VictorJuiz/thesis huggingface dataset:
Development of Novel Adeno-Associated Virus-Mediated Gene Therapies for the Treatment of Inherited Retinal Degeneration

The retina contributes to the first steps in processing visual information. Rods and cone photoreceptors are the two main retina cells contributing to the initial steps in sensing light and translating it to an electrical signal to the downstream neuronal cells finally to be processed in the primary visual cortex. Many cells and hundreds of genes are involved in the light response and keeping retinal cells metabolically active. This high degree of activity makes the retina more vulnerable to mutations and degeneration. The majority of mutations identified in patients affect genes involved in either the photoreceptor structural integrity or in the phototransduction cascade. Many inherited retinal degenerative (IRDs) diseases, such as retinitis pigmentosa, lead to blindness as a result of initial rod photoreceptor cell death followed by cones and remodeling of the retina./nGene therapy has been a growing field in the past decade and has proven to be an efficient and safe way of treating single-gene mutations leading to blindness by providing therapeutic DNA to targeted cells in the retina. The clinical trials for Leber congenital amaurosis type 2 (LCA) were the first to validate the proof-of-concept for gene therapy in the retina, after the successful use of adeno-associated viruses (AAVs) to deliver a healthy copy of the RPE65 gene to the affected cells. AAV, a small and nonpathogenic virus, has been used widely in many clinical trials, due to its safety profile and efficiency at targeting a wide range of tissues and cell types./nHowever, many obstacles remain from the optimization of delivery and design of viral vectors to elucidating molecular mechanisms behind the heterogenous genetic complexity in retinal diseases. While over 250 gene-causing diseases have been identified, more than 30-40% of genes involved remain unknown or outside of canonical coding sequences. For these patients, a gene replacement is not yet possible or applicable and therefore requires novel approaches./nMy dissertation focuses on the use and optimization of engineered AAV vectors to achieve cell-selective targeting of retinal cells and organelles, to design novel mutation-independent gene therapies adapted for progressive degenerative diseases such as retinitis pigmentosa. It also aims at elucidating and characterizing molecular mechanisms underlying non-coding region mutations, with the use of genome editing tools to engineer mouse models of untranslated region mutations found in LCA patients. My thesis provides new knowledge and AAV toolkit to better tackle patients’ unmet need for novel gene therapy strategies addressing undiagnosed and noncanonical mutations in inherited retinal diseases.

Advisor: Flannery, John G
Enhancing Performance of Analog Mixed Signal Circuits using Integrated Silicon-Photonics

Silicon-photonics (SiPh) has emerged as a viable solution to handle exponentially growing/ndata trac in today's data centers. It transfers data faster and over a distance longer than/nthat possible with traditional electronics, while leveraging eciency and cost benets of existing/nhigh-volume CMOS manufacturing infrastructure. As the SiPh platforms mature, new/nhigh-performance photonics blocks integrated close to CMOS transistors are made available./nBy moving certain functionality to these optical blocks, the performance of conventional/nanalog mixed-signal circuits can be improved to enable exciting new integrated applications/nlike LiDAR, biosensing, high-performance computing, etc./nThis thesis demonstrates an optical SiPh link with a reduced laser power requirement/nand an optically sampled analog-to-digital converter. Both of these systems benet from the/navailability of integrated SiPh blocks next to CMOS transistors. The laser power used by/na SiPh link can be reduced by improving the optical receiver (Rx) sensitivity and reducing/nthe optical path loss. To improve the Rx sensitivity, a dierential detector is monolithically/nintegrated with the low-noise CMOS analog frontend (AFE), while the optical path loss is/nreduced by adopting a laser-forwarded architecture. The dierential detector enables the/nfully dierential operation of AFE to suppress power supply and common-mode noise. Measurement/nand performance comparison of two variants of dierential detector implemented/non two test-chips is presented. The proposed microring resonator dierential detector enables/nthe receiver to achieve a record OMA sensitivity of -18 dBm at 12 Gb/s. Modeling/nand characterization of this detector are also covered in this thesis. Further, a coherent/nlaser-forwarded binary-phase-shift-keying (BPSK) link at 10 Gb/s is shown with all the required/nphotonic blocks, like phase modulator, 3-dB coupler, and balanced detectors, fully/nintegrated into a monolithic zero-change 45nm SOI CMOS. This link operates with 3 dB less/nlaser power than state-of-the-art NRZ monolithic SiPh links./nLastly, the performance of conventional CMOS ADCs is often limited by sampling clockjitter,/ninput sampling bandwidth, and routing of input and clock to the sub-ADCs. To/novercome these limitations, this thesis demonstrates an optically sampled ADC that moves the sampling function to the optical domain where ultra low-jitter (<10 fsrms) optical pulses/nfrom a mode-locked laser sample an RF input signal with very high sampling bandwidth. An/nADC prototype, realized in a 3D integrated silicon-photonic platform, achieves 37 dB SNDR/n(6b ENOB) for 45GHz input with <36fs estimated sampling jitter. Circuit techniques used/nfor overcoming issues like single-ended to dierential conversion and cross-talk are described/nin detail.

Advisor: Stojanovic, Vladimir
Essays on Workplace Consolidation and Labor Markets

An important fact that has emerged from the past decade of research in labor economics is that the identity of a worker's employer is an important determinant of their labor market outcomes. More recent work in the field has emphasized a correlation between consolidation of industries and worse outcomes for workers employed in those industries. Both of these findings are consistent with employers' having substantive wage-setting power in the labor market, a consideration that is at odds with standard competitive models of labor markets./nThis dissertation contributes to the field of labor economics by providing empirical evidence about how mergers and acquisitions --- events that lead to changes in the identity of a worker's employer and which tend to increase the concentration of an industry --- affect labor markets. I do so in two complementary ways./nIn the first chapter, which was coauthored with Joerg Heining of the Institute for Employment Research (IAB) in Germany, I use matched employer-employee data from West Germany to study how acquisitions --- specifically the acquisition of an establishment by another similar establishment close by --- affect workers. Using an event study framework with a control group of workers at unaffected plants, I find that acquisitions lead to employment losses for workers initially employed at the acquired (or ``target'') firm, mainly associated with labor force withdrawals by older female workers. At the same time I find evidence of a rise in wages for workers initially employed at targets and at the acquiring (or ``buyer'') firm who remain with the combined enterprise, concentrated among lower-wage workers. I interpret these findings as suggesting that consolidations lead to a reduction in overall employment but a rise in rents per worker that lead to a pattern of losers and winners in the labor market. The contribution of this chapter is that it is the first study to identify establishment acquisitions and their impacts on workers who are directly impacted by them./nIn the second chapter, I consider how merger and acquisition activity affects local labor market aggregates. I examine how merger-driven consolidation of hospitals in different local labor markets in the United States affected the wage and employment growth of Registered Nurses (RNs). This chapter finds that MSAs where there was merger activity had higher rates of growth in hospital market concentration than markets that did not. I find that the reduced form relationship between the presence of merger activity and changes in the average RN wage in each MSA indicates that merger activity is also associated with lower rates of wage growth for nurses. These results are consistent with prior research indicating that merger-driven consolidation depresses local labor market-level wage growth. The contribution of this chapter is to measure concentration, mergers, and labor market data for a specific profession in the United States./nThe empirical results of both chapters are consistent with employers' exercising some degree of wage-setting power in labor markets.

Advisor: Card, David E
The 'Cat's Paw of Dictatorship': State Security and Self-Rule in the Gold Coast, 1948 to 1957

On February 28th, 1948, a deadly police shooting at a veteran’s demonstration in the Gold Coast sparked three days of rioting in the capital city of Accra and surrounding communities. It was the first crisis of its kind for the British colony and a clear indication of the shifting political realities of the post-war era. Though colonial rule had been in place for several generations, the people of the Gold Coast would increasingly balk at an imperial system that denied them a voice in their own government. The following nine years would witness the Gold Coast’s extraordinary transition from British colony, to self-ruled territory, and eventually an independent state that renamed itself the Republic of Ghana./nIn the more than sixty years since Ghana’s independence in 1957, scholars and commentators alike have recognized the February riots as a turning point in Ghanaian and imperial history, signaling the new wave of decolonization that would sweep across sub-Saharan Africa in the years to follow. What has remained unknown and relatively unstudied is the fact that the riots also compelled the development of a government intelligence network in the Gold Coast. Before British officials accepted that colonial rule was as its end in West Africa, they sought to safeguard the state by providing it a domestic intelligence organization. This organization operated throughout the terminal years of British rule in the Gold Coast and succeeded in both altering the nature of the colonial state and the process of decolonization in unexpected ways./nThis dissertation interrogates the role of government intelligence in the Gold Coast between the years of 1948 and 1957. By examining police superintendents, Security Service officers, and colonial administrators, it reconstructs the establishment and application of intelligence resources to better understand the process and politics of decolonization in the Britain’s West African empire.

Advisor: Kanogo, Tabitha
Searching for the invisible: how dark forces shape our Universe

Astrophysical observations on a wide range of scales indicate that the majority of matter in our Universe seems to be approximately inert and non-luminous. The existence of this dark matter implies the existence of an undiscovered particle, since there is no viable dark matter candidate within the Standard Model. Many terrestrial searches for dark matter particles are underway; however, there is no evidence to date that the dark matter interacts with particles in the Standard Model except through gravity. It highly conceivable that the dark matter exists as part of a rich hidden sector with diverse matter content and its own dark forces (in analogy to the Standard Model) which would imply that terrestrial searches may not pose an optimal path to discovering dark matter. Instead, observing astrophysical systems — where dark matter is known to be present through its gravitational influence — would be the best available way to test theories of dark matter where dark forces play a role in altering the properties of those systems. The complementarity of observing various astrophysical systems is a powerful asset for exploring the physics of dark sectors: one can explore broad classes of theories with dark forces in different environments, on different length scales, and at different epochs in the history of our Universe. This dissertation explores several scenarios where astrophysical observations inform our understanding of dark forces in a way that would not necessarily be possible on Earth. In particular, we consider dark sector energy dissipation, dark matter self-interaction, and the early Universe production of dark matter through dark channels. We propagate the implications of these effects for stars, supernovae, the Milky Way stellar disk, dwarf galaxies, galaxy clusters, large-scale structure, the epoch of reionization, and the cosmic microwave background.

Advisor: Murayama, Hitoshi
"An Undeniable Presence": Racial justice work among South Asian American musicians

This dissertation concerns four well known South Asian American musicians based in New York/nCity and the San Francisco Bay Area: Vijay Iyer, Sunny Jain, Rekha Malhotra (DJ Rekha), and/nRupa Marya. It is based on ethnographic fieldwork conducted from 2016-2017, supported by a/nMargery Lowens Dissertation Fellowship from the Society for American Music and a grant from/nthe Center for Race and Gender at UC Berkeley. My work, which included conducting/ninterviews, archival research, and attending numerous concerts, rallies, and protests, investigates/nhow the four central artists use their work in music as a means to further aims of achieving racial/nequity. Ultimately, I argue that contemporary racialization of brown people, particularly in the/npost-9/11 and Trump Era United States, has led to increased involvement in racial justice/nadvocacy work among South Asian American musicians./nIn the first chapter of my dissertation, I use Howard Becker’s theory on art worlds and Benedict/nAnderson’s idea of imagined communities as starting points to show how political solidarities, as/ndefined by Sally Scholz, create and constitute activist networks among these musicians. Each of/nthe central chapters concerns one of the artists, highlighting how their musical practice advances/nracial justice causes. My chapter on Iyer shows how he uses his privileged status to re-orient his/nprimarily White audiences’ attention toward structural racism in public concerts, interviews, and/nlectures. My chapter on Sunny Jain highlights how his seemingly utopic musical and political/nideals emanate from the religious Jain concept of anekantavada (“pluralism”). In the third/nchapter, on Malhotra (DJ Rekha), I show how Basement Bhangra, a party she organized monthly/nfrom 1997-2017, served as a space to fundraise and organize for progressive political causes./nFinally, I look at Rupa Marya’s simultaneous careers as a physician and musician as extensions/nof her work as a healer and anti-capitalist. Throughout the chapters, I examine how these artists’/nleft-leaning music networks overlap, maintaining that these connections have as much to do with/ntheir politics as their shared cultural heritage.

Advisor: Roberts, T. Carlis
REGULATION OF SYNAPSE AND NEURONAL FUNCTION BY LOSS OF TSC1 IN THE STRIATUM

mTORC1 is a central signaling hub that integrates intra- and extracellular signals to regulate a variety of cellular metabolic processes. Mutations in regulators of mTORC1 lead to neurodevelopmental disorders associated with autism, which is characterized by repetitive, inflexible behaviors. These behaviors likely result from alterations in striatal circuits that control motor learning and habit formation. However, the consequences of mTORC1 dysregulation on striatal neuron physiology are largely unknown. To investigate this, I deleted the mTORC1 negative regulator Tsc1 postnatally and prenatally from identified striatonigral and striatopallidal neurons and examined how cell autonomous upregulation of mTORC1 activity affects their morphology and physiology. I find that postnatal loss of Tsc1 increases the excitability of striatonigral, but not striatopallidal, neurons and selectively enhances corticostriatal synaptic transmission. I find that prenatal deletion of Tsc1 also enhances excitability of striatonigral, but not striatopallidal, neurons, and that this occurs through an increase in cortico-striatonigral synaptic transmission. I also observe that a loss of endocannabinoid-LTD drives enhanced cortical excitation of striatonigral neurons, and that this is associated with improved motor routine learning./nTo investigate the molecular mechanism driving these synaptic changes, I performed translating ribosome affinity purification to determine gene expression changes in mice with loss of Tsc1 from either striatonigral or striatopallidal neurons. I find that Tsc1 deletion results in numerous translational differences in striatal neurons, and that many of these differences are specific to either striatonigral or striatopallidal neurons. Further, I extend my findings in the Tsc1 model to the Cntnap2-/- ASD mouse model, and find that corticostriatal transmission and motor routine learning are also enhanced by deletion of Cntnap2. These findings highlight the critical role of corticostriatal transmission in ASD mouse models, with implications for striatonigral pathway dysfunction in neuropsychiatric disease.

Advisor: Bateup, Helen S
Smart Traffic Operation: from Human-Driven Cars to Mixed Vehicle Autonomy

The goal of my research is to enhance urban mobility by developing reliable and efficient traffic control and management strategies. As cities grow everywhere, and urban roadways become overburdened, the need for the development of such strategies becomes more evident. With the prevalence of smart sensing devices, such as smart phones and smart intersections, cities are becoming smart. Moreover, with the emergence of new and inevitable technologies, such as autonomous and connected vehicles, electric vehicles, and mobility on demand systems, smart cities are rapidly evolving. As we experience the arrival of such technologies, there is an opportunity to reclaim urban mobility. However, a blind utilization of these technologies may deflect us from reaching this goal. In this dissertation, we study the efficient operation of smart cities via management strategies that can guarantee overall societal benefits both in the cities of today and future./nWe focus on two natural instances of this agenda. In the first part, we tackle some of the existing challenges in the smart operation of traffic networks which are solely shared by human-driven cars. If all vehicles are human-driven, there is room for improving the efficiency of traffic networks by appropriate coordination and control of traffic signal lights. For these networks, we develop signal control algorithms that are capable of minimizing the number of stop-and-go movements, encoding fairness among vehicular arrivals, and are robust to the knowledge of system parameters. In the second part, we analyze fundamentals of traffic networks with mixed vehicle autonomy, where both human-driven and autonomous cars coexist on roadways. We study the mobility implications of selfish autonomy, i.e. autonomous cars that are not concerned about their overall impact and simply attempt to optimize their own travel benefits. Having shown the negative consequences that the increased deployment of selfish autonomy may have, we develop a pricing mechanism which can guarantee the overall societal-scale efficiency of traffic networks with mixed vehicle autonomy. Finally, we show how autonomy can act altruistically, i.e. by taking into account the decision making process of humans, autonomous cars can potentially plan for their actions in the favor of the overall good.

Advisor: Horowitz, Roberto
A search for new physics in multijet final states of pp collisions at $\sqrt{s} = 13~TeV$ using the ATLAS detector at the Large Hadron Collider

Supersymmetry, one of the of the most promising extensions to the Standard Model of Particle Physics, predicts a number of as-yet-undiscovered particles, evidence of which could be found in LHC collision events. This thesis presents a search for R-parity violating Supersymmetric signal events in ATLAS proton-proton collision data. The search uses $36.1~fb^{-1}$ of $\sqrt{s}=13~TeV$ collision data, taken by ATLAS in 2015 and 2016. As no excess of events above the background prediction was found, limits are set on the production cross sections of gluinos and neutralinos under two different decay scenarios. The resulting limits are a significant extension beyond the reach of the Run-1 search for the same process.

Advisor: Shapiro, Marjorie
Microlocal sheaves and mirror symmetry

In this thesis, based on the work completed by the author during his time in graduate school, we explain various ways in which microlocal sheaf methods in symplectic geometry can be used to prove homological mirror symmetry. We explain how tropical methods originally developed by Mikhalkin can be used to prove homological mirror symmetry for any hypersurface in (C*)^n, and we also present a proof of homological mirror symmetry in the case of multiplicative hypertoric varieties, emphasizing the features which we expect will prove common to all K-theoretic Coulomb branches.

Advisor: Nadler, David
Far-Field Optical Thermometry Techniques for Challenging Environments

Temperature and thermal conductivity are key parameters in applications ranging from microelectronics to energy conversion. As we strive to advance the state of the art, feature sizes continue to shrink, operating temperatures are pushed even higher, and in general devices must function in increasingly extreme regimes. Consequently, many of the traditional methods used to measure temperature or thermal conductivity are no longer applicable. This continued paradigm shift thus necessitates the development of new thermal metrology./nIn this dissertation, I develop far-field optical thermometry techniques to measure temperature and thermal conductivity in challenging environments – namely, at temperatures up to 3,000 K and in systems with sub-50 nm features. All of these techniques have the benefit of far-field, non-contact operation, which allows for measurements in scenarios where many conventional methods fail for both practical and fundamental reasons. I begin by describing a Planck spectral fitting method developed to measure the peak temperature of reduced graphene oxide (RGO)-based films that are Joule heated to temperatures as high as 3,000 K. I also describe a “conduction shoulder” fitting method that combines image processing with a nonlinear, multimode heat transfer model in order to experimentally determine the high-temperature thermal conductivity of these same RGO films. Next, I introduce a far-field optical nanothermometry technique based on the temperature-dependent luminescence of individual NaYF4:Yb3+,Er3+ nanoparticles. This technique allows for single-point temperature measurements with spatial resolution of 50 nm or better. I then report apparent self-heating effects at high excitation intensities that indicate an apparent temperature rise > 50 K at an excitation intensity of 2.5 x 105 W cm-2 if interpreted as thermal; however, I demonstrate that these effects are in fact non-thermal in nature. Instead, rate equation modeling shows that these effects are due to both radiative and non-radiative relaxation from high energy excited states in Er3+ that are heavily populated at high excitation intensities. Finally, I demonstrate that individual nanoparticle thermometers can be used to measure nanoscale hotspots that result from both optical heating via a tightly focused laser beam and non- uniform Joule heating caused by a geometric effect known as current crowding.

Advisor: Dames, Chris