VictorJuiz/thesis huggingface dataset:
Emotional acknowledgment in organizations : the benefits and risks of verbalizing the affect of others
Keywords: Business.

Emotions are omnipresent in organizations, but emotional sensemaking is not. Although emotions have the potential to serve as rapid conduits of social information, organizational practices often impede effective communication using emotions. In this dissertation, I investigate how using verbal language can facilitate the co-construction, calibration, and clarification of emotional communication. In everyday conversations, people acknowledge the emotions of others using language (e.g., saying "You seem excited" or "You look distraught"). I examine the role of this simple, but potentially meaningful act of emotional acknowledgment—verbal communication by which a perceiver signals the recognition of an expresser's emotions—in facilitating emotional sensemaking (Weick, 1995). Because emotional communication usually relies heavily on drawing inferences from non-verbal cues (van Kleef, 2009), I argue that explicitly verbalizing these inferences through emotional acknowledgment can reap important social and informational benefits while also coming with considerable risk. Using an organizational lens, I explore the consequences of emotional acknowledgment in three dissertation chapters. In the first chapter, I examine how emotional acknowledgment provides information about the quality of our social relationships, thereby facilitating the development of interpersonal trust. In the second chapter, I show how emotional acknowledgment can facilitate team performance by surfacing hidden team information. In the third and final chapter, I investigate how expressers use emotional acknowledgment as feedback to change their own self-presentation
Emotional disturbance and its constructive role in the learning process of collaborative design
Keywords: Mechanical Engineering.

Design work is filled with rich emotions and feelings resulting from resolving team conflicts to breaking impasses to discovering creative insight. In this dissertation, I have furthered the theoretical understandings about the constructive role of emotion and emotional disturbance in group design innovation activities and proposed a method of studying it. With a field study of novice designers and a mixed-methods study of experienced designers, I have presented ample evidence about the relationship between intense emotional experiences of disturbance and knowledge construction. In the mixed-methods study, I integrated speech acoustics (e.g., vocal pitch) and other bodily signals into video interaction analysis and examined how emotions develop as self-organizing social processes, how they are experienced as ongoing constructed interactions, and how they interact with other key processes of learning and discovery. Together, the current dissertation (1) advances theorizing on the emotional process underlying designers' learning, growth and performance, and (2) proposes a situated and integrated methodology for accessing, characterizing and understanding designers' moment-by-moment emotional dynamics in naturalistic settings. My work on the inherently emotional nature of design fills a gap in research that most often leaves out emotion in the study of designer cognition and behavior. For engineering and design practitioners, my work challenges the stereotypical view that emotion is separate from the intellectual process of engineering and design. My work affords a new way of seeing emotion as functional to creative engineering and design work, and opens up an important path for improving its practice and education
Empire in Action: US Operations and the Making of Narratives Around the 1953 Iranian Coup d'État
Keywords:  Program in Science
STS
science technology and society
ethnography
Iran
coup
coup d'état
archives
empire
imperialism
United States
covert operations
Cold War
intelligence
diplomacy
narratives
sublime
prestige
Tehran
memoirs
foreign policy
history
habitus
Thesis

How did US diplomatic and intelligence officers construct narratives of the 1953 Iranian coup d'état, one of the most famous and foundational instances of Anglo-American foreign intervention of the Cold War? The US role in the 1953 coup has been examined through myriad lenses, including post-World War II historical analysis, early Cold War foreign policy, consequences of covert intervention, and intelligence successes and failures. Historians, social scientists, and other scholars of political, intelligence, and military history have also long debated the significance of the 1953 coup. However, the coup has yet to be studied through an anthropological lens and examined as a site for the perpetuation and expansion of US empire as well as the imagination of narratives characterized by a new form of imperial mythos. As such, this thesis takes an ethnographically and historiographically inspired approach by investigating volumes of foreign policy writings, intelligence histories, personal memoirs produced by American planners, administrators, and governmental historians of the 1953 coup. This thesis argues that US operatives from the Central Intelligence Agency and the US Department of State embodied and reproduced empire via a set of practices that constituted a collective US imperial habitus. These practices involved exerting textual control over Tehran and Iranian individuals, construing themselves as committed to a sublime struggle against terror, and constantly repositioning covert operations as a form of valiant resistance in their written accounts. This thesis also contends that the narratives initially created by US operatives in archival and personal writings have imbued the history of the coup with a form of their ideological character and become the accepted US history of events.
Empire in the backlands : mobility and the interiorization of Portuguese colonization in Brazil, seventeenth and eighteenth centuries
Keywords: History.

This dissertation examines the process of interiorization of the Portuguese colonization in Brazil during the seventeenth and eighteenth centuries. Portuguese empire-building in the early modern era was a quintessentially maritime enterprise based on settlements established along the coast of Africa, Asia, and South America. In parallel with seaborne expansionism, the Portuguese adopted the vague spatial concept of the backlands—sertão—to refer to regions in the interior that were beyond imperial control. However, in the last decade of the seventeenth century, the discovery of gold deposits in central Brazil prompted a massive spatial transformation, leading to the formation of permanent pockets of settlement in the interior. This dissertation asks how the Portuguese came to integrate vast portions of the backlands into the empire. Specifically, it examines the mechanisms that enabled movement and exchanges over long distances in this fragmented geographic setting. I argue that the mobility of imperial subjects at the margin of the empire enabled the formation of Luso-Brazilian settlements away from the coast as well as formed and maintained inter-regional linkages that made them part of the empire. These spatial practices were not extraordinary acts of pioneering nor centrally directed by the crown, but part of routinized acts carried out by colonists and often rooted in family ties to incorporate resources from the backlands, exploit indigenous labor, and unlock new economic opportunities created by the settlement of the interior. While historians tend to emphasize the transplantation of institutions and the formation of territorial jurisdictions as the primary mode of the imperial territorial extension, this dissertation reveals the practices of mobility that enabled and sustained this process of occupation
Empowering disease diagnostics and deriving biological insight with publicly available gene expression data
Keywords: Immunology.

Public data repositories and other data sharing platforms have been a massive boon to researchers in the biomedical sciences. Data sharing can reduce costs, save valuable time, and helps ensure the transparency of public research. In our lab, these public data have become the foundation of most of our analyses -- many projects would not be possible without access to a wide array of datasets comprising many different diseases, regions, ethnicities, medical histories, and so on. Furthermore, as we have repeatedly demonstrated, the robustness that we can achieve from integrating large amount of heterogeneous data has allowed us to make findings that are both significant and durable. However, designing projects around public data can be a double-edged sword. When relevant data is available, it can allow for more efficient and more powerful analyses. But when the data is not present or lacking in quality, it can impose severe limitations on the types of analyses that can be done and on the types of questions that can be asked. Here, we designed a novel multi-cohort analysis framework called Multicohort ANalysis of AggregaTed gEne Expression (MANATEE) to integrate large numbers of gene expression datasets for use in generating signatures of disease. MANATEE utilizes a conormalization method to pool samples across many datasets, as long as each dataset contains healthy control samples. This framework lets us utilize far more datasets than was previously possible, which not only allows for existing analyses to be made substantially more robust, but it also opens new avenues of exploration that were previously impossible to analyze using publicly available data. By utilizing MANATEE with publicly available gene expression datasets, we developed multiple host-response-based signatures of disease, all of which were derived from gene expression in human blood. These include a diagnostic for differentiating between bacterial and viral infection in febrile individuals, a prognostic for assessing whether a patient with viral infection will have a severe or mild outcome, and a signature for both distinguishing tuberculosis from other conditions and for predicting when patients with latent tuberculosis infection will progress to active tuberculosis. We validated each of these signatures in prospective cohorts, demonstrating their ability to generalize to new data. These results highlight MANATEE's ability to leverage public data in creating signatures that maintain performance across the heterogeneity present in real-world patient populations. Furthermore, the signatures we have developed are in the process of being translated into point-of-care, non-invasive diagnostic and prognostic tests which have the potential to significantly improve clinical practice
Engineered biosynthesis of high-value therapeutics in a plant chassis
Keywords: Chemical Engineering.

Plants are known to produce a wide array of chemicals, and many plant natural products display medicinal properties beneficial to human health. These compounds have served as an inspiration to modern medicine, and recent technological advances have accelerated discovery and engineering of plant biosynthetic pathways. With the improved understanding of plant chemistry, we engineered biosynthesis of natural products and their analogs for therapeutic development. To demonstrate the value of engineered biosynthesis, we sought to improve production of etoposide aglycone, the complete biosynthetic pathway of which has been fully elucidated and reconstituted in a plant chassis, Nicotiana benthamiana. We first demonstrate milligram-scale production of a late-stage intermediate to etoposide aglycone and its desmethoxy analog through overexpression of primary metabolic enzymes and engineering of secondary metabolism. We then aimed to exploit the native transcriptional regulation for metabolic engineering and show that a single transcription factor can not only improve the pathway flux for etoposide aglycone biosynthesis but also suppress the competing metabolism. Additionally, we proposed to improve etoposide through development of its analogs with an altered activity profile. Previously, a hepatic metabolite of the chemotherapeutic etoposide has been implicated with treatment-related leukemogenesis. To address this issue, we hypothesized that etoposide analogs resistant to hepatic metabolism could be biosynthetically prepared. The first step of the pathway, coupling of coniferyl alcohol, is stereoselectivity-guided by a plant dirigent protein. We show that the plant dirigent protein demonstrates expanded substrate versatility, promoting asymmetric heterocoupling of coniferyl alcohol and its analog. Furthermore, we show that the heterocoupled (+)-pinoresinol analogs can be further processed by the rest of the pathway enzymes and display reduced propensity for oxidation. Taken together, we showcase flexibility of heterologous biosynthetic pathways in a plant chassis for improved biosynthetic yields of high-value therapeutic compounds and expanded chemical space of therapeutic analogs previously inaccessible by traditional synthetic approaches
Engineered methods for studying and manipulating in vitro culture systems
Keywords: Chemistry.

The development of new cell culture techniques allows in vitro cell cultures to replicate in vivo biology more faithfully. In this thesis, I will discuss two projects that broadly seek to expand the modalities for manipulating cell cultures and interrogating cell behavior. Magnetogenetics is a new field that leverages genetically encoded proteins and protein assemblies that are sensitive to magnetic fields to study and manipulate cell behavior. Theoretical studies show that many proposed magnetogenetic proteins do not contain enough iron to generate substantial magnetic forces. Here, we have engineered a genetically encoded ferritin-containing protein crystal that grows inside mammalian cells. Each of these crystals contains more than 10 million ferritin subunits and is capable of mineralizing substantial amounts of iron. When isolated from cells and loaded with iron in vitro, these crystals generate magnetic forces that are 9 orders of magnitude larger than the forces from the single ferritin cages used in previous studies. These protein crystals are attracted to an applied magnetic field and move toward magnets even when internalized into cells. While additional studies are needed to realize the full potential of magnetogenetics, these results demonstrate the feasibility of engineering protein assemblies for magnetic sensing. Brain organoids are an emerging three-dimensional cell culture system that models human brain development. Derived from clusters of induced pluripotent stem cells, brain organoids develop over many months and recapitulate key aspects of brain organization, such as cell identity and diversity, gene expression, and functional characteristics such as electrical activity. As a result, they have been employed to model various neurodevelopmental disorders. To date, electrophysiology in brain organoids has employed traditional techniques, such as multi-elecrode recordings and patch clamp. Here, we have developed a flexible mesh electrode for the long-term chronic integration of electrodes into the growing organoid. Over two generations of meshes, one made from SEBS and PEDOT:PSS and one made from SU-8 and gold, we have demonstrated that such electrodes have good biocompatibility, and are able to electrically stimulate organoids. Work is currently ongoing to establish consistent extracellular recordings of action potentials using the mesh
Engineering ammonia production in free-living diazotrophs for plant fertilization
Keywords: Bioengineering.

In this dissertation we engineer ammonia production in the plant-symbiotic associative diazotroph Azospirillum brasilense towards addressing the engineering grand challenge of nitrogen fixation. Our approach leverages synthetically controllable post-translational deactivation of glutamine synthetase by unidirectional adenylyltransferases (uATs) causing nitrogen over-fixation and release. We demonstrate that uAT strains can promote the growth of the model grass Setaria viridis in mono-association and prove using isotope labeling that 15N2 is transferred from the air into the plant specific chlorophyll derivative pheophytin. To improve our strains, we study the evolutionary pressure on ammonia production and show that multicopy genetic redundancy extends their ammonia production lifetime in culture. By finetuning multicopy uAT expression strength, we then demonstrate that an optimal expression strength maximizes ammonia production rate. These expression optimized multicopy strains further increase the growth promotion of Setaria viridis, as well as promote the growth of Zea mays in nitrogen-poor, non-sterile soil compared to wild-type and mock inoculation. Finally, we show throughout our work that uAT strains can be used as tools to probe questions in fundamental biology, such as what metabolism is regulated by ammonia versus glutamine
Engineering and Characterizing D5_AR, a Monoclonal Antibody that Targets the gp41 N-Heptad Repeat of HIV-1 with Broad Tier-2 Neutralizing Activity
Keywords:  Department of Biology
Biology
Virology
Immunology
HIV-1
Antibodies
Vaccines
Thesis

HIV-1 infection is initiated by the viral glycoprotein Env, which, after interaction with cellular coreceptors, adopts a transient conformation known as the pre-hairpin intermediate (PHI). The N-heptad repeat (NHR) is a highly conserved region of gp41 exposed in the PHI; it is the target of the FDA-approved drug enfuvirtide and of neutralizing monoclonal antibodies (mAbs). However, to date these mAbs have only been weakly effective against tier-1 HIV-1 strains, which are most sensitive to neutralizing antibodies. Here, we engineered and tested 11 IgG variants of D5, an anti-NHR mAb, by recombining previously described mutations in four of D5’s six antibody complementarity-determining regions. One variant, D5_AR, demonstrated 6-fold enhancement in ID50 against lentivirus pseudotyped with HXB2 Env. D5_AR exhibited weak cross-clade neutralizing activity against a diverse set of tier-2 HIV-1 viruses, which are less sensitive to neutralizing antibodies than tier-1 viruses and are the target of current antibody-based vaccine efforts. In addition, the neutralization potency of D5_AR IgG was greatly enhanced in target cells expressing FcγRI, with ID50 values below 0.1 μg/mL; this immunoglobulin receptor is expressed on macrophages and dendritic cells, which are implicated in the early stages of HIV-1 infection of mucosal surfaces. D5 and D5_AR have equivalent neutralization potency in IgG, Fab, and scFv formats, indicating that neutralization is not impacted by steric hindrance. Taken together, these results provide support for vaccine strategies that target the PHI by eliciting antibodies against the gp41 NHR and support investigation of anti-NHR mAbs in non-human primate passive immunization studies.
Engineering better treatments for diabetes : from next-gen insulin drugs to autonomous insulin delivery
Keywords: Bioengineering.

Insulin was first isolated a century ago, yet commercial formulations of insulin and its analogues for hormone replacement therapy falls short of mimicking the endogenous glycemic control that occurs in non-diabetic individuals. Moreover, diabetes management is increasingly relying automated insulin delivery using closed-loop systems to improve glucose management and reduce patient burden. However improvements in insulin formulations, sensors, and algorithms are required to shift from hybrid systems to fully autonomous delivery. Insulin formulations that better mimic secretion from the beta-cells, by enabling more rapid insulin absorption kinetics and/or co-delivering complementary hormones (i.e. amylin), would improve diabetes management. However, formulation innovation is complicated by the poor stability of insulin monomers and amylin. During my time in the Appel lab, I have developed two polymeric excipient platforms (non-covalent PEGylation and amphiphilic copolymer excipients) that can be used to increase the stability of insulin in formulation. Using these designer excipients, I have developed three enhanced insulin formulations: (i) an ultrafast monomeric insulin lispro (ii) an insulin-amylin co-formulation and (iii) an ultra-stable insulin for improved global access. These three enhanced insulin formulations are promising candidates for improving glucose control and reducing burden for patients with diabetes. Beyond formulation engineering, through collaborations I have investigated the use of open-source algorithms in a full closed-loop setting as well as helped to develop a continuous real-time ELISA microfluidic device for continuous monitoring of insulin and glucose. Together, this collection of work describes the development of new technologies towards insulin delivery with the goal of improving glucose management in patients with diabetes
Engineering contact layers in metal halide perovskite solar cells using atomic layer deposition
Keywords: Chemical Engineering.

Solar energy is an attractive, renewable energy source because of its massive abundance and its capacity for distributed generation. Photovoltaics (PV) allow us to convert this solar energy directly into usable electricity. Metal halide perovskite solar cells are a new, thin film PV technology on the cusp of commercialization; however, more research is needed to improve their power conversion efficiency and long-term stability, as well as to scale-up their manufacturing. Contact layers and their interfaces with the perovskite absorber are an important component in each of these facets of research. Engineering these contact layers to improve the collection of photogenerated charge carriers often requires precise control over their film properties, such as thickness, composition, and crystallinity. Atomic layer deposition is a versatile, nanoscale synthesis tool that is well-suited for these applications. In this dissertation, we develop low temperature (< 100 C) ALD processes to grow metal oxide contact layers above the perovskite absorber. We focus primarily on vanadium oxide and tin oxide, which are hole- and electron-selective contact materials, respectively. Conformal ALD vanadium oxide contacts enable the fabrication of semi-transparent devices which have potential applications as the wide band gap subcell in tandem solar cells. Tuning the organic hole contact in these devices also leads to improvements in device photocurrent. We show that the ALD vanadium oxide is morphologically stable at temperatures (70 C) relevant to solar cell operation in the field, resulting in devices with good long-term stability. The growth behavior of ALD contacts also has important implications for overall solar cell performance and stability. We find that functionalizing the ALD growth surface to help initiate film growth leads to more compact ALD tin oxide contacts that extend the lifespan of perovskite solar cells. Lastly, we investigate strategies to limit adverse reactions between ALD metal-organic precursor molecules and the perovskite that lead to a poor interface for charge extraction from the solar cell