Evolutionary synthesis of stochastic gene network models using feature-based search spaces

A feature-based fitness function is applied in a genetic programming system to synthesize stochastic gene regulatory network models whose behaviour is defined by a time course of protein expression levels. Typically, when targeting time series data, the fitness function is based on a sum-of-errors involving the values of the fluctuating signal. While this approach is successful in many instances, its performance can deteriorate in the presence of noise. This thesis explores a fitness measure determined from a set of statistical features characterizing the time series' sequence of values, rather than the actual values themselves. Through a series of experiments involving symbolic regression with added noise and gene regulatory network models based on the stochastic 'if-calculus, it is shown to successfully target oscillating and non-oscillating signals. This practical and versatile fitness function offers an alternate approach, worthy of consideration for use in algorithms that evaluate noisy or stochastic behaviour.

Search engine advertising in web retailing : an efficiency analysis

This study examines the efficiency of search engine advertising strategies employed by firms. The research setting is the online retailing industry, which is characterized by extensive use of Web technologies and high competition for market share and profitability. For Internet retailers, search engines are increasingly serving as an information gateway for many decision-making tasks. In particular, Search engine advertising (SEA) has opened a new marketing channel for retailers to attract new customers and improve their performance. In addition to natural (organic) search marketing strategies, search engine advertisers compete for top advertisement slots provided by search brokers such as Google and Yahoo! through keyword auctions. The rationale being that greater visibility on a search engine during a keyword search will capture customers' interest in a business and its product or service offerings. Search engines account for most online activities today. Compared with the slow growth of traditional marketing channels, online search volumes continue to grow at a steady rate. According to the Search Engine Marketing Professional Organization, spending on search engine marketing by North American firms in 2008 was estimated at $13.5 billion. Despite the significant role SEA plays in Web retailing, scholarly research on the topic is limited. Prior studies in SEA have focused on search engine auction mechanism design. In contrast, research on the business value of SEA has been limited by the lack of empirical data on search advertising practices. Recent advances in search and retail technologies have created datarich environments that enable new research opportunities at the interface of marketing and information technology. This research uses extensive data from Web retailing and Google-based search advertising and evaluates Web retailers' use of resources, search advertising techniques, and other relevant factors that contribute to business performance across different metrics. The methods used include Data Envelopment Analysis (DEA), data mining, and multivariate statistics. This research contributes to empirical research by analyzing several Web retail firms in different industry sectors and product categories. One of the key findings is that the dynamics of sponsored search advertising vary between multi-channel and Web-only retailers. While the key performance metrics for multi-channel retailers include measures such as online sales, conversion rate (CR), c1ick-through-rate (CTR), and impressions, the key performance metrics for Web-only retailers focus on organic and sponsored ad ranks. These results provide a useful contribution to our organizational level understanding of search engine advertising strategies, both for multi-channel and Web-only retailers. These results also contribute to current knowledge in technology-driven marketing strategies and provide managers with a better understanding of sponsored search advertising and its impact on various performance metrics in Web retailing.

The Salmon Algorithm - A New Population Based Search Metaheuristic

This thesis introduces the Salmon Algorithm, a search meta-heuristic which can be used for a variety of combinatorial optimization problems. This algorithm is loosely based on the path finding behaviour of salmon swimming upstream to spawn. There are a number of tunable parameters in the algorithm, so experiments were conducted to find the optimum parameter settings for different search spaces. The algorithm was tested on one instance of the Traveling Salesman Problem and found to have superior performance to an Ant Colony Algorithm and a Genetic Algorithm. It was then tested on three coding theory problems - optimal edit codes, optimal Hamming distance codes, and optimal covering codes. The algorithm produced improvements on the best known values for five of six of the test cases using edit codes. It matched the best known results on four out of seven of the Hamming codes as well as three out of three of the covering codes. The results suggest the Salmon Algorithm is competitive with established guided random search techniques, and may be superior in some search spaces.

Keyword Competition and Determinants of Ad Position in Sponsored Search Advertising

Given the significant growth of the Internet in recent years, marketers have been striving for new techniques and strategies to prosper in the online world. Statistically, search engines have been the most dominant channels of Internet marketing in recent years. However, the mechanics of advertising in such a market place has created a challenging environment for marketers to position their ads among their competitors. This study uses a unique cross-sectional dataset of the top 500 Internet retailers in North America and hierarchical multiple regression analysis to empirically investigate the effect of keyword competition on the relationship between ad position and its determinants in the sponsored search market. To this end, the study utilizes the literature in consumer search behavior, keyword auction mechanism design, and search advertising performance as the theoretical foundation. This study is the first of its kind to examine the sponsored search market characteristics in a cross-sectional setting where the level of keyword competition is explicitly captured in terms of the number of Internet retailers competing for similar keywords. Internet retailing provides an appropriate setting for this study given the high-stake battle for market share and intense competition for keywords in the sponsored search market place. The findings of this study indicate that bid values and ad relevancy metrics as well as their interaction affect the position of ads on the search engine result pages (SERPs). These results confirm some of the findings from previous studies that examined sponsored search advertising performance at a keyword level. Furthermore, the study finds that the position of ads for web-only retailers is dependent on bid values and ad relevancy metrics, whereas, multi-channel retailers are more reliant on their bid values. This difference between web-only and multi-channel retailers is also observed in the moderating effect of keyword competition on the relationships between ad position and its key determinants. Specifically, this study finds that keyword competition has significant moderating effects only for multi-channel retailers.

Generator Matrix Based Search for Extremal Self-Dual Binary Error-Correcting Codes

Self-dual doubly even linear binary error-correcting codes, often referred to as Type II codes, are codes closely related to many combinatorial structures such as 5-designs. Extremal codes are codes that have the largest possible minimum distance for a given length and dimension. The existence of an extremal (72,36,16) Type II code is still open. Previous results show that the automorphism group of a putative code C with the aforementioned properties has order 5 or dividing 24. In this work, we present a method and the results of an exhaustive search showing that such a code C cannot admit an automorphism group Z6. In addition, we present so far unpublished construction of the extended Golay code by P. Becker. We generalize the notion and provide example of another Type II code that can be obtained in this fashion. Consequently, we relate Becker's construction to the construction of binary Type II codes from codes over GF(2^r) via the Gray map.

In Search of Convergence: A Co-citation Analysis of Three Sport Management Journals

Responding to a series of articles in sport management literature calling for more diversity in terms of areas of interest or methods, this study warns against the danger of excessively fragmenting this field of research. The works of Kuhn (1962) and Pfeffer (1993) are taken as the basis of an argument that connects convergence with scientific strength. However, being aware of the large number of counterarguments directed at this line of reasoning, a new model of convergence, which focuses on clusters of research contributions with similar areas of interest, methods, and concepts, is proposed. The existence of these clusters is determined with the help of a bibliometric analysis of publications in three sport management journals. This examination determines that there are justified reasons to be concerned about the level of convergence in the field, pointing out to a reduced ability to create large clusters of contributions in similar areas of interest.

In search of the Holy Grail : how viable is John Rawls' purely political conception of justice?

Please consult the paper edition of this thesis to read. It is available on the 5th Floor of the Library at Call Number: Z 9999 P65 Y68 1995

Prostate Cancer and the Search for Novel Biomarkers

The primary objective of this research project was to identify prostate cancer (PCa) -specific biomarkers from urine. This was done using a multi-faceted approach that targeted (1) the genome (DNA); (2) the transcriptome (mRNA and miRNA); and (3) the proteome. Toward this end, urine samples were collected from ten healthy individuals, eight men with PCa and twelve men with enlarged, non-cancerous prostates or with Benign Prostatic Hyperplasia (BPH). Urine samples were also collected from the same patients (PCa and BPH) as part of a two-year follow-up. Initially urinary nucleic acids and proteins were assessed both qualitatively and quantitatively for characteristics either unique or common among the groups. Subsequently macromolecules were pooled within each group and assessed for either protein composition via LC-MS/MS or microRNA (miRNA) expression by microarray. A number of potential candidates including miRNAs were identified as being deregulated in either pooled PCa or BPH with respect to the healthy control group. Candidate biomarkers were then assessed among individual samples to validate their utility in diagnosing PCa and/or differentiating PCa from BPH. A number of potential targets including deregulation of miRNAs 1825 and 484, and mRNAs for Fibronectin and Tumor Protein 53 Inducible Nuclear Protein 2 (TP53INP2) appeared to be indicative of PCa. Furthermore, deregulation of miR-498 appeared to be indicative of BPH. The sensitivities and specificities associated with using deregulation in many of these targets to subsequently predict PCa or BPH were also determined. This research project has identified a number of potential targets, detectable in urine, which merit further investigation towards the accurate identification of PCa and its discrimination from BPH. The significance of this work is amplified by the non-invasive nature of the sample source from which these candidates were derived, urine. Many cancer biomarker discovery studies have tended to focus primarily on blood (plasma or serum) and/or tissue samples. This is one of the first PCa biomarker studies to focus exclusively on urine as a sample source.

The Search for Scholarly Teaching in Elementary Education

Elementary teachers are expected to prepare students to work efficiently with others, solve complex problems and self-regulate their own learning. Considering the importance of a solid educational foundation in the early years, students would benefit if elementary teachers engaged in scholarly teaching. The purpose of this study was to investigate Boyer’s (1990) four dimensions of scholarship, application, integration, teaching and discovery, to better understand if there is scholarly teaching in elementary education. Four professional teaching documents were analyzed using a hermeneutic orientation. A deductive analysis suggests that we do have scholarly teaching in elementary education, with strong evidence that elementary teachers are scholars of application and integration. An inductive analysis of latent and manifest content suggests that underlying humanistic values run deeply through elementary education driving current curricular, instructional and pedagogical practices.

In Search of Advice for Physicians in Entry-Level Medical Markets

We consider entry-level medical markets for physicians in the United Kingdom. These markets experienced failures which led to the adoption of centralized market mechanisms in the 1960's. However, different regions introduced different centralized mechanisms. We advise physicians who do not have detailed information about the rank-order lists submitted by the other participants. We demonstrate that in each of these markets in a low information environment it is not beneficial to reverse the true ranking of any two acceptable hospital positions. We further show that (i) in the Edinburgh 1967 market, ranking unacceptable matches as acceptable is not profitable for any participant and (ii) in any other British entry-level medical market, it is possible that only strategies which rank unacceptable positions as acceptable are optimal for a physician.

The Secession Reference: A Ruling in Search of a Nation

This short article will address the two following issues: the new vision of the Canadian constitutional order entertained by the Supreme Court in the Reference re Secession of Quebec (I) nd the impact of this new vision. upon the fate of Canada (II)

Genome wide search for genetic determinants of habitual alcohol, tobacco and coffee use, obesity-related traits, response to mental and physical stress and hemodynamic traits

Les habitudes de consommation de substances psychoactives, le stress, l’obésité et les traits cardiovasculaires associés seraient en partie reliés aux mêmes facteurs génétiques. Afin d’explorer cette hypothèse, nous avons effectué, chez 119 familles multi-générationnelles québécoises de la région du Saguenay-Lac-St-Jean, des études d’association et de liaison pangénomiques pour les composantes génétiques : de la consommation usuelle d’alcool, de tabac et de café, de la réponse au stress physique et psychologique, des traits anthropométriques reliés à l’obésité, ainsi que des mesures du rythme cardiaque (RC) et de la pression artérielle (PA). 58000 SNPs et 437 marqueurs microsatellites ont été utilisés et l’annotation fonctionnelle des gènes candidats identifiés a ensuite été réalisée. Nous avons détecté des corrélations phénotypiques significatives entre les substances psychoactives, le stress, l’obésité et les traits hémodynamiques. Par exemple, les consommateurs d’alcool et de tabac ont montré un RC significativement diminué en réponse au stress psychologique. De plus, les consommateurs de tabac avaient des PA plus basses que les non-consommateurs. Aussi, les hypertendus présentaient des RC et PA systoliques accrus en réponse au stress psychologique et un indice de masse corporelle (IMC) élevé, comparativement aux normotendus. D’autre part, l’utilisation de tabac augmenterait les taux corporels d’épinéphrine, et des niveaux élevés d’épinéphrine ont été associés à des IMC diminués. Ainsi, en accord avec les corrélations inter-phénotypiques, nous avons identifié plusieurs gènes associés/liés à la consommation de substances psychoactives, à la réponse au stress physique et psychologique, aux traits reliés à l’obésité et aux traits hémodynamiques incluant CAMK4, CNTN4, DLG2, DAG1, FHIT, GRID2, ITPR2, NOVA1, NRG3 et PRKCE. Ces gènes codent pour des protéines constituant un réseau d’interactions, impliquées dans la plasticité synaptique, et hautement exprimées dans le cerveau et ses tissus associés. De plus, l’analyse des sentiers de signalisation pour les gènes identifiés (P = 0,03) a révélé une induction de mécanismes de Potentialisation à Long Terme. Les variations des traits étudiés seraient en grande partie liées au sexe et au statut d’hypertension. Pour la consommation de tabac, nous avons noté que le degré et le sens des corrélations avec l’obésité, les traits hémodynamiques et le stress sont spécifiques au sexe et à la pression artérielle. Par exemple, si des variations ont été détectées entre les hommes fumeurs et non-fumeurs (anciens et jamais), aucune différence n’a été observée chez les femmes. Nous avons aussi identifié de nombreux traits reliés à l’obésité dont la corrélation avec la consommation de tabac apparaît essentiellement plus liée à des facteurs génétiques qu’au fait de fumer en lui-même. Pour le sexe et l’hypertension, des différences dans l’héritabilité de nombreux traits ont également été observées. En effet, des analyses génétiques sur des sous-groupes spécifiques ont révélé des gènes additionnels partageant des fonctions synaptiques : CAMK4, CNTN5, DNM3, KCNAB1 (spécifique à l’hypertension), CNTN4, DNM3, FHIT, ITPR1 and NRXN3 (spécifique au sexe). Ces gènes codent pour des protéines interagissant avec les protéines de gènes détectés dans l’analyse générale. De plus, pour les gènes des sous-groupes, les résultats des analyses des sentiers de signalisation et des profils d’expression des gènes ont montré des caractéristiques similaires à celles de l’analyse générale. La convergence substantielle entre les déterminants génétiques des substances psychoactives, du stress, de l’obésité et des traits hémodynamiques soutiennent la notion selon laquelle les variations génétiques des voies de plasticité synaptique constitueraient une interface commune avec les différences génétiques liées au sexe et à l’hypertension. Nous pensons, également, que la plasticité synaptique interviendrait dans de nombreux phénotypes complexes influencés par le mode de vie. En définitive, ces résultats indiquent que des approches basées sur des sous-groupes et des réseaux amélioreraient la compréhension de la nature polygénique des phénotypes complexes, et des processus moléculaires communs qui les définissent.

« Resolution Search » et problèmes d’optimisation discrète

Thèse réalisée en cotutelle avec l'Université d'Avignon.