VictorJuiz/thesis huggingface dataset:
How Does Medical Science Inform Medical Practice?

In the past few decades, the role of basic science and controlled clinical trials has changed the communication of function and utility of diagnostics and therapies. This resulted in efforts promoting clinical decisions to follow evidence-based medicine, precision medicine and personalized medicine. The communication concerning a drug’s utility, and the advantage it provides to an individual patient influence patients and physicians attitudes. How? The history of Tamoxifen’s development and its use in the treatment of breast cancer will serve as the example for the changes in medical practice. The rationale for tamoxifen’s development is the growth dependency of breast cancer cells on estrogen. Yet, the development originated from the understanding of the physiological relationship between the ovaries and the breasts, prior to the discovery of the hormone estrogen and the estrogen receptor (ER) its target protein. Does the fact that majority (70%) of women with breast cancer express ER and/or progesterone receptor (PR) while only a fraction (25%- 50%) respond to the treatment, puts the generalizability of the rationale in question? The empirical discoveries and the explanations provide an important platform to interrogate the relationship between the science utilized by contemporary medicine and the practice of medicine. Claims of specificity and robustness made in scientific work may not support causal relatedness. Therefore, such claims may not support explaining or predicting medical problems or generate plausible hypothesis to paths to treatment. While a mechanistic causality model is hailed rhetorically for supporting scientific and clinical rationale, in practice associative descriptions, at times inductive and at times deductive, are employed in practice. When correlated or combined they form weak probabilities in support of predictive outcome in practice. In summary, understanding the limits each data set provides, may help develop specific quantitative models to test utility, context and predictive value.

Advisor: deacon, terrance
Targeted machine learning approaches for leveraging data in resource-constrained settings

Researchers in the field of public and global health continue seeking ways to reduce the disproportionate burden of disease on marginalized communities and in resource-constrained settings, for example, in low-middle income countries (LMIC). While progress towards this goal has been made by increasing the uptake of evidence-based practices (EBP) in LMIC, many barriers to sustainable implementation of EBP in LMIC remain. This dissertation is comprised of three studies which harness data-adaptive methods as a tool for supporting uptake of EBP in LMIC./nThe first study sought to inform allocation of viral load tests by proposing a differentiated care approach for persons living with HIV. Our results indicate that, in comparison to current non-targeted approaches, a hypothetical machine learning approach may reduce testing frequency relative to resource-rich settings while obtaining similar sensitivity, and while maintaining delay time to viremia detection low. Relative to WHO viral load testing standards, this approach greatly improved the sensitivity and delay time to detection of viremia./nThe second study sought to determine whether easily attainable maternal-infant characteristics can predict risk of preterm birth, while maintaining accuracy similar to that of more expensive gestational age (GA) dating methods. Our results indicate that, among women who entered antenatal care (ANC) in the first trimester, an algorithm based on simple maternal-infant characteristics can predict GA and preterm risk within a clinically valuable margin of error. Therefore, this has the potential to inform clinical care surrounding the time of delivery and can be used for preterm birth rate reporting. The last study sought to compare methods for estimating intervention effects in small-scale cluster randomized trials (CRT), which are commonly used, particularly in resource-constrained settings. We assessed the robustness of various methods in analyzing hierarchical data, both in simulation and using a real-data example. We concluded that analyses of small-sample CRT require careful consideration surrounding weighting scheme, covariate adjustment, and target parameter specification.

Advisor: Petersen, Maya
REGULATION OF BI-DIRECTIONAL TRANSPORT BY CARGO-SPECIFIC ADAPTORS

Cytoskeletal motors play essential roles in controlling both the internal organization and divisionof eukaryotic cells. Much of this organization is maintained through the precise trafficking and delivery of intracellular components to specific destinations within the cell. Intracellular transport is driven by motor proteins that move unidirectionally along cytoskeletal filaments. Although the mechanisms of motor stepping and motility have been well studied, it remains unclear how motors are correctly coupled to their cargoes and how this information is transmitted to direct the cargo to its proper destination./nIn my doctoral work, I studied how the activity of dynein and kinesin are regulated by specificadaptor proteins that link these motors to intracellular cargoes. I showed that different cargo adaptor proteins can tune dynein force generation and velocity by recruiting multiple motors to the same complex. Furthermore, I discovered that cargo adaptors adjust dynein’s force generation and velocity through separate mechanisms. While cargo adaptors control force generation by modulating motor stoichiometry, velocity is altered through allosteric interactions that increase the enzymatic activity of dynein’s motor domain./nIn addition, I studied how both kinesin and dynein regulate the transport and directionality ofmitochondria. I used an in vitro reconstitution approach to determine how mitochondrialassociated proteins interact with both dynein and kinesin. Interestingly, I discovered that two proteins, TRAK1 and TRAK2, are activating cargo adaptors that are sufficient to induce dynein’s processive motility. Furthermore, I found that TRAK1 and TRAK2 can also bind to kinesin, suggesting that they may act as scaffolds to bridge both motors together. In summary, this study provides mechanistic detail into the motor transport complex that drives bidirectional mitochondrial transport.

Advisor: Yildiz, Ahmet
A Frequency Domain Approach to Characterizing and Modeling Single Phased, Forced Circulation Advanced Nuclear Reactor Designs

This work presents techniques for characterizing the nuclear and thermal hydraulic performance of liquid-cooled, solid fueled advanced reactors during start-up testing and normal operation. A technique is proposed that uses periodic perturbations to obtain the frequency response characterization of the systems of interest. This characterization provides a description of the dynamic behavior which can then be used for model validation, safety and stability analysis, fault detection, controller design, among other uses./nThis is done by first reviewing the use of frequency response testing, how tests should be designed, and what information can be obtained from tests. The techniques were then used on a non-nuclear integral effects test facility to characterize the transient heat transfer of the loop for model validation purposes. A new model was developed of the U.C. Berkeley Compact Integral Effects Test primary flow circuit to model the frequency response tests and to study a new frequency domain approach to model validation./nThe electric heater controls for the facility were updated to utilize simulated reactivity feedback control, allowing for a controlled study of the relationship between the simulated reactivity and heater power using frequency domain techniques. This provides a non-nuclear method for developing techniques that could be used for determining reactor kinetics parameters. Parameters like feedback coefficients and delayed neutron precursor concentrations can be changed easily to study their effects on reactor behavior./nWhile the integral effects test is designed to replicate the behavior of a molten salt cooled reactor, it does not operate at prototypical temperatures, and does not have the added complexity of nuclear fuel. After testing the use of these techniques with the integral effects test, similar techniques are applied to a model of the Molten Salt Reactor Experiment which operated at Oak Ridge National Laboratory from 1965 to 1969./nThe Molten Salt Reactor Experiment is modeled using the Modelica based modeling library, TRANSFORM. Historical frequency response data were used to validate the model using a frequency domain comparison. From this work, there are several lessons learned that are important to incorporate into the pre-installation testing and testing during initial operation of future advanced reactors./nThis provides the groundwork for techniques that can be used to characterize the performance of future reactors. This characterization could then be used to validate models of the facility that were used to make the safety case for their licensing. These techniques may also prove to be valuable in detecting changes in the nuclear or thermal hydraulic behavior during operation, as a means by which faults can be detected.

Advisor: Peterson, Per F
Engineering production of fluorinated polyketide natural product analogs

Fluorination is an important tool for the discovery and production of synthetic pharmaceuticals, as it allows fine-tuning their pharmacokinetic properties and metabolic stability. However, unlike chemists, Nature rarely utilizes fluorine to enhance its molecules, and the few known naturally occurring organofluorines generally lack structural complexity. Despite advances in chemical fluorination methods, the regiospecific fluorination of complex natural products remains a challenge. Thus, we have taken a metabolic engineering approach to develop a novel platform for fluorine incorporation into polyketide natural products. Polyketide natural products are synthesized from one starter unit and multiple acyl-CoA extender units. We designed a modular system in which an inactivating mutation was introduced to the acyltransferase (AT) domain of interest to reduce the native activity of the module, while an alternative fluorine-selective AT enzyme was provided in trans to incorporate fluorine as a fluoromalonyl-CoA extender unit. A malonate transporter and a malonyl-CoA synthetase were introduced to support the intracellular accumulation of fluoromalonate and its enzymatic activation into fluoromalonyl-CoA extender unit, respectively. By engineering a single module construct of 6-deoxyerythronolide B (6dEB) synthase (DEBS), fluorinated triketide lactone was produced as the major polyketide product at mg/L levels in an Escherichia coli host. Extending these engineering concepts to a complete DEBS pathway allowed us to produce novel fluorine-containing 6dEB analogs in E. coli production host in a regiospecific manner. This platform can allow the precise incorporation of fluorine into many positions in the backbones of polyketides. These results open the door to producing a new class of drug-like molecules with potentially diverse and improved properties.

Advisor: Chang, Michelle C Y
Responsive Law considerations for Mexican public officials’ Declarations of Assets and of Interests

Preventing corruption and, particularly, the one initiated from the Public Sector itself, is a shared concern amongst democracies from the OECD. Comparative studies carried out by that international organization have found persuasive arguments in favor of implementing the public policies commonly referred as Declarations of Assets and of Interests. Mexico introduced them into its legal system since 2002 and passed major legal reforms in the 2015-2016 period. Yet, in my opinion, the results in that jurisdiction are, as of today, questionable.The public policies’ rationale argues that corruption in the Public Sector as a whole can be prevented by coercively requiring public officials to periodically declare to the government detailed personal information concerning their wealth’s evolution and potential conflicts of interests. Such information is to be used for two main purposes: (a) enhancing the investigators’ capabilities for detecting potential acts of corruption, especially illicit enrichment, and (b) making mandatory disclosures of what officials declare and of what anticorruption institutions perform, so that democratic accountability upon them can be exerted. Considering intricacies of Mexico’s legal framework, trying to look at the public public policies through the eyes of bureaucracy and drawing from a variety of literature that can be connected using the theory of Responsive Law formulated by Berkeley Law Professors Philippe Nonet & Philip Selznick, I argue that the aforementioned Declarations’ effectiveness could have important improvements in Mexico by exploring three measures: (1) Balancing the values of privacy and governmental transparency; (2) Standardizing investigators’ methods for the verification of what officials declare and the detection of red flags for the initiation of legal cases; (3) Generating public information to evaluate the integrity of officials and the performance of anticorruption institutions. Based on a purposive reading of current statutes’ provisions instead of major legal reforms, I delineate three proposals —one for each measure— aiming to entice speculation and discussion. In this regard, I argue that it is important to bear in mind Mexico’s society context of a generalized use of information technologies, particularly those whose functioning require access to internet, and to expand on the idea that the worldwide access to such technologies —as well as their sophistication— are expected to increase as time passes by.

Advisor: Bamberger, Kenneth
3D Printing with Post-processing for Piezoelectret Energy Harvesters and Vacuum Electronics

Additive manufacturing has been at the forefront of manufacturing research with advances in basic printing techniques, materials, and post-processing schemes. This work addresses two technical challenges in the broad spectrum of 3D printed structures: (1) functional surfaces and devices; (2) the surface finishing in terms of roughness./nIn the first part of this dissertation, a post-fabrication process is investigated to create functional 3D printed structures that can be used for energy harvesting applications by converting mechanical energy to electricity. Chemical vapor deposition (CVD) of various Parylene layers is used to coat a thin film on top of the 3D printed polymer surfaces. The corona discharge method is then used to implant surface charges on the film to construct multi-layered energy harvesting structures. Experimentally, the prototypes can produce 12.5 µW/cm2. Then, a wearable shoe sole energy harvester has been created using 3D printing and CVD of Parylene C and tested in real-life scenarios such as walking, running, and jumping. The system can produce a peak power output of 8 µW/cm2 from a single layer design./nIn the second part of this dissertation, a novel surface polishing method has been developed to polish enclosed structures by 3D printed waveguide structures for vacuum electronics for high frequency applications with very stringent surface finish requirements. Magnetic particles have been used in an abrasive slurry and a linear actuator system has been developed to move a magnet. The moving magnetic field can move the slurry inside an enclosed structure to polish the surface. The system has been tested on sample waveguide structures made of copper powders via the electron beam 3D printing process with an initial surface roughness of 40 µm. By using the method developed in this dissertation, the surface roughness has been reduced to reach 1.5 µm in a waveguide.

Advisor: Lin, Liwei
From Redlining to Greenlining: The Political Ecology of Race, Class, and Access to Green Space in Oakland, California from 1937-2020

Since the 1960s, Oakland, California, has been represented as a predominantly African American, low-income, and high crime urbanity. In the 2000s, the municipality started to become recognized as a top green city, and by the 2010s the city began to emerge as a gentrification hot spot. This dissertation elucidates how the relationships between race, class, housing, and access to green spaces have changed from redlining—prior to the Civil Rights Acts of 1964, 1965, and 1968—to 2020, after Oakland adopted an environmental agenda and began to establish itself as a green city starting in the 1990s. I question how Oakland’s urban environmental “sustainable development” agenda has impacted residents’ access to green spaces, and to what extent and how are these policies and practices creating, exacerbating, and/or mitigating urban environmental (in)justice issues. I examine both sides of environmental (in)justice, uneven distribution of environmental harms and the uneven development of environmental goods in which low-income residents and communities of color are disproportionally exposed to environmental hazards while also being prevented from benefiting from environmental amenities. I interrogate Oakland as a 21st century sustainable green city while also examining the historical urban policies and practices embedded in legal residential segregation and the current green gentrification processes which influence and contribute to the environmental (in)justices being (re)produced today.

Advisor: Morelli-Frosch, Rachel
The Effects of Arsenic Exposure on Fatty Liver Disease Development and the Glucocorticoid Response

Arsenic, a naturally occurring metalloid, has been linked to a wide variety of metabolic disorders and diseases, including type II diabetes and non-alcoholic fatty liver disease. However, the exact mechanism of action of which arsenic leads to these maladies is not well understood. Research has elucidated the importance of other external factors, such as stress and diet, that may be increasing the development and severity of arsenic’s negative impacts. This dissertation aims to explore the combinatorial effects of arsenic and the lifestyle factors: diet and stress. Chapter I is an overview of how ubiquitous arsenic is in the world and how one unique population located in Antofagasta, Chile, has become a natural experiment in epidemiology given their clear start and stop exposure time frame and subsequent arsenic-linked disease incidence. This population in addition to others around the world, most notably those in Mexico, Bangladesh, and India, are the inspiration for the studies included in this dissertation. Chapter II evaluates a high fructose diet in combination with both low and high dose arsenic in an in vivo model. Both fructose and arsenic are metabolized in the liver and when in surplus can lead to dysregulation of triglyceride processing and storage. This study contributes to existing research on dietary influence on the adverse effects of arsenic exposure, which until now has been focused solely on high fat diets. Chapter III seeks to evaluate if arsenic antagonizes the glucocorticoid receptor by using an in vivo model exposed to both arsenic and a synthetic glucocorticoid. . Furthermore, there is a large person-to-person variation in susceptibility, but the majority of the reasons are unknown, making these studies crucial to determine where that susceptibility may lie.

Advisor: Smith, Martyn
How welfare shapes beneficiaries' political and economic behavior: evidence from two programs in India

How do welfare programs shape the economic and political behavior of recipients? This dissertation is a series of three empirical articles that examine the effects of two programs in India. The first paper finds that a subsidized housing program increases the educational attainment and employment prospects of beneficiaries' children. The second finds that this same program increases everyday local level political participation to improve public goods and services. The third paper finds that a national rural employment guarantee decreases participation in state-level elections among the target beneficiary group. Overall, the dissertation finds that welfare programs can alter beneficiaries' economic and political behavior in important and unexpected ways, thereby providing a vast open agenda for future research.

Advisor: Chhibber, Pradeep K
Synthesis and Application of Multicomponent Metal Nanostructure in a Colloidal System

Natural and artificial photosynthesis both require a precisely organized structure with multiple components for an efficient charge transfer pathway. The development of nanotechnology enables us to scale these sophisticated structures from bulk to nanometer-size by providing tunable physical and electronic properties. In order to achieve sophisticated nanostructures, lithographic techniques are commonly used to arrange those components in arbitrary patterns. However, lithographed materials are not easy to be scaled up, and it is hard to study the electronic picture due to the lack of well-defined facets and crystalline structure. There has been a surge of interest in exploring the effect of metal colloidal nanoparticle in photochemistry. The localized surface plasmon resonance property of the metal nanoparticle generates energetic charge carriers above the fermi energy of the metal. Interestingly, the energy of the charge carrier is greatly dependent on the morphology of the structure which can harvest photons over the entire solar spectrum. However, since the lifetime of carriers is extremely short compared to the semiconductor nanoparticles, other components are required to capture the energetic electrons from the metal nanoparticle. Thus, sophistically incorporating multiple components on the metal nanoparticle offers an effective way to use hot carriers of the metal nanoparticle. These complex structures based on the metal nanoparticle can further shed light on diverse applications such as plasmonics and photocatalysis. This dissertation lays out a novel synthetic approach to fabricate a function-oriented colloidal polyelement nanostructure using a solution-phase redox chemistry. Furthermore, we demonstrate that such a sophisticated nanostructure can effectively improve the photocatalytic efficiency of hydrogen and oxygen evolution reaction without the use of any scavenger. I truly believe that this thesis work can inspire the material research community for the development of a new library to manipulate the chemical and physical properties of matter.

Advisor: Alivisatos, Paul A