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The major spreading and trapping mechanisms of carbon dioxide in geological media are subject to spatial variability due to heterogeneity of the physical and chemical properties of the medium. For modelling to make a useful contribution to the understanding of carbon dioxide sequestration and its associated risk assessment, the impact of heterogeneity on flow, transport and reaction processes and their uncertainties must be identified, characterised, and its consequences quantified. Complex computer simulation models based on systems of partial differential equations with random inputs are often used to describe the flow of groundwater through this heterogeneous media. The Monte Carlo method is a widely used and effective approach to quantify uncertainty in such systems of partial differential equations with random inputs. This thesis investigates two alternatives to Monte Carlo for solving the equations with random inputs; the first of these are techniques developed for improving the computational performance of Monte Carlo, namely methods such as, multilevel Monte Carlo, quasi Monte Carlo, multilevel quasi Monte Carlo. The second alternative, Gaussian process emulation, is an approach based on Bayesian non parametric modelling, in which we build statistical approximations of the simulator, called emulators. Numerical calculations carried out in this thesis have demonstrated the effectiveness of the proposed alternatives to the Monte Carlo method for solving two dimensional model problems arising in groundwater flow and Carbon capture and storage processes. Multilevel quasi Monte Carlo has been proven to be the more efficient method, in terms of computational resources used, among Monte Carlo, multilevel Monte Carlo and quasi Monte Carlo. Gaussian process emulation has been proven to be a reliable surrogate for these simulators and it has been concluded that the use of Gaussian process emulation is a powerful tool which can be satisfactorily used when the physical processes are modelled through computationally expensive simulators.

Autism is a disorder that affects children at an alarming rate. One out of every 88 children is diagnosed with autism in the United States. The disorder is characterized by communication, social, and behavioral deficits. Children with autism often require specialized teaching methods to learn basic skills that most children acquire without specialized instruction. Relatively few studies have examined strategies for teaching safety skills to individuals with autism. The current study utilized a multiple baseline across participants' design to evaluate whether a modeling and rehearsal strategy is effective for teaching fire safety skills to children with autism between 4 and 5 years of age. Results indicated that modeling and rehearsal were effective in teaching fire safety skills, the skills generalized to novel settings, and maintained 5-weeks following the completion of training. Implications for safety skill instruction and future research are discussed. [The dissertation citations contained here are published with the permission of ProQuest LLC. Further reproduction is prohibited without permission. Copies of dissertations may be obtained by Telephone (800) 1-800-521-0600. Web page: http://www.proquest.com/en-US/products/dissertations/individuals.shtml.]

ABSTRACT OF THE THESISIdentifying the function of cGAS-Cap2b protein complex in Type-II Short CBASS SystemsbyDavid GarciaMaster of Science in BiochemistryUniversity of California San Diego, 2022 Professor Elizabeth A. Komives, ChairTwo sides, in an infinite battle for survival, as one side gets stronger, so does the other. As described by the Red Queen hypothesis, this is the dilemma between bacteria and bacteriophages (or phages), where both sides are constantly evolving to try and eliminate their opponent. Phages are simple organisms and outnumber all other organisms on earth, and their means of survival requires the destruction of bacteria. During infection, phages inject their DNA into bacterium and as a response bacterium will destroy itself but not before the phage has successfully replicated. This allows for further bacterial infection upon the destruction of bacterium from initial phage infection and can be recurrent until all bacteria has been destroyed. As a means for survival, bacteria have evolved a myriad of defense systems that allow it to fight phage infection. In this thesis I will cover some of the most well-known defense systems: the restriction-modification (R-M) systems that target phage sequences, the CRISPR-Cas systems where cells obtain immunity from previous phage infection, and the abortive infection systems (Abi) that upon phage detection will program cell death. Although each of these systems is unique and important for phage defense, I will focus on a type of abortive infection systems that were recently discovered in bacteria known as cyclic-oligonucleotide based antiphage signalling systems or ‘CBASS’. In this thesis, I also discuss the defense mechanisms of the different types of CBASS currently identified and discuss my study of a unique type of CBASS systems described as Type II (short) CBASS systems. Previously identified Type II (long) systems were discovered to have operons containing ancillary genes that share similarities with the non-canonical E1 and E2 signaling machinery described in the noncanonical autophagic ubiquitination pathway. Type II (short) CBASS systems have similar operons but with only one ancilliary gene related to ubiquitin E2 proteins. I was able to demonstrate how the bacterial E2-like protein, Cap2b, and the nucleotidyltransferase, cGAS, in Type II (short) systems using the artificial intelligence (AI) structural prediction tool, AlphaFold. Using the structural prediction, I focused on three strains to study and clone these proteins in order to isolate and purify them for structural determination using X-ray crystallography.

Additive friction stir deposition (AFSD) is an emerging solid-state metal additive manufacturing technology that uses deformation bonding to create near-net shape 3D components. As a developing technology, a deeper understanding of the processing science is necessary to establish the process-structure relationships and enable improved control of the as-printed microstructure and material properties. AFSD provides a unique opportunity to explore the friction stir fundamentals via direct observation of the material during processing. This work explores the relationship between the processing parameters (e.g., tool rotation rate Ω, tool velocity V, and material feed rate F) and the thermomechanical history of the material by process monitoring of i) the temperature evolution, ii) the force evolution, and iii) the interfacial contact state between the tool and deposited material. Empirical trends are established for the peak temperature with respect to the processing conditions for Cu and Al-Mg-Si, but a key difference is noted in the form of the power law relationship: Ω/V for Cu and Ω2/V for Al-Mg-Si. Similarly, the normal force Fz for both materials correlates to V and inversely with Ω. For Cu both parameters show comparable influence on the normal force, whereas Ω is more impactful than V for Al-Mg-Si. On the other hand, the torque Mz trends for Al-Mg-Si are consistent with the normal force trends, however for Cu there is no direct correlation between the processing parameters and the torque. These distinct relationships and thermomechanical histories are directly linked to the contact states observed during deformation monitoring of the two material systems. In Cu, the interfacial contact between the material and tool head is characterized by a full slipping condition (δ=1). In this case, interfacial friction is the dominant heat generation mechanism and compression is the primary deformation mechanism. In Al-Mg-Si, the interfacial contact is characterized by a partial slipping/sticking condition (0

As our understanding of the microbial world has progressed, so too has the backlog of information and open questions generated from the thousands of uncharacterized proteins and metabolites with potential applications as biofuels, therapeutics, and biomaterials. To address this problem, new tools need to be developed in order to rapidly test and take advantage of uncharacterized proteins and metabolites. Cell-free systems have developed into a high-throughput and scalable tool for synthetic biology and metabolic engineering with applications across multiple disciplines. The work presented in this dissertation leverages cell-free systems as a conduit for the exploration of protein function and metabolite production using two complementary approaches. The first elucidates interaction networks associated with secondary metabolite production using a computationally assisted pathway description pipeline that employs bioinformatic searches of genome databases, structural modeling, and ligand-docking simulations to predict the gene products most likely to be involved in a metabolic pathway. In vitro reconstructions of the pathway are then modularly assembled and chemically verified in Escherichia coli lysates in order to differentiate between active and inactive pathways. The second takes a systems and synthetic biology approach to engineer Escherichia coli extracts capable of directing flux towards specific metabolites. Using growth and genome engineering-based methods, we produced cell-free proteomes capable of creating unconventional metabolic states with minimal impact on the cell in vivo. As a result of this work, we have significantly expanded our ability to use cell extracts outside of their native context to solve metabolic engineering problems and provide engineers new tools that can rapidly explore the functions of proteins and test novel metabolic pathways.

This study investigates how public gathering places directly relate to the formation of social movements in the Española Valley of northern New Mexico. Specifically, the project examines la Resolana, a local tradition of congregating in a public place where the sun reflects its warmth off a southern-facing wall in a plaza or courtyard. This study brings together anthropological and ethno historical data in order to contextualize the emergence of new politically active gathering spaces that invoke the historical name of resolana. Following the production and circulation of the term resolana, this project pursues three lines of investigation: first, I will present ethnographic research of contemporary resolana practices in public places such as town plazas, restaurants and department stores. Next, I will discuss the cultural production of a local Chicano think tank, La Academia de la Nueva Raza, (LADLNR) from the late 1960s to the mid-1980s. Then, the dissertation will address LADLNR’s theorization and deployment of the concept of resolana as a cultural metaphor for political action and local knowledge production. Finally, I will address how today these forms of resolana articulate and factor into its contemporary implementation in the growing social movements in the state by socially disadvantaged farmers and ranchers in acequia (communal irrigation) communities. This study engages a fundamental question in anthropology, which asks, how does place and space shape the formation of social movements? This question is explored in a new way theoretically in this study by looking at how resolana as a cultural form constitutes larger subjectivities called publics and counter-publics. In other words, this study offers an approach to cultural public spheres in northern New Mexico by examining discursive forms of speaking, gathering, and social mobilization.

Overweight and obesity are a significant public health concern. Behavioral treatment is considered the first line of intervention for individuals attempting to lose weight. Behavioral weight loss interventions are capable of producing an 8-10% weight loss of initial body weight at six-months. However, not all individuals achieve this magnitude of weight loss. Therefore, the development of alternative approaches to standard behavioral weight loss programs is needed to improve weight loss and weight maintenance efforts. PURPOSE: The purpose of this study was to examine a stand-alone campaign as an alternative strategy for weight management when compared to a standard behavioral weight loss intervention. METHODS: Twenty six sedentary, overweight and obese adult men and women (Age: 43.1 ± 8.9 years; BMI: 33.3 ± 3.7 kg/m²) participated in a behavioral weight loss intervention and were randomized to one of two groups: Standard Behavioral Weight Loss Intervention (SBWL) or Campaign Intervention (CI). Participants in the SBWL attended weekly group meetings, were prescribed 1200-1800 kcal/day, and 200 minutes of moderate intensity physical activity per week. Participants randomized to the CI received the same SBWL components described previously, in addition to an incentive-based point system, a lottery system, and an e-mail based self-monitoring and intervention delivery. Body weight was assessed at week 0 and 12. RESULTS: Both groups achieved significant weight loss from week 0 to week 12 (SBWL group: -5.6 ± 2.9 kg; CI group -3.1 ± 3.4 kg) (p

The mevalonate pathway is of critical importance to cellular function as it is the conduit for the production of terpenoids, hormones, and steroids. These molecules are also valuable on an industrial scale because they are used as antibiotics, flavoring agents, and fragrances, examples of which are clerocidin, cinnamon, and sandalwood, respectively. Because the biosynthetic route for the production of these compounds is the deoxyxylulose 5-phosphate pathway in E. coli, by engineering the heterologous mevalonate pathway into E. coli the native forms of pathway regulation were overcome to successfully create a bio-industrial route for the production of artemisinin, an antimalarial drug. Advanced biofuels can also be biosynthesized via the mevalonate pathway with some minor alterations to the final enzymatic conversions.However, the toxicity of intermediates and products, as well as regulation internal to the pathway, limited our ability to increase production. The mevalonate pathway enzymes we used were native to S. cerevisiae, two of which had not been kinetically characterized. We set out to determine the nature of these enzymes and how they might be regulated by mechanisms internal to the mevalonate pathway, such as feedback inhibition. Because both mevalonate kinase (MK) and phosphomevalonate kinase (PMK) were derived from S. cerevisiae they had to be codon-optimized for production in E. coli, particularly because they had already been identified as expressing poorly in laboratory production strains through targeted protein studies. By cloning the codon-optimized sequences into high copy expression vectors with a six-histidine tag at the C- or N-terminus (PMK and MK, respectively) we were able to produce large enough amounts of the active proteins to purify on a Ni2+ resin column.Kinetic characterization of MK revealed a KMATP of 315 ± 21 μM and a vmax of 50 ± 3 μM/min/μgE (or Kcat = 41 ± 3 s-1). Additionally, substrate inhibition of MK by mevalonate was determined to exist at concentrations above 2.5 mM, and Ki values for farnesyl pyrophosphate (79 ± 11 nM), geranyl pyrophosphate (147 ± 6 nM), geranylgeranyl pyrophosphate (303 ± 64 nM), dimethylallyl pyrophosphate, (29 ± 12 μM), and isopentenyl pyrophosphate (36 ± 5 μM) were determined.Kinetic characterization of PMK revealed that maximum activity occurs at pH = 7.2 and [Mg2+] = 10 mM. KMATP was determined to be 98.3 μM and 74.3 μM at 30 °C and 37 °C, respectively. KMmev-p was determined to be 885 μM and 880 μM at 30 °C and 37 °C, respectively. vmax was determined to be 45.1 μmol/min/μgE and 53.3 μmol/min/μgE at 30 °C and 37 °C, respectively. From the high KMmev-p value it appears as if PMK might have very poor activity at normal cellular concentrations of mevalonate-5-phosphate, indicating that MK and PMK might play a very coordinated role in balancing intermediate levels within the pathway.