VictorJuiz/thesis huggingface dataset:
The Nature of Tomorrow: Inbreeding in Industrial Agriculture and Evolutionary Thought in Britain and the United States, 1859-1925

Historians of science have long recognized that agricultural institutions helped shape the first generation of geneticists, but the importance of academic biology to scientific agriculture has remained largely unexplored. This dissertation charts the relationship between evolutionary thought and industrial agriculture from Charles Darwin's research program of the nineteenth century through the development of professional genetics in the first quarter of the twentieth century. It does this by focusing on a single topic that was important simultaneously to evolutionary thinkers as a conceptual challenge and to agriculturalists as a technique for modifying organism populations: the intensive inbreeding of livestock and crops./nChapter One traces zoological inbreeding and botanical self-fertilization in Darwin's research from his articles published in The gardeners' chronicle in the 1840s and 1850s through his The effects of cross and self fertilisation in the vegetable kingdom of 1876. In doing so, it demonstrates how Darwin metaphorically linked natural selection to methodical selection in order to authorize the naturalist to become an experimental evolutionist. It also explores the potential of Darwin's program as an ideology for actors intent on transforming the political economy of agriculture./nChapter Two moves away from scholarly discussions of evolution to consider how intensive inbreeding was pioneered as a method for modifying crops by the Bureau of Plant Industry of the U.S. Department of Agriculture between 1897 and 1907, the decade following William Jennings Bryan's loss to William McKinley in the election of 1896. By analyzing both Robert Bakewell's livestock inbreeding system of the eighteenth century and Archibald Shamel's Connecticut River tobacco self-fertilization program of the early twentieth, the chapter explains the political economy of intensive inbreeding. It concludes by exploring the broader context of the experiments devoted to livestock inbreeding that George Rommel initiated at the Bureau of Animal Industry of the U.S. Department of Agriculture in the early 1900s./nChapter Three combines the intellectual history of Chapter One with the political and economic history of Chapter Two by illustrating how the research program of experimental evolution that Darwin formulated in the nineteenth century mapped onto the large-scale industrial agriculture projects of the USDA between 1903 and 1925. The chapter follows ideas on inbreeding as they moved across various academic and professional communities, paying particular attention to institutional arrangements like the American Breeders' Association and the Bussey Institution of Harvard University that facilitated these transfers. It also examines various inbred organism populations that became prototypes for industrial production and the scientists who became their shepherds: the Wistar rats of Helen Dean King, the hybrid corn of Edward Murray East and Donald Forsha Jones, and the guinea pigs of Sewall Wright.

Advisor: Lesch, John E.
The Politics of Polarization: Legitimacy Crises, Left Political Mobilization, and Party System Divergence in South America

The rise of the left across much of South America in the aftermath of market reforms catalyzed a major divergence in regional party systems. In some countries, polarizing party systems emerged, marked by conflictual patterns of contestation between major political parties and the politicization of class cleavages in party competition. In other countries, integrative party systems consolidated, characterized by largely consensual patterns of competition and class cleavages that remain unexpressed in party competition. This variation in party systems represents a critical macropolitical legacy to emerge from the tumultuous recent decades and offers fruitful ground for developing and testing theory regarding the causes of political and social polarization in the younger democracies of the highly unequal developing world./nExamining the cases of Venezuela, Brazil, and Chile, this dissertation develops an argument that centers on the avoidance or occurrence of "legitimacy crises": anti-systemic episodes involving protracted failures of governance and steep erosions of public confidence in state institutions. The presence or absence of legitimacy crisis decisively shaped factional contestation within the partisan left in each country, leading to party system divergence along two dimensions. Whether radical or moderate left coalitions consolidated entailed the establishment of conflictual or consensual patterns of contestation within party systems. Once in office, the radical and moderate left also pursued different strategies of political mobilization - mass-organizational in Venezuela and catchall in Brazil and Chile - that subsequently drove variation in the translation of class cleavages into party competition./nThe study relies on a variety of qualitative and quantitative data sources, including those gathered during 11 months of fieldwork in Venezuela, and utilizes both process-tracing and statistical methods (primarily genetic matching) to draw causal inferences. A concluding chapter shows that the argument can also explain variation in party systems in two other countries where the left has taken power (Bolivia and Uruguay), suggesting that the framework in the study might provide a broader model of macropolitical divergence in the region during the last decades.

Advisor: Collier, Ruth
Collier, David
Beyond the Seas: Eighteenth-Century Convict Transportation and the Widening Net of Penal Sanctions

Convict transportation is an important, and under-explored, link in the evolution of punishment, and can illuminate the ways that states transform their capacities to exercise penal power. This dissertation argues that eighteenth-century North American convict transportation dramatically "widened the net" of penal sanctions. The increased penal capacity of the state was made possible by the combination of delegation to commercial actors and the increasing involvement of the national government in the financial, political and regulatory aspects of the administration of transportation. Transportation, unlike imprisonment at hard labor, was not seen as violating traditional English liberties because it "widened the net" without creating new state structures and practices, and it drew on the accepted logic of governing the poor through labor.

Advisor: Lieberman, David
A Quantification of Deep Core Trunk Muscles Impact on Lumbar Lordosis and Spine Stability

The lumbar multifidus (LM) plays a unique role for adjustment and support of lumbar lordosis. Although exercise therapies have shown that strengthening the multifidus produces reductions in low back pain, the quantification of the LMs role is undetermined. The goal of this in vitro study was to test the hypothesis that LM atrophy significantly reduces lumbar lordosis for spines in the upright posture./nThe paraspinal muscles of six fresh human thoracolumbar spine (T12-pelvis) were surgically removed, leaving the spinal segments intact. The T12 level was fixed to a torso plate that facilitated anatomically appropriate trunk muscle attachment and dead weight simulation of torso weight (245 N). The pelvis was attached to a custom fixture that allowed pelvic tilt adjustment to the appropriate value for upright stance. In this experiment, three muscle groups were simulated using steel cables: the deep LM, erector spinae (ES), and rectus abdominus (RA). These cables were inserted at anatomically appropriate vertebral sites and were routed directly to digitally controlled torque motors. A total of five loading cases were investigated for three sets of experiments: neutral posture, axial rotation, and flexion/extension stability perturbation./nResults indicated a small change in lumbar lordosis for L4/L5 motion segment for atrophy while in the neutral posture. The data highlights how variations in muscle activation patterns alter lumbar lordosis and tissue stress distribution.

Advisor: O'Reilly, Oliver M
Lotz, Jeffrey C
Ga(III)-Catalyzed Cycloisomerization Approach to the Icetexones and Nominine

The icetexane diterpenoids is a group of natural products isolated from various members of the Salvia genus. These compounds contain a [6-7-6] tricyclic motif and vary by the level of oxidation on the seven-membered ring and oxygenation of the arene moiety. The synthesis of these compounds has been achieved by our group through the use of a Ga(III)-catalyzed cycloisomerization of indenyl alkynes. This thesis explores the synthesis of the icetexone subclass of diterpenoids, which contain extra functionalization, using a similar cycloisomerization strategy./nThe synthesis of icetexone was first attempted through the use of a remote functionalization strategy to form the desired lactone. However, all attempts were unsuccessful. Therefore, a second generation approach using a pre-functionalized indenyl alkyne in the Ga(III)-cycloisomerization reaction yielded the desired tricyclic intermediate. A tandem epoxide opening, lactone formation, and reductive transposition sequence completed the formal synthesis of both icetexone and 5-epi-icetexone. Progress toward anastomosine, another member in this subclass, was also made./nAnother family of compounds that was targeted using the Ga(III)- catalyzed cycloisomerization is the C20 diterpenoid alkaloids. This large family of natural products is found in traditional Eastern medicines and has unique and complex structures. The hetisine type of natural products is characterized by their rigid heptacyclic core and a bicyclo[2.2.2]octane motif. We believed that our Ga(III) cycloisomerization methodology would enable access to the [6-7-6] tricyclic core of these molecules as a starting point for their successful synthesis./nThe synthesis of nominine was first attempted through an acid catalyzed hydroamination of a cycloheptadiene accessed from the Ga(III)-cycloisomerization. Low yields of the hydroamination as well as later transformations led us to develop a second- generation strategy that involved dihydroxylation of the cycloheptadiene and monoprotection of a resulting diol. Both routes are currently being explored to complete the synthesis of nominine.

Advisor: Sarpong, Richmond
Neural Effects of Beta Amyloid in Normal Aging

In this dissertation, I examine neural effects of beta-amyloid (Aβ) deposition, a primary pathological feature of Alzheimer's disease (AD), that also appears in cognitively "normal" elderly controls. This work represents a conjunction between the fields of AD research and the cognitive neuroscience of aging. Whereas the former strives to understand early disease mechanisms and potential treatment approaches, the latter aims to characterize neural changes in the aged brain and corresponding effects on cognition. Despite their differences, these fields are interconnected by the fact that Aβ pathology is very common amongst "normal" aged individuals. Therefore, an understanding of the effects of Aβ in aging has important implications for uncovering disease processes, and for providing biological mechanisms for neural changes observed in studies of aging./nThe research herein employs a multimodal approach to investigating Aβ in aging. Throughout the experiments, particular emphasis was placed on brain regions subserving episodic memory (EM)--this domain is the first compromised in AD and shows decline in normal aging, therefore it was hypothesized that the earliest effects of Aβ would relate to this cognitive domain. Specifically, PET imaging with 'Pittsburgh Compound-B' (PIB) was used to assess Aβ burden, magnetic resonance imaging was used to assess brain structure (hippocampus volume) and function (functional connectivity during rest and activation during EM encoding), and neuropsychological testing was used to assess cognitive function./nIn the first experiment, I provide support for a sequential relationship between Aβ burden, hippocampus volume and EM in stages preceding dementia. This model is consistent with a cascade model of AD, such that Aβ deposition is an early event that initiates downstream neuronal atrophy, which in turn leads to cognitive decline. In the second experiment, I show that brain functional connectivity in the EM subcomponent of the DMN is reduced, whereas functional connectivity in non-EM regions of the DMN is increased in NCs with high Aβ burden. Finally, in experiment 3 I show that NCs with high Aβ burden have increased task-related activation during successful EM encoding. Importantly, these activations were related to better overall memory performance, suggesting that these increases reflect a beneficial process to elderly individuals with high Aβ burden./nOverall, these experiments support a biological relevance of Aβ in aging. Specifically, these results suggest that Aβ is related to early signs of dysfunction in regions subserving EM. However, it is also shown that NCs with high Aβ burden display a capacity for neuronal compensation in the face of this pathology. Taken together, these results suggest that although Aβ likely reflects the beginning stages of AD development, compensatory mechanisms exists that may enable individuals to cope with this pathology, or at least prolong the period between initial deposition and impending cognitive decline.

Advisor: Jagust, William J
Mild Heat Stress Induces Mitochondrial Biogenesis Associated with Activation of the AMPK-SIRT1-PGC-1alpha Pathway in C2C12 Myotubes

During endurance exercise, most (about 75%) of the energy derived from the oxidation of metabolic fuels and ATP hydrolysis of muscle contraction is liberated as heat, the accumulation of which leads to an increase in body temperature. For example, the temperature of exercising muscles can rise to 40 degrees C. Although severe heat injury can be deleterious, several beneficial effects of mild heat stress (HS), such as the improvement of insulin sensitivity in patients with type 2 diabetes have been reported. However, among all cellular events induced by mild HS from physical activities, the direct effects and mechanisms of mild HS on mitochondrial biogenesis in skeletal muscle are least characterized. AMP-activated protein kinase (AMPK) and Sirtuin 1 (SIRT1) are key energy-sensing molecules regulating mitochondrial biogenesis. In C2C12 myotubes, we found that one-hr mild HS at 40 degrees C increased both AMPK activity and SIRT1 expression, as well as increased the expression of several mitochondrial biogenesis regulatory genes including peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) and transcription factors involved in mitochondrial biogenesis. In particular, PGC-1alpha expression was found to be transcriptionally regulated by mild HS. Additionally, after repeated mild HS for 5 days, protein levels of PGC-1alpha and several mitochondrial oxidative phosphorylation subunits also increased. Repeated mild HS also significantly increased mitochondrial DNA copy number. In conclusion, these data suggest that mild HS is sufficient to induce mitochondrial biogenesis associated with activation of the AMPK-SIRT1-PGC-1alpha pathway in C2C12 myotubes. Therefore, it is possible that muscle heat production during exercise plays a role in mitochondrial biogenesis.

Advisor: Brooks, George A
Oriented Attachment of Cytochrome P450 2C9 to a Self-Assembled Monolayer on a Gold Electrode as a Biosensor Design

Cytochrome P450s (CYPs) are a family of enzymes implicated in the metabolism of drugs in the body. Consequently, P450 reactions are of high interest to the pharmaceutical industry, where lead compounds in drug development are screened as potential substrates of CYPs. The P450 reaction involves electron transfer to an iron heme via NADPH and the electron transfer partner enzyme P450 reductase (CPR). By immobilizing CYPs on an electrode however, NADPH and CPR are potentially no longer needed and the immobilized CYP can act as a biosensor by accepting electrons directly from the electrode. Such a biosensor could be used as an initial screening tool for CYP reactivity of pharmaceuticals in development. In this study, the drug-metabolizing enzyme CYP 2C9 was immobilized to a self-assembled monolayer (SAM) on a gold electrode in three different orientations to investigate the effect that orientation has on the direct electrochemistry of CYP and to evaluate oriented attachment of CYP to an electrode as a biosensor design. Three attachment methods were investigated: random attachment via amine coupling to a carboxy-terminated SAM, oriented attachment via C-terminal His-tag coupling to a Ni-NTA-functionalized SAM, and oriented attachment via maleimide/thiol coupling to a maleimide-functionalized SAM. Three 2C9 mutants (R125C, R132C, and K432C) were developed with a single cysteine mutation at the binding site for CPR on the side of the enzyme closest to the heme; attachment of these mutants to a gold electrode via maleimide/thiol coupling would orient the enzyme such that electron transfer occurs on the electrode in the same orientation that it does in vivo with CPR. Therefore, we expected oriented attachment via maleimide/thiol coupling to produce the most electroactive CYP biosensor. Electrochemical analysis and surface characterization of the SAMs on gold electrodes confirmed that electron transfer occurs through the SAMs, and activity assays of the 2C9 electrodes confirmed that wild-type 2C9 and the single Cys mutants R125C, R132C, and K432C were immobilized to the gold electrode via all three attachment methods. Cyclic voltammetry of the 2C9 electrodes revealed however, that direct electron transfer to 2C9 was not possible for all three attachment methods. Similar redox processes were observed for both the 2C9 electrodes and no-enzyme electrodes modified only with SAMs, suggesting that the redox process observed on the 2C9 electrodes is related to the underlying SAM. Thus, we were unable to make any conclusions regarding the effectiveness of oriented attachment in creating a 2C9 biosensor. However, to our knowledge, there are no examples in the literature of the oriented attachment of 2C9 to an electrode via coupling of an engineered cysteine to a maleimide-functionalized SAM on gold and therefore this study represents the first attempt towards such an electrode system.

Advisor: Clark, Douglas S
Characterization of Fuel-Cell Diffusion Media

Achieving proper water management in proton-exchange-membrane fuel cells (PEMFC) is an ongoing challenge. Current quantitative treatments of two-phase flow in fuel-cell diffusion media (DM) often assume saturation-dependent transport relations. However, these relations are not validated for the complex physical and chemical structure of the DM, and therefore lack predictive capabilities. Characterization of DM and their water-uptake profiles enables a fundamental understanding of the driving forces behind flooding and facilitates targeted improvement in the form of physically representative simulations. The objective of this work is to characterize, analyze, and explain the wettability and water-uptake behavior of fuel-cell components, namely the DM and catalyst layer (CL), based on manufacturing parameters and physiochemical structure, e.g., fiber structure and hydrophobic treatment of the DM, and chemical composition and crack formation of the CL./nA combination of capillary-pressure saturation (PC-S) measurements, visual-imaging, and physical-characterization techniques is used to quantify water-uptake behavior and identify causal factors. On an intuitive level, Pc-S curves show the propensity of a material to uptake or eject water. The PC-S curves demonstrate that DM are neutrally wetting materials that neither spontaneously imbibe nor eject water. DM from various manufacturers exhibit signature features that can be explained partially by visual differences in fiber structure and deposition of a hydrophobic agent, polytetrafluoroethylene (PTFE). Although the initial addition of PTFE improves hydrophobicity of the sample, increasing PTFE loading does not show significant improvements and instead, as evidenced by pore-size-distribution (PSD) measurements, decreases porosity. Systematic studies of the PSDs demonstrate the level of variation that exists within DM and between DM produced by different manufacturers./nTo date, there have not been data on the wettability and water-uptake behavior of CLs. Isolated CLs were made in-house and commercially and tested for their PC-S response. CLs have the propensity to be highly hydrophilic and require capillary pressures as low as -80 kPa to eject water. The presence of Pt or surface cracks increases hydrophilicity. These findings suggest that saturation in CLs, especially cracked CLs, may exacerbate poor transport./nLastly, this work includes early-stage development of a limiting-current measurement that can be used to calculate effective transport properties as a function of saturation. Results indicate that the method is valid, and different DM have higher transport depending on the operating condition. The technique is yet in a formative stage, and this work includes advice and recommendations for operation and design improvements.

Advisor: Newman, John S
Cellular interactions during gastrulation in the amphipod crustacean, Parhyale hawaiensis

How animals develop the complex structures and morphologies that result in diversification and speciation is a fundamental question in evolutionary biology that can be addressed through studies of embryogenesis. Gastrulation is an early morphogenetic event that establishes the embryonic tissue layers that will give rise to the various organs and characteristics of the adult. Cells and their interactions are the basis of this process. Outside of Drosophila melanogaster, little is known about the behavior of cells during gastrulation in arthropods./nThis dissertation focuses on cell behavior during gastrulation in the amphipod crustacean Parhyale hawaiensis. Using a variety of techniques, we make novel observations about cell shape change, the autonomy of cell behavior, and investigate possible molecular regulators of the entire process. I found cell shape change in the rosette that confirms previous hypotheses suggesting that gastrulation in Parhyale proceeds through ingression or invagination. I also found that the rosette and epithelial sheet act autonomously, and that the descendants of different lineages within the rosette are able to internalize independently. Using drug inhibition, I identified rho-kinase as important to epithelial integrity during gastrulation, and discovered a phenotype that may be associated with abnormal cell division. Finally, I investigated several candidate genes in an effort to discover a molecular marker for early mesoderm and ectoderm fate. This study provides valuable information about the process of cell internalization, cell autonomy during gastrulation, and suggests potential highly conserved mechanisms for cell behavior during Parhyale gastrulation.

Advisor: Patel, Nipam H