VictorJuiz/thesis huggingface dataset:
Activation and Functionalization of Strong Bonds with N-Heterocyclic Carbene-Ligated Nickel Catalysts

The following dissertation discusses the development and mechanistic understanding of reactions catalyzed by N-heterocyclic carbene-ligated Ni complexes. The focus of this work will be directed towards the activation and functionalization of C–O, C–H, and C–Br bonds in diaryl ethers, arenes and alkenes, and alkyl bromides, respectively./nChapter 1 provides a review of the structural and electronic properties of N-heterocyclic carbenes (NHCs) as well as an introduction to the role of Ni catalysts in organometallic chemistry. A discussion of the nature of NHC–M bonds is discussed and representative classes of reactions catalyzed by NHC-ligated Ni complexes are presented./nChapter 2 presents a detailed mechanistic analysis of the hydrogenolysis of diaryl ethers catalyzed by the combination of a Ni metal precursor and an N-heterocyclic carbene. Catalytic experiments revealed the key role of base in this catalytic reaction. The resting state of the catalyst was identified and kinetic analysis showed that the base is not involved in the rate-limiting C−O bond cleavage. Catalytically relevant Ni complexes have been independently prepared, fully characterized, and their role in the catalytic cycle has been studied./nChapter 3 discusses the first undirected hydroarylation of unactivated alkenes with unactivated arenes that occurs with high regioselectivity for the anti-Markovnikov product. The reaction occurs with a Ni catalyst ligated by a highly sterically hindered NHC. Catalytically relevant arene- and alkene-bound Ni complexes have been characterized, and the rate-limiting step was shown to be reductive elimination to form the C-C bond. DFT calculations, combined with second-generation, absolutely-localized molecular orbital energy decomposition analysis (ALMO- EDA), suggest that the difference in activity between catalysts containing large and small carbenes results more from stabilizing intramolecular, non-covalent interactions in the secondary coordination sphere than from steric hindrance./nChapter 4 discusses the development of a cross-coupling reaction between secondary alkyl bromides and an imine substrate catalyzed by an NHC-ligated Ni complex. Various reaction parameters have been investigated and an initial substrate scope of alkyl halides that participate in this reaction is presented.

Advisor: Hartwig, John F
Assured Autonomy for Safety-Critical and Learning-Enabled Systems

Autonomous systems are becoming ever more complex. This growth in complexity stems primarily from continual improvements in computational power, which have enabled, among many things, the use of more sophisticated high-dimensional dynamical models or the use of deep neural networks for perception and decision-making. Unfortunately, this increase in complexity is coupled with an increase in uncertainty on how these systems might behave in safety-critical settings where guarantees of performance are needed./nIn this dissertation, we will first address the challenges involved in the computation of safety certificates for high-dimensional safety-critical systems and how machine learning, and in particular artificial neural networks, can provide scalable approximate solutions which work well in practice. However, reliance on neural networks for autonomy poses itself a challenge, since these function approximators can sometimes produce erroneous behaviors when exposed to noise or adversarial attacks, for example. With this in mind, in the second half of the dissertation we will address the challenges involved in the verification of neural networks, and in particular, how to assess whether deep feedforward neural networks adhere to safety specifications.

Advisor: Tomlin, Claire
Phasor-Based Control on Islanded Networks

The advancement of sensing technologies for the power grid has allowed the development of new strategies for the control of distributed energy resources (DERs). In particular, the emergence of phasor measurement units (PMUs) designed for deployment at the distribution level has presented an exciting opportunity. These PMUs have enabled the development of phasor-based control (PBC), a strategy that formulates DER power dispatch in terms of voltage phasor targets to be tracked by local controllers./nThis dissertation focuses on the optimal power flow (OPF) component of PBC’s supervisory control layer, which has previously been conceptualized and demonstrated in simulation on distribution networks. We expand its applicability to medium-voltage minigrids and microgrids operating in island mode, networks where PBC has the potential to deliver important benefits./nThe work is carried out in two stages. After a discussion of PBC and other relevant background topics, we address one of the primary challenges to PBC at the medium voltage level: the need for extreme accuracy in the supervisory controller’s generation of phasor targets. This accuracy is achieved through an adaptation of an iterative OPF methodology that refines a linearized model of power flow through successive exchanges with a nonlinear solver. We discuss the changes that were made to both linear model and nonlinear solver, as well as the determination of phasor targets on networks that include tap-changing transformers and other realistic equipment. The accuracy of the adapted iterative method is then shown in simulation./nThe second stage of the work covers the extension of our OPF implementation to islanded systems. We present a strategy for the treatment of the slack bus used by our nonlinear solver and apply it to several test cases in simulation. We then analyze a specific case in which our iterative solution method fails, and demonstrate the use of a penalty factor in our linearized OPF formulation as a means of overcoming that failure. A full, end-to-end implementation of PBC’s supervisory layer is then proposed and tested on a number of DER distributions at different feeder penetration levels./nWe end with a presentation of data relevant to instrument-transformer-induced error in PMU measurements. This final portion stands alone from the primary work of the dissertation, but remains highly relevant to PBC. From an experimental deployment of two PMUs measuring an identical distribution-grid voltage, we determine a ratio of the errors induced by their individual potential transformers. Monitoring this quantity over the course of a year allows us to track the drift in those induced errors over time, motivating a discussion of the expected impact of error drift on PBC and the frequency with which transformers will need to be recalibrated in operational settings.

Advisor: von Meier, Alexandra
Sanders, Seth R
Exploring Covalently Acting Natural Products: Synthesis of Gymnastatin Family of Alkaloids and Development of Nimbolide- and Bardoxolone-Based Protein Degraders

Natural products have long been a rich source of medicinal compounds and inspirations for drug discovery. Among these, molecules that interact with their targets through covalent bonds are highly attractive in biological applications. This dissertation describes our studies on the biosynthetic relationship and chemical synthesis of potentially covalently acting natural products of gymnastatin family, as well as the application of the cysteine-targeting limonoid natural product nimbolide and triterpene derivative bardoxolone for targeted protein degradation.Gymnastatins are a family of cytotoxic natural products derived from tyrosine, which possess a variety of electrophilic functional groups. Through bio-inspired strategies, the total syntheses of gymnastatin G, dankastatin B and dankastatin C was achieved. The previously presumed biomimetic strategy failed to provide the desired stereochemistry during formation of the bicyclo[3.3.1]nonane core of gymnastatin G, complicating our understanding of the biosynthesis of gymnastatins. In addition, the connection between gymnastatin G and a related natural product aranorosin was established through a simple chemical transformation. These results provide further insight into the biosynthesis and chemical reactivity of gymnastatins (Chapter 1). In Chapter 2, we describe the use of nimbolide as a novel E3 ligase recruiter in targeted protein degradation (TPD) applications. While TPD and proteolysis-targeting chimeras (PROTACs) have arisen as powerful therapeutic modalities, the lack of E3 ligase recruiters remains one of the major limitations of current TPD strategies. Extending our recent discovery of nimbolide as a covalent recruiter for the E3 ligase RNF114, we show the broader utility of this E3 ligase recruitment by developing a nimbolide-based PROTAC BT1, which selectively degrades oncogenic fusion protein BCR-ABL over c-ABL in leukemia cancer cells. The selectivity profile of BT1 is opposite to existing cereblon or VHL-recruiting BCR-ABL degraders of similar linker composition. This work further establishes nimbolide as an additional general E3 ligase recruiter for use in PROTACs and demonstrates the importance of expanding the arsenal of E3 ligase recruiters. In Chapter 3, an unexplored mode of E3 ligase recruitment, namely, covalent, reversible E3 ligase recruitment was explored. Efficient proteasome-mediated degradation of BRD4 was achieved by a bifunctional small molecule linking the KEAP1-Nrf2 activator bardoxolone to a BRD4 inhibitor JQ1, which further expanded the TPD toolbox to include bardoxolone as an easily prepared E3 ligase recruiter and further highlighted the power of natural products in such applications.

Advisor: Maimone, Thomas J
Compatibility Between Commands: How Organizational Similarities Drive Cooperation Between State Militaries and Foreign Militants

My dissertation explains the variation in the types of support that third-party governments and foreign militants provide each other. While certain government-foreign militant partners exchange intelligence, logistical support, and weapons, others engage in much more intense types of cooperation like forming joint commands and carrying out joint attacks. I argue that, when state armed forces and foreign militant groups have similar standard operating procedures (SOPs) and chains of command, they provide each other more intense forms of support, like forming joint commands, carrying out joint attacks, and providing anti-tank missiles. SOPs and chains of command constrain members’ actions, stabilizing an organization’s behavior. Partners similar on these characteristics mutually understand and believe they can predict how the other will react to unexpected events, bolstering their trust that the other will adhere to agreed-upon commitments. When dissimilar on these characteristics, partners provide less intense forms of support like weapons, money, and logistical aid. I assess my theory through a mixed-methods research design. I conduct statistical analyses on two datasets: first is a novel cross-national, longitudinal dataset of all dyadic provisions of support between government and foreign militants from 1975-2016; second is the Integrated Crisis Early Warning System dyadic events data, which contains daily interactions between state-militant partners from 1995-2017. To assess the underlying mechanism, I conduct three in-depth case studies of state-foreign militant partnerships in the recent Syrian civil war and Iraqi insurgency. My case studies draw on one year of fieldwork in Jordan and 68 interviews conducted in Arabic and English with U.S. and Jordanian officials and Syrian militants. First, I compare the types of support that the Central Intelligence Agency and the Department of Defense provided to Syrian militants. I supplement this case study with analysis of a novel data set of over 150 Syrian rebel brigades that received U.S. support between 2012-2017. Second, I compare Hezbollah’s provision of troops and training to the Syrian Armed Forces to its coordination with Russian Special Forces. Lastly, I compare U.S. forces’ formation of joint patrols with and provision of money, weapons, and training to various militias in Anbar in the mid-2000s.

Advisor: Mattes, Michaela
Techniques for Battery Management: Modeling, Estimation, Learning & Controls

This dissertation develops an advanced battery management system where lithium-ion battery dynamics are governed by electrochemical principles, and estimation & control techniques are applied to enhance the performance and longevity. The rapid progress in electrified transportation, electronic devices, and energy storage system needs cutting-edge management system that can monitor and control the electric battery system safely. We address this topic in three phases: i) modeling, ii) estimation, and iii) controls respectively./nFirst, we provide an overview of battery fundamentals and develop mathematical models for electrochemical battery phenomena. Electrochemical modeling is an important tool for simulating the performance of a battery. With the electrochemical model as a simulator, one can demonstrate prototypes of battery management system without conducting expensive experimental protocols. Furthermore, designing reduced-order electrochemical models helps to develop real-time estimation/control algorithms for large-scale battery systems./nSecond, we propose a systematic framework to identify battery cell using the electrochemical model. To accurately represent the cell chemistry, the model parameters must be correctly identified. Good fitting parameters take a long time to identify. Often, it requires disassembling the cell and performing specialized electrochemical characterization tests, a costly and difficult process. The proposed parameter estimation framework for an electrochemical model enables to estimate electrochemical parameters by using input-output data./nLastly, we then develop a novel battery charging strategy for the identified electrochemical model while accounting for the electrochemical constraints associated to aging mechanism. The model-based optimal solutions reveal that the characteristic of optimal charging protocol is Bang-Ride control, which provides theoretical supports on the existing charging strategy. Furthermore, learning-based controller design via reinforcement learning is highlighted as an adaptive controller for battery charging strategy. The performance of this learning-based feedback controller is demonstrated with other charging strategies.

Advisor: Moura, Scott J.
Next-Generation Systems Biology Approaches for the Study of Bacteriophages

Bacteriophages (phages) are viruses that specifically infect bacteria including diverse, notable pathogens. They constitute the most abundant biological entities on earth, have driven the evolution of critical biotechnological tools, and are proposed as an emerging solution to treat the rise of antimicrobial resistant bacterial pathogens. Although these bacterial predators have been studied for nearly a century, our understanding of host-specificity, gene function, and the consequences of phage infection remain limited to a handful of model phage-host pairs. In this dissertation, we employ high-throughput genetic screening technologies to rapidly and economically assess genetic function for bacterial fitness against diverse phages. We rapidly identify phage-host interactions in competitive fitness experiments through the use of loss-of-function and gain-of-function screening technologies: RB-TnSeq (barcoded transposon insertion), CRISPRi (dCas9-mediated transcriptional repression), and Dub-seq (barcoded overexpression). We employ all 3 technologies to study phage-host interactions in E.coli and systematically elucidate the phage resistance landscape for this model organism and 14 of its phages, discovering new routes to phage resistance, and providing a comprehensive resource that can be mapped against hundreds of fitness conditions. We subsequently extended our investigations an additional model pathogen, Salmonella enterica serovar Typhimurium, one of the world’s most common sources of food poisoning and an emerging antibiotic resistance threat. We introduce two new barcoded libraries in Salmonella and investigate its interactions with 11 additional phages. In addition to the resource provided, we uncover an unanticipated phage cross-resistance network. This network includes multiple ties to Salmonella virulence and lifestyle associated with phage resistance, introducing new considerations for therapeutic avenues. In aggregate, we report the results of over hundreds of genome wide assays, corroborating known and discovering new modes of phage resistance. Here, we also further extend Dub-seq and genome engineering technologies for the study of phage gene function, which too remains limited. By employing Dub-seq as a co-expression platform, we re-tool Dub-seq overexpression assays to rapidly characterize the function of 8 single gene lysis systems from ssDNA and ssRNA phages. We discover new putative target inhibitors, introduce new factors in resistance acquisition, and put forward a target hypothesis for a general role of these proteins. The forementioned library screens were enabled by genome-engineering technologies. Finally, we report a genome-engineering chassis in E.coli based off of the integrative prophage, Lambda, that can be modified at enhanced rates and any nonessential position. We believe that the development of such chassis will be critical towards not only synthetic biology applications, but also the rapid development of strains to characterize phage-host interactions.

Advisor: Arkin, Adam P
Inventing the Working Parent: Work, Gender, and Feminism in Neoliberal Britain

Since the 1980s, it has become commonplace to suggest that families across the developed West have lived through a revolution on a scale unprecedented since industrialization. The rapid rise in maternal employment and the emerging middle class norm of the dual-income household in the last third of the twentieth century heralded declarations of a new era of the ‘working parent.’ My dissertation charts the politics that shaped the invention of the working parent in Britain as it arose out of a new institutional culture of work./nI take as my starting points the shifting political-economic terrain of the 1970s and feminist campaigns for childcare, flexible work, and a more equitable division of affective labor. I tell the story of efforts to embed new forms of support for workers with caring responsibilities in institutions across the charitable, public, and private sectors, and explore the advent of the ‘family friendly’ corporate workplace. I also highlight the ways in which individuals sought to make sense of their day-to-day lives as ‘working parents,’ and to reckon with the associated imperative of ‘work-life balance.’ In the process I engage the classed and racialized notion of a new working parent and touch on the experiences of single parents, childcare workers, and men and women of a variety of backgrounds./nDrawing on previously unstudied archival sources in Britain, as well as oral history interviews with more than a dozen activists, I situate the British experience in a broader Euro-American context. I show that charitable and public sector efforts to remake the workplace on behalf of working parents were a minor detour alongside a more enduring and politically and culturally significant re-imagination of work, and of parents as workers, within the private sector. I argue that while the notion of ‘working parenthood’ has consolidated the gains of second wave feminism – predominately gains for white, middle class women - it has also masked the realities of ongoing inequality in the distribution of caring work and facilitated an intensification of contemporary work culture. It has nonetheless been an enduring category of identity and political mobilization, including for some working class women and men, and people of color, as a result of the abiding feminist promise of more equal marriages, households, and working lives.

Advisor: Vernon, James
Living Low: Alternative Housing and Life in Guangzhou Villages-by-the-City

Among the numerous questions about China’s ongoing transformations, a crucial one is: how did ninety million peasants transform themselves into new social subjects in the reform era? This research responds to this general inquiry by identifying housing in “villages-by-the-city” (城边村) as a key spatial arena in making what I call “post-peasantry subjects”. In doing so, it criticizes two main bodies of literature in China Studies by filling in two of their lacuna. It foregrounds village housing as a key, yet largely overlooked analytical site for peasantry research; and it adds an under-investigated locale, “villages-by-the city” to housing studies./nThis dissertation provides an architectural ethnography of the housing practices in Guangzhou villages-by-the-city. While focusing on Guangzhou, it notes broader social and housing trends in contemporary China. It draws on extensive documentations and ethnographic fieldwork. I examine the roles of housing design, construction, management, and consumption in re-configuring village domestic spaces, lifestyles, and village organizations from 1978 to 2017. Through their housing practices, they empowered and reinvented themselves as a broad spectrum of post-peasantry subjects, such as urban villager, peasant-worker master, village middle class, etc. In highlighting their housing creativity, I argue that the village inhabitants have produced a form of spatial agency—what I call “housing agency”—in reaction to the limits of their social and political conditions and to achieve self-reinvention, which is both productive yet contested./nThis dissertation comprehensively documents, for the first time, the transformation and creativity of the Chinese rural population in their housing practices and building cultures. While pointing out limits and controversies, it also shows the abundant possibilities and opportunities in the village-by-the-city habitation. Thus, it is also an attempt to both question and offer alternatives to the large-scale developer-produced xiaoqu (gated community) housing that dominates contemporary China.

Advisor: Crawford, Margaret L
Secure, Expressive, and Debuggable Large-Scale Analytics

Growing volumes of data collection, outsourced computing, and demand for complex analytics have led to the rise of big data analytics frameworks such as MapReduce and Apache Spark. However, these systems fall short in processing sensitive data, graph querying, and debugging. This dissertation addresses these remaining challenges in analytics by introducing three systems built on top of Spark: Oblivious Coopetitive Queries (OCQ), GraphFrames, and Arthur. OCQ focuses on the setting of coopetitive analytics, which refers to cooperation among competing parties to run queries over their joint data. OCQ is an efficient, general framework for oblivious coopetitive analytics using hardware enclaves. GraphFrames is an integrated system that lets users combine graph algorithms, pattern matching, and relational queries, each of which typically requires a specialized engine, and optimizes work across them. Arthur is a debugger for Apache Spark that provides a rich set of analysis tools at close to zero runtime overhead through selective replay of data flow applications. Together, these systems bring Apache Spark closer to the goal of a unified analytics platform that retains the flexibility, extensibility, and performance of relational systems.

Advisor: Stoica, Ion