In April of 2002, the Swedish National Food Administration conducted a study where they found significant levels of the chemical acrylamide in fried foods such as potatoes and breakfast cereals [2]. Acrylamide forms at temperatures above 350o F (180o C) when the amino acid asparagine reacts with starch or sugars via Maillard reaction [6,7]. Although this chemical has been shown to be carcinogenic in rats [4], a study could not correlate any increase in risk of bowel, kidney or bladder cancer with the heavy intake of these fried foods containing acrylamide [10]. A possible explanation for this lack of correlation is that acrylamide is not present in sufficient quantities in these foods to cause appreciable toxicity or oncogenicity.

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## Scholarly Works (309 results)

In recent decades, advances in sequencing technologies have led to an explosion of discoveries in cancer. While observing large chromosomal abnormalities under the microscope has demonstrated genome rearrangements can drive cancer progression, more recent technologies enabled discoveries of mutations private to single cancer patients and uncovered a broader mutation diversity. My dissertation introduces novel connections between computational methods and sequencing techniques to solve open problems in genome rearrangement research. To improve non-invasive cancer monitoring, genome rearrangements can serve as the ideal cancer biomarker for accurately monitoring tumor burden and catching relapse earlier. My approach, AmBre (Amplication of Breakpoints), characterizes a target genome rearrangement's breakpoints for use as a quantitative marker in measuring amounts of tumor DNA. For a target genome rearrangement such as CDKN2A deletion, AmBre accounts for diverse deletion breakpoints and amplies any DNA harboring the CDKN2A deletion. Since only the tumor DNA is amplied, breakpoints can be detected in tissues or blood with little tumor DNA in high background of unmutated DNA. Furthermore, AmBre relies on sequencing technologies to read the enriched DNA. For parallel detection of breakpoints across numerous samples, a geometry based rearrangement caller was developed to handle long reads generated by Pacific Biosciences sequencing instruments. In addition, I will discuss the limitations of sequencing technologies in inferring mechanisms for rearranging genomes. Specifically, sequencing data alone cannot infer a complex cancer chromosome was formed by a single shattering and repair mechanism (chromothripsis) or a series of progressive rearrangements. Lastly, genomes are diploid and genome rearrangements can appear on one or both homologous chromosomes. Detecting genome rearrangements is challenging and inferring which chromosome is affected by the rearrangement is even more difficult. Having already called genome rearrangements such as deletions, I will show how proximity-ligation sequencing can be repurposed to assign deletions to a chromosome by phasing deletions with variants. In effect, my endeavors in genome rearrangement research show the field is constantly evolving with advances being made by complementing sequencing strategies and computational methods

We first consider communication complexity which arises in applications where a system needs to compute a function whose value depends on data distributed among several parties. As the total data is available to none of the parties, they need communicate with each other to accomplish their task. Communication complexity is the least amount of communication required to compute the function. The concept of communication complexity is relevant in many practical applications such as VLSI circuit design, sensor networks, etc., where one wants to minimize the amount of energy used by the various components of the system. Since the components consume energy to communicate it is important to minimize the total amount of communication by decreasing the number of signals exchanged by them. In this dissertation we consider a novel way of communication where silence is used to convey information. For this model we study the worst-case and average-case complexities of symmetric functions. For binary-input functions we determine the average- and worst-case complexities and describe the protocols achieving them. For functions of non-binary inputs we consider one-round communication, where each party is restricted to communicate in consecutive stages. We analyze the extra amount of communication required by one- over multi-round communication for symmetric and asymmetric functions. For the special case of ternary- input functions we provide close lower and upper bounds on the worst-case one-round complexity and describe protocols achieving them. Protocols achieving the average-case one- round complexity for ternary-input functions are also described. These protocols can be generalized to inputs of arbitrary size. We then consider universal compression, i.e. compression when the statistics of data are unknown, involving data drawn from sources with memory over large alphabets. It has long been know that data generated by sources over large alphabets, such as i.i.d. and Markov distributions incur unbounded extra number of bits over their entropy. We consider a recently introduced concept of compressing a string by separately conveying its pattern---the order in which the symbols appear. For example, the pattern of "abracadabra'' is 12314151231. It was shown that the patterns of i.i.d. strings can be losslessly compressed with diminishing per-symbol redundancy. We first consider the pattern redundancy of distributions with memory. We show that patterns of Markov sources cannot be compressed with diminishing redundancy. We next consider Hidden Markov distributions and establish close lower and upper bounds on the on the pattern redundancy of HMM sources, showing in particular that they can be compressed as well as when their source distribution is known

Abstract Development of the vasculature is a complex, dynamic process orchestrated by a balance of pro and anti-angiogenic signaling pathways. The same signaling pathways are mis-regulated and exploited during pathological angiogenesis in cancer, inflammation and cardiovascular diseases and contribute to disease progression. In the last decade, small non-coding RNA molecules termed microRNAs (miRs) have emerged as key regulators of several cellular processes including angiogenesis. It is becoming clear that miRs function in complex networks and regulate gene expression both at the mRNA and protein levels thereby altering cellular signaling responses to specific stimuli. In the vasculature, miRs can function either in a pro-angiogenic manner and potentiate angiogenesis or act as anti-angiogenic miRs by enhancing cell death and decreasing endothelial proliferation. This review aims to provide an update on how microRNAs regulate gene expression and illustrate miR function in the vasculature with a discussion of potential applications of miRs as anti-angiogenic therapeutics.

MOTIVATION: A fundamental problem in population genetics, which being also of importance to forensic science, is to compute the match probability (MP) that two individuals randomly chosen from a population have identical alleles at a collection of loci. At present, 11-13 unlinked autosomal microsatellite loci are typed for forensic use. In a finite population, the genealogical relationships of individuals can create statistical non-independence of alleles at unlinked loci. However, the so-called product rule, which is used in courts in the USA, computes the MP for multiple unlinked loci by assuming statistical independence, multiplying the one-locus MPs at those loci. Analytically testing the accuracy of the product rule for more than five loci has hitherto remained an open problem. RESULTS: In this article, we adopt a flexible graphical framework to compute multi-locus MPs analytically. We consider two standard models of random mating, namely the Wright-Fisher (WF) and Moran models. We succeed in computing haplotypic MPs for up to 10 loci in the WF model, and up to 13 loci in the Moran model. For a finite population and a large number of loci, we show that the MPs predicted by the product rule are highly sensitive to mutation rates in the range of interest, while the true MPs computed using our graphical framework are not. Furthermore, we show that the WF and Moran models may produce drastically different MPs for a finite population, and that this difference grows with the number of loci and mutation rates. Although the two models converge to the same coalescent or diffusion limit, in which the population size approaches infinity, we demonstrate that, when multiple loci are considered, the rate of convergence in the Moran model is significantly slower than that in the WF model. AVAILABILITY: A C++ implementation of the algorithms discussed in this article is available at http://www.cs.berkeley.edu/ approximately yss/software.html.

It is known that in various random matrix models, large perturbations create outlier eigenvalues which lie, asymptotically, in the complement of the support of the limiting spectral density. This thesis studies fluctuations of these outlier eigenvalues of iid matrices $X_n$ under bounded rank and bounded operator norm perturbations $A_n$, namely the fluctuations $\lam(\frac{X_n}{\sqrt{n}}+A_n)-\lam(A_n)$. The perturbations $A_n$ that we consider belong to a large class, where we allow for arbitrary Jordan types and almost minimal assumptions on the left and right eigenvectors. We obtain the joint convergence of the normalized asymptotic fluctuations of the outlier eigenvalues in this setting with a unified approach.

© 2016 IEEE. This paper expands our previous work on planar tunable capacitive coupling structures in substrate-integrated cavities using lumped components. We demonstrate both frequency and bandwidth tunable filters with adjustable transmission zeros (TZs). By the appropriate choice of the absolute and relative strength of magnetic and electric coupling coefficients, we demonstrate: 1) tunable bandwidth and the ability to maintain either a constant absolute bandwidth or a constant fractional bandwidth; 2) adjustable TZ location at a prescribed bandwidth; and 3) the ability to switch OFF the filter with high isolation. Filter design methodologies based on a dispersive coupling structure are presented using lumped circuit models, coupling matrix, and full-wave simulations. With this planar capacitive coupling, it is also convenient to realize cross-coupling in higher order filters to produce additional TZs for rejecting spurious resonances or interferes. Fabricated two-pole filters with one or two TZs and four-pole filters with three or four TZs validate the filter design. A two-pole filter with tunable center frequency and tunable bandwidth along with a four-pole filter with tunable center frequency and tunable TZs are also demonstrated.