VictorJuiz/thesis huggingface dataset:
Causal Evidence for Neural Oscillations in Cognition

Since early recordings of the human brain, rhythmic electric fields have been observed emanating from regions involved in the specific information processing demands of which the human subject is engaged. Different oscillatory frequencies have been associated with different types of information processing. Neuroscience in the 21st century has seen a revival in research studying the neural basis of oscillatory activity that has deepened our understanding of the complex network level coordination of brain regions. However, causal evidence for the mechanistic role of neural oscillations is sparse, yet provides vital implications for the neural basis of cognition./nThe first experiment examines the specific role of beta (15-30 hertz) and gamma (30-50 hertz) frequency oscillations in top-down and bottom-up attention. By applying rhythmic transcranial magnetic stimulation (TMS), the purported cognitive contributions of beta and gamma oscillations are analyzed with respect to a visual search task that varies the level of top-down attention required for optimal performance./nThe second experiment examines the specific role of theta (3-8 hertz) and alpha (8-12 hertz) frequency neural oscillations in the reactivation and suppression of working memory representations. Rhythmic TMS in a retro-cued delayed match-to-sample task causally tested previously reported oscillatory neural signatures for their mechanistic contributions to working memory. The degree to which subjects engaged the regions targeted by TMS in functional magnetic resonance imaging (fMRI) predicted the frequency specific effect of rhythmic TMS./nSimultaneous TMS and fMRI offers a unique opportunity to causally test the communication through coherence proposed with neural oscillations. By stimulating a single brain region in multiple frequency bands, the frequency-by-network specific spread of activation can be quantified. Towards this end, the third experiment develops the methodology of concurrent TMS-fMRI with a proof of principle experiment demonstrating the spread of TMS effects through a functional network. In sum, these projects test for the causal role of neural oscillations in cognition and pave the way for future research to study the network level organization of the brain via neural oscillations.

Advisor: D'Esposito, Mark T
Spatial and temporal dynamics of Ulva assemblages in central San Francisco Bay, U.S.A.

Harmful blooms of green macroalgae, known as green tides, have been increasing in frequency and intensity world-wide over the last decade. Composed mainly of the macroalgae, Ulva, these blooms occur in areas of low wave energy and high nutrient input from anthropogenic sources; they often result in massive die-offs in the impacted ecosystem. My dissertation addressed three key questions concerning the potential for green tides to occur in central San Francisco Bay: 1) what species of Ulva inhabit the bay and which of them have been identified as bloom-forming taxa in other locations? 2) does an overwintering, benthic bank of dormant propagules contribute to the rapid growth of spring Ulva populations? 3) does waterborne spore availability limit the recruitment of Ulva populations? Within central San Francisco Bay, I identified six species of Ulva using genetic barcoding, only four of which were previously reported within the bay. Several of these species are known to produce economically costly green tides in other regions of the world. While previous studies on the control of algal blooms focused on post-recruitment processes such as herbivory and space competition, I investigated two pre-recruitment processes: banks of benthic microscopic forms and supply of waterborne propagules. A multifactorial lab experiment demonstrated that banks of dormant benthic microscopic Ulva forms (i.e. gametes, zoospores or thallus fragments) survive winter incubation periods (12 weeks of darkness undisturbed at 11°C), but at a depressed growth rate. Successful recruitment from these banks is strongly influenced by seasonal increases in water temperature. A regular regime of water column sampling and laboratory culturing demonstrated that waterborne propagule supply varied with location within the central bay, and that the abundance of propagules in the water column varied strongly with season. Although water samples from all sites yielded recruits, sites north of the bay mouth yielded more Ulva recruits than southern sites during the spring recruitment period while sites south of the bay mouth yielded more recruits in fall. Together, this information indicates that propagule supply, hydrographic patterns that mediate dispersal, and environmental and physiological constraints on juvenile development impose important limitations on dynamics of green tide algae in the central San Francisco Bay. These interacting factors must be included in management as future global climate change is expected to stimulate more rapid development of spring green algal blooms.

Advisor: Sousa, Wayne P
Lindberg, David R
Integrated electrophoretic cytometry separations and immunoassays for proteins and their complexes

Protein complexes, such as filamentous actin (F-actin) complexes, regulate key cell processes such as cell motility and division. Disruption of F-actin result in highly motile and invasive cancer cells. Cancer therapeutics have thus aimed to maintain F-actin, but cell-to-cell variation in F-actin levels in response to such therapeutics necessitate single-cell measurements of dynamic actin protein complexes, including the binding actin binding proteins that determine actin polymerization state. Protein complex levels cannot be inferred from an immunoassay, as most lack selective antibodies. Size-based separations of such protein species provide selectivity when coupled with an immunoassay for protein detection and quantitation. While this selectivity has been demonstrated at the single-cell level by the introduction of electrophoretic (EP) cytometry in our lab, we sought to establish a single-cell electrophoretic assay for protein complex identification and quantitation./nIn order to understand the regulation of actin polymerization and depolymerization in heterogeneous cells requires four key separation assay features: i) quantifiable technical variation to discern biological variation in the cell population ii) sufficient analytical sensitivity to detect F-actin bound actin binding proteins, iii) high-selectivity separations to detect actin and its binding proteins, and iv) sample preparation with assay stage-optimized buffers to isolate dynamic complexes without disrupting the complexes. We will share our studies to elucidate chemical and physical underpinnings of each of these needed features. First, we will describe algorithm development and applications to establish a technical variation threshold and protein sizing standards for electrophoretic (EP) cytometry to distinguish biological variation of protein expression and size in single cells. Next, we will discuss the impact of in-gel immunoassay performance and open microfluidic device design on analytical sensitivity. Given fundamental tradeoffs between in-gel immunoassay sensitivity and separation performance, we consider alternative sieving matrices tuned to separate proteins in specific molecular weight ranges. We then describe unique impacts of Joule heating on separation performance in open microfluidic electrophoresis. Joule heating is mitigated with a buffer exchange approach that reduces variation in separation performance and introduces assay stage-optimized buffers without further protein loss./nFinally, we will discuss the design of EP cytometry to fractionate actin protein complexes from single cells with assay stage-optimized buffers. The microscale device achieves rapid, arrayed on-chip sample preparation and EP fractionation without perturbing complexes. We demonstrated F-actin separations from monomeric actin, and the measurement of F-actin binding proteins that regulate actin polymerization. We anticipate the single-cell protein complex measurements described here will be broadly applicable to protein complexes that drive human health.

Advisor: Herr, Amy E.
Iridium-Catalyzed Asymmetric Allylic Substitution Reactions with Unstabilized Enolates and Prochiral Enolates

The following dissertation discuss the development of iridium-catalyzed asymmetric allylic substitution reactions with unstabilized enolates and prochiral enolates. These reactions include the enantioselective allylic substitutions with silyl ketene acetals, diastereo- and enantioselective allylic substitutions with α-alkoxy ketones, and stereodivergent allylic substitutions with aryl acetic acid esters, azaaryl acetamides and azaaryl acetates./nChapter 1 provides a brief overview of transition-metal-catalyzed asymmetric allylic substitutions with enolates. This overview focused on the mechanism of allylations of enolates catalyzed by palladium complexes and iridium complexes. Additionally, methodologies for asymmetric allylations of unstabilized enolates are discussed in detail. Furthermore, this overview highlights the challenges and the strategies for the control of diastereoselectivity for the allylic substitutions with prochiral enolates./nChapter 2 describes the development of iridium-catalyzed enantioselective allylic substitution reactions with silyl ketene acetals, the silicon enolates of esters, under relatively neutral conditions. The ester products contain a quaternary carbon atom at the nucleophile moiety and a chiral tertiary carbon atom at the electrophile moiety./nChapter 3 describes the study on diastereoselective and enantioselective allylic substitution reactions with acyclic α-alkoxy ketones. A metallacyclic iridium complex catalyzes the allylation of unstabilized copper(I) enolates generated in situ from acyclic α-alkoxy ketones to form products with contiguous stereogenic centers./nChapter 4 describes the development of stereodivergent allylic substitutions with aryl acetic acid esters catalyzed synergistically by a metallacyclic iridium complex and a Lewis base co-catalyst. Through permutations of the enantiomers of the two chiral catalysts, all four stereoisomers of the products bearing two adjacent stereocenters are accessible with high diastereoselectivity and enantioselectivity. A stereochemical model is provided to understand the origin of high stereoselec-tivity./nChapter 5 describes a combination of catalysts that enable stereodivergent allylic substitution reactions with azaaryl acetamides and acetates. This combination of catalysts comprises a chiral metallacyclic iridium complex and a chiral bisphosphine-ligated copper(I) complex, which individually control the configuration of the electrophilic and nucleophilic carbon atoms, respectively./nChapter 6 extends from the work discussed in Chapter 5 and demonstrates iridium and copper complexes synergistically catalyze stereodivergent allylations to construct vicinal fully substituted and tertiary stereogenic centers in acyclic structures. In particular, fluorine-containing fully substituted stereocenters are readily constructed from fluorinated acetates.

Advisor: Hartwig, John F
Mass Transfer Phenomena and Pharmacokinetics in Topical Delivery of anti-HIV Microbicides

Topically applied anti-HIV microbicides are placed within a cultural, economic, and ethical context in order to motivate research into their development. This leads to the creation of a multi-scale, multi-step numerical model that incorporates gel spreading and drug diffusion. Use of this model allows conclusions to be drawn about how rheological characteristics of non-Newtonian gels affects the ultimate amount of drug being delivered into tissue. Dilution of the gels by natural fluid production has a strong effect on drug delivery, and osmolarity is investigated as a potential driver of fluid flow into (or out of) the lumen. The equations governing osmolarity driven solvent flow yield two dimensionless groups that can be optimized to produce improved drug delivery. Finally, osmolarity driven fluid flux is incorporated into the numerical model of gel spreading and drug diffusion, and an engineered gel is proposed.

Advisor: Azeri, Andrew J
Teaching Tolerance: Citizenship, Religious Difference, and Race in Contemporary Germany

This dissertation deals with the question of citizenship in contemporary Germany. By taking the field of civic education as a site of inquiry it probes into the educational methods of civic practices geared to train youth and professionals of migrant backgrounds to cultivate a sense of German citizenship. The dissertation demonstrates that the key question of citizenship, as one of tolerant conduct, is framed by the post-Holocaust condition. Thus, the dissertation focuses on civic educational programs funded to combat Islamic extremism and to foster secular tolerance by way of relating to the Holocaust and the murdered Jews. By doing so, the research focuses on programs dealing with the Holocaust as an exceptional event, yet constitutive of liberal democracy and tolerant subjects in the political present. The unit of analysis of the study is the group of civic educators hired to target and work with members from immigrant communities as Muslims. Here the dissertation focuses on how the Muslim subject is produced and bifurcated into tolerant German Muslim vs. Islamic extremist./nThe thesis argues that the wider policies aimed at incorporating immigrants as Muslims into the German nation, becomes traceable as racializing effects in civic education. The position of the Muslim is an unstable category at risk to fail to be a recognizably secular citizen. Part of this failure, as it is accounted for throughout the dissertation, is a secularization paradigm applied to Muslims as religious subjects, who are asked to shed their religiosity from public. Secularization in the sense of historicism intersects with the notion of racial historicism, a civilizational betterment of Muslim subjects. Yet the same form of secularization cannot be applied to relating to the Holocaust. Rather, here Muslims have to submit to the Holocaust as “the constitutive exception” for the post-Holocaust episteme and the contemporary political order. The failure to do so, is read by public institutions as signs of Islamic extremism or religious intolerance./nThe dissertation accounts for the strategies and moments in which formal German citizens are at risk to be further racialized as Muslims only, without ever fully being perceived as German citizens. Conversely a wider effect of these educational strategies and the discourse around them contributes to a moral superiority of the ethnic German Christian-secularized majority leading up to a sense of rightful owning of the nation and entitled to discriminate against Muslims, because of their assumed religious intolerance. The thesis defines this national superiority as moral nationalism in a reciprocal and co-constitutive relation with the racialized Muslim subject.

Advisor: Hirschkind, Charles K
Chemical Tools for Detecting Transition Metals for Biological and Environmental Applications

Copper, iron and sodium are essential elements for life. The potent redox activity of copper and iron are essential to redox-dependent cellular processes, including respiration and biology spanning oxygen transport, nucleotide synthesis, and electron transfer. At the same time, however, mismanagement of copper and iron stores and subsequent oxidative stress and damaging events are implicated to many diseases such as Wilson’s disease and neurodegenerative disorders. The non-redox active metal, sodium, has been recognized as regulating acid-base homeostasis and participating in maintaining membrane potential and triggering the activation of diverse signal transduction pathways. Therefore, we seek to develop new methods for monitoring copper, iron, and sodium in biological and environmental samples and in turn, to apply these chemical tools to help study the roles of these essential metals in healthy and disease states. The aims of my graduate research in Prof. Chris Chang’s lab at UC Berkeley have been focused on developing new material-based binding platforms to enable monitoring of copper and iron levels in biological and environmental samples without complex and expensive instrumentation, designing novel imaging probes for copper based on protein tagging technique in living cells and in the neurons, and developing sodium fluorescent sensors based on a photoinduced electron transfer mechanism.

Advisor: Chang, Christopher J
CRISPR-guided DNA polymerases for targeted genetic diversification

The capacity to diversify genetic codes advances our ability to understand and engineer biological systems. A method for continuously diversifying user-defined regions of a genome would enable forward genetic approaches in systems that are not amenable to efficient homology-directed oligonucleotide integration. It would also facilitate the rapid evolution of biotechnologically useful phenotypes through accelerated and parallelized rounds of mutagenesis and selection, as well as cell-lineage tracking through barcode mutagenesis. Programmable nucleases, such as CRISPR/Cas9, have revolutionized our ability to easily disable targeted genetic elements; however, substituting nucleotides in user-defined regions of a genome using programmable nucleases remains inefficient in many contexts due to the need for homology-directed repair (HDR), donor templates, cytotoxic double-stranded breaks, and competition with non-homologous end-joining (NHEJ). Here I will present EvolvR, the first system that can continuously diversify all nucleotides within a tunable window length at user-defined loci without relying on HDR, donor templates, double-stranded breaks, or NHEJ. This is achieved by enzymatically generating mutations using engineered DNA polymerases targeted to loci via CRISPR-guided nickases. I identified nickase and polymerase variants that offer a range of targeted mutation rates that are up to 7,770,000-fold greater than rates seen in wild-type cells, and editing windows with lengths of up to 350 nucleotides. I used EvolvR to identify novel ribosomal mutations that confer resistance to the antibiotic spectinomycin and adapted EvolvR for use in human cells. My results demonstrate that CRISPR-guided DNA polymerases enable multiplexed and continuous diversification of user-defined genomic loci, which will be useful for a broad range of basic and biotechnological applications.

Advisor: Schaffer, David
Dueber, John
Optimization Everywhere: Convex, Combinatorial, and Economic

In this thesis we study fundamental problems that arise in optimization and its applications. We present provably efficient algorithms that achieve better running times or approximation guarantees than previously known. Our method draws on the toolkit from convex and combinatorial optimization as well as economics. By intertwining techniques from these disciplines, we are able to make progress on multiple old and new problems, some of which have stood open for many years. Main results of this thesis include the following:/nConvex Programming: We show how to solve convex programming with an expected O(n log(nR/\epsilon)) evaluations of the separation oracle and additional time O(n^3\log^{O(1)}(nR/\epsilon)). This matches the oracle complexity and improves upon the O(n^{\omega+1}\log(nR/\epsilon)) additional time of the previous fastest algorithm achieved over 25 years ago for the current value of the matrix multiplication constant when R/\epsilon=O(\poly(n))./nSubmodular Function Minimization: We provide new weakly and strongly polynomial time algorithms with a running time of O(n^{2}\log nM\cdot\text{EO}+n^{3}\log^{O(1)}nM) and O(n^{3}\log^{2}n\cdot\text{EO}+n^{4}\log^{O(1)}n), improving upon the previous best of O((n^{4}\cdot\text{EO}+n^{5})\log M) and O(n^{5}\cdot\text{EO}+n^{6}) respectively. We also provide the first subquadratic time algorithm for computing an approximately optimal solution./nMatroid Intersection: We provide new algorithms with a running time of O(nr\mathcal{T_{\text{rank}}}\log n\log(nM)+n^{3}\log^{O(1)}nM) and O(n^{2}\mathcal{T_{\text{ind}}}\log(nM)+n^{3}\log^{O(1)}nM , achieving the first quadratic bound on the query complexity for the independence and rank oracles. In the unweighted case, this is the first improvement since 1986 for independence oracle./nSubmodular Flow: We obtain a faster weakly polynomial running time of O(n^{2}\log(nCU)\cdot\EO+n^{3}\log^{O(1)}(nCU)), improving upon the previous best of O(mn^{5}\log(nU)\cdot\EO) and O\left(n^{4}h\min\left\{ \log C,\log U\right\} \right) from 15 years ago by a factor of \tilde{O}(n^{4})./nSemidefinite Programming: We obtain a running time of \tilde{O}(n(n^{2}+m^{\omega}+S)), improving upon the previous best of \tilde{O}(n(n^{\omega}+m^{\omega}+S)) for the regime S is small./nMarket Equilibrium: We present the first polynomial time algorithm for computing market equilibrium in an economy with indivisible goods and general buyer valuations having only access to an aggregate demand oracle./nVertex Cover with Hard Capacity: We give a f-approximation algorithm for the minimum unweighted Vertex Cover problem with Hard Capacity constraints on f-hypergraphs This improves over the previous 2f-approximation and is the best possible assuming the unique game conjecture./nNetwork Design for Effective Resistance: We initiate the study of network design for s-t effective resistance. Among other results we present a constant factor approximation by applying classic techniques to a convex quadratic programming relaxation.

Advisor: Papadimitriou, Christos H
Raghavendra, Prasad
Accounting Choices and the Legal Environment: the Impact of the Ex Post Loss Rule

Using a landmark Supreme Court decision as a natural experiment, I examine the impact of a fundamental requirement in securities litigation, the ex post loss rule, on income-decreasing accounting choices. Dura Pharmaceuticals v. Broudo (2005) established that plaintiffs must show that the alleged misrepresentations caused an actual economic loss. The case resolved a circuit split, allowing me to identify a treatment jurisdiction affected by Dura, and control jurisdictions in which the rule was already the prevailing legal standard. Motivated by legal analyses suggesting that Dura incentivizes firms to delay negative corrections, I hypothesize and find that treatment firms in high-litigation industries became more likely to delay write-downs and income-decreasing accrual error reversals at the firm level after Dura, relative to matched control firms. This dissertation sheds light on the relationship between securities law and accounting practices, and informs policy makers on the accounting impact of a key feature of the legal environment.

Advisor: Dechow, Patricia M
Techniques for Inelastic Effective Field Theory Measurements with the Large Underground Xenon Experiment

Cosmological evidence indicates that nonbaryonic dark matter makes up a quarter of the energy density of the universe. One hypothesis for the particle nature of dark matter is the weakly-interacting massive particle (WIMP). The Large Underground Xenon (LUX) experiment is a dual-phase xenon WIMP search experiment with a 250kg active volume. Computational tools developed to support LUX analyses include data mirroring and a data visualization web portal./nWithin the LUX detector, particle interactions produce pulses of scintillation light. A pulse shape discrimination (PSD) technique is shown to help classify interaction events into nuclear recoils and electron recoils based on the time-structure of the pulses. This approach is evaluated in the context of setting limits on inelastic effective field theory (IEFT) dark matter models. Although PSD is not found to provide significant improvement in the limits, LUX is nevertheless able to set world-leading limits on some IEFT models, while limits for other IEFT models are reported here for the first time.

Advisor: Jacobsen, Robert G.