Somatic Copy Number Alterations (CNAs) are common events in human cancers. Identifying CNAs and Significant Copy number Aberrations (SCAs) in cancer genomes is a critical task in searching for cancer-associated genes. Advanced genome profiling technologies, such as SNP array technology, facilitate copy number study at a genome-wide scale with high resolution. However, due to normal tissue contamination, the observed intensity signals are actually the mixture of copy number signals contributed from both tumor and normal cells. This genetic confounding factor would significantly affect the subsequent copy number analyses. In order to accurately identify significant aberrations in contaminated cancer genome, we develop a Java AISAIC package (Accurate Identification of Significant Aberrations in Cancer) that incorporates recent novel algorithms in the literature, BACOM (Bayesian Analysis of Copy number Mixtures) and SAIC (Significant Aberrations in Cancer). Specifically, BACOM is used to estimate the normal tissue contamination fraction and recover the "true" copy number profiles. And SAIC is used to detect SCAs using large recovered tumor samples. Considering the popularity of modern multi-core computers and clusters, we adopt concurrent computing using Java Fork/Join API to speed up the analysis. We evaluate the performance of the AISAIC package in both empirical family-wise type I error rate and detection power on a large number of simulation data, and get promising results. Finally, we use AISAIC to analyze real cancer data from TCGA portal and detect many SCAs that not only cover majority of reported cancer-associated genes, but also some novel genome regions that may worth further study. / Master of Science

Within the home environment there exits a host of digital color imaging (DCI) system configurations. The combination of devices and software at the consumer's desktop with devices and services at a remote location (e.g., Print at Kodak), creates a complex interaction of device, contextual, and observer characteristics. In particular, the cathode-ray tube (CRT) display has the potential to influence consumers' perceptions of image quality and their subsequent image manipulation activities. Depending on the inherent color bias and apparent contrast of the CRT, extensive image manipulation may occur, significantly altering the digital values of the image. Output generated by a remote printer will reflect any image manipulation undertaken by the consumer. If manipulation was extensive, what the consumer receives from a remote printer will appear quite different from the softcopy version and thus, may be deemed unacceptable. This research was designed to address the softcopy-hardcopy matching issues that arise from the home DCI system configuration just described. The primary study examined how the CRT display influenced perceived color quality of photographs generated at two points in a DCI system; on-screen photographs (softcopy) and photographic quality prints (hardcopy). CRT gamma, color temperature, and excitation purity were manipulated using an orthogonal, blocked, central composite design. Twenty-two Eastman Kodak Company employees viewed 6 photographs under each of the 15 CRT conditions. Participants rated the color quality of each softcopy photograph, then were given an opportunity to edit color balance, brightness, and contrast for each photograph. The edited photos were printed and rated once again for color quality and acceptability. Results indicated that monitor calibration influenced perceived softcopy color quality, softcopy editing behavior, and subsequent perceived hardcopy color quality. Perception of softcopy color quality ratings was determined predominantly by the CRT gamma level. Participants responded to CRT color balance differences through their editing behavior. In some cases, edits were large enough to significantly and negatively impact perceived hardcopy color quality. Gamma in particular, was the most significant predictor of hardcopy color quality ratings and rejection rates. Additional differences were observed between first- and third-party photographs. Results from this research may be applied to the development of monitor calibration tools, scene balancing algorithms, and software, for the purpose of accommodating consumer image manipulation behavior, in the context of the home DCI system presented herein. / Ph. D.

No description available.

Acute myeloid leukaemia (“AML”) is a clonal disease characterised by increased, uncontrolled abnormal white blood cells and the accumulation of leukaemia immature cells in the bone marrow and bloodstream. Chromosomal rearrangements have been detected in almost half of AML cases. It has been proven that the chromosomal rearrangements constitute a marker for the diagnosis and prognosis of AML and have therapeutic consequences. The discovery of these rearrangements has led to a new World Health Organization (“WHO”) classification system. However, small regions of cryptic chromosomal rearrangements have been identified among these cases. Such cryptic rearrangements can be explained by the identification of small regions which cannot be found by conventional chromosome banding techniques. Moreover, approximately 50% of AML cases have been found with normal karyotypes. The improvement of cytogenetic techniques, including fluorescence in situ hybridization (“FISH”) and single nucleotide polymorphism (“SNP”) platforms, have allowed the detection of small rearranged regions (such as copy number changes) both in normal and abnormal karyotype AML. This study identifies: (i) cryptic chromosomal translocations in leukaemia cells of AML patients; (ii) DNA copy number changes in patients with known chromosomal translocations; and (iii) the proliferating state of leukemic cells harbouring chromosomal abnormalities within a series of patients. In the initial study, the FISH technique was performed on 7 AML patient samples to validate a novel three colour probe for the detection of t(7; 12). The results demonstrated that the new three-colour FISH approach used in this study has enabled the detection of a cryptic t(7;12) translocation as part of a complex rearrangement in one patient previously been described as having t(7;16) and ETV6-HLXB9 fusion transcript at the molecular level. To date there are only two cases of a cryptic t(7; 12) translocation reported in the literature. Additionally, the new three-colour FISH approach also enabled identification of t(7; 12) in a new seven year-old AML patient (the first case of childhood leukaemia with an onset after infancy to be found positive for t(7; 12)). In the second study the FISH technique was used to validate three colour probe sets for the detection of 7(q22-q31) and 7(q22-q36.1) regions on several myeloid cell lines. The results indicate that the probes found chromosome 7 rearrangements in myeloid cell lines with complex rearrangements. The three colour probe sets enabled detection of a new rearrangement in the k562 cell line, described as a duplication of 7q36 region, followed by intrachromosomal insertion of long arm material into the short arm of chromosome 7. The intrachromosomal insertion identified in k562 cell line is an uncommon form of chromosomal rearrangement in myeloid leukaemia which has not been previously reported. In the third study, the Illumina BeadArray approach was used to assess copy number alterations (“CNAs”) and copy number loss of hertrozygosity (“CN-LOH”) regions in 22 AML patients samples with inv(16)(p13;q22) and t(8;21)(q22;q22) rearrangements. In order to distinguish between true CNAs and false-positive findings as well as to verify whether CNAs are present in the same clone harbouring inv (16), FISH was used on fixed chromosome and cell suspensions from the same patients. The results showed a low number of copy number losses and copy number gains in 17 (77.27%) out of 22 cases, with an average of 1.86 CNAs per case as well as copy neutral-LOH with an average of 6.7% per patient. Furthermore, interphase FISH was carried out on four cases showing a 7q36.1 deletion, 4q35.1 deletion, 16.13.11 deletion and 8q24.21-q24.3 gain identified by array. The FISH results confirmed CNAs in most cases while CNA was not confirmed in one patient. Moreover, the FISH data analysis showed that the CNAs were found in both cells without inv (16) and cells harbouring the inv (16) rearrangement. In the final study, indirect immunofluorescence (IF) was used to determine the ki67 staining patterns in 8 stimulated and unstimulated peripheral blood samples and k562 cell lines. The results showed a high percentage of ki67 positive staining in the stimulated samples in comparison with unstimulated samples, which showed a low percentage of ki67 positive staining. In addition, a high percentage of proliferating cells were detected in the k562 cell line. ImmunoFISH was performed on five different patient samples and leukaemia cell lines using specific probes in the regions of interest to detect the chromosomal abnormalities and using the ki67 antibody to assess the proliferation state of the cells. The results showed that the proliferation state of the cells carrying chromosomal abnormalities in two patients was higher than the proliferation state of the cells carrying abnormalities in three patients; in other words, most of the cells carrying abnormalities were proliferating in two cases and non-proliferating in three cases.

International Telemetering Conference Proceedings / October 17-20, 1994 / Town & Country Hotel and Conference Center, San Diego, California / In this paper, by using computer simulations, the interference of channel data in the SDM telemetry system is investigated, the performance of the copy demultiplexing is examined, and finally the selection rule of Walsh functions is recommended.

International Telemetering Conference Proceedings / October 25-28, 1999 / Riviera Hotel and Convention Center, Las Vegas, Nevada / The mathematics basis that can form a telemetry system is orthogonal functions. Three kinds of orthogonal functions are used up to now. First of them is sine and cosine function family. The second one is block pulse function family. The third one is Walsh function family. Their corresponding telemetry systems are FDM, TDM and SDM (CDM). Later we introduced an orthogonal function which is called Bridge function. The corresponding system is named telemetry system based on Bridge function. Now a new kind of orthogonal function, Generalized Bridge function, has been found. It can be applied to practical multiplex of information transmission. In this paper the author provides the design concept, block diagram, operational principle and technical realization of telemetry system based on Generalized Bridge function.

Psiguria Arn. is a small genus of Neotropical vines in the Cucurbitaceae that grows in both wet and dry tropical forests from southern Mexico to Paraguay, and on Caribbean islands. The genus is estimated to be very young with natural history characteristics that have contributed to confusing species circumscriptions. The unique relationship of plants in the group with their butterfly pollinators makes Psiguria an interesting and important genus in tropical ecosystems. Both molecular and morphological approaches were used to investigate the monophyly of Psiguria, to elucidate the number of species in the genus, to discover sister relationships, and to identify characteristics for delineating species. Toward that end, an intensive screening of 141 primer combinations in search of phylogenetically informative low-copy nuclear markers was conducted along with a molecular phylogenetic analysis and a complete taxonomic revision of Psiguria. From the screening study, three potentially phylogenetically informative low-copy nuclear markers were discovered for Psiguria, 11 were found to be potentially useful in rosids, and 32 in other angiosperms. DNA sequences for eight chloroplast intergenic spacers (ndhF-rpL32, ndhC-trnV, rps16-trnQ, trnS-trnG, psbZ-trnM, psbM-trnD, rpoB-trnC, and psbE-petL), ITS, and the nuclear serine/threonine phosphatase intron were obtained for 70 samples of Psiguria plus 14 outgroups. Phylogenetic analyses support the monophyly of Psiguria and a sister relationship between P. umbrosa and P. warscewiczii. In the final chapter, two reviews on the genus are presented – one encapsulating the nomenclatural history, and one summarizing 35 years of ecological and natural history studies. In addition, morphological characters were databased, descriptions were written, and maps of geographic distribution were produced for all species. Considering both molecular and morphological data, six species of Psiguria are defined. To distinguish those species missing identifiable morphological characters, a set of DNA barcodes was developed. At least four chloroplast regions are required to differentiate species (ndhC-trnV, rps16- trnQ, rpoB-trnC, and ndhF-rpL32). Because of the absence of many morphological characters, two taxonomic keys are presented – one using male flowers, and the other using the set of DNA barcodes along with consistent leaf characteristics and geographic distribution. / text

We address the problem of the DNA sequences developing a "dynamical" method based on the assumption that the statistical properties of DNA paths are determined by the joint action of two processes, one deterministic, with long-range correlations, and the other random and delta correlated. The generator of the deterministic evolution is a nonlinear map, belonging to a class of maps recently tailored to mimic the processes of weak chaos responsible for the birth of anomalous diffusion. It is assumed that the deterministic process corresponds to unknown biological rules which determine the DNA path, whereas the noise mimics the influence of an infinite-dimensional environment on the biological process under study. We prove that the resulting diffusion process, if the effect of the random process is neglected, is an a-stable Levy process with 1 < a < 2. We also show that, if the diffusion process is determined by the joint action of the deterministic and the random process, the correlation effects of the "deterministic dynamics" are cancelled on the short-range scale, but show up in the long-range one. We denote our prescription to generate statistical sequences as the Copying Mistake Map (CMM). We carry out our analysis of several DNA sequences, and of their CMM realizations, with a variety of techniques, and we especially focus on a method of regression to equilibrium, which we call the Onsager Analysis. With these techniques we establish the statistical equivalence of the real DNA sequences with their CMM realizations. We show that long-range correlations are present in exons as well as in introns, but are difficult to detect, since the exon "dynamics" is shown to be determined by theentaglement of three distinct and independent CMM's. Finally we study the validity of the stationary assumption in DNA sequences and we discuss a biological model for the short-range random process based on a folding mechanism of the nucleic acid in the cell nucleus.

Thesis advisor: Gabor T. Marth / Structural variations (SVs), like single nucleotide polymorphisms (SNPs) and short insertion-deletion polymorphisms (INDELs), are a ubiquitous feature of genomic sequences and are major contributors to human genetic diversity and disease. Due to technical difficulties, i.e. the high data-acquisition cost and/or low detection resolution of previous genome-scanning technologies, this source of genetic variation has not been well studied until the completion of the Human Genome Project and the emergence of next-generation sequencing (NGS) technologies. The assembly of the human genome and economical high-throughput sequencing technologies enable the development of numerous new SV detection algorithms with unprecedented accuracy, sensitivity and precision. Although a number of SV detection programs have been developed for various SV types, such as copy number variations, deletions, tandem duplications, inversions and translocations, some types of SVs, e.g. copy number variations (CNVs) in capture sequencing data and mobile element insertions (MEIs) have undergone limited study. This is a result of the lack of suitable statistical models and computational approaches, e.g. efficient mapping method to handle multiple aligned reads from mobile element (ME) sequences. The focus of my dissertation was to identify and characterize CNVs in capture sequencing data and MEI from large-scale whole-genome sequencing data. This was achieved by building sophisticated statistical models and developing efficient algorithms and analysis methods for NGS data. In Chapter 2, I present a novel algorithm that uses the read depth (RD) signal to detect CNVs in deep-coverage exon capture sequencing data that are originally designed for SNPs discovery. We were one of the early pioneers to tackle this problem. In Chapter 3, I present a fast, convenient and memory-efficient program, Tangram, that integrates read-pair (RP) and split-read (SR) signals to detect and genotype MEI events. Based on the results from both simulated and experimental data, Tangram has superior sensitivity, specificity, breakpoint resolution and genotyping accuracy, when compared to other recently published MEI detection methods. Lastly, Chapter 4 summarizes my work for SV detection in human genomes during my PhD study and describes the future direction of genetic variant researches. / Thesis (PhD) — Boston College, 2013. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Biology.

Copy Number Variants (CNVs) are defined as DNA segments of 1kb or more in length and present in a variable number of copies in the human genome. It has been recently shown that many human genetic diseases including organ malformations are caused by CNVs in a patient's genome. However, the genetic and molecular basis for Renal Agenesis (RA), which is a medical condition whereby unilateral or bilateral fetal kidneys fail to develop, has not yet been extended to CNV studies. By using array-based Comparative Genomic Hybridization, we are analyzing DNA from patients who have RA in order to identify CNVs that are causative for RA; genes within the CNVs will then be assessed for their potential involvement in RA by altering their dose in Xenopus embryos.