VictorJuiz/thesis huggingface dataset:
State-dependent modulation of subthreshold activity in mouse visual cortex [electronic resource]

Decades of extracellular recording in primate, cat and rodent cortex have established that an animal's behavioral state profoundly modulates the spiking response of sensory cortical neurons to external stimuli. Attention and arousal have been shown to affect not only neuronal responsiveness but also psychophysical thresholds, suggesting a direct link between the cortical sensory representation and perception. However, despite this tremendous progress, the cellular mechanisms by which behavioral states modulate the spiking of cortical neurons remain poorly understood. Here I describe two approaches aimed at understanding how the subthreshold activity of cortical cells is modulated across behavioral states. First, I discuss an in vitro study characterizing the ascending basal forebrain cholinergic system, one of the main neuromodulatory systems in the mammalian brain. Cholinergic cells in the basal forebrain project throughout the cortex and are thought to play an important role in state-dependent modulation of cortical activity. By optogenetically labeling and stimulating cholinergic axons in cortical slices, we were able to characterize 1) what cortical cell types are targeted by cholinergic axons, 2) the relevant time course over which endogenous acetylcholine (ACh) release acts on target cells, and 3) the synaptic properties of cholinergic axons in cortex. We found that cholinergic axons target specific subtypes of cortical interneurons. Moreover, we found clear evidence for classical synaptic transmission between cholinergic release sites and specific interneuron classes, challenging the predominant view that the cholinergic system works primarily by nonsynaptic transmission. Next, to better understand how the subthreshold activity of cortical cells is modulated in the intact brain, we performed intracellular recordings from the visual cortex of awake, head-fixed mice. We showed that the membrane potential of neurons in superficial layers is highly variable during quiet wakefulness and that this variability is quenched when the animal moves. In addition, we found that responses to visual stimulation are larger and more reliable during locomotion, which, together with the decrease in baseline variability, drastically improves the signal to noise ratio. Moreover, by recording from pairs of neurons simultaneously, we showed that the membrane potentials of neighboring cells is highly correlated during quiet wakefulness, but that this correlation subsides during active states. Finally, we demonstrated that neurons in the deep cortical layers display similar state-dependent membrane potential dynamics and that correlated membrane potential fluctuations in superficial cells may originate in deep layers.

Advisor: Hestrin Shaul
Huguenard John advisor. Thesis advisor
Knudsen Eric I. advisor. Thesis advisor
Ricci Anthony advisor. Thesis advisor
Statistical analysis and modeling of lightning using radio remote sensing [electronic resource]

Lightning is one of the most fascinating, naturally abundant, and powerful electrical processes on Earth. On average, ~50 lightning flashes occur around the globe every second, each releasing billions of Joules of energy. Lightning leads annually to billions of dollars in damages and to thousands of deaths, injuries, and fires, and is of great practical interest to those concerned with the safety of aircraft, spacecraft, ground-based electronic systems and urban environments. Interestingly, to date, the physical nature of lightning is not fully understood, in part due the difficulty of making direct ground-truth measurements inside thunderclouds or inside the lightning channel, and in part due to the wide range of timescales (from nanoseconds to hours) that are involved and the seemingly random nature of these processes. However, using radio emissions from individual discharges and leveraging the abundance of naturally occurring lightning enables a wide range of experimental techniques. Recent studies also suggest that lightning flashes have larger peak currents over the ocean than over land, which has important implications on the safety and design of aviation and navigation systems. These observations remain poorly understood. In this dissertation, we use remote sensing data in tandem with statistical techniques and electromagnetic modeling to investigate the lightning discharge process, quantify the lightning occurrence probability and recovery time as a function of distance and time, and introduce a proxy method for monitoring the charging processes in the cloud. To better understand oceanic lightning, we conduct observations with a sensitive Very Low Frequency/Low Frequency (1-450 kHz) radio receiver system deployed aboard the NOAA Ronald W. Brown research vessel to collect magnetic field radio emissions from deep-ocean lightning. We construct electromagnetic models to simulate lightning waveforms and compare them with the data acquired to infer properties of causative lightning currents. We analyze thousands of land and oceanic waveforms and compare lightning properties of land and oceanic thunderstorms.

Keywords: Electrical Engineering.
Advisor: Gill John T.
Inan Umran S. primary advisor. Thesis advisor
Cohen Morris
Statistical models of language in financial disclosure [electronic resource]

This thesis is a study of narrative financial disclosure via the application of statistical models of language. In the first chapter, I introduce the topic and motivate the use of statistical models of language in the study of financial disclosure. In particular, statistical models can be applied to narrative financial disclosure to gain insight into the incentives and actions of corporate managers. I also explain the structure of the thesis and summarize my major findings. In the second chapter, I provide an overview of language models that can be used in studying narrative disclosure. I begin by motivating the study of narrative disclosure. I then briefly discuss various approaches that have been taken to studying narrative disclosure. These approaches include laboratory experiments, manual coding of documents, dictionary methods, and more sophisticated techniques for automatically summarizing textual content. Some of the techniques and algorithms that I discuss are applied in my thesis for studying narrative disclosure, whereas others are being applied in ongoing research, are useful in planned extensions to the study, and provide opportunity for future research. In the third chapter, I first discuss prior research related to my work from diverse social science fields as well as computational linguistics. I then develop key hypotheses of the study. I review relevant literature in psychology, sociology, and organizational behavior that provides guidance on formulating research questions and corresponding hypotheses. In the fourth chapter, I first describe my research design. I then describe the data used and the sample selection procedure. I provide descriptive statistics that give some insight into the data sample used. In the fifth chapter, I discuss the application of statistical models of language in studying causal attribution. I describe my main empirical tests and report my findings. The sixth chapter concludes and describes planned extensions to the study.

Keywords: Business.
Advisor: Larcker David F. primary advisor. Thesis advisor
McNichols Maureen
Kasznik Ron advisor. Thesis advisor
Stereoselective syntheses of (-)-Batrachotoxin, (+)-Batrachotoxin, and related structural analogues [electronic resource]

(--)-Batrachotoxin (BTX), a poisonous constituent of the Colombian poison dart frog, is distinguished among small molecule natural products as one of the most lethal. The stereochemically rich, highly oxidized steroidal architecture of BTX, which underlies its unique function as an agonist of voltage-gated sodium ion channels (NaVs), presents a complex, contemporary challenge in synthetic chemistry. Our interest in elucidating the molecular details of BTX binding to NaV and its influence on channel gating has motivated efforts to synthesize this unique natural product. Ultimately, we discovered that a C8−C14 bond connection united A/B- and D-ring steroid building blocks and facilitated a stereoselective synthesis of BTX. This route is highlighted by a n-Bu3SnH-mediated radical cyclization cascade, a strategy that has enabled expedient access to the steroidal core of the toxin. In this reaction, assembly of the central C-ring occurs with concomitant installation of the C13 quaternary center, a latent C18 aldehyde for homomorpholine ring construction, and an allyl stannane that can be oxidatively manipulated to the desired C11 alcohol. Additional highlights of this work include a novel CuCl2 and O2-mediated allylic stannane oxidation reaction, acid-catalyzed Curtius rearrangement, Stille cross-coupling reaction, and stereoselective 8-electron reduction of an oxidized precursor to batrachotoxinin A. Optimization of a final-step esterification of batrachotoxinin A has enabled preparation of ~4 mg of BTX, or 2.5% of the available world supply. The studies presented in this thesis lay the foundation for future experiments aimed at resolving questions regarding the differential activity of BTX analogues, which will likely reveal unique molecular insights into NaV function.

Keywords: Chemistry.
Advisor: Du Bois Justin primary advisor. Thesis advisor
Chen James
Wender Paul A. advisor. Thesis advisor
Stochastic program optimization for x86_64 binaries [electronic resource]

The optimization of short sequences of loop-free fixed-point x86_64 code sequences is an important problem in high-performance computing. Unfortunately, the competing constraints of transformation correctness and performance improvement often force even special purpose compilers to produce sub-optimal code. We show that by encoding these constraints as terms in a cost function, and using a Markov Chain Monte Carlo sampler to rapidly explore the space of all possible programs, we are able to generate aggressively optimized versions of a given target program. Beginning from binaries compiled by gcc -O0, we are able to produce provably correct code sequences that either match or outperform the code produced by gcc -O3, and in some cases expert hand-written assembly. Because most high-performance applications contain floating-point computations, we extend our technique to this domain and show a novel approach to trading full floating-point precision for further increases in performance. We demonstrate the ability to generate reduced precision implementations of Intel's handwritten C numerics library that are up to six times faster than the original code, and achieve end-to-end speedups of over 30% on a direct numeric simulation and a ray tracer. Because optimizations that contain floating-point computations are not amenable to formal verification using the state of the art, we present a technique for characterizing maximum error and providing strong evidence for correctness.

Advisor: Aiken Alexander primary advisor. Thesis advisor
Hanrahan P. M. (Patrick Matthew) advisor. Thesis advisor
Horowitz Mark (Mark Alan) advisor. Thesis advisor
Stratification and sorting [electronic resource] : variable student experiences and outcomes in New Orleans' post-Katrina public schools

With a nearly 100% charter operated school system, New Orleans is a model for the market-based charter reform movement in the US. After Hurricane Katrina, the state legislature significantly expanded the definition of a failing school thereby transferring the majority of Orleans Parish schools to the control of the state-run Recovery School District. Since 2005, the RSD has withdrawn from operating direct-run schools and has turned over the daily management and oversight of public schools to independent charter operators. In the wake of such drastic changes in the school landscape, schools in New Orleans continue to be academically, racially, and socioeconomically stratified. This qualitative study documents the lived experiences of students, educators, and community members in the hierarchically tiered system of schools. I employ an analytic lens that examines the perceived effects of stratification through the analysis of school demographics, academic programming, discipline practices, and enrollment policies and practices within the context of school choice in an accountability system hinged on state-testing. Based on participant responses, the system is set up in such a way that a student's academic and demographic characteristics predict the range of school options available and the corresponding academic and social experiences he/she is likely to have in school. Findings indicate that students who enter schools with lower or fewer academic skills are likely to experience a more stringent disciplinary atmosphere and a more narrow curriculum; whereas, students who enter school more academically advanced are likely to experience more academic and social freedoms in school. As a result, students are segregated from one another in a form of city-wide ability tracking where schools are organized and managed in direct relation to the student population they serve thereby reproducing social stratification and inequity.

Keywords: Education.
Advisor: Darling-Hammond Linda
Carter Prudence L.
Lotan Rachel A. advisor. Thesis advisor
Structural Changes in the Primary Visual Cortex of Alzheimer's Disease Model Mice As A Correlate to Diminished Plasticity

Amyloid-β (Aβ) accumulation has been implicated in Alzheimer’s disease pathogenesis. Mice with transgenic expression of mutant amyloid precursor protein (APP) and presenilin-1 (PS1) accumulate Aβ and have therefore been used as models of the disease. Previous research has shown that critical period ocular dominance (OD) plasticity is defective in these mice, which indicate an early effect of Alzheimer’s on neural plasticity, even before the typical Aβ plaques accumulate. In an attempt to determine the mechanism responsible for this defect, I investigated layer 5 apical dendritic spine density and morphology in the primary visual cortex of juvenile (P30) and adult (P74) APP/PS1 mice. We found that wildtype and APP/PS1 transgenic juvenile and adult mice both displayed comparable spine densities and initially concluded that the critical period ocular dominance plasticity defect observed in APP/PS1 transgenic mice is not associated with a decrease in spine density in layer 5 apical dendrites. However, recent discoveries within the lab have led us to believe that the APP/PS1;YFP-H+ mouse line used in these experiments may have epigenetic or other modifications that would inhibit transcription of YFP and/or APP/PS1. Further experiments should be conducted to verify the presence of Aβ accumulation in this mouse line before continuing research.

Keywords:  Department of Biology
Alzheimer's
APP/PS1
Neurodevelopment
Neurobiology
Stanford University
Department of Biology
Thesis
Advisor: Shatz Carla
McConnell Susan
Structural determinants of Smoothened regulation in the Hedgehog pathway

The seven-transmembrane oncoprotein Smoothened (Smo) is a key activator in the Hedgehog (Hh) signaling pathway, and thus a driver of many processes in tissue patterning and postembryonic stem cell regulation. In normal pathway activity, Smo is repressed by the tumor suppressor protein Patched (Ptch), and this repression is relieved when the Hh morphogen binds to and inactivates Ptch. However, the mechanism of Ptch action on Smo is poorly understood. In this study, the approaches of cyclopamine pocket mutagenesis and functional phylogenetic comparisons of five Smo orthologs (urchin, tunicate, lamprey, skate, and coelacanth) were used to identify key determinants of the regulatory interaction between Ptch and Smo. Mouse-lamprey Smo chimeras provided evidence for a role of the cysteine-rich domain in restraining signaling activity, and suggested a two-site model of Ptch regulation. To address the difficulty of measuring pathway activity of basal orthologs in vertebrate cells, a new FRET assay was developed that provides a more direct readout of Smo activity state. This assay, based on Smo coupling to a G protein alpha subunit, has broad applications in the Hedgehog field. The regulatory mechanism of Smo is an open question in developmental and oncogenic signaling, and a better understanding of the Ptch-Smo interaction will lay the groundwork for more effective cancer therapies.

Keywords:  Department of Biology
Biology
Hedgehog
Smoothened
Thesis
Advisor: Beachy Philip
Simon Michael
Structure, mechanism, and electronic properties of organic molecular n-dopants and n-doped materials [electronic resource]

The low ionization potentials of highly reducing organic n-dopants and host radical anions makes n-doping a much greater challenge than p-doping. However, many modern electronics such as transistors, complementary circuits, light-emitting diodes, photovoltaics, and thermoelectrics either require or benefit from both n- and p-type conduction. It is a long-standing and partially realized goal of the organic electronics community to mass produce devices by exploiting modern printing processes. To accomplish this will require new materials, device architectures, and processing methods. The goal of this thesis was to advance the state of solution-processable conductive n-type organic materials for use in printed organic solar cells, transistors, and thermoelectric devices. In this thesis, a bottom-up mechanistic approach was used to design new organic n-dopants and n-dopable host semiconductors. First, the n-doping mechanism of 1,3-dimethylbenzimidazole (DMBI) derived dopants was studied in solution, and it was discovered that DMBI dopants react with fullerenes by hydride transfer. Following this study, a new class of dimeric dopants ((DMBI)2) were developed to eliminate the dependence of the doping reaction on the hydrogenation thermodynamics of the host. The (DMBI)2 dopants were employed in a thorough synthetic, spectroscopic, and electrical study of new n-dopable conjugated polymers. Ultimately, several polymers with higher conductivities when n-doped than current state-of-the-art materials were identified. The results of this study indicate that the polaron delocalization length is the most relevant parameter to optimize to achieve high conductivity n-doped polymer films. Building upon this work, a class of self-n-doped polymers with remarkable stability in air were developed. Finally, as a demonstration of the utility of the new materials reported in this thesis, fully solution-processed logic gates and organic solar cells with n-doped layers were fabricated.

Keywords: Chemistry.
Advisor: Bao Zhenan primary advisor. Thesis advisor
Kanan Matthew William
Salleo Alberto
Structured estimation in healthcare and quantized matrix recovery [electronic resource]

We find ourselves in the era of modern data, where new collection technologies provide us with vast amounts of data at an unprecedented speed. While this data provides us with ample opportunities for advancing research efforts in a variety of areas, we must understand how we can use it to achieve our objectives. Structured estimation gives researchers the tools to take advantage of this data, to help overcome the challenges associated with it, and help shape it to be more suitable for our application needs. As a result, we are able to use this data to, for example, enhance patient outcomes, provide recommendations to users of online music or movie streaming services, and predict reliability and identify power tampering of electricity meters. In the first part of this thesis, we use structured estimation to help us design a model for assessing a patients' risk for multiple diseases. While combining models used for individual disease prediction presents one solution, this approach can be improved upon in complexity as well as accuracy. We use methods from machine learning and dimensionality reduction to allow us to select a small set of biomarkers which are accurate predictors of multiple diseases. We validate our methods on real patient data. In the second part of this thesis, we investigate the problem of recovering a matrix from a subset of its entries. We focus on low rank matrices whose entries are from a finite set, especially those whose observations result from quantization of a noisy real-valued matrix. We present a performance guarantee for our approach, which is formulated as a rank-constrained maximum likelihood parameter estimation problem. We develop an algorithm for this approach, based on matrix factorization techniques, for which we provide convergence guarantees. Our proposed method provides a solution to many practical problems, such as collaborative filtering, network localization, and image denoising.

Keywords: Electrical Engineering.
Advisor: Montanari Andrea primary advisor. Thesis advisor
Bayati Mohsen advisor. Thesis advisor
Hastie Trevor advisor. Thesis advisor
Structure-function studies of drosophila Mip120 [electronic resource]

The Drosophila dMyb-MuvB (MMB)/Drosophila RBF, dE2F2, and dMyb- interacting proteins (dREAM) is a multi-protein transcriptional regulator that regulates many biological processes including the cell cycle, development, and differentiation. MMB/dREAM contains multiple members that have DNA binding domains: dMyb, dE2F2-dDP, and Mip120. It is currently unclear which of these members can localize the rest of the complex to DNA. My studies focused on Mip120/LIN54. We wanted to determine which domains of Mip120 were necessary for its function, because previous studies of dMyb unexpectedly showed that the highly conserved dMyb DNA binding domain was not necessary to rescue Myb null lethality. In addition, we also wanted to determine which domains of Mip120 were sufficient for nuclear localization in different Drosophila cell types, including the egg chambers, wing discs, salivary glands, and eye discs. mip120 null females were sterile, had an ovary development phenotype, and did not lay eggs. Using the ovary development phenotype and egg laying defect as an assay for mip120 gene function, we conducted rescue experiments to determine which domains of Mip120 were necessary for its function. We found that multiple domains of Mip120, including the N-terminus, which contains two putative nuclear localization signals, and the C-terminus, which contains a highly conserved cysteine rich DNA binding domain (CXC) and a helix-coil-helix protein interaction domain (HCH) were necessary for mip120 function. From the nuclear localization experiments, we found that all of the Mip120 fragments were sufficient for nuclear localization. We found a previously unreported mip120 null phenotype. mip120 null nurse cell chromosomes were very condensed and had blobbier DNA than controls. The phenotype occurred very early in egg chamber development because even egg chambers as early as stage 2-4 chambers appeared blobbier in mip120 null mutants than controls. We attempted to determine the mechanism of mip120 null mutants. We found that global expression of many common epigenetic marks including H3K9me2/3, HP1, H3S10P, H3K4me3, and H4Ac remained similar in mip120 null mutants compared to controls. In mip120 null mutants, we also assayed which dREAM complex members still localized to DNA. Mip40 and dMyb no longer localized to DNA without Mip120, suggesting that Mip120 is necessary for dMyb and Mip40 nuclear and DNA localization. dE2F2 and p55 Caf1 still localized to DNA without Mip120, suggesting that dE2F2 and p55 Caf1 can localize to DNA independently of Mip120. Unexpectedly, Mip130 was also still able to localize to DNA without Mip120. Though Mip130 does not have a traditional DNA binding domain, it does have an AT hook, which may be able to localize Mip130 to the complex.

Keywords: Genetics.
Advisor: Lipsick Joseph Steven
Fuller Margaret
Pollack Jonathan D.
Sage Julien advisor. Thesis advisor