Zugl.: Kassel, Univ., Diss., 2008 / Includes bibliographical references (p. 227-240).

Despite the steady growth of electronic commerce (e-commerce), Lesotho and SADC users are uncertain of how to securely sign e-communications practicably. This results in users' lack of confidence in the use of e-commerce. SADC and Lesotho regulatory bodies have developed legal instruments including model laws and bills in an attempt to regulate electronic signatures (e-signatures) in e-commerce to address this problem amongst others. However, it is unclear whether the approach adopted will ensure that the regulatory instruments effectively regulate e-signatures and consequently promote the growth of e-commerce and enhance the socio-economic development of the state. This study examines what the information and communications technology regulatory principles of functional equivalence and technology neutrality entail, their interpretation by the United Nations Commission on International Trade Law (UNCITRAL), and their appropriateness for effective regulation of e-signatures through conceptual analysis. In particular it examines the UNCITRAL Model Laws on e-commerce, UNCITRAL Model on e-signature and the United Nations Convention on the Use of Electronic Communications in International Contracts. The study describes the technical operation of different offline and online signatures in order to appreciate how e-signatures should be regulated. Through textual analysis, it examines whether regulatory instruments of Lesotho and SADC correctly apply the theories in a way that will render use of e-signatures practicable and their regulation effective. It also examines initiatives on regulation of e-signatures in South Africa, the United States of America and the European Union. The study reveals that the purpose of the signature formality is to promote certainty, prevent fraud and provide evidence of a contract despite the form of signature. Although not perfect, functional equivalence and technology neutrality principles render regulation of electronic signatures effective since rules that align with them promote equivalence of legal treatment between offline and online signatures. Consequently, the UNCITRAL's Convention reflects that ordinary e-signatures can meet purposes of the signature formality where appropriate if they observe its functional equivalence criteria. However, the reliability of such electronic signatures is a question of evidence as is the case in offline contracts. Thus, soft laws on electronic evidence must complement the e-signature rules to ensure equivalent legal treatment of signatures. The study reveals that the Lesotho instruments do not fully align with the regulatory principles whereas the SADC instrument closely aligns with them. To different extents, these instruments do not adequately address the problems of users and may inhibit the growth of e-commerce. It further found that the instruments erroneously exclude certain matters such as wills from e-signature application while they correctly exclude others such as negotiable instruments from e-signature application. Lastly it found that the UNCITRAL convention and the US instruments provide better models for effective regulation of e-signatures. By implementing amendments suggested by this study, Lesotho and SADC will address the challenges faced by e-commerce users and make the use of e-signatures feasible for all. Consequently, the instruments will effectively increase the growth of e-commerce and in turn enhance the development of socio economic growth of the SADC region.

Universiẗat, Diss., 2006--Saarbrücken.

Le cancer est une maladie du génome. La transformation tumorale résulte de l’acquisition de mutations somatiques via divers processus mutagènes opérant tout au long de la vie du patient. Les mécanismes à l’origine des mutations incluent les erreurs de réplication, les défauts de réparation de l’ADN, les modifications de base spontanées ou catalysées par des enzymes cellulaires, et l’exposition à des agents mutagènes endogènes (ROS) ou exogènes (tabac, UV…). Au cours de ma thèse, j’ai analysé des données de séquençage exome et génome complet de tumeurs hépatiques pour décortiquer les mécanismes à l’origine des mutations dans ces tumeurs, leur interaction avec les facteurs de risque, les processus cellulaires, les gènes drivers, et leur évolution au cours de la maladie. J’ai utilisé des méthodes statistiques existantes et dévoloppé des outils bioinformatiques innovants pour:- extraire les signatures de mutations et de réarrangements structuraux à l’aide de données de séquençage à haut débit- identifier les facteurs de risque et/ou les altérations génétiques à l’origine de chacune- prédire les mécanismes mutagènes à l’origine de chaque mutation somatique- explorer les corrélations entre la densité des mutations et les processus cellulaires comme la réplication et la transcription- reconstruire l’histoire clonale des tumeurs et dater l’apparition des signatures mutationnelles et des aberrations chromosomiques.Ces approches innovantes m’ont permis d’identifier 10 signatures mutationnelles: 5 signatures ubiquitaires à l’œuvre dans toutes les tumeurs hépatiques mais modulées par les facteurs de risque (sexe, alcool, tabac), et 5 signatures sporadiques opérant dans moins de 5% des tumeurs et associées à des étiologies connues (aflatoxine B1, acide aristolochique) ou restant à identifier. J’ai aussi mis en évidence 6 signatures de réarrangements structuraux, notamment des phénotypes duplicateurs et déléteurs, spécifiques de petits groupes de tumeurs. Chaque processus mutagène est modulé différemment par la réplication et la transcription. Les signatures liées à des molécules formant des adducts sur l’ADN (hydrocarbures polycycliques aromatiques, aflatoxine B1, acide aristolochique) sont nettement moins actives dans les gènes fortement exprimés suite à l’action du transcription-coupled repair, alors que la signature 16, liée à l’alcool, présente un motif unique de transcription-coupled damage. Une corrélation étonnante entre la densité des petites insertions et délétions (indels) et l’expression des gènes a été identifiée, conduisant à une accumulation considérable d’indels dans les gènes très forterment exprimés dans les cellules hépatiques. Enfin, l’histoire clonale des tumeurs hépatiques montre l’évolution des signatures mutationnelles au cours du temps et identifie l’accumulation de gains chromosomiques multiples comme un évènement tardif entraînant probablement une croissance de la tumeur jusqu’à une taille détactable en clinique. Ces résultats nous éclairent sur les mécanismes à l’origine des altérations génomiques dans l’histoire naturelle des cancers du foie. / Cancer is a disease of the genome. A normal cell goes rogue and is transformed into a cancerous cell due to acquired somatic mutations in its genome. The catalogue of these somatic mutations observed in the cancer genome is the outcome of multiple mutational processes that have been operative over the lifetime of a patient. These mutational processes that have occurred throughout the development of cancer may be infidelity of the DNA replication machinery, impaired DNA repair system, enzymatic modifications of DNA, or exposures to exogenous or endogenous mutagens. Each mutational process leaves a characteristic pattern – a “mutational signature” on the cancer genome. Various genomic features related to genome architecture, including DNA replication and transcription, modulate these mutational processes. During my PhD, I analyzed whole exome and whole genome sequencing data from liver tumors to understand the mutational processes remodeling these tumor genomes, their interaction with risk factors, cellular processes, and driver genes, and their evolution along the tumor histories. For that aim, I used existing statistical methods and I developed innovative computational tools to:- extract mutational and structural variant signatures from next-generation sequencing data- identify risk factors or genetic alterations underlying each process- predict the mutational process at the origin of each somatic mutation- explore correlations between mutation rates and cellular processes like replication and transcription- reconstruct the clonal history of a tumor and the timing of mutational processes and copy-number changes These innovative analytical strategies allowed me to identify 10 mutational signatures: 5 ubiquitous signatures operative in every liver cancer but modulated by risk factors (gender, alcohol, tobacco), and 5 sporadic signatures operative in <5% of HCC and associated with specific known (aflatoxin B1, aristolochic acid) or unknown mutational processes. I also identified 6 structural variant signatures, including striking duplicator or deletor phenotypes in rare tumors. Each mutational process showed a different relationship with replication and transcription. Signatures of bulky DNA adducts (polycyclic aromatic hydrocarbons, aflatoxin B1, aristolochic acid) strongly decreased in highly expressed genes due to transcription-coupled repair, whereas the alcohol-related signature 16 displayed a unique feature of transcription-coupled damage. A striking positive correlation between indel rate and gene expression was observed, leading to recurrent mutations in very highly expressed tissue-specific genes. Finally, reconstructing the clonal history of HCC revealed the evolution of mutational processes along tumor development and identified synchronous chromosome duplications as late events probably leading to fast tumor growth and clinical detection of the tumor. Together, these findings shed new light on the mechanisms generating DNA alterations along the natural history of liver cancers.

京都大学 / 0048 / 新制・課程博士 / 博士(情報学) / 甲第20511号 / 情博第639号 / 新制||情||111(附属図書館) / 京都大学大学院情報学研究科社会情報学専攻 / (主査)教授 石田 亨, 教授 中村 佳正, 教授 岡部 寿男, 岡本 龍明 / 学位規則第4条第1項該当 / Doctor of Informatics / Kyoto University / DFAM

Thesis (Ph.D.)--Boston University / PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you. / Similarities between patterns of differential gene expression can be used to establish connections between the experimental and biological conditions that give rise to them. The growing volume of gene expression data in repositories such as NCBI's Gene Expression Omnibus (GEO) presents an opportunity to identify such similarities on a large scale across a diverse collection of datasets. In this work, I have developed a pattern-based approach, named openSESAME, to identify datasets enriched in samples displaying coordinate differential expression of a query signature. Importantly, openSESAME performs this search without knowledge of the experimental groups in the datasets being searched, which allows it to identify perturbations of gene expression due to attributes that may not have been recorded. First, I demonstrated the utility of openSESAME using two gene expression signatures to query a set of more than 75,000 human expression profiles obtained from GEO. A query using a signature of estradiol treatment identified experiments in which estrogen signaling was perturbed and also discriminated between estrogen receptor-positive and -negative breast cancers. A second query using a signature of silencing of the transcription factor p63 (a key regulator of epidermal differentiation) identified datasets related to stratified squamous epithelia or epidermal diseases such as melanoma. Next, to improve the utility of openSESAME, I expanded the collection of profiles to include samples from mouse and rat, and automatically translated expression signatures for cross-species queries. Furthermore, I processed the sample annotation associated with these samples in GEO, extracting informative words and phrases and continuous (e.g., age) and categorical (e.g., disease state) variables. I have also recorded sample-specific dates and quality metrics to assess whether batch effects or outliers are affecting individual query results. Finally, I used openSESAME to query this repository with over 800 gene expression signatures from the Broad Institute's Molecular Signatures Database (MSigDB). I then used the scores of the association of each signature with each sample in the repository to build a network of the relatedness of these signatures to each other. This "constellation" of signatures can be used to determine the relationship of a query signature to other biological and experimental perturbations. / 2031-01-02

No description available.

by Chan Hing Che. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2000. / Includes bibliographical references (leaves 59-[61]). / Abstracts in English and Chinese. / Chapter 1 --- Introduction --- p.1 / Chapter 2 --- Background --- p.8 / Chapter 2.1 --- Abstract Algebra --- p.8 / Chapter 2.1.1 --- Group --- p.9 / Chapter 2.1.2 --- Ring --- p.10 / Chapter 2.1.3 --- Field --- p.11 / Chapter 2.1.4 --- Useful Theorems in Number Theory --- p.12 / Chapter 2.2 --- Discrete Logarithm --- p.13 / Chapter 2.3 --- Solving Discrete Logarithm --- p.14 / Chapter 2.3.1 --- Exhaustive Search --- p.14 / Chapter 2.3.2 --- Baby Step Giant Step --- p.15 / Chapter 2.3.3 --- Pollard's rho --- p.16 / Chapter 2.3.4 --- Pohlig-Hellman --- p.18 / Chapter 2.3.5 --- Index Calculus --- p.23 / Chapter 3 --- Forging ElGamal Signature --- p.26 / Chapter 3.1 --- ElGamal Signature Scheme --- p.26 / Chapter 3.2 --- ElGamal signature without hash function --- p.29 / Chapter 3.3 --- Security of ElGamal signature scheme --- p.32 / Chapter 3.4 --- Bleichenbacher's Attack --- p.34 / Chapter 3.4.1 --- Constructing trapdoor --- p.36 / Chapter 3.5 --- Extension to Bleichenbacher's attack --- p.37 / Chapter 3.5.1 --- Attack on variation 3 --- p.38 / Chapter 3.5.2 --- Attack on variation 5 --- p.39 / Chapter 3.5.3 --- Attack on variation 6 --- p.39 / Chapter 3.6 --- Digital Signature Standard(DSS) --- p.40 / Chapter 4 --- Quadratic Field Sieve --- p.47 / Chapter 4.1 --- Quadratic Field --- p.47 / Chapter 4.1.1 --- Integers of Quadratic Field --- p.48 / Chapter 4.1.2 --- Primes in Quadratic Field --- p.49 / Chapter 4.2 --- Number Field Sieve --- p.50 / Chapter 4.3 --- Solving Sparse Linear Equations Over Finite Fields --- p.53 / Chapter 4.3.1 --- Lanczos and conjugate gradient methods --- p.53 / Chapter 4.3.2 --- Structured Gaussian Elimination --- p.54 / Chapter 4.3.3 --- Wiedemann Algorithm --- p.55 / Chapter 5 --- Conclusion --- p.57 / Bibliography --- p.59

The Elliptic Curve Digital Signature Algorithm (ECDSA) is the elliptic curve analog of the Digital Signature Algorithm (DSA) and a federal government approved digital signature method. In this thesis work, software optimization techniques were applied to speed up the ECDSA for a particular NTST curve over GF(p). The Montgomery multiplication is used extensively in the ECDSA. By taking advantage of the algorithmic properties of the Montgomery multiplication method, special structure of the curve parameters and also applying certain fundamental and specific software optimization techniques, we have achieved an overall 26% speed improvement. Further enhancements were made by implementing the Montgomery multiplication in the ARM assembly language that resulted in 44% speed improvement. The optimizations discussed in this thesis could easily be adapted to other curves with or without changes. / Graduation date: 2002

The Elliptic Curve Digital Signature Algorithm (ECDSA) is one of the most popular algorithms to digitally sign streams or blocks of data. In this thesis we concentrate on porting and optimizing the ECDSA on the ARM7 processor for a particular NIST curve over GF(2[superscript m]). The selected curve is a binary curve of order 233. We show that for this particular curve, the ECDSA can be implemented significantly faster than the general case. The optimized algorithms have been implemented in C and the ARM assembly. The analysis and performance results indicate that by using certain machine and curve specific techniques, the ECDSA signature can be made up to 41% faster. / Graduation date: 2002