Doctor of Philosophy

dissertationWith numerous options for mitigating CO2 emissions, the need to address global climate change, and limited financial resources, it is essential to evaluate greenhouse gas (GHG) mitigation strategies to prioritize investments of time and capital. This research adopts a life-cycle approach toward this prioritization for three GHG mitigation strategies: (1) aqueous CO2 mineralization, (2) oxyfiring for unconventional transportation fuels, and (3) underground coal thermal treatment (UCTT). As this research moves from strategy (1) to strategy (3), it progresses from using literature data to close collaboration with other researchers to design and perform experiments and simulations needed to assess GHG impacts. The evaluation of each strategy includes quantitative consideration of all major energy and GHG flows and a qualitative consideration of other potential barriers, i.e., resource availability and hazardous byproducts. Commercial-scale, aqueous CO2 mineralization involves the reaction of CO2 with an industrial caustic or a waste containing a reactive metal oxide to form a solid mineral carbonate. The evaluation revealed that once the full-life cycle material and energy balance are considered, this technology has limited applicability at the large scale. The industrial caustic pathway has a high energy penalty (50 to > 100%) and produces toxic byproducts (chlorine gas). The reactive metal oxide/waste pathway has a lower energy penalty (10 to 20%), but its applicability is limited by the availability of wastes containing reactive metal oxides. Oxyfiring with CO2 capture is one of the most promising CO2 mitigation strategies for the fossil energy sector. Chapter 3 discusses whether oxyfiring with CO2 could help fuels derived from oil sand and shale meet a low-carbon fuel standard. The results showed that this strategy is feasible, but it will likely place these fuels at a competitive disadvantage. UCTT is a novel technology to heat coal in situ and produce a lower carbon content, higher heating value syngas or liquid fuel. Results indicate that UCTT has a limited potential for CO2 mitigation because of the large energy ""losses"" to the coal in situ caused by the large volumes of coal that are heated to low temperatures, resulting in limited product

Planning for the Strategic Redevelopment of Downtown Detroit

Executive Summary Since its founding in 1701, Downtown Detroit has evolved from a major shipping port and industrial mega-power, to a place of racial unrest and economic troubles, to its present incarnation as a gritty city looking for a comeback. At this point, the main question for the downtown area concerns how to revitalize this once glorious city into a major hub of entertainment, retail, office and residential for residents and visitors alike. Our goal for the city was to create an oasis of walkable urbanity that would be a destination place for visitors and a safe, clean and attractive city for residents. This study begins with a summary of Detroit’s history. In our historical review, we concentrated on information that pertained to the downtown’s layout and character and could help inform future redevelopment. Additionally, an inventory of the historic buildings, public spaces, and known sites of environmental concern was conducted to get an accurate snapshot of some of the key features of the study area. Working closely with the Brookings Institution Metropolitan Policy Program Urban Markets Initiative and the Social Compact, we conducted an in-depth market analysis. The market analysis included a review and revision of the widely available demographic information. Using alternative data sources to the census, we found that the current downtown population is higher than previously thought and the earning potential, aggregate income, and disposable income are all higher than previously anticipated.Master of ScienceSchool of Natural Resources & EnvironmentA. Alfred Taubman College of Architecture and Urban PlanningStephen M. Ross School of BusinessUniversity of Michiganhttps://deepblue.lib.umich.edu/bitstream/2027.42/48791/4/Strategic Redevelopment of Dtwn Detroit Jan 07.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/48791/6/downtown_detroit.mp4Description of Strategic Redevelopment of Dtwn Detroit Jan 07.pdf : OpusDescription of downtown_detroit.mp4 : Video: Downtown Detroit, Oct. 24, 200

Protocols for an Aboriginal-led, Multi-methods Study of the Role of Aboriginal and Torres Strait Islander Health Workers, Practitioners and Liaison Officers in Quality Acute Health Care

ObjectivesAboriginal and Torres Strait Islander Health Workers/Practitioners and Liaison Officers play an important, often critical role providing advocacy and cultural and emotional support for Aboriginal and Torres Strait Islander patients. The main goals of this research are to explore i) how Aboriginal and Torres Strait Islander Health Workers/Practitioners and Liaison Officers are integrated in the routine delivery of care for Aboriginal and Torres Strait Islander peoples in hospital, and ii) how the role of Aboriginal and Torres Strait Islander Health Workers/Practitioners and Liaison Officers facilitates quality health outcomes. MethodsThis study is being conducted in three different hospitals using a multi-method approach including: yarning and Dadirri, patient journey mapping, survey and semi-structured interviews. Ethics approval has been provided from four ethics committees covering the three project sites in Australia (Adelaide, South Australia; Sydney, New South Wales and Alice Springs, Northern Territory). SignificanceThis study uses innovative methodology founded on the privileging of Aboriginal and Torres Strait Islander knowledges to collect Aboriginal and Torres Strait Islander perspectives and understand patient journeys within acute health care systems. This project is led by Aboriginal and Torres Strait Islander researchers and guided by the Project Steering Committee comprised of stakeholders. ImplicationsThere is limited research that explores quality acute care processes and the integration of Aboriginal and Torres Strait Islander Health Workers/Practitioners work within health care teams. This research will make a valuable contribution to understanding how hospital services can achieve quality acute health care experiences for Aboriginal and Torres Strait Islander People

The Demographics, Stellar Populations, and Star Formation Histories of Fast Radio Burst Host Galaxies: Implications for the Progenitors

We present a comprehensive catalog of observations and stellar population properties for 23 highly secure host galaxies of fast radio bursts (FRBs). Our sample comprises six repeating FRBs and 17 apparent non-repeaters. We present 82 new photometric and eight new spectroscopic observations of these hosts. Using stellar population synthesis modeling and employing non-parametric star formation histories (SFHs), we find that FRB hosts have a median stellar mass of $\approx 10^{9.9}\,M_{\odot}$, mass-weighted age $\approx 5.1$ Gyr, and ongoing star formation rate $\approx 1.3\,M_{\odot}$ yr$^{-1}$ but span wide ranges in all properties. Classifying the hosts by degree of star formation, we find that 87% (20/23 hosts) are star-forming, two are transitioning, and one is quiescent. The majority trace the star-forming main sequence of galaxies, but at least three FRBs in our sample originate in less active environments (two non-repeaters and one repeater). Across all modeled properties, we find no statistically significant distinction between the hosts of repeaters and non-repeaters. However, the hosts of repeating FRBs generally extend to lower stellar masses, and the hosts of non-repeaters arise in more optically luminous galaxies. While four of the galaxies with the most clear and prolonged rises in their SFHs all host repeating FRBs, demonstrating heightened star formation activity in the last $\lesssim 100$ Myr, one non-repeating host shows this SFH as well. Our results support progenitor models with short delay channels (i.e., magnetars formed via core-collapse supernova) for most FRBs, but the presence of some FRBs in less active environments suggests a fraction form through more delayed channels.Comment: 52 pages, 32 figures, 6 tables, submitte

Chemogenomics identifies acetyl-coenzyme A synthetase as a target for malaria treatment and prevention

We identify the Plasmodium falciparum acetyl-coenzyme A synthetase (PfAcAS) as a druggable target, using genetic and chemical validation. In vitro evolution of resistance with two antiplasmodial drug-like compounds (MMV019721 and MMV084978) selects for mutations in PfAcAS. Metabolic profiling of compound-treated parasites reveals changes in acetyl-CoA levels for both compounds. Genome editing confirms that mutations in PfAcAS are sufficient to confer resistance. Knockdown studies demonstrate that PfAcAS is essential for asexual growth, and partial knockdown induces hypersensitivity to both compounds. In vitro biochemical assays using recombinantly expressed PfAcAS validates that MMV019721 and MMV084978 directly inhibit the enzyme by preventing CoA and acetate binding, respectively. Immunolocalization studies reveal that PfAcAS is primarily localized to the nucleus. Functional studies demonstrate inhibition of histone acetylation in compound-treated wild-type, but not in resistant parasites. Our findings identify and validate PfAcAS as an essential, druggable target involved in the epigenetic regulation of gene expression

Minimally Symptomatic Infection in an Ebola ‘Hotspot’: A Cross-Sectional Serosurvey

Introduction: Evidence for minimally symptomatic Ebola virus (EBOV) infection is limited. During the 2013–16 outbreak in West Africa, it was not considered epidemiologically relevant to published models or projections of intervention effects. In order to improve our understanding of the transmission dynamics of EBOV in humans, we investigated the occurrence of minimally symptomatic EBOV infection in quarantined contacts of reported Ebola virus disease cases in a recognized ‘hotspot.’ Methodology/Principal Findings We conducted a cross-sectional serosurvey in Sukudu, Kono District, Sierra Leone, from October 2015 to January 2016. A blood sample was collected from 187 study participants, 132 negative controls (individuals with a low likelihood of previous exposure to Ebola virus), and 30 positive controls (Ebola virus disease survivors). IgG responses to Ebola glycoprotein and nucleoprotein were measured using Alpha Diagnostic International ELISA kits with plasma diluted at 1:200. Optical density was read at 450 nm (subtracting OD at 630nm to normalize well background) on a ChroMate 4300 microplate reader. A cutoff of 4.7 U/mL for the anti-GP ELISA yielded 96.7% sensitivity and 97.7% specificity in distinguishing positive and negative controls. We identified 14 seropositive individuals not known to have had Ebola virus disease. Two of the 14 seropositive individuals reported only fever during quarantine while the remaining 12 denied any signs or symptoms during quarantine. Conclusions/Significance: By using ELISA to measure Zaire Ebola virus antibody concentrations, we identified a significant number of individuals with previously undetected EBOV infection in a ‘hotspot’ village in Sierra Leone, approximately one year after the village outbreak. The findings provide further evidence that Ebola, like many other viral infections, presents with a spectrum of clinical manifestations, including minimally symptomatic infection. These data also suggest that a significant portion of Ebola transmission events may have gone undetected during the outbreak. Further studies are needed to understand the potential risk of transmission and clinical sequelae in individuals with previously undetected EBOV infection

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Remodeling of the Cortical Structural Connectome in Posttraumatic Stress Disorder:Results from the ENIGMA-PGC PTSD Consortium

BACKGROUND: Posttraumatic stress disorder (PTSD) is accompanied by disrupted cortical neuroanatomy. We investigated alteration in covariance of structural networks associated with PTSD in regions that demonstrate the case-control differences in cortical thickness (CT) and surface area (SA). METHODS: Neuroimaging and clinical data were aggregated from 29 research sites in >1,300 PTSD cases and >2,000 trauma-exposed controls (age 6.2-85.2 years) by the ENIGMA-PGC PTSD working group. Cortical regions in the network were rank-ordered by effect size of PTSD-related cortical differences in CT and SA. The top-n (n = 2 to 148) regions with the largest effect size for PTSD > non-PTSD formed hypertrophic networks, the largest effect size for PTSD < non-PTSD formed atrophic networks, and the smallest effect size of between-group differences formed stable networks. The mean structural covariance (SC) of a given n-region network was the average of all positive pairwise correlations and was compared to the mean SC of 5,000 randomly generated n-region networks. RESULTS: Patients with PTSD, relative to non-PTSD controls, exhibited lower mean SC in CT-based and SA-based atrophic networks. Comorbid depression, sex and age modulated covariance differences of PTSD-related structural networks. CONCLUSIONS: Covariance of structural networks based on CT and cortical SA are affected by PTSD and further modulated by comorbid depression, sex, and age. The structural covariance networks that are perturbed in PTSD comport with converging evidence from resting state functional connectivity networks and networks impacted by inflammatory processes, and stress hormones in PTSD

Transcriptional Profiling of Synovial Macrophages Using Minimally Invasive Ultrasoundâ Guided Synovial Biopsies in Rheumatoid Arthritis

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/144312/1/art40453_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144312/2/art40453.pd