VictorJuiz/thesis huggingface dataset:
Change-point models on point processes and applications in genomics [electronic resource]
Keywords: Statistics

In this thesis, we present advancements in some change-point problems and their applications to genomic problems that arises from massively parallel sequencing. Change-point problems are concerned with abrupt changes in the generating distribution of a stochastic process evolving over time, space, or any ordered set. This thesis focuses on a number of change-point models and inference problems on point processes. We provide a change-point model and efficient algorithms to detect change-points in relative intensity of non-homogeneous Poisson processes. A model selection approach is constructed in the spirit of classical Baysian Information Criterion, but tailored to the irregularity of change-point problems. We review an array of inference problems surrounding the change-point construct; and propose a point-wise Bayesian credible interval for the parameter of the generating distribution for exponential family. An asymptotic result on the relationship between frequentist and Baysian change-point estimator is shown. We investigate how data characteristics, such as sample size, signal strength, and change-point location, influences the inference procedures through a simulation study. On the application front, modern massively parallel sequencing generates enormous and rich data with much systematic and random noise. We provide a survey of the sequencing technologies and some statistical challenges in various steps of sequencing data analysis. A recent application of sequencing in population and tumor genomics is the profiling of genome copy number and detection of copy number variations across sample. We demonstrate in this thesis that sequencing reads can be viewed naturally as a stochastic process along the genome. Copy number variants are modeled as abrupt jumps in the read intensity function. This modeling assumption resembles the biological reality of mutations that leads to copy number change. We demonstrate the application of change-point methods on actual sequencing data. Our method is found to compare favorably against a commonly used existing method in a spike-in simulation study. We lastly discuss a direction in which our change-point methods can be extended. It is often of interest to find recurrent copy number variants among a collection of biological samples. We review existing array-based multi-sample copy number profiling methods. Estimation and model selection procedures for the multi-sample sequencing setting are derived as extensions of our two-sample methods. A key challenge is the treatment of carrier status, which is whether a sample carries the recurrent variant of question. We present two sets of methods, one based on the assumption that all samples are carriers and the other based on a known carrier set. The statistical characteristics of the two methods are compared in a number of simulation scenarios.
Changing meanings of fat [electronic resource] : fat, obesity, epidemics, and America's children
Keywords: Education.

This dissertation falls within a tradition that investigates the making of health-related problems into social problems. Using literature reviews, document analysis, and qualitative and quantitative coding of medical publications from 1950 to 2010, I argue that both our increasingly individualistic culture and our collective faith in science fuel the current fear of obesity and lead to the expansion of the medical discourse on fat. In Part I, I review the main medical research paradigm on obesity, which argues that fat is bad for your health, before turning to the critique of this paradigm, and show how both sides of the debate use science to justify their stance. I then combine both views to identify which educational strategies are most likely to be implemented, and efficient. The importance of stigma in the health and well-being of obese people appears to be critical to this effort. Part II contributes a timeline for distinct but overlapping conceptualizations of bodily fat in the medical literature, and shows the massive and recent increase in medical interest in obesity. From merely an individual trait, fatness has become a medical problem (obesity), a social problem and an epidemic, and has culminated in recent years into a focus on children: the so-called epidemic of childhood obesity. This longitudinal approach to the medical literature at both the aggregate level (in the PubMed database) and in the most cited articles on obesity highlights the historical contingency of our cultural and medical obsession with fat, meanwhile identifying the role schools are expected to play.
Chaos and Noise in Dynamical Systems with Applications to Measurement
Keywords: chaos
noise
dynamical systems
Lyapunov exponent
LE
chaotic dynamics
nonlinear science
Thesis

One of the best quantifiers of chaos for a dynamical system is the maximal Lyapunov exponent (denoted as LE), which measures the exponential rate at which nearby trajectories in phase space diverge. However, when noise is introduced into the system, it becomes unclear as to how the LE is even defined, or whether it is defined at all. For instance, when considering two nearby trajectories in phase space with noise, there is an inherent ambiguity as to whether the same noise realization should be taken for both trajectories when calculating the rate at which they exponentially diverge, or whether each trajectory should have its own noise realization. The first part of this thesis extends the definition of the LE to systems with noise, and shows that the treatment is dependent on whether the noise is internal or external. In particular, we show that the LE is still a well-defined notion in systems with noise, in that different noise realizations of the same noise do not affect the rate at which nearby trajectories diverge.
In the second part of the thesis, we will outline how to apply the techniques in Part I to study systems subjected to measurement. Because the term in the Lagrangian of a measured system can be treated as Gaussian white noise, the machinery developed in the first part will play a crucial role. We will explicitly calculate how the new measurement terms in the master equation affect the dynamics of the system, thus developing an intuition for what physical quantities the additional terms correspond to. We will finally describe how we plan to study the evolution of chaos in classical and quantum systems, which will shed some light on the quantum-classical transition of chaos. Because this is an ongoing project, the second part will mainly emphasize on how to use the results derived in the first part in future work.
Characterization and optimization of silicon nanowires for biosensing and photovoltaic applications [electronic resource]
Keywords: Mechanical Engineering

One-dimensional nanowires, due to their excellent electrical, optical, and chemical properties, and large surface to volume ratios, offer the promise of producing revolutionary advances in many areas of technology. This study investigates two application examples of Si nanowires (SiNWs) in the areas of biosensing and solar cells, respectively. First, SiNWs have been highlighted as real-time, label-free, multiplexing, and femtomolar level accuracy biosensors. However, SiNWs are frequently placed on the bottom wall of a microfluidic channel in the sensing process where the convection velocity is almost zero such that the performance of SiNW biosensors is restrained by the analyte transport. Moreover, although the sensing is carried out in a microfluidic environment where the charged analytes coexist with charged ions of the electrolytic solution, efforts are lacking in understanding the effects of charged ions in the electrolytic solution on the sensing performance of SiNWs. Herein, this study focuses on the characterization and optimization of microfluidic sensing environment for SiNW biosensors in terms of the response time, sensitivity, and selectivity. Our numerical studies suggest that the diffusive analyte transport currently limits the response time of SiNW biosensors. Through microfluidic optimization, about 17.4 times faster response time and doubled sensitivity are achievable in SiNW biosensing. In addition, our experimental investigation shows that SiNWs can also detect ionic movements and distributions other than targeted species inside the microfluidic channel, which can affect the selectivity of SiNW biosensors and lead to false signals. Second, vertically aligned radial junction Si wire array solar cells can offer the opportunity to use lower grade material to produce efficient solar cells, due to the decoupling of light absorption and charge-carrier collection directions, and enhanced light trapping. Nevertheless, radial junction Si wire array solar cells still face critical challenges such as large junction and surface recombination losses of photogenerated charge carriers due to their inherent large surface area, which is one of the primary reasons responsible for the gap between reported experimental efficiencies (typically below 10%) and the estimated 17% theoretical efficiency. Therefore, we experimentally investigated junction and surface passivation strategies to effectively suppress large junction and surface recombinations of vertically aligned radial junction Si wire array solar cells. The inclusion of intrinsic polycrystalline Si layer between the p-n junction layers increases the efficiency by about 30% by reducing the dark current, and the top amorphous silicon nitride layer improves the efficiency by about 20% due to its combined surface passivation and antireflection effects. With the combination of both passivation layers, the maximum efficiency of our solar cells is improved from 7.2% to 11.0% under AM 1.5G illumination.
Characterization of lysine methylation in epigenetic regulation [electronic resource]
Keywords: Biology.

Chromatin is the physiological template for all DNA processing events in eukaryotic cells. Dynamic regulation of chromatin between open and silent states determines the accessibility of underlying DNA to transcription factors or other effector proteins and hence influences biological processes epigenetically without alterations of DNA sequences. The dynamics of chromatin structure regulates diverse cellular functions, and the disruption of chromatin homeostasis is thought to fundamentally impact on the development and progression of cancers and other human diseases. One principal mechanism for regulating chromatin structure involves the reversible covalent post-translational modification of histone proteins by chemical moieties such as acetyl-, methyl- and phospho- groups. In recent years, emerging evidence has suggested a key role of lysine methylation in the regulation of dynamic chromatin structure. Various histone methyl marks orchestrate proper programming of the genome, and aberrant methylation signaling is implicated in the initiation and the progression of various types of cancers. In this article, we described the development of a novel microarray-based high-throughput methodology, human epigenome microarray platform (HEMP), to discover rapidly and accurately methyl lysine-sensitive readers. A number of proteome-wide studies were performed utilizing HEMP as screening approach, and many novel interactions were identified since the establishment of this powerful technology. Utilizing HEMP as screening approach, we identified that the non-canonical Plant Homeodomain (PHD) finger of recombination activating gene 2 (RAG2) specifically recognizes histone H3 tri-methylated at lysine 4 (H3K4me3), revealing for the first time the molecular link between histone methylation and V(D)J recombination. In addition, this article described the characterization of a protein lysine methyltransferase, NSD2, demonstrating the molecular mechanisms by which overexpression of NSD2 contributes to multiple myeloma pathogenesis. This study established biological and pathologic modes of action for NSD2 and presented a novel mechanism by which disruption of chromatin homeostasis contributes to cancer.
Characterization of the novel IK complex and its role in the DNA damage response [electronic resource]
Keywords: Cancer Biology.

Defects in a plethora of cellular processes can lead to genomic instability in the cells, corresponding to activation of the DNA damage response (DDR). The scope of the diversity of these cellular processes is only beginning to be understood. We found that down-regulation of IK, inhibitor of K562, leads to activation of the DNA damage response and defects in gene expression. Previous works in B cells showed that the overexpression of IK abrogates the gamma-interferon induction of major histocompatibility (MHC) class II expression, suggesting that IK is a negative regulatior of MHC class II expression. Additionally, several large-scale mass spectrometry studies identified IK in pre-mRNA processing complexes along with other transcription cofactors. Through coimmunoprecipitation and mass-spectrometry, we identified two other interactors of IK that when down-regulated also lead to activation of the DNA damage response and defects in expression of many genes. Here we characterized this novel IK complex and its role in the DNA damage response. Components of the complex colocalize with RNA polymerase II foci, in agreement with a role of the complex in regulating gene expression. Interestingly, one of the components is phosphorylated by the central regulators of the DNA damage response, ATM/ATR, in response to a wide variety of DNA damaging agents, suggesting that the function of the complex is regulated by the DNA damage response and that this complex may play an important role in the DNA damage response. Altogether, the results presented highlight the integral relationship between processes involved in gene expression and genomic stability. These processes, such as transcription and pre-mRNA metabolism, occur on chromatin and pose a threat to genomic stability. However, they are necessary for life and for the expression of the gatekeepers of the genome. Hence, these processes must be tightly regulated to preserve genome integrity while at the same time allow gene expression to occur. Future studies will provide mechanistic details of the interface between these processes and genomic stability. An understanding of this interface may help elucidate potential mechanisms employed by precancerous lesions to become overt malignant tumors and perhaps lead to identification of novel therapeutic targets for blocking tumorigenesis.
Characterizing expert and novice differences in problem solving in heat transfer [electronic resource]
Keywords: Mechanical Engineering

This research investigates adaptive expertise through the analysis of written open-ended questions. The open-ended questions were given to experts (advanced graduate students) and to novices (undergraduates taking an introductory heat transfer course). Analysis of the experts' responses to these questions indicated that experts make qualifying statements in their responses, a newly identified characteristic of expertise. Analysis of the novices' responses indicates areas for future work in research and teaching. Additionally, the wording of the open-ended questions appears to be important: the responses to questions that asked participants to choose an outcome showed greater differences between the expert and novice participants than questions that asked participants to explain how or why something happens.
Chemical genetic screen for novel AMPKalpha2 substrates reveals a role for AMPK in regulating a network of proteins involved in mitosis, cytokinesis and cytoskeletal reorganization [electronic resource]
Keywords: Genetics

The ability to adapt to nutrient deprivation is a key characteristic of all organisms. The energy-sensing AMP-activated protein kinase (AMPK) is activated by low nutrient levels. Functions of AMPK, other than its role in cellular metabolism, are just beginning to emerge. For the study presented in this thesis, I used a chemical genetics screen to identify direct substrates of AMPK in human cells. I found that AMPK phosphorylates 28 novel substrates, several of which are involved in mitosis, cytokinesis, and cytoskeletal rearrangements. I identified the residues phosphorylated by AMPK in vivo in several substrates, including protein phosphatase 1 regulatory subunit 12C (PPP1R12C) and p21-activated protein kinase (PAK2). Activation or inhibition of AMPK activity is sufficient to disrupt the proper completion of cytokinesis and results in the formation of multinucleated cells. Furthermore, AMPK-induced phosphorylation is necessary for PPP1R12C interaction with 14-3-3[lowercase Zeta], phosphorylation of myosin regulatory light chain, and mitotic progression of human cells. These findings suggest that AMPK coordinates nutrient status with mitosis completion, which may be critical for the organism's response to low nutrients during development, or in adult stem and cancer cells.
The chemoselective catalytic oxidation of alcohols, diols, and polyols to ketones and hydroxyketones [electronic resource]
Keywords: Chemistry

The chemoselective oxidation of vicinal diols to [Alpha]-hydroxyketones is a challenge in organic syntheses because not only does the diol need to be oxidized selectively to a monocarbonyl compound, but diols are also prone to overoxidation and oxidative cleavage. Employing a cationic palladium complex, [(neocuproine)Pd(OAc)]2(OTf)2, we were able to demonstrate the selective oxidation of glycerol to dihydroxyacetone mediated by either benzoquinone or O2 as the terminal oxidant, an accomplishment that has little precedent in homogeneous catalysis. Mechanistic studies were undertaken to uncover the nature of this remarkable chemoselectivity. Kinetic and deuterium-labeling studies implicate reversible [Beta]-hydride elimination from isomeric Pd alkoxides and turnover-limiting displacement of the dihydroxyacetone product by benzoquinone. We successfully extended this methodology to other terminal 1,2-diols and symmetric vicinal 1,2-diols and have carried out aerobic oxidation of these substrates catalyzed by 1. Examination of the reactivity of 1 with conformationally-restricted 1,2-cyclohexanediols suggests that the diol must chelate to the Pd center for effective oxidation to the hydroxyketone product. In a separate project, we have also investigated the electrocatalytic reduction of dioxygen by several dinuclear copper complexes, an important reaction for fuel cell applications.
The Chinese must go [electronic resource] : immigration, deportation and violence in the 19th-century Pacific Northwest
Keywords: History.

In 1882, the Chinese Restriction Act barred Chinese laborers from immigrating to the United States, but implementing this policy proved impossible. This dissertation focuses primarily on the Pacific Northwest and examines the local attempt to enforce Chinese Restriction along the U.S.-Canadian border. When the federal government failed to stop illegal immigration along the border, white locals systematically expelled thousands of their Chinese neighbors. This study argues that the history of Chinese Exclusion cannot be understood without the history of anti-Chinese violence in the West and vice versa. The federal government's efforts to bar Chinese immigration starting with the Chinese Restriction Act of 1882 were fundamentally connected to a grassroots movement to expel Chinese laborers in the mid-1880s. Not only did this vigilante movement affect the lives of the local Chinese, it also transformed American immigration policy and set in motion negotiations between the United States, Canada, and China. By combining a detailed social history of racial violence with a transnational political history of immigration policy, this dissertation presents a new history of the anti-Chinese movement and the rise of Chinese Exclusion.
Chip multiprocessor generator [electronic resource] : automatic generation of custom and heterogeneous compute platforms
Keywords: Electrical Engineering

Recent changes in technology scaling have made power dissipation today's major performance limiter. As a result, designers struggle to meet performance requirements under stringent power budgets. At the same time, the traditional solution to power efficiency, application specific designs, has become prohibitively expensive due to increasing nonrecurring engineering (NRE) costs. Most concerning are the development costs for design, validation, and software for new systems. In this thesis, we argue that one can harness ideas of reconfigurable designs to build a design framework that can generate semi-custom chips --- a Chip Generator. A domain specific chip generator codifies the designer knowledge and design trade-offs into a template that can be used to create many different chips. Like reconfigurable designs, these systems fix the top level system architecture, amortizing software and validation and design costs, and enabling a rich system simulation environment for application developers. Meanwhile, below the top level, the developer can "program" the individual inner components of the architecture. Unlike reconfigurable chips, a generator "compiles" the program to create a customized chip. This compilation process occurs at elaboration time --- long before silicon is fabricated. The result is a framework that enables more customization of the generated chip at the architectural level, because additional components and logic can be added if the customization process requires it. At the same time this framework does not introduce inefficiency at the circuit level because unneeded circuit overheads are not taped out. Using Chip Generators, we argue, will enable design houses to design a wide family of chips using a cost structure similar to that of designing a single chip --- potentially saving tens of millions of dollars --- while enabling per-application customization and optimization.
Chirality distributions [electronic resource] : effects of carbon source and growth condition changes on the single-walled carbon nanotubes grown by CVD
Keywords: Chemistry

Single walled carbon nanotubes (SWNTs) are an interesting material with many possible applications including nanoelectronics, flexible electronics and sensors. One of the current challenges in the application of SWNTs is the fact that their synthesis procedures yield SWNTs with a distribution of chiralities, radii, and properties, instead of a homogenous material. It is also not currently possible to selectively fabricate specific distributions for different applications. In an effort to understand and control SWNT growth, we explored a range of growth conditions in the chemical vapor deposition (CVD) growth of SWNTs, including the use of liquid carbon sources instead of gaseous carbon sources. Some of the condition variables explored were carbon source composition, carbon source concentration, growth temperature, and carrier gas composition. Using a combination of Raman spectroscopy and SEM imaging, we demonstrate a clear dependence of changes in the distribution of SWNTs on that growth conditions varied. Of particular interest was the ratio of semiconducting SWNTs to metallic SWNTs, which was determined by correlating Raman spectroscopy data with device measurements. Distribution changes were seen using a range of carbon source molecules and can be used to tune as required for different applications. The greatest single chirality enrichment was seen at high temperatures using 2-butanol as the carbon source, while the greatest range of chiralities within a single growth was seen with ethanol as the carbon source. Correlating the SWNT distribution changes with the growth conditions varied also yielded insight into the growth mechanism of CVD grown SWNTs. This insight and a better understanding of the SWNT growth mechanism will lead to a further realization of SWNT application potentials.