ASU Scholarship Showcase

In this study, we examine how development status and water scarcity shape people's perceptions of "hard path" and "soft path" water solutions. Based on ethnographic research conducted in four semi-rural/peri-urban sites (in Bolivia, Fiji, New Zealand, and the US), we use content analysis to conduct statistical and thematic comparisons of interview data. Our results indicate clear differences associated with development status and, to a lesser extent, water scarcity. People in the two less developed sites were more likely to suggest hard path solutions, less likely to suggest soft path solutions, and more likely to see no path to solutions than people in the more developed sites. Thematically, people in the two less developed sites envisioned solutions that involve small-scale water infrastructure and decentralized, community-based solutions, while people in the more developed sites envisioned solutions that involve large-scale infrastructure and centralized, regulatory water solutions. People in the two water-scarce sites were less likely to suggest soft path solutions and more likely to see no path to solutions (but no more likely to suggest hard path solutions) than people in the water-rich sites. Thematically, people in the two water-rich sites seemed to perceive a wider array of unrealized potential soft path solutions than those in the water-scarce sites. On balance, our findings are encouraging in that they indicate that people are receptive to soft path solutions in a range of sites, even those with limited financial or water resources. Our research points to the need for more studies that investigate the social feasibility of soft path water solutions, particularly in sites with significant financial and natural resource constraints.

Many population centers in the American West rely on water from the Colorado River Basin, which has faced shortages in recent years that are anticipated to be exacerbated by climate change. Shortages to urban water supplies related to climate change will not be limited to cities dependent on the Colorado River. Considering this, addressing sustainable water governance is timely and critical for cities, states, and regions facing supply shortages and pollution problems. Engaging in sustainability transitions of these hydro-social systems will increase the ability of such systems to meet the water needs of urban communities. In this paper, we identify historical transitions in water governance and examine their context for three sites in the Colorado River Basin (Denver, Colorado, Las Vegas, Nevada, and Phoenix, Arizona) to provide insight for intentional transitions towards sustainable, or “water sensitive” cities. The comparative historical approach employed allows us to more fully understand differences in present-day water governance decisions between the sites, identify past catalysts for transitions, and recognize emerging patterns and opportunities that may impact current and future water governance in the Colorado River Basin and beyond.

There are an increasing variety of applications in which peptides are both synthesized and used attached to solid surfaces. This has created a need for high throughput sequence analysis directly on surfaces. However, common sequencing approaches that can be adapted to surface bound peptides lack the throughput often needed in library-based applications. Here we describe a simple approach for sequence analysis directly on solid surfaces that is both high speed and high throughput, utilizing equipment available in most protein analysis facilities. In this approach, surface bound peptides, selectively labeled at their N-termini with a positive charge-bearing group, are subjected to controlled degradation in ammonia gas, resulting in a set of fragments differing by a single amino acid that remain spatially confined on the surface they were bound to. These fragments can then be analyzed by MALDI mass spectrometry, and the peptide sequences read directly from the resulting spectra.

Recent infectious outbreaks highlight the need for platform technologies that can be quickly deployed to develop therapeutics needed to contain the outbreak. We present a simple concept for rapid development of new antimicrobials. The goal was to produce in as little as one week thousands of doses of an intervention for a new pathogen. We tested the feasibility of a system based on antimicrobial synbodies. The system involves creating an array of 100 peptides that have been selected for broad capability to bind and/or kill viruses and bacteria. The peptides are pre-screened for low cell toxicity prior to large scale synthesis. Any pathogen is then assayed on the chip to find peptides that bind or kill it. Peptides are combined in pairs as synbodies and further screened for activity and toxicity. The lead synbody can be quickly produced in large scale, with completion of the entire process in one week.

Understanding the food-energy-water nexus is necessary to identify risks and inform strategies for nexus governance to support resilient, secure, and sustainable societies. To manage risks and realize efficiencies, we must understand not only how these systems are physically connected but also how they are institutionally linked. It is important to understand how actors who make planning, management, and policy decisions understand the relationships among components of the systems. Our question is: How do stakeholders involved in food, energy, and water governance in Phoenix, Arizona understand the nexus and what are the implications for integrated nexus governance? We employ a case study design, generate qualitative data through focus groups and interviews, and conduct a content analysis. While stakeholders in the Phoenix area who are actively engaged in food, energy, and water systems governance appreciate the rationale for nexus thinking, they recognize practical limitations to implementing these concepts. Concept maps of nexus interactions provide one view of system interconnections that be used to complement other ways of knowing the nexus, such as physical infrastructure system diagrams or actor-networks. Stakeholders believe nexus governance could be improved through awareness and education, consensus and collaboration, transparency, economic incentives, working across scales, and incremental reforms.

Antigen-antibody complexes are central players in an effective immune response. However, finding those interactions relevant to a particular disease state can be arduous. Nonetheless many paths to discovery have been explored since deciphering these interactions can greatly facilitate the development of new diagnostics, therapeutics, and vaccines. In silico B cell epitope mapping approaches have been widely pursued, though success has not been consistent. Antibody mixtures in immune sera have been used as handles for biologically relevant antigens, but these and other experimental approaches have proven resource intensive and time consuming. In addition, these methods are often tailored to individual diseases or a specific proteome, rather than providing a universal platform. Most of these methods are not able to identify the specific antibody’s epitopes from unknown antigens, such as un-annotated neo antigens in cancer. Alternatively, a peptide library comprised of sequences unrestricted by naturally-found protein space provides for a universal search for mimotopes of an antibody’s epitope. Here we present the utility of such a non-natural random sequence library of 10,000 peptides physically addressed on a microarray for mimotope discovery without sequence information of the specific antigen. The peptide arrays were probed with serum from an antigen-immunized rabbit, or alternatively probed with serum pre-absorbed with the same immunizing antigen. With this positive and negative screening scheme, we identified the library-peptides as the mimotopes of the antigen. The unique library peptides were successfully used to isolate antigen-specific antibodies from complete immune serum. Sequence analysis of these peptides revealed the epitopes in the immunized antigen. We present this method as an inexpensive, efficient method for identifying mimotopes of any antibody’s targets. These mimotopes should be useful in defining both components of the antigen-antibody complex.

Immunosignaturing shows promise as a general approach to diagnosis. It has been shown to detect immunological signs of infection early during the course of disease and to distinguish Alzheimer’s disease from healthy controls. Here we test whether immunosignatures correspond to clinical classifications of disease using samples from people with brain tumors. Blood samples from patients undergoing craniotomies for therapeutically naïve brain tumors with diagnoses of astrocytoma (23 samples), Glioblastoma multiforme (22 samples), mixed oligodendroglioma/astrocytoma (16 samples), oligodendroglioma (18 samples), and 34 otherwise healthy controls were tested by immunosignature. Because samples were taken prior to adjuvant therapy, they are unlikely to be perturbed by non-cancer related affects. The immunosignaturing platform distinguished not only brain cancer from controls, but also pathologically important features about the tumor including type, grade, and the presence or absence of O⁶-methyl-guanine-DNA methyltransferase methylation promoter (MGMT), an important biomarker that predicts response to temozolomide in Glioblastoma multiformae patients.

Background: The success of new sequencing technologies and informatic methods for identifying genes has made establishing gene product function a critical rate limiting step in progressing the molecular sciences. We present a method to functionally mine genomes for useful activities in vivo, using an unusual property of a member of the poxvirus family to demonstrate this screening approach.

Results: The genome of Parapoxvirus ovis (Orf virus) was sequenced, annotated, and then used to PCR-amplify its open-reading-frames. Employing a cloning-independent protocol, a viral expression-library was rapidly built and arrayed into sub-library pools. These were directly delivered into mice as expressible cassettes and assayed for an immune-modulating activity associated with parapoxvirus infection. The product of the B2L gene, a homolog of vaccinia F13L, was identified as the factor eliciting immune cell accumulation at sites of skin inoculation. Administration of purified B2 protein also elicited immune cell accumulation activity, and additionally was found to serve as an adjuvant for antigen-specific responses. Co-delivery of the B2L gene with an influenza gene-vaccine significantly improved protection in mice. Furthermore, delivery of the B2L expression construct, without antigen, non-specifically reduced tumor growth in murine models of cancer.

Conclusion: A streamlined, functional approach to genome-wide screening of a biological activity in vivo is presented. Its application to screening in mice for an immune activity elicited by the pathogen genome of Parapoxvirus ovis yielded a novel immunomodulator. In this inverted discovery method, it was possible to identify the adjuvant responsible for a function of interest prior to a mechanistic study of the adjuvant. The non-specific immune activity of this modulator, B2, is similar to that associated with administration of inactivated particles to a host or to a live viral infection. Administration of B2 may provide the opportunity to significantly impact host immunity while being itself only weakly recognized. The functional genomics method used to pinpoint B2 within an ORFeome may be more broadly applicable to screening for other biological activities in an animal.

Background: Immunosignaturing is a new peptide microarray based technology for profiling of humoral immune responses. Despite new challenges, immunosignaturing gives us the opportunity to explore new and fundamentally different research questions. In addition to classifying samples based on disease status, the complex patterns and latent factors underlying immunosignatures, which we attempt to model, may have a diverse range of applications.

Methods: We investigate the utility of a number of statistical methods to determine model performance and address challenges inherent in analyzing immunosignatures. Some of these methods include exploratory and confirmatory factor analyses, classical significance testing, structural equation and mixture modeling.

Results: We demonstrate an ability to classify samples based on disease status and show that immunosignaturing is a very promising technology for screening and presymptomatic screening of disease. In addition, we are able to model complex patterns and latent factors underlying immunosignatures. These latent factors may serve as biomarkers for disease and may play a key role in a bioinformatic method for antibody discovery.

Conclusion: Based on this research, we lay out an analytic framework illustrating how immunosignatures may be useful as a general method for screening and presymptomatic screening of disease as well as antibody discovery.

Complexities and uncertainties surrounding urbanization and climate change complicate water resource sustainability. Although research has examined various aspects of complex water systems, including uncertainties, relatively few attempts have been made to synthesize research findings in particular contexts. We fill this gap by examining the complexities, uncertainties, and decision processes for water sustainability and urban adaptation to climate change in the case study region of Phoenix, Arizona. In doing so, we integrate over a decade of research conducted by Arizona State University’s Decision Center for a Desert City (DCDC). DCDC is a boundary organization that conducts research in collaboration with policy makers, with the goal of informing decision-making under uncertainty. Our results highlight: the counterintuitive, non-linear, and competing relationships in human–environment dynamics; the myriad uncertainties in climatic, scientific, political, and other domains of knowledge and practice; and, the social learning that has occurred across science and policy spheres. Finally, we reflect on how our interdisciplinary research and boundary organization has evolved over time to enhance adaptive and sustainable governance in the face of complex system dynamics.