellin-deficient OMVs may represent a new vaccine platform that could be exploited to facilitate the production of a broadly protective vaccine.

In spite of the recent interest and advances in linear controllability of complex networks, controlling nonlinear network dynamics remains an outstanding problem. Here we develop an experimentally feasible control framework for nonlinear dynamical networks that exhibit multistability. The control objective is to apply parameter perturbation to drive the system from one attractor to another, assuming that the former is undesired and the latter is desired. To make our framework practically meaningful, we consider restricted parameter perturbation by imposing two constraints: it must be experimentally realizable and applied only temporarily. We introduce the concept of attractor network, which allows us to formulate a quantifiable controllability framework for nonlinear dynamical networks: a network is more controllable if the attractor network is more strongly connected. We test our control framework using examples from various models of experimental gene regulatory networks and demonstrate the beneficial role of noise in facilitating control.