Matching Items (87)
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Description
Urban areas across the Unites States are facing a housing affordability crisis. One approach some cities and states have taken is to reduce or eliminate single-family zoning. Single-family zoning prevents the construction of more-affordable apartments in vast swaths of the American urban landscape. This policy shift has already occurred in

Urban areas across the Unites States are facing a housing affordability crisis. One approach some cities and states have taken is to reduce or eliminate single-family zoning. Single-family zoning prevents the construction of more-affordable apartments in vast swaths of the American urban landscape. This policy shift has already occurred in Minneapolis, Sacramento, and Oregon, and is under discussion in California, Massachusetts, and North Carolina, among others. Independent of any effects on housing affordability, changes to land use will have effects on transport. I evaluate these effects using a microsimulation framework. In order for land use policies to have an effect on transport, they need to first have an effect on land use, so I first build an economic model to simulate where development will occur given a loosening of single-family zoning. Transport outcomes will vary depending on which households live in which parts of the region, so I use an equilibrium sorting model to forecast how residents will re-sort across the region in response to the land use changes induced by new land-use policies. This model also jointly forecasts how many vehicles each household will choose to own. Finally, I apply an activity-based travel demand microsimulation model to forecast the changes in transport associated with the forecast changes from the previous models. I find that while there is opportunity for economically-feasible redevelopment of single-family homes into multifamily structures, the amount of redevelopment that will occur varies greatly depending on the exact expectations of developers about future market conditions. Redevelopment is focused in higher-income neighborhoods. The transport effects of the redevelopment are minimal. Average car ownership across the region does not change hardly at all, although residents of new housing units do have somewhat lower car ownership. Vehicles kilometers traveled, mode choice, and congestion change very little as well. This does not mean that upzoning does not affect transport in general, but that more nuanced proposals may be necessary to promote desirable transport outcomes. Alternatively, the results suggest that upzoning will not worsen transport outcomes, promising for those who support upzoning on affordability grounds.
ContributorsConway, Matthew Wigginton (Author) / Salon, Deborah (Thesis advisor) / Pfeiffer, Deirdre (Committee member) / Fotheringham, A Stewart (Committee member) / van Eggermond, Michael AB (Committee member) / Arizona State University (Publisher)
Created2021
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Description
RNA aptamers adopt tertiary structures that enable them to bind to specific ligands. This capability has enabled aptamers to be used for a variety of diagnostic, therapeutic, and regulatory applications. This dissertation focuses on the use RNA aptamers in two biological applications: (1) nucleic acid diagnostic assays and (2) scaffolding

RNA aptamers adopt tertiary structures that enable them to bind to specific ligands. This capability has enabled aptamers to be used for a variety of diagnostic, therapeutic, and regulatory applications. This dissertation focuses on the use RNA aptamers in two biological applications: (1) nucleic acid diagnostic assays and (2) scaffolding of enzymatic pathways. First, sensors for detecting arbitrary target RNAs based the fluorogenic RNA aptamer Broccoli are designed and validated. Studies of three different sensor designs reveal that toehold-initiated Broccoli-based aptasensors provide the lowest signal leakage and highest signal intensity in absence and in presence of the target RNA, respectively. This toehold-initiated design is used for developing aptasensors targeting pathogens. Diagnostic assays for detecting pathogen nucleic acids are implemented by integrating Broccoli-based aptasensors with isothermal amplification methods. When coupling with recombinase polymerase amplification (RPA), aptasensors enable detection of synthetic valley fever DNA down to concentrations of 2 fM. Integration of Broccoli-based aptasensors with nucleic acid sequence-based amplification (NASBA) enables as few as 120 copies/mL of synthetic dengue RNA to be detected in reactions taking less than three hours. Moreover, the aptasensor-NASBA assay successfully detects dengue RNA in clinical samples. Second, RNA scaffolds containing peptide-binding RNA aptamers are employed for programming the synthesis of nonribosomal peptides (NRPs). Using the NRP enterobactin pathway as a model, RNA scaffolds are developed to direct the assembly of the enzymes entE, entB, and entF from E. coli, along with the aryl-carrier protein dhbB from B. subtilis. These scaffolds employ X-shaped RNA motifs from bacteriophage packaging motors, kissing loop interactions from HIV, and peptide-binding RNA aptamers to position peptide-modified NRP enzymes. The resulting RNA scaffolds functionalized with different aptamers are designed and evaluated for in vitro production of enterobactin. The best RNA scaffold provides a 418% increase in enterobactin production compared with the system in absence of the RNA scaffold. Moreover, the chimeric scaffold, with E. coli and B. subtilis enzymes, reaches approximately 56% of the activity of the wild-type enzyme assembly. The studies presented in this dissertation will be helpful for future development of nucleic acid-based assays and for controlling protein interaction for NRPs biosynthesis.
ContributorsTang, Anli (Author) / Green, Alexander (Thesis advisor) / Yan, Hao (Committee member) / Woodbury, Neal (Committee member) / Arizona State University (Publisher)
Created2020
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Description
Elucidation of Antigen-Antibody (Ag-Ab) interactions is critical to the understanding of humoral immune responses to pathogenic infection. B cells are crucial components of the immune system that generate highly specific antibodies, such as IgG, towards epitopes on antigens. Serum IgG molecules carry specific molecular recognition information concerning the antigens that

Elucidation of Antigen-Antibody (Ag-Ab) interactions is critical to the understanding of humoral immune responses to pathogenic infection. B cells are crucial components of the immune system that generate highly specific antibodies, such as IgG, towards epitopes on antigens. Serum IgG molecules carry specific molecular recognition information concerning the antigens that initiated their production. If one could read it, this information can be used to predict B cell epitopes on target antigens in order to design effective epitope driven vaccines, therapies and serological assays. Immunosignature technology captures the specific information content of serum IgG from infected and uninfected individuals on high density microarrays containing ~105 nearly random peptide sequences. Although the sequences of the peptides are chosen to evenly cover amino acid sequence space, the pattern of serum IgG binding to the array contains a consistent signature associated with each specific disease (e.g., Valley fever, influenza) among many individuals. Here, the disease specific but agnostic behavior of the technology has been explored by profiling molecular recognition information for five pathogens causing life threatening infectious diseases (e.g. DENV, WNV, HCV, HBV, and T.cruzi). This was done by models developed using a machine learning algorithm to model the sequence dependence of the humoral immune responses as measured by the peptide arrays. It was shown that the disease specific binding information could be accurately related to the peptide sequences used on the array by the machine learning (ML) models. Importantly, it was demonstrated that the ML models could identify or predict known linear epitopes on antigens of the four viruses. Moreover, the models identified potential novel linear epitopes on antigens of the four viruses (each has 4-10 proteins in the proteome) and of T.cruzi (a eukaryotic parasite which has over 12,000 proteins in its proteome). Finally, the predicted epitopes were tested in serum IgG binding assays such as ELISAs. Unfortunately, the assay results were inconsistent due to problems with peptide/surface interactions. In a separate study for the development of antibody recruiting molecules (ARMs) to combat microbial infections, 10 peptides from the high density peptide arrays were tested in IgG binding assays using sera of healthy individuals to find a set of antibody binding termini (ABT, a ligand that binds to a variable region of the IgG). It was concluded that one peptide (peptide 7) may be used as a potential ABT. Overall, these findings demonstrate the applications of the immunosignature technology ranging from developing tools to predict linear epitopes on pathogens of small to large proteomes to the identification of an ABT for ARMs.
ContributorsCHOWDHURY, ROBAYET (Author) / Woodbury, Neal (Thesis advisor) / LaBaer, Joshua (Committee member) / Sulc, Petr (Committee member) / Arizona State University (Publisher)
Created2020
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Description
Interactions between proteins form the basis of almost all biological mechanisms. The majority of proteins perform their functions as a part of an assembled complex, rather than as an isolated species. Understanding the functional pathways of these protein complexes helps in uncovering the molecular mechanisms involved in the interactions. In

Interactions between proteins form the basis of almost all biological mechanisms. The majority of proteins perform their functions as a part of an assembled complex, rather than as an isolated species. Understanding the functional pathways of these protein complexes helps in uncovering the molecular mechanisms involved in the interactions. In this thesis, this has been explored in two fundamental ways. First, a biohybrid complex was assembled using the photosystem I (PSI) protein complex to translate the biochemical pathways into a non-cellular environment. This involved incorporating PSI on a porous antimony-doped tin oxide electrode using cytochrome c. Photocurrent was generated upon illumination of the PSI/electrode system alone at microamp/cm2 levels, with reduced oxygen apparently as the primary carrier. When the PSI/electrode system was coupled with ferredoxin, ferredoxin-NADP+ reductase (FNR), and NADP+, the resulting light-powered NADPH production was coupled to a dehydrogenase system for enzymatic carbon reduction. The results demonstrated that light-dependent reduction readily takes place. However, the pathways do not always match the biological pathways of PSI in nature. To create a complex self-assembled system such as the one involving PSI that is structurally well defined, there is a need to develop ways to guide the molecular interactions. In the second part of the thesis, this problem was approached by studying a well-defined system involving monoclonal antibodies (mAbs) binding their cognate epitope sequences to understand the molecular recognition properties associated with protein-protein interactions. This approach used a neural network model to derive a comprehensive and quantitative relationship between an amino acid sequence and its function by using sparse measurements of mAb binding to peptides on a high density peptide microarray. The resulting model can be used to predict the function of any peptide in the possible combinatorial sequence space. The results demonstrated that by training the model on just ~105 peptides out of the total combinatorial space of ~1010, the target sequences of the mAbs (cognate epitopes) can be predicted with high statistical accuracy. Furthermore, the biological relevance of the algorithm’s predictive ability has also been demonstrated.
ContributorsSingh, Akanksha (Author) / Woodbury, Neal (Thesis advisor) / Liu, Yan (Committee member) / Gould, Ian (Committee member) / Arizona State University (Publisher)
Created2021
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Description

Swinging arms are a key functional component of multistep catalytic transformations in many naturally occurring multi-enzyme complexes. This arm is typically a prosthetic chemical group that is covalently attached to the enzyme complex via a flexible linker, allowing the direct transfer of substrate molecules between multiple active sites within the

Swinging arms are a key functional component of multistep catalytic transformations in many naturally occurring multi-enzyme complexes. This arm is typically a prosthetic chemical group that is covalently attached to the enzyme complex via a flexible linker, allowing the direct transfer of substrate molecules between multiple active sites within the complex. Mimicking this method of substrate channelling outside the cellular environment requires precise control over the spatial parameters of the individual components within the assembled complex. DNA nanostructures can be used to organize functional molecules with nanoscale precision and can also provide nanomechanical control. Until now, protein–DNA assemblies have been used to organize cascades of enzymatic reactions by controlling the relative distance and orientation of enzymatic components or by facilitating the interface between enzymes/cofactors and electrode surfaces. Here, we show that a DNA nanostructure can be used to create a multi-enzyme complex in which an artificial swinging arm facilitates hydride transfer between two coupled dehydrogenases. By exploiting the programmability of DNA nanostructures, key parameters including position, stoichiometry and inter-enzyme distance can be manipulated for optimal activity.

ContributorsFu, Jinglin (Author) / Yang, Yuhe (Author) / Johnson-Buck, Alexander (Author) / Liu, Minghui (Author) / Liu, Yan (Author) / Walter, Nils G. (Author) / Woodbury, Neal (Author) / Yan, Hao (Author) / Biodesign Institute (Contributor)
Created2014-07-01
Description

A structurally and compositionally well-defined and spectrally tunable artificial light-harvesting system has been constructed in which multiple organic dyes attached to a three-arm-DNA nanostructure serve as an antenna conjugated to a photosynthetic reaction center isolated from Rhodobacter sphaeroides 2.4.1. The light energy absorbed by the dye molecules is transferred to

A structurally and compositionally well-defined and spectrally tunable artificial light-harvesting system has been constructed in which multiple organic dyes attached to a three-arm-DNA nanostructure serve as an antenna conjugated to a photosynthetic reaction center isolated from Rhodobacter sphaeroides 2.4.1. The light energy absorbed by the dye molecules is transferred to the reaction center, where charge separation takes place. The average number of DNA three-arm junctions per reaction center was tuned from 0.75 to 2.35. This DNA-templated multichromophore system serves as a modular light-harvesting antenna that is capable of being optimized for its spectral properties, energy transfer efficiency, and photostability, allowing one to adjust both the size and spectrum of the resulting structures. This may serve as a useful test bed for developing nanostructured photonic systems.

ContributorsDutta, Palash (Author) / Levenberg, Symon (Author) / Loskutov, Andrey (Author) / Jun, Daniel (Author) / Saer, Rafael (Author) / Beatty, J. Thomas (Author) / Lin, Su (Author) / Liu, Yan (Author) / Woodbury, Neal (Author) / Yan, Hao (Author) / Department of Chemistry and Biochemistry (Contributor)
Created2014-11-26
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Description

What's a profession without a code of ethics? Being a legitimate profession almost requires drafting a code and, at least nominally, making members follow it. Codes of ethics (henceforth “codes”) exist for a number of reasons, many of which can vary widely from profession to profession - but above all

What's a profession without a code of ethics? Being a legitimate profession almost requires drafting a code and, at least nominally, making members follow it. Codes of ethics (henceforth “codes”) exist for a number of reasons, many of which can vary widely from profession to profession - but above all they are a form of codified self-regulation. While codes can be beneficial, it argues that when we scratch below the surface, there are many problems at their root. In terms of efficacy, codes can serve as a form of ethical window dressing, rather than effective rules for behavior. But even more that, codes can degrade the meaning behind being a good person who acts ethically for the right reasons.

Created2013-11-30
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Description

Online communities are becoming increasingly important as platforms for large-scale human cooperation. These communities allow users seeking and sharing professional skills to solve problems collaboratively. To investigate how users cooperate to complete a large number of knowledge-producing tasks, we analyze Stack Exchange, one of the largest question and answer systems

Online communities are becoming increasingly important as platforms for large-scale human cooperation. These communities allow users seeking and sharing professional skills to solve problems collaboratively. To investigate how users cooperate to complete a large number of knowledge-producing tasks, we analyze Stack Exchange, one of the largest question and answer systems in the world. We construct attention networks to model the growth of 110 communities in the Stack Exchange system and quantify individual answering strategies using the linking dynamics on attention networks. We identify two answering strategies. Strategy A aims at performing maintenance by doing simple tasks, whereas strategy B aims at investing time in doing challenging tasks. Both strategies are important: empirical evidence shows that strategy A decreases the median waiting time for answers and strategy B increases the acceptance rate of answers. In investigating the strategic persistence of users, we find that users tends to stick on the same strategy over time in a community, but switch from one strategy to the other across communities. This finding reveals the different sets of knowledge and skills between users. A balance between the population of users taking A and B strategies that approximates 2:1, is found to be optimal to the sustainable growth of communities.

ContributorsWu, Lingfei (Author) / Baggio, Jacopo (Author) / Janssen, Marco (Author) / ASU-SFI Center for Biosocial Complex Systems (Contributor)
Created2016-03-02
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Description

Although emerging evidence indicates that deep-sea water contains an untapped reservoir of high metabolic and genetic diversity, this realm has not been studied well compared with surface sea water. The study provided the first integrated meta-genomic and -transcriptomic analysis of the microbial communities in deep-sea water of North Pacific Ocean.

Although emerging evidence indicates that deep-sea water contains an untapped reservoir of high metabolic and genetic diversity, this realm has not been studied well compared with surface sea water. The study provided the first integrated meta-genomic and -transcriptomic analysis of the microbial communities in deep-sea water of North Pacific Ocean. DNA/RNA amplifications and simultaneous metagenomic and metatranscriptomic analyses were employed to discover information concerning deep-sea microbial communities from four different deep-sea sites ranging from the mesopelagic to pelagic ocean. Within the prokaryotic community, bacteria is absolutely dominant (~90%) over archaea in both metagenomic and metatranscriptomic data pools. The emergence of archaeal phyla Crenarchaeota, Euryarchaeota, Thaumarchaeota, bacterial phyla Actinobacteria, Firmicutes, sub-phyla Betaproteobacteria, Deltaproteobacteria, and Gammaproteobacteria, and the decrease of bacterial phyla Bacteroidetes and Alphaproteobacteria are the main composition changes of prokaryotic communities in the deep-sea water, when compared with the reference Global Ocean Sampling Expedition (GOS) surface water. Photosynthetic Cyanobacteria exist in all four metagenomic libraries and two metatranscriptomic libraries. In Eukaryota community, decreased abundance of fungi and algae in deep sea was observed. RNA/DNA ratio was employed as an index to show metabolic activity strength of microbes in deep sea. Functional analysis indicated that deep-sea microbes are leading a defensive lifestyle.

ContributorsWu, Jieying (Author) / Gao, Weimin (Author) / Johnson, Roger (Author) / Zhang, Weiwen (Author) / Meldrum, Deirdre (Author) / Biodesign Institute (Contributor)
Created2013-10-11
Description

On-going efforts to understand the dynamics of coupled social-ecological (or more broadly, coupled infrastructure) systems and common pool resources have led to the generation of numerous datasets based on a large number of case studies. This data has facilitated the identification of important factors and fundamental principles which increase our

On-going efforts to understand the dynamics of coupled social-ecological (or more broadly, coupled infrastructure) systems and common pool resources have led to the generation of numerous datasets based on a large number of case studies. This data has facilitated the identification of important factors and fundamental principles which increase our understanding of such complex systems. However, the data at our disposal are often not easily comparable, have limited scope and scale, and are based on disparate underlying frameworks inhibiting synthesis, meta-analysis, and the validation of findings. Research efforts are further hampered when case inclusion criteria, variable definitions, coding schema, and inter-coder reliability testing are not made explicit in the presentation of research and shared among the research community. This paper first outlines challenges experienced by researchers engaged in a large-scale coding project; then highlights valuable lessons learned; and finally discusses opportunities for further research on comparative case study analysis focusing on social-ecological systems and common pool resources. Includes supplemental materials and appendices published in the International Journal of the Commons 2016 Special Issue. Volume 10 - Issue 2 - 2016.

ContributorsRatajczyk, Elicia (Author) / Brady, Ute (Author) / Baggio, Jacopo (Author) / Barnett, Allain J. (Author) / Perez Ibarra, Irene (Author) / Rollins, Nathan (Author) / Rubinos, Cathy (Author) / Shin, Hoon Cheol (Author) / Yu, David (Author) / Aggarwal, Rimjhim (Author) / Anderies, John (Author) / Janssen, Marco (Author) / ASU-SFI Center for Biosocial Complex Systems (Contributor)
Created2016-09-09