VictorJuiz/thesis huggingface dataset:
Exploring cancer biology using integrative genomics [electronic resource]
Keywords: Genetics

Advances in genomic technologies have allowed investigators to survey diverse molecular properties of cancer cells including DNA copy number alterations, RNA transcript abundance, and protein-DNA binding events. While each data type offers a unique snapshot of the tumor cell, an integrated analysis of two or more complementary data types can reveal much more than the sum of its parts. In this dissertation, I describe new integrative genomic methodologies and novel biologic insights gleaned from their application. In one such analysis of 52 breast cancer cell lines, we identify genomic alterations and gene-expression profiles that largely resemble those identified in primary breast tumors, therefore defining relevant tumor models of breast cancer subtypes. Additionally, we identify 80 high-level DNA amplifications and 13 multi-copy deletions, harboring known and novel cancer genes, thereby providing a rich resource for new breast cancer gene discovery and characterization. In an integrative analysis of colorectal cancers, we unveil a region of amplification highly specific to colorectal-derived tumors. We identify and characterize caudal type homeobox transcription factor 2 (CDX2), a master regulator of intestinal cell survival and differentiation, as the target gene of this amplification, and show a CDX2 amplification-specific dependency for tumor cell survival, proliferation, and anchorage-independent growth. Moreover, by integrating protein-DNA binding and gene expression data, we uncover a novel relationship between CDX2 and Wnt/[beta]-catenin signaling. Taken together, these data show that for a subset of colorectal-derived tumors, cell survival and proliferation are dependent on the abnormal amplification and overexpression of CDX2, thereby characterizing CDX2 as a novel lineage-survival oncogene in colorectal cancer. In the last portion of the dissertation, I reflect on how the rapidly growing knowledgebase of genetic associations with disease and drug response will help usher in a new era of personalized medicine. To help prepare for a future that includes an array of available genomic laboratory tests, I discuss the necessity to reform medical school curricula to educate students about the interpretation, limitations, and impact of genomic testing in clinical medicine. I describe the challenges and considerations relevant to the development of a novel educational curriculum that includes personal genomic testing.
Fast algorithms for the digital computation of linear canonical transforms [electronic resource]
Keywords: Electrical Engineering

Although it is straightforward to determine the relationship between the in-focus image and the object of a simple optical system such as a lens, it is far more challenging to compute the input/output relationships of general first-order and astigmatic optical systems. Such optical systems are known as quadratic-phase systems (QPS) and they include the Fresnel propagation in free space, propagation in graded-index media, passage through thin lenses, and arbitrary concatenations of any number of these, including anamorphic, astigmatic, nonorthogonal elements. Such computation is accomplished by representing the physical system with a general mathematical framework of integrations against kernels and then distilling the entire system into one input-output relationship that can be represented by a linear integral transform. The underlying mathematical integral transforms can be applied to a wider field of signal processing where they are known as the linear canonical transform (LCT) of a signal. Conventional numerical integration methods have a computational complexity of O(N^2) where N is the space-bandwidth product of the sampling scheme, e.g. the number of pixels in the field for an optical system. The algorithms described here yield a complexity of only O(Nlog N). The key is the use of different decompositions (or factorizations) of a given input/output relationship into simpler ones. Instead of following the general physical subparts in cascaded systems and computing input-output relations separately, these algorithms use the simplest possible decompositions to represent the entire system in terms of least possible number of steps. The algorithms are Fast Fourier Transform (FFT) based methods and the only essential deviation from exactness arises from approximating a continuous Fourier transform (FT) with the discrete Fourier transform (DFT). Thus the algorithms work with a performance similar to that of the fast Fourier transform algorithm in computing the Fourier transform, both in terms of speed and accuracy. Unlike conventional techniques these algorithms also track and control the space-bandwidth products, in order to achieve information that is theoretically sufficient but not wastefully redundant.
Filtering and parameter estimation for partially observed generalized Hawkes processes [electronic resource]
Keywords: Mathematics

We consider the nonlinear filtering problem for partially observed Generalized Hawkes Processes, which can be applied in the context of portfolio credit risk. The problem belongs to the larger class of hidden Markov models, where the counting process is observed at discrete points in time and the observations are sparse, while the intensity driving process in unobservable. We construct the conditional distribution of the process given the information filtration and we discuss the analytical and numerical properties of the corresponding filters. In particular, we study the sensitivity of the filters with respect to the parameters of the model, and we obtain a monotonicity result with respect to the jump and the volatility terms driving the intensity. Using the scaled process, we provide necessary and sufficient conditions for the frequency of time observations in terms of the parameters of the model, to ensure a good performance of the filter. We also address the problem of parameter estimation for the Generalized Hawkes Process in the framework of the EM algorithm, and we analyze the effect of the self-exciting feature of our process on the asymptotic and numerical properties of the estimators.
Fine-scale spatial organization of face- and limb-selective regions in human high-level visual cortex [electronic resource]
Keywords: Psychology

Neurophysiology and optical imaging studies in monkeys and functional magnetic resonance imaging (fMRI) studies in both monkeys and humans have localized clustered neural responses in high-level visual cortex selective for images of biologically relevant categories such as faces and limbs. Implementing higher resolution (1.5mm voxels) fMRI scanning methods than prior studies (3-5mm voxels), the results reported in this dissertation illustrate a topographic organization of face- and limb-selective regions in adjacent and alternating clusters in both ventral temporal and lateral occipitotemporal cortices. Region of interest analyses in a series of experiments indicate distinct category and position sensitivities within these clusters and multivoxel pattern analyses indicate different amounts of information in highly-, weakly-, and non-selective voxels for these categories. These results mediate the debate between modular and distributed theories of high-level visual cortex, as well as support a novel, sparsely-distributed organization including both locally clustered and distributed elements for face and limb representations. These results also reveal two new basic organization principles of high-level visual cortex where there is both a consistency in the anatomical location of functional regions, as well as a preserved spatial relationship among functional regions. Employing these two principles enables the first framework for consistent parcellation of high-level visual regions outside of retinotopic cortex. Importantly, this framework can also be applied to other sensory and nonsensory cortical systems.
First principles molecular dynamics and control of photochemical reactions [electronic resource]
Keywords: Chemistry

In this thesis, we develop and use an ab initio molecular dynamics method to investigate the mechanisms of photochemical reactions, working towards the goal of controlling these reactions. We use and extend the ab initio multiple spawning (AIMS) method for this purpose. AIMS solves the Schrodinger equation for both the nuclear and electronic wavefunctions on multiple potential energy surfaces (PESs) and adaptively expands the nuclear basis set at critical regions on the PES to account for nonadiabatic events. In this thesis, we improve the accuracy of the electronic wavefunction by implementing a higher level quantum chemical method, multi-state second-order perturbation theory (MS-CASPT2). AIMS with MS-CASPT2 is then applied to the photochemistry of ethylene, the prototype of photoisomerization reactions. Good agreement in terms of the excited state lifetime is achieved between theory and time-resolved experiments. The agreement demonstrates the importance of faithful comparison between experiment and simulation, and provides us with mechanistic insights for photoisomerization reactions, which lies at the center of many important phenomena in nature. AIMS is then applied to two molecules where the excited state dynamics may be controlled in different ways. In the case of propanal cation, we show that careful initial state preparation can lead to distinct excited state dynamics and the effects of this distinct dynamics persist in the product distribution which is formed through dissociation on the ground electronic state. AIMS reveals the mechanism of the dramatic branching ratio difference between two product channels measured by experimentalists, and identifies the critical role of conical intersections and dark states in causing the observed conformational selectivity. We follow our study of the excited dynamics with modeling of the ground state kinetics, which allows us to make a quantitative comparison with experiment. We then investigate the potential for control of the ring-opening reaction of cyclohexadiene (CHD), using an external laser field to alter the dynamics after photoexcitation. We explicitly incorporate light-matter interactions within the framework of AIMS. The augmented method is first tested on one- and two-dimensional model problems before applying it to the CHD ring-opening reaction. The results of the extended AIMS method are compared to recent experiments on CHD and we are able to successfully predict the change in product branching ratio as a function of the time delay between the excitation and control pulses. In conclusion, our recent improvements in the accuracy of the underlying electronic structure and the incorporation of an explicit treatment of light-matter interactions have made AIMS more powerful as a means of understanding photochemical reactions and designing control strategies.
Flow reactor study of oxidation of dimethyl ether and methane binary mixtures at intermediate temperatures [electronic resource]
Keywords: Mechanical Engineering

Oxygenated fuels, such as dimethyl ether (DME), are hydrocarbon fuels with oxygen incorporated in the fuel molecule. These fuels can be made from a variety of feedstocks, and a major advantage is their ability to reduce the formation of soot. This makes them particularly well suited for use in Diesel engines, in addition to power generation and utility fuel applications. The combustion chemistry of oxygenated fuels is not well understood, motivating the present study. As the simplest ether, DME oxidation chemistry is present in the oxidation of all larger oxygenates. In this work, the pre-ignition oxidation chemistry of DME was investigated under vitiated conditions in a variable pressure flow reactor (VPFR) facility at a temperature of 1200 K and pressures of 1-2 atm for six different DME and DME-methane mixtures. The study of DME-methane mixtures was motivated by the role of methane as a major reaction intermediate in DME oxidation. An existing reaction mechanism for DME oxidation was updated based on recent literature developments, and a one-dimensional mixing-reacting modeling approach was used to describe the reacting flow. Measured species time histories are in good agreement with the proposed model. Validation of the reaction mechanism against experimental data reported elsewhere in the literature shows reasonable agreement. The effects of equivalence ratio, pressure and methane addition, as well as weak points in the present description of DME oxidation kinetics are discussed.
Food vs Fuel: Can Biofuels Improve the Incomes of Rural Farmers in Nigeria?
Keywords:  Department of Economics
Stanford Department of Economics
biofuels
Nigeria
rural poverty
ethanol
rural economy
Thesis

In 2007, the Nigerian government made plans to develop a biofuel sector to reduce dependence on imported gasoline and improve the welfare of farmers. This paper investigates the effect of biofuel on rural farmers’ incomes. In Nigeria, 70% of the 150 million inhabitants are employed in the Agricultural sector; the majority are farmers, many of which are low skilled, low income and reside in underdeveloped areas. When biofuels are introduced in any society, farmers experience a trade off between increased revenue from biofuel sales and increased food expenditures as food prices rise, thus an increase in their income is not inevitable. The Nigerian government appears to be neglecting the consequences of this trade off; officials consistently highlight that the increased demand for biofuel will increase farmers incomes, while ignoring potential negative consequences. I run simulations to determine whether farmers can realize positive net income without jeopardizing ethanol production and my results indicate that this is possible. However, the result depends on how consumption demand and biofuel production interact with the price of biofuel.
Foodways and sociopolitics in the Wari Empire of Peru, A.D. 600 - 900 [electronic resource]
Keywords: Anthropology.

Food is at the intersection of nature and culture, being a requirement of human life but always being socially transformed and loaded with cultural meaning. This dissertation shows that it is possible to study ancient sociopolitical roles of animal food through the analysis of meal refuse in the archaeological record. Specifically, the project expands beyond the traditional focus in zooarchaeology on human subsistence by seeing food as a critical element in the creation, negotiation, and manipulation of human relationships. In particular, it shows how during the ancient Wari Empire of Peru (A.D. 600 -- 900) meat feasts and animal offerings played different roles in consolidating the empire both in the province and in the heartland. This study compares faunal remains from the Middle Horizon sites of Conchopata (Ayacucho), Cotocotuyoc (Cuzco), and Chokepukio (Cuzco). Expectations are developed to evaluate, analyze, and contrast quotidian trash, feasting remains, and animal offerings deposits. Feasts and offerings can be instruments of political action to pursue economic and political goals. They served a variety of roles in articulating the politics of the Wari Empire. During the early times of the Wari influence in provincial Cotocotuyoc, offerings of camelids served to acquire and maintain symbolic capital by the local leaders. At Conchopata, a site in the Wari heartland, feasts in public open patios served to legitimize institutionalized relations of power, while feasts related to mortuary activity in private rooms functioned to naturalize status differences across this socially stratified town. Although certainly not the only practice used to retain power differences, offerings and feasts involving camelid meat, chicha beverages, and special Wari ceramics were key to build and maintain a vast and complex polity such as the Wari Empire.
The Frankencamera [electronic resource] : building a programmable camera for computational photography
Keywords: Electrical Engineering

Digital cameras, both in traditional form factors and as parts of cell phones, have become ubiquitous over the last decade. But for the most part, they remain black boxes to the end-user, and cannot be reprogrammed or modified. This has become an obstacle to researchers in the new field of computational photography, who want to use the growing computing power of digital cameras to create images no traditional camera could produce. This dissertation presents the Frankencamera platform, a digital camera system designed for computational photography. The Frankencamera is a fully open, fully programmable digital camera, which can be easily modified to test out new research ideas. The Frankencamera architecture allows for per-frame control of the capture process, and accurate synchronization of all the components that make up the camera. Based on this architecture, this dissertation details two hardware platforms: the F2, a flexible custom-built camera; and the Nokia N900, a commercial smartphone. Both platforms can be easily programmed at a high level using the FCam API, written to embody the Frankencamera architecture. Finally, this dissertation presents several sample applications for the Frankencamera platform. Several of these applications could not have been developed for any existing camera platform, and the ease and speed at which they were written show that the Frankencamera platform is a compelling tool for computational photography.
Frequency stability of MEMS timing references with nonlinearities [electronic resource]
Keywords: Mechanical Engineering

The increasing demand for miniaturized electronic devices has heightened the need for tiny oscillators suitable to provide an accurate reference signal to electronics. In this sense, MEMS (microelectromechanical systems) resonator and oscillator have drawn a great deal of attention because they can be integrated onto silicon chips in a small form factor. This work describes the design, theory, and demonstration of MEMS resonator and oscillator with improved mid-term and short-term stability, especially when a resonator has nonlinearities. In the temperature stability study, electrostatic tuning was applied to Si−SiO2 composite resonators, which were made of single- crystal silicon with a silicon dioxide coating. The hybrid of these two temperature compensation methods achieved less than ± 2.5 parts per million frequency variation over a 90°C-wide temperature range, which is comparable with commercial quartz oscillators. In addition, the effect of nonlinearities of resonators on temperature sta- bility was analyzed: the temperature-dependent nonlinear effect model was theorized and verified with single-crystal silicon and Si−SiO2 composite resonator-based oscil- lators; a new feedback circuit architecture that improves temperature stability was then developed based on the model. In the phase-noise performance study, oscillator stability far above the critical vibration amplitude in the nonlinear regime was first demonstrated by using a novel variable-phase closed-loop setup. After that, more than twentyfold improvement in the power-handling and far-from-carrier phase-noise performances were achieved by operating an oscillator in the nonlinear regime. In addition, the nonlinear phase-noise model was verified by using the same closed-loop setup. In conjunction with the recently developed nonlinear motional impedance model, this phase-noise model enables further improvement in the phase-noise per- formance of MEMS resonator-based oscillators.
From single molecules to single cells [electronic resource] : mechanistic studies of myosin VI and cardiac myosin
Keywords: Biochemistry

Myosins are a superfamily of molecular motors that couple the chemical energy derived form adenosine triphosphate (ATP) hydrolysis to precise mechanical movements along the filamentous cytoskeletal protein actin. There exist more than 20 distinct classes of myosins within this superfamily, and their specific biophysical and biochemical properties likely allow them to function accordingly in vivo. My research has focused on understanding the how the structural and kinetic characteristics of a particular myosin, myosin VI, relate to its proposed trafficking and tethering functions. In the first section of this dissertation, I perform single molecule studies on the contribution of an unexpected structural domain in the myosin VI tail to the efficiency of processive stepping, especially against external forces. I additionally use optical trapping to examine the load-dependent kinetics of the motor in the second section, and propose that external load in vivo likely regulates myosin VI's dual functions as cellular transporter and cytoskeletal anchor. The specific cellular cargoes as well as oligomerization states of different myosins are defined by their tail domain, which is the most divergent structural region among myosin classes. Myosin VI, shown to be monomeric when purified in its native form, likely dimerizes upon cargo binding. As most in vitro work on myosin VI so far have been performed on a truncated, artificially forced myosin VI dimer, I discuss in the third section steps taken toward achieving a more native, biochemically reconstituted full-length myosin VI molecule bound to its bona fide cargo. Having gained a better understanding of the biophysics, kinetics and biochemistry of myosin at the single molecule level, I moved on to studying myosin function at the cellular level. In the forth section of this dissertation, I examine the effects of a familial hypertrophic cardiomyopathy (FHC) mutation, R403Q in cardiac myosin, on the contractile function of single mouse cardiomyocytes. I find that the functional effects of the R403Q mutation in the diseased FHC heart are manifest at the level of cardiomyocytes as well, suggesting that these effects are cell autonomous. From these studies, we can better appreciate the structural and kinetic properties of myosin VI that make it uniquely suited for its functions. This knowledge is also beneficial in aiding the understanding of other molecular motors that may employ similar mechanisms. We are now also aware of the cell-autonomy of particular dysfunctions exhibited by diseased R403Q FHC hearts, and are better poised to understand the complex disorder as a whole.