VictorJuiz/thesis huggingface dataset:
Alternate exons in Caenorhabditis elegans slo-1 diversify BK channel calcium dependence [electronic resource]

Ion channels coordinate the movement of ions across biological membranes in response to a diversity of cellular signals to regulate most if not all aspects of physiology. The large-conductance Ca2+- and voltage-activated potassium (BK) channel is widely expressed across tissues and functions to repolarize action potentials, regulate smooth muscle tone and endocrine function, and tune auditory hair cells. In all tissues, BK channels provide a functional link between cytosolic Ca2+ and membrane excitation. Extensive alternate splicing of the slo-1 gene, encoding the BK channel, significantly diversifies channel function. We identified all twelve predicted BK channel splice variants expressed by the nematode Caenorhabditis elegans, and measured the Ca2+ and voltage dependence for each. Alternate exons encode portions of two regions of the cytoplasmic tail: the RCK domain, important for Ca2+ coordination, and an unstructured region, termed the C-linker. Using the patch clamp technique, we determined that alternate splicing across multiple sites diversifies activation kinetics and Ca2+ sensitivity by manipulating the functional interaction between the RCK domain and C-linker. We recovered two slo-1 alleles (pg34 and pg52) that contain point-mutations near an alternative splice site in the C-linker from a mutant screen. Using real-time PCR, we determined that both mutations change slo-1 splice variant expression profiles. The pg34 mutation encodes an A698T substitution, and the pg52 mutation is located in an intron. When heterologously expressed, the A698T mutation changes BK channel Ca2+ sensitivity in specific splice variant backgrounds by disrupting the functional connection between the C-linker and the RCK domain. Using in vivo electrophysiology, we determined that the pg34 mutation reduces but does not abolish BK channel function in C. elegans neurons. These results suggest that alternate splicing of slo-1 modulates the functional connection between the RCK domain and the C-linker of the BK channel to establish a proper balance between intracellular Ca2+ and membrane excitation in a variety of cell type and physiological conditions.

Keywords: Molecular and Cellular Physiology.
Advisor: Goodman Miriam Beth primary advisor. Thesis advisor
Aldrich Richard
Clandinin Thomas R. (Thomas Robert)
Lewis Richard (Richard Sheridan) advisor. Thesis advisor
Shen Kang
Alternative splicing analysis using RNA-seq data [electronic resource]

A single gene may produce multiple variants of a protein called isoforms. This process is mediated by alternative splicing of the mRNA transcript. We discuss some of the challenges inherent in the tasks of isoform quantification and novel isoform discovery on a given sample, and steps we have taken to address these challenges. In particular, in the first portion of this thesis we discuss the isoform quantification problem and give a technical condition describing under what conditions it is identifiable. In the second half of this thesis, we present a mathematical formulation of a novel approach to solving the isoform discovery problem. We show that our approach performs well on simulated data under both uniform read sampling and significantly biased sampling, and that it also returns a reasonable result on several test genes taken from an actual RNA-seq data set.

Keywords: Statistics
Advisor: Wong Wing Tak Jack Wong primary advisor. Thesis advisor
Olshen Richard A.
Owen Art B. advisor. Thesis advisor
Amplitude and phase modulation of single photons and biphotons [electronic resource]

Single photons and entangled photons are valuable resources in quantum information science. We describe, in this dissertation, the generation of time-frequency entangled pairs of photons with narrow linewidths and coherence times that are about six orders of magnitude longer than those of photons produced via spontaneous parametric downconversion in nonlinear crystals. These photons are produced using the mechanism of electromagnetically induced transparency and the associated slow light effect. Using existing detectors it is possible to temporally resolve the structure of these narrowband photons and commercial electro-optic modulators may be used to manipulate their amplitude and phase. In this context, we discuss three recent experiments. In the first, we demonstrated amplitude modulation, with arbitrary shapes, of heralded single photons. In the second, we demonstrated a Fourier technique to measure the shapes of biphoton wavepackets using fast amplitude modulators and slow detectors. The third experiment is a demonstration of spread spectrum techniques at the single photon level.

Keywords: Applied Physics
Advisor: Harris S. E. (Stephen Ernest)
Kasevich Mark A. primary advisor. Thesis advisor
Mabuchi Hideo advisor. Thesis advisor
Amyloid-beta inhibits E-S plasticity and LTP through inhibition of cannabinoid receptor 1-dependent synaptic disinhibition [electronic resource]

Alzheimer's disease (AD) is a progressive neurodegenerative disorder affecting the elderly that is characterized by loss of short-term memory and cognitive decline. Studies in both human patients and animal models of AD point to over-accumulation of soluble oligomers of amyloid-beta peptide (Abeta) as a mediator of learning and memory impairments early in the disease (Rowan, Klyubin et al. 2005; Selkoe 2008). Support for Abeta's role in learning deficits comes from studies demonstrating impaired plasticity of synaptic inputs to neurons, as measured in the paradigm of long-term potentiation (LTP) of synaptic strength in hippocampal slices (Chen, Kagan et al. 2000; Freir, Holscher et al. 2001; Walsh, Klyubin et al. 2002; Wang, Pasternak et al. 2002; Townsend, Shankar et al. 2006), the prime candidate for the neuronal substrate of learning and memory behavior (Bliss and Collingridge 1993). Induced concurrently with synaptic LTP is an increase in the electrical coupling between the dendritic synaptic inputs and the soma, such that a greater proportion of the EPSP survives at the spike trigger zone, resulting in greater action potential output for a given EPSP. This potentiation of EPSP-spike coupling (E-S coupling) provides an additional boost to the efficacy of the EPSP on top of the potentiation (LTP) that occurs at the synapse (Bliss and Lomo 1973). While LTP of synaptic strength is an essential component of memory storage, in all models of learning, memory recall occurs only when spikes are evoked in the neurons participating in a representation. Thus E-S potentiation exerts control over the essential substrate of memory retrieval. Although LTP and E-S potentiation are mechanistically distinct processes, several features during the induction phase are shared. Studies have shown that Abeta impairs the induction, but not maintenance of LTP (Wang, Walsh et al. 2004; Townsend, Shankar et al. 2006), leaving the possibility that Abeta-mediated impairment to memory is not specific to LTP. Nevertheless, focus has centered on pathways central to LTP, while impairment to other forms of plasticity have not been explored. Here we show a mechanism by which Abeta peptides impairs post-tetanic suppression of inhibition, thereby inhibiting E-S potentiation. This impairment to E-S potentiation was occluded by GABAA-receptor, Cannabinoid 1 receptor (CB1R), and muscarinic acetylcholine receptor (mAChR), but not mGluR block. This suggests that the impairment is mediated by mAChR-initiated endocannbinoid signaling. Together, the results provide a mechanism to explain learning and memory impairments in early Alzheimer's disease.

Keywords: Molecular and Cellular Physiology.
Advisor: Madison Daniel V.
MacIver M. Bruce (Murdo Bruce) advisor. Thesis advisor
Smith Stephen J.
Wyss-Coray Anton advisor. Thesis advisor
An Analysis of the Timing of Fertility in Rural India

Fertility has long been modeled as the household supply and demand for children. However, very little empirical work has been done on understanding the timing of fertility in the developing country setting. Assuming that households are utility maximizing, it is expected that they choose when to begin reproduction, when to have the next child and when to cease reproduction. This paper looks at how the timing of fertility decisions is affected by household wealth and parental education across maternal cohorts. Modeling births in a survival analysis function framework, this paper finds that education delays all births and wealth delays the first birth but accelerates subsequent births. Lastly, cohort effects play a significant role in the time to the first birth but not the latter births, suggesting that only the preference of when to have the first child has changed over time.

Keywords:  Department of Economics
Stanford Department of Economics
fertility
India
birth spacing
survival analysis
Thesis
Advisor: Kochar Anjini
An Implementation of Quad-fragment Merging for Micropolygon Rendering

Current graphics cards (GPUs) shade small polygons inefficiently. When surfaces are represented using micropolygons of less than a pixel in size, many shading computations performed by a GPU are redundant. Since shading is typically the most expensive operation in a graphics pipeline, this leads to poor rendering performance.
This thesis presents a prototype implementation of quad-fragment merging, which reduces redundant shading work by buffering and selectively merging rasterized fragments prior to shading. The prototype quad-fragment merger is described in detail, and evidence is presented that it is amenable to implementation in fixed-function hardware. Performance results indicate that our implementation decreases shader executions by a factor of eight when rendering micropolygons, and effectively makes use of a number of optimizations to yield high performance. Finally, an early prototype of a corollary technique that shades scenes with motion blur is described, and preliminary results are presented.

Keywords: Computer Science.
Computer Graphics
Geometry > Data processing
Thesis
Advisor: Hanrahan Patrick
Analog signal processing circuits in organic transistor technology [electronic resource]

Low-voltage organic thin-film transistors offer potential for many novel applications. Because organic transistors can be fabricated near room temperature, they allow integrated circuits to be made on flexible plastic substrates. This physical flexibility allows organic transistors to integrate with bendable organic displays, polymeric muscles, and conformal sensors. Additionally, organic semiconductors are inherently sensitive to specific molecules, making organic transistors naturally suited for chemical and biological sensors. In all these applications, data converters are the essential link between the digital processors and the analog media. However, because of the inherent non-uniformities in organic processing, organic analog circuits suffer from large variations that lead to inaccurate and unreliable data conversion. Dielectric leakage and large parasitic capacitances further limit the available design space. This dissertation describes the sources of these process handicaps and offers design techniques to counter them. By applying these techniques, this research demonstrated the world's first organic-transistor digital-to-analog converter and the first organic-transistor analog-to-digital converter. Both data converters operate at 3 V, 100 Hz and resolve 6 bits. Similar design methodology can be utilized in designing other organic-transistor based analog signal processing circuits.

Keywords: Electrical Engineering
Advisor: Murmann Boris primary advisor. Thesis advisor
Bao Zhenan advisor. Thesis advisor
Dutton Robert W. advisor. Thesis advisor
Analysis of national strategies for combating the proliferation of nuclear weapons [electronic resource]

Analysis of strategies for stemming the proliferation of nuclear weapons is often considered too difficult for quantitative rigor. Qualitative arguments abound for how to best influence potential proliferators, but these often arise as reactionary statements to immediate events without explicitly accounting for future uncertainties. Further, without detailed analysis of the costs and benefits resulting from the recommended actions it is unclear how to best compare the proposed actions. The goal of this research is to provide national decision makers with a framework for evaluating different counter-proliferation strategies and to help identify courses of action that optimally trade-off the potential ramifications of a country's acquisition of nuclear weapons against the U.S. cost for interdiction. A framework was developed to analyze the effectiveness of national strategies for interdicting a targeted country's nuclear weapons program. This framework models both the intent and capabilities of the potential proliferant using a combination of Bayesian networks and semi-Markov decision processes. Interdiction strategies are then evaluated based on their expected costs and the resulting level of militarized conflict. Historical and current/future case studies are provided to demonstrate framework validity and for illustrating potential insights from the proposed methodology. The contrasting cases of South Africa and Pakistan were modeled in their historical context. The results demonstrate the framework's ability to accurately represent different nuclear weapons scenarios. Sensitivity analyses on these cases depict plausible futures and are used as examples of insights attributable to the described approach. Modern day Iran was modeled to depict a current/future analysis using the developed framework. An optimal U.S. strategy was identified leveraging military, diplomatic, and economic interdiction options. Sensitivity analysis on the probability of Iran's leadership and on the probability of an attack against the U.S. or allies highlights the flexibility of the proposed approach for modeling a variety of possible situations and the ability to identify plausible interdiction strategies.

Keywords: Management Science and Engineering
Advisor: Paté-Cornell M. Elisabeth (Marie Elisabeth) primary advisor. Thesis advisor
Hecker Siegfried S. advisor. Thesis advisor
Howard Ronald A. (Ronald Arthur)
Perry William James
Approximate message passing algorithms for compressed sensing [electronic resource]

Compressed sensing refers to a growing body of techniques that `undersample' high-dimensional signals and yet recover them accurately. Such techniques make fewer measurements than traditional sampling theory demands: rather than sampling proportional to frequency bandwidth, they make only as many measurements as the underlying `information content' of those signals. However, as compared with traditional sampling theory, which can recover signals by applying simple linear reconstruction formulas, the task of signal recovery from reduced measurements requires nonlinear, and so far, relatively expensive reconstruction schemes. One popular class of reconstruction schemes uses linear programming (LP) methods; there is an elegant theory for such schemes promising large improvements over ordinary sampling rules in recovering sparse signals. However, solving the required LPs is substantially more expensive in applications than the linear reconstruction schemes that are now standard. In certain imaging problems, the signal to be acquired may be an image with

Keywords: Electrical Engineering
Advisor: Donoho David Leigh primary advisor. Thesis advisor
Gray Robert M.
Montanari Andrea advisor. Thesis advisor
Array architecture for a nonvolatile 3-dimensional cross-point memory [electronic resource]

This work explores the design and capabilities of a three-dimensional cross-point array structure suitable for use with resistance-change non-volatile memory. The resistance-change cell serves as both the access element and the memory element, eliminating the need for individual selection transistors or diodes. This enables the memory to be fabricated in arrays with a line spacing of F, the minimum feature size for a given process technology. By stacking the cross-point arrays in n layers, we achieve an effective cell size of 4F^2/n. Previous works describing transistor-free memory arrays have been limited by excessive leakage current across unselected bitlines and wordlines during memory access. This work presents novel architecture and circuit techniques that minimize leakage current effects while maintaining a high effective bit density. A test chip fabricated in 0.18 um CMOS technology allows us to verify the architecture and circuit functionality. The performance of a 8 Gb memory chip build in 65 nm technology has been simulated. A random access time of 104 ns is achieved with a power dissipation of 61.2 uW. This makes the 3-D cross-point memory competitive with NOR flash in terms of read time, and competitive with NAND flash in terms of area efficiency.

Keywords: Electrical Engineering
Advisor: Wong S. primary advisor. Thesis advisor
Lee Thomas advisor. Thesis advisor
Nishi Yoshio
Array imaging of sparse scatterers [electronic resource]

We consider narrow band (single frequency) array imaging of localized scatterers. We introduce a hybrid approach for coherent imaging using both the singular value decomposition (SVD) and L1 minimization so as to fully exploit the intrinsic sparsity contained in the array data. We compare the results with other imaging methods such as multiple signal classification, least squares and migration. We show that well-separated point scatterers can be recovered exactly with the hybrid L1 minimization. Moreover, using the SVD we determine the optimally subsampled array data for the L1 minimization. Numerical simulations confirm that this imaging approach is robust with respect to additive noise. Furthermore, with a simple random phase model for a heterogeneous medium, we also show that the hybrid L1 method is efficient for imaging with correlated noise arising from the random medium. For imaging without knowing the phase of data explicitly, we introduce a new approach for narrow band array imaging of localized scatterers from intensity-only measurements by considering the possibility of reconstructing the positions and reflectivities of the scatterers exactly from only partial knowledge of the array data. We reformulate this intensity-only imaging problem as a non-convex optimization problem and show that we can have exact recovery by minimizing the rank of a positive semidefinite matrix associated with the unknown reflectivities. Since this optimization problem is NP-hard and is computationally intractable, we replace the rank of the matrix by its nuclear norm, the sum of its singular values, which is a convex programming problem that can be solved in polynomial time. Numerical experiments explore the robustness of this approach, which recovers sparse reflectivity vectors exactly as solutions of a convex optimization problem.

Advisor: Papanicolaou George primary advisor. Thesis advisor
Garapon Pierre advisor. Thesis advisor
Ryzhik Leonid advisor. Thesis advisor
The assembly and interactions of MreB in the maintenance of cell shape in Caulobacter crescentus [electronic resource]

This work focuses on the mechanism by which MreB contributes to the maintenance of cell shape in the gram-negative alpha-proteobacterium Caulobacter crescentus. The gene mreB encodes a protein that resembles actin, a eukaryotic cytoskeletal protein. Previously, it was shown that mreB is required to maintain a rod-like shape and localizes to a helical pattern near the cytoplasmic membrane. Here, we show that MreB is associated with regions of active growth in Caulobacter, as mutant strains that mislocalize MreB to the cell poles direct new growth at or near the poles. We present evidence to suggest that MreB contributes to the determination of proper length, width, and curvature through partially distinct mechanisms. The determination of proper width involves the essential proteins MreC and Pbp2, which are encoded in the mreB operon. While MreB and MreC are both required to position the cell wall transpeptidase Pbp2 along the lateral sidewalls and away from midcell, the two do not colocalize and each can maintain its localization in the absence of the other. When MreB is mislocalized to the poles, MreC and Pbp2 do not follow. These data argue against the idea that MreB provides a scaffold-like structure to localize enzymes that directly modify the cell wall. The determination of proper curvature, involves the intermediate filament-like protein, Crescentin. We identify a putative binding site on MreB for Crescentin or other curvature-mediating factors. We also show that the extent to which the subcellular localization of MreB changes over the cell cycle is correlated with cell size, indicating that MreB is involved in the coordination between elongation and division. In addition, we show that in vitro purified MreB spontaneously forms very stable polymers in the presence or absence of nucleotide. These polymers are globular or amorphous and only filamentous when placed on a highly positively charged surface of Poly-L-lysine. These in vitro data suggest that MreB is likely to be regulated at the disassembly step in the cell and that the cellular environment may influence the structure of MreB polymers. Lastly, we present biochemical evidence to support the existence of a disassembly factor in cytoplasmic Caulobacter extract. Together our data suggest that the maintenance of the crescent-rod cell shape in Caulobacter is the result of a complicated balance between MreB's dynamic subcellular localization, polymeric structure, and communication with cellular components.

Keywords: Biochemistry
Advisor: Shapiro Lucy primary advisor. Thesis advisor
Theriot Julie primary advisor. Thesis advisor
Spudich James A.
Straight Aaron
Astrophysics of the intracluster medium in X-ray bright galaxy clusters [electronic resource]

Clusters of galaxies are the most massive, gravitationally-bound structures in the universe. Detailed studies of their properties are applicable to a wide variety of astrophysical problems. These include, but are not limited to galaxy formation, large-scale structure formation, and cosmology. A cornerstone of such studies is the use of X-ray satellite observations to study the X-ray radiation from the diffuse, hot intracluster gas, which dominates the baryonic matter content. This thesis records the analysis and results of some of the deepest observations of X-ray bright galaxy clusters ever made with the Chandra X-ray Observatory, NASA's flagship X-ray observatory. The studies presented focus upon the detailed physics of the intracluster medium (ICM) including the ram-pressure stripping and the possible destruction of cool cores within clusters; the interaction between the central active galactic nucleus with the intracluster gas in cool cores; and searches for non-thermal X-ray emission components. With deep observations of the nearest and brightest galaxy clusters, the astrophysics can be probed in exquisite detail. However, the conclusions drawn are expected to be applicable to the general cluster population, with implications for statistical cluster studies and cosmology.

Keywords: Physics
Advisor: Allen Steven W. (Steven Ward) primary advisor. Thesis advisor
Church Sarah Elizabeth advisor. Thesis advisor
Funk Stefan
Kahn Steven M. (Steven Michael)