VictorJuiz/thesis huggingface dataset:
Bioanalytical Microfluidic Devices and Methods for Analysis of Cancer Gene Expression

Transcriptional profiling is essential in fundamental studies of pathogenesis. In particular, multiplexed analysis of gene expression enables the identification of cancer-specific expression signatures that correlate with clinical disease and which can be used for the prediction of tumor presence and disease progression. Microfabricated capillary electrophoresis (CE) devices feature reduced sample and reagent requirements, faster analysis times, and increased automation. These advantages make microdevices ideal analytical platforms for the quantitative monitoring of biomarkers, and their potential as point-of-care devices for facilitating cancer detection in the clinical setting is explored in this thesis./nFirst, an integrated microdevice capable of performing low-volume, rapid, and highly sensitive expression analysis was developed. To further the goal of quantitative measurements of transcript levels from a small amount of sample, an affinity capture gel approach was used to address the problem of inefficient CE sample injection which limits sensitivity. Photopolymerization protocols were developed to define a small plug of oligonucleotide-modified polyacrylamide gel inline with the CE channel in order to accomplish efficient capture and sample microinjection for quantitative analysis. This concentration and purification step also demonstrated increased detection sensitivity and improved separation resolution./nTo perform multiplexed analysis of cancer genes, an optimized protocol for transcript analysis with aid of affinity capture was used in conjunction with the integrated CE microdevice. The expression of genes implicated in prostate cancer was assayed directly from cells by solution hybridization with complementary fluorescently-labeled detection probes, followed by affinity bead capture of mRNA-probe complexes. Released detection probes were then injected on-chip and captured on a photopolymerized capture gel for concentration prior to CE separation and detection. The ability of the assay and microdevice system to evaluate gene expression was demonstrated by the measurement of absolute transcript levels of ten genes, enabling the successful identification of distinct expression signatures for the human prostate cancer cell lines LNCaP, VCaP, 22Rv1, and PC-3 with high sensitivity./nFinally, a microdevice also including on-chip PCR amplification is presented for improving the sensitivity of detection to enable the analysis of clinical samples. The functionality of the proposed microsystem is further expanded by the integration of upstream sample processing steps on-chip. By performing several bioanalytical processes on a single microfabricated platform, high-sensitivity expression analysis from complex biological samples should be possible, all the while reducing cost and analysis time. Based on the technologies developed in this thesis, these fully integrated devices could be implemented as diagnostic tools and play a key role in the future of clinical detection.

Advisor: Mathies, Richard A
Exchange Rates, Information, and Crises

In this dissertation, I theoretically investigate how the actions of central banks affect the information and beliefs of rational agents. I focus primarily on my models' equilibrium predictions during crisis episodes, including situations in which agents' actions are strategic complements. The first two parts explore the implications of central bank transparency during foreign exchange interventions and develop dynamic models in which investors are heterogeneously informed about both interventions and fundamentals. In the first part, the benchmark two-period model presents the main result that transparency can often exacerbate any misalignment between the exchange rate and fundamentals. This is a consequence of two distinct effects of transparency. First, transparency reveals some information about fundamentals to investors (the truth-telling effect). Second, transparency increases the precision of the exchange rate as a signal of those fundamentals that remain unknown (the signal-precision effect). If a central bank announcement reveals little information about fundamentals, then this second effect dominates and transparency magnifies exchange rate misalignment. In effect, partial information revelation is worse than no information revelation. An important implication of this result is that a policy of ambiguity can increase the effectiveness of intervention to support a declining currency during times of crisis. In the second part, the benchmark model is extended to an infinite horizon and also expanded into a Bayesian signalling game. In both cases, I demonstrate that the principal results do not change./nIn the third part, I examine a global coordination game in which the information of the agents is manipulated before it reaches them. I assume that the regime is imperfectly informed about the underlying state of fundamentals and must trade off the cost of biasing the signals of agents upwards with the benefit of being more likely to defeat the agents' attack. The main conclusion is that the effect of information manipulation depends on the extent to which the regime is better informed about the outcome of the game. In the limit as both the regime and the agents' information becomes arbitrarily precise, the effectiveness of information manipulation depends on whether the regime learns about fundamentals faster than the agents. If agents learn faster than the regime, then information manipulation is ineffective and incurs costs for the regime without diminishing the size of coordinated attacks. In these cases, the regime prefers to take no action but cannot credibly commit to do so.

Advisor: Gourinchas, Pierre-Olivier
Agency and First-Person Authority

Ordinarily when someone tells us about her psychological states, we presume that she is right. By deferring to her in this way, we treat her as a kind of authority on her own psychological life. Although a person usually has this authority, she lacks it whenever she takes a more detached, indirect, or third-personal point of view toward her psychological states. We see this, for example, when she learns about a belief or desire from a friend or therapist. For this reason an adequate account of the phenomenon of "first-person authority" must explain why we have it only for some but not all of our psychological states. Most philosophers believe first-person authority is an epistemic phenomenon, consisting in each of us being better situated to know about our own psychological states than anyone else. Against all such epistemic views, I argue that, because they base their accounts on epistemic privileges that are in principle available to anyone, they cannot capture the exclusively first-personal character of our authority./nAs an alternative to the traditional approach, I argue that first-person authority is derived from a person's agency with respect to her own psychological states. By relating to her psychological states in a first-personal way, a person is able to change or maintain them directly on the basis of what she takes to be good reasons for them. Since no other person can affect her psychological states in this way, her capacities as an agent guarantee her a unique kind of authority for them. A person ordinarily expresses this kind of agential authority over her psychological states in what she says about them. This is what justifies our deferring to her psychological self-ascriptions. On the view I develop in this dissertation, first-person authority is not primarily a matter of special epistemic access to psychological facts and deference is not a response to the epistemic status of what someone says. It is an acknowledgment of the special role that a person's agency plays in determining her psychological life.

Advisor: Stroud, Barry
Finite Deformation of Magnetoelastic Film

A nonlinear two-dimensional theory is developed for thin magnetoelastic films capable of large deformations. This is derived directly from three-dimensional theory. Significant simplifications emerge in the descent from three dimensions to two, permitting the self field generated by the body to be computed a posteriori. The model is specialized to isotropic elastomers with two material models. First weak magnetization is investigated leading to a free energy where magnetization and deformation are un-coupled. The second closely couples the magnetization and deformation. Numerical solutions are obtained to equilibrium boundary-value problems in which the membrane is subjected to lateral pressure and an applied magnetic field. An instability is inferred and investigated for the weak magnetization material model.

Advisor: Steigmann, David
Acts, practices, and the creation of place: Geoarchaeology of a Terra Preta de Índio site in the Central Amazon

My dissertation investigates inconsistencies in the ways Amazonia has been presented to the public and within archaeology as a discipline. It does so by bringing methods from the earth sciences to bear on sites that resist interpretation under widely accepted models for habitation of pre-Columbian Amazonia. Terra Preta de Índio, a type of Amazonian Dark Earth, is a dark soil produced by deliberate human action that functions as key evidence for intensive environmental and landscape remodeling in pre-Columbian Amazonia. Terra preta sites have been recognized in recent decades as likely resulting from large, permanently settled populations previously believed to be absent from Amazonia. My dissertation reconstructs patterns of daily life and village organization at a terra preta site, Antônio Galo, as a means of constructing an alternative narrative about Amazonia's past./nPrevalent narratives about Amazonia cast the region as homogenous and static, exotic, yet culturally decadent. These deeply embedded images of Amazonia have roots in early narratives of `discovery' and `exploration,' which are tightly interwoven with colonialist projects. Historically, archaeological contributions to knowledge about Amazonia, which make use of notions of social complexity that emerge from colonialist notions about `civilization,' also cast Amazonia as empty and its people as passive in its development. Through an exploration of place, I examine the construction of these narratives, and then employ data that speak to Native Amazonians' active role in constructing the landscape to propose alternative narratives for Amazonia and its people./nIn order to detect material traces of past acts of remodeling embedded in the archaeological soil and sediment matrix, I developed a geoarchaeological approach to investigating the household scale at Antônio Galo. I approach the matrix as a particulate body that mediates the relationship between people and their environments and also serves as the stage upon which lives are enacted. Moving away from indices of social complexity, which do not adequately address the scale of daily life in Amazonia, I examine macroscopically visible and invisible traces of the past to reconstruct places created and inhabited by people in the past. Field observations of landscape and environmental remodeling are supplemented by chemical, sedimentological, and microartifactual signatures that help to identify and characterize ancient habitation surfaces and features. Through this nuanced understanding of the various iterations of activity areas, houses, and villages that existed at Antônio Galo, I consider village organization, spatial parsing of activities, and the movement of bodies, in an attempt to recapitulate the lives of people that created and inhabited these places in the past.

Advisor: Joyce, Rosemary A
Stress effects on adult hippocampal neurogenesis and sexual reproductive function

Stress can dramatically alter the brain. Comprised of both neural and hormonal components, response to a perceived stressor can reorganize neural circuits, disrupt cell cycle and shift central control of a variety of systemic regulatory systems. While highly adaptive in many acute scenarios, if too prolonged or too extreme, the brain and bodily response to stress can be detrimental, such as in post-traumatic stress disorder, anxiety disorders and depression. Understanding how the basic environmental and psychological challenge of stress affects the brain is therefore important not only as a window into the basic neurobiology of adaptation to a changing environment, but also as an exploration into neuropathology. The following studies all address the issue of how the stress response alters the brain and thereby the body. Chapter 2 addresses the promotion of adult hippocampal neurogenesis by the basolateral amygdala, a brain region key to fear processing. Chapter 3 addresses how stress can interact with amygdala control of adult neurogenesis, depending on amygdala input for acute stress effects on neurogenesis but not for chronic stress effects. Chapter 4 focuses on how stress regulates sexual reproduction, exploring the role of a novel neuropeptide, gonadotropin-inhibitory hormone, in stress-induces suppression of sexual reproduction. All of the studies confirm the powerful effect of stress on the brain, and furthermore emphasize the complex nature of the relationship.

Advisor: Kaufer, Daniela
The Empire of the Dead: British Burial Abroad and the Formation of National Identity

This dissertation concerns the politics, aesthetics, and meanings of the British dead around the world. It argues that caring for the dead articulated views of the British Empire and Britain's standing in the world as well as how the British people understood their nation and their own identities within and outside of national communities. Broadly speaking this history tells a story of the state's increasing involvement in one of the most deeply personal, and traditionally familial, activities; but it is also an account of how the living came to define themselves through the care of the dead. Initially, in the seventeenth through nineteenth centuries, this took the form of establishing specifically British spaces for civilians who died away from home. Sometimes these distinct burial grounds came about as a way to deal with the problem of confessional difference and became distinctly Protestant while in other cases they reflected the desires of British merchants to fashion themselves as permanent imperial rulers. During the nineteenth century, the state took an increasingly active role in the establishment and operation of these spaces through the professionalization of the Consular Service and the cemeteries themselves became a synecdoche for British liberalism. Somewhat unexpectedly, considering the vast historiography on modern war commemoration and nationalism, the British government spent money and attention on caring for civilians who died overseas chronologically earlier than it concerned itself with dead soldiers. Nevertheless, during the period between the Napoleonic Wars and the Great War the idea that those who fell in battle deserved decent burial gained widespread resonance. The Crimean War of 1853-6 marked a turning point when for the first time most British soldiers received marked graves through the individual efforts of their comrades and manifesting a religiously inspired humanization of common soldiers. These burial grounds only became understood as "national cemeteries" and the government's responsibility after the war following widespread reports of their desecration and neglect. The British public increasingly understood providing Christian burial and marking soldiers graves, even if they died far from home, as a moral imperative for the army, the government, and civil society. During the Great War with the establishment in 1917 of a permanent commemoration bureaucracy, the Imperial War Graves Commission, caring for dead soldiers became infused with the political ideology of empire. The global network of sacred spaces created by the Commission following both world wars manifest not only a desire to care for the dead but also a way of using them to represent a united and victorious imperial polity. This commemoration style itself became untenable during decolonization as the British Empire itself disintegrated. The dead took on new meanings for the living in the late twentieth century even as those of the past as well as the spaces for them remained associated with empire and nation.

Advisor: Laqueur, Thomas W
X-ray Spectroscopy and Pulse Radiolysis of Aqueous Solutions

The interaction of radiation and matter plays a crucial role in studies of aqueous solutions. Depending on the type of radiation, it can either be used a probe or as a source of excitation. With X-ray spectroscopy, high-energy photons are tuned to excite core electrons, giving insight into electronic structure and the local chemical environment of both the solvent and solute. In pulse radiolysis, an accelerated electron beam is used as an excitation source to create transient radiolytic products. Here, I present detailed studies using both X-rays and electron beams to investigate aqueous solutions and phenomena./nIn Chapter 2, I discuss the probing of the pH-dependent aqueous carbonate system by soft X-rays. Spectral changes between carbonate, bicarbonate, carbonic acid, and carbon dioxide are analyzed by comparison with theoretically computed spectra. I also give an introduction to Near Edge X-ray Absorption Fine Structure (NEXAFS) spectroscopy and discuss experimental details for the design and employment of liquid microjets./nChapter 3 describes a variety of different projects aimed at expanding the capabilities of the X-ray absorption experiments. These new directions include characterizing free radicals in solution, developing a new detection technique, exploring X-ray induced damage to solid biomolecules, and potentially investigating unusual nitrogen compounds./nIn Chapter 4, I explore the interaction of high-energy electrons (8 MeV) with aqueous nickel (II) solutions. Pulse radiolysis combined with UV-visible absorption spectroscopy is used to investigate the kinetics of Ni2+ with water radiolysis products. The rate constant for the solvated electron reaction with Ni2+ is measured up to 300°C, and the electronic spectrum for the monovalent nickel ion is also recorded at high temperatures.

Advisor: Saykally, Richard J
Regularization Methods for Canonical Correlation Analysis, Rank Correlation Matrices and Renyi Correlation Matrices

In multivariate analysis, canonical correlation analysis is a method that enable us to gain insight into the relationships between the two sets of variables. It/ndetermines linear combinations of variables of each type with maximal correlation/nbetween the two linear combinations. However, in high dimensional data analysis, insufficient sample size may lead to computational problems, inconsistent estimates of parameters./nIn Chapter 1, three new methods of regularization are presented to improve the traditional CCA estimator in high dimensional settings. Theoretical results have been derived and the methods are evaluated using simulated data./nWhile the linear methods are successful in many circumstances, it certainly has some limitations, especially in cases where strong nonlinear dependencies exist. In Chapter 2, I investigate some other measures of dependence, including the rank correlation and its extensions, which can capture some non-linear relationship between variables. Finally the Renyi correlation is considered in Chapter 3. I also complement my analysis with simulations that demonstrate the theoretical results.

Advisor: Bickel, Peter J
Investigating the Role(s) of LHCSRs in Chlamydomonas reinhardtii

Photosynthetic organisms must balance light absorption and light utilization. Excess absorbed light leads to the production of reactive oxygen species that can cause photo-oxidative damage to the cell and even cell death. To counteract the excess absorbed light, plants and algae turn on the rapid component of non-photochemical quenching (NPQ) known as qE to dissipate the extra energy as heat. From studies of higher plants, it is known that three factors are needed for the activation of qE: 1) de-epoxidized xanthophylls synthesized by a xanthophyll cycle, 2) a high proton gradient across the thylakoid membrane, and 3) the PsbS protein, a member of the light-harvesting complex (LHC) protein superfamily. Although the first two components are also involved in qE in the green alga Chlamydomonas reinhardtii, PsbS does not appear to play a role in quenching. The role of a different protein, called light-harvesting complex stress-related (LHCSR), was demonstrated by molecular genetic analysis of the npq4 mutant of Chlamydomonas. This mutant is deficient in qE and lacks two closely linked LHCSR genes (LHCSR3.1 and LHCSR3.2) that encode identical LHCSR3 proteins. A third gene, LHCSR1, encodes a second LHCSR isoform that is also involved in qE. The LHCSR1 protein is overexpressed in a suppressor of npq4 that partially restores the qE capacity of the mutant. A loss-of-function lhcsr1 mutation was isolated using reverse genetics, and an lhcsr1 npq4 double mutant exhibited no qE. Thus, all qE in Chlamydomonas is dependent on LHCSR proteins. Based on biochemical and biophysical analysis of a reconstituted LHCSR3 pigment-protein complex and site-directed mutagenesis of LHCSR3, LHCSRs have a dual function in Chlamydomonas, acting as sensors of lumen pH and as the sites of quenching, unlike in higher plants where the role of high light sensing is attributed to PsbS and the sites of quenching are in the minor and/or major antenna complexes. These findings have interesting implications for the evolution of qE in the green lineage.

Advisor: Niyogi, Krishna K.
Enhanced Iterative Learning Control with Applications to A Wafer Scanner System

This thesis addresses the improvement of wafer scanner technology from the controls aspect. In particular, the thesis proposes to enhance basic Iterative Learning Control (ILC) in several ways. ILC is a feedforward control strategy used to improve the performance of a system that performs a repeated task by considering the error from previous iterations of the process. The existence of non-repeating events, however, degrades the performance of ILC. Furthermore, the selection of the Q-filter and learning function in the iterative control law also limits the performance of ILC. To relax these limitations, we first introduce a disturbance observer into the learning scheme. As a result, we are able to reduce the effect of non-repetitive disturbances on the ILC scheme. The combination of ILC and DOB information when performing one task can also be used to provide valuable information for selecting initial ILC effort for a different task. By doing so, we can improve the convergence rate of the ILC algorithm for the new task. Studies performed in this thesis will show that by properly selecting the initial ILC effort, one can reduce the number of iterations before ILC achieves high tracking accuracy./nIn addition to the ILC effort, we also apply a pre-designed optimal feedforward control input to minimize the initial tracking error. An optimization strategy is presented to obtain this optimal feedforward input as well as the optimal feedback controller for integration with the ILC scheme. By using this optimal feedback-feedforward controller combination, which replaces the standard PID feedback controller, it becomes possible to utilize a simple P-type ILC algorithm without compromising performance./nThis thesis also investigates the synchronization problem to ensure small alignment mismatch between the wafer stage and reticle stage. The challenge is to meet tracking requirements of each individual stage as well as maintaining the relative positioning between the two stages in the presence of cross-coupling dynamics. Therefore, to achieve the ultrahigh precision motion control requirements demanded for such scanners, a synchronization ILC algorithm is proposed and designed to reduce the synchronization error while minimizes the individual tracking error.

Advisor: Tomizuka,, Masayoshi