Knowledge discovery using multiple sources of biological data

The primary aim of this dissertation is to develop data mining tools for knowledge discovery in biomedical data when multiple (homogeneous or heterogeneous) sources of data are available. The central hypothesis is that, when information from multiple sources of data are used appropriately and effectively, knowledge discovery can be better achieved than what is possible from only a single source. ^ Recent advances in high-throughput technology have enabled biomedical researchers to generate large volumes of diverse types of data on a genome-wide scale. These data include DNA sequences, gene expression measurements, and much more; they provide the motivation for building analysis tools to elucidate the modular organization of the cell. The challenges include efficiently and accurately extracting information from the multiple data sources; representing the information effectively, developing analytical tools, and interpreting the results in the context of the domain. ^ The first part considers the application of feature-level integration to design classifiers that discriminate between soil types. The machine learning tools, SVM and KNN, were used to successfully distinguish between several soil samples. ^ The second part considers clustering using multiple heterogeneous data sources. The resulting Multi-Source Clustering (MSC) algorithm was shown to have a better performance than clustering methods that use only a single data source or a simple feature-level integration of heterogeneous data sources. ^ The third part proposes a new approach to effectively incorporate incomplete data into clustering analysis. Adapted from K-means algorithm, the Generalized Constrained Clustering (GCC) algorithm makes use of incomplete data in the form of constraints to perform exploratory analysis. Novel approaches for extracting constraints were proposed. For sufficiently large constraint sets, the GCC algorithm outperformed the MSC algorithm. ^ The last part considers the problem of providing a theme-specific environment for mining multi-source biomedical data. The database called PlasmoTFBM, focusing on gene regulation of Plasmodium falciparum, contains diverse information and has a simple interface to allow biologists to explore the data. It provided a framework for comparing different analytical tools for predicting regulatory elements and for designing useful data mining tools. ^ The conclusion is that the experiments reported in this dissertation strongly support the central hypothesis.^

``This is your brain on drugs'': The public policy of anti -drug programming. An exploratory analysis of media and other sources of drug information for adolescents

In the 1980s, government agencies sought to utilize research on drug use prevention to design media campaigns. Enlisting the assistance of the national media, several campaigns were designed and initiated to bring anti-drug use messages to adolescents in the form of public service advertising. This research explores the sources of information selected by adolescents in grades 7 through 12 and how the selection of media and other sources of information relate to drug use behavior and attitudes and perceptions related to risk/harm and disapproval of friends' drug-using activities.^ Data collected from 1989 to 1992 in the Miami Coalition School Survey provided a random selection of secondary school studies. The responses of these students were analyzed using multivariate statistical techniques.^ Although many of the students selected media as the source for most of their information on the effects of drugs on the people who use them, the selection of media was found to be positively related to alcohol use and negatively related to marijuana use. The selection of friends, brothers, or sisters was a statistically significant source for adolescents who smoke cigarettes, use alcohol or marijuana.^ The results indicate that the anti-drug use messages received by students may be canceled out by media messages perceived to advocate substance use and that a more persuasive source of information for adolescents may be friends and siblings. As federal reports suggest that the economic costs of drug abuse will reach an estimated $150 billion by 1997 if current trends continue, prevention policy that addresses the glamorization of substance use remains a national priority. Additionally, programs that advocate prevention within the peer cluster must be supported, as peers are an influential source for both inspiring and possibly preventing drug use behavior. ^

Resistance Performances: (Re)constructing Spaces of Resistance and Contention in the 2010-2011 University of Puerto Rico Student Movement

On the night of April 20, 2010, a group of students from the University of Puerto Rico (UPR), Río Piedras campus, met to organize an indefinite strike that quickly broadened into a defense of accessible public higher education of excellence as a fundamental right and not a privilege. Although the history of student activism in the UPR can be traced back to the early 1900s, the 2010-2011 strike will be remembered for the student activists’ use of new media technologies as resources that rapidly prompted and aided the numerous protests. This activist research entailed a critical ethnography and a critical discourse analysis (CDA) of traditional and alternative media coverage and treatment during the 2010 -2011 UPR student strike. I examined the use of the 2010-2011 UPR student activists’ resistance performances in constructing local, corporeal, and virtual spaces of resistance and contention during their movement. In particular, I analyzed the different tactics and strategies of resistance or repertoire of collective actions that student activists used (e.g. new media technologies) to frame their collective identities via alternative news media’s (re)presentation of the strike, while juxtaposing the university administration’s counter-resistance performances in counter-framing the student activists’ collective identity via traditional news media representations of the strike. I illustrated how both traditional and alternative media (re)presentations of student activism developed, maintained, and/or modified students activists’ collective identities. As such, the UPR student activism’s success should not be measured by the sum of demands granted, but by the sense of community achieved and the establishment of networks that continue to create resistance and change. These networks add to the debate surrounding Internet activism and its impact on student activism. Ultimately, the results of this study highlight the important role student movements have had in challenging different types of government policies and raising awareness of the importance of an accessible public higher education of excellence.

Sources of nutrition information for persons living in Trinidad and Tobago

Health consumers worldwide obtain nutrition information from various sources; however, the sources Trinidadians and Tobagonians accessed were unclear. This cross-sectional, descriptive study ascertained from which sources Trinidadians and Tobagonians obtained nutrition information. Participants (n = 845) were surveyed with questions regarding demographics and nutrition information sources. Nearly 100% agreed nutrition information was important. Persons 18-64 years old mainly accessed print media (p<0.01) and ≥ 65years old predominantly accessed the non-print media. Significantly more tertiary educated people, ≥ 35 years old, retrieved information from print media (p=0.001), health care professionals (p=0.001), food labels (p=0.006), and non-print media (p=0.03) when compared to those < 35 years with similar education. Tertiary educated people (67%), selected the Internet when compared to those with without tertiary education (33%) (p<0.001). Knowing the nutrition information sources accessed, dietitians will be able to provide consistent, accurate, age specific nutrition information and promote healthy eating among Trinidadians and Tobagonians.

The World Heritage vs. Local Comnuty : identifying the sources of conflicts

The presented work is an essay rather than a scientific dissertation. The author wants to put an impact on the source of conflicts regarding the complex subject of heritage management and conservation in comparison with the local needs and the given context. The paper attempts to show the role of local communities and their cooperation with authorities as well as the effects of such cooperation. The area of research comprises the problems arising in the field of implementing external rules on the local field, challenges appearing regarding the needs of local communities and the efforts of official authorities trying to implement the principles of the conventions. The problems arise when local communities display the lack of understanding and do not share the common idea of heritage conservation. This is caused mainly by the decreasing possibilities of comfortable life. The author tries to identify the main and wrongful approaches as ‘Gone with the Wind’, ‘The Prince and The Pauper’, ‘Heart of Darkness’ or ‘Scarlet letter’. The focus will be put to explain what the areas are where a mutual misunderstanding arise and why all parts to the problem present different points of view. What creates a value? Is it a heritage object or maybe the other values need a stronger protection? When the general duty and the need to protect the heritage is regarded as a controversy and when it is considered as a value within a given community? The international public interest in heritage protection is often regarded as an attempt to diminish the sovereign power of the community and provokes severe controversies and tensions. The major problem envisaged today seems to be the massive and increasing urbanisation and the destruction of the vestiges still existing of traditional cultures, when we consider century urban post-industrial districts of Upper Silesia in Poland, the medieval cities in Western Europe, the traditional nomad Masaya villages in Kenya or the remains of vanished cultures in various regions of Asia. The preferred platform of cooperation between the parts of the conflict includes divergent needs, beliefs and practices of communities and the possible fields of reconciling the abovementioned. Chosen examples of the best practices considering mutual cooperation will be underlined.

Traduction et validation transculturelle du questionnaire Sources of Sport-Confidence : questionnaire auprès d'une population canadienne-française

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Resistance and symbiosis : Québec discourses of resistance in the context of postcolonial theory

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Traduction et validation transculturelle du questionnaire Sources of Sport-Confidence : questionnaire auprès d'une population canadienne-française

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Resistance and symbiosis : Québec discourses of resistance in the context of postcolonial theory

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Understanding Sources of Knowledge for Coaches of Athletes with Intellectual Disabilities

Background: Recent research has investigated development of coaching knowledge; however, less research has investigated the development of coaches who coach athletes with intellectual disabilities. The purpose of this study was to understand how coaches of athletes with intellectual disabilities gain their knowledge. Method Forty-five Special Olympics Canada coaches participated in structured telephone interviews investigating actual and ideal sources of coaching knowledge. Coaching knowledge was categorized across the dimensions of competition, organization and training. Results Coaches primarily learned by doing and by consulting with coaching peers. Information about ideal sources of coaching knowledge demonstrates that coaches would value structured coaching courses, learning from mentors and from administrative support, in addition to learning on their own and from peers. Discussion Results suggest that a broader approach to education should be incorporated into coaching athletes with intellectual disabilities. Recommendations for achieving such goals are provided.

FLIP: a targetable mediator of resistance to radiation in non-small cell lung cancer

Resistance to radiotherapy due to insufficient cancer cell death is a significant cause of treatment failure in non-small cell lung cancer (NSCLC). The endogenous caspase-8 inhibitor, FLIP, is a critical regulator of cell death that is frequently overexpressed in NSCLC and is an established inhibitor of apoptotic cell death induced via the extrinsic death receptor pathway. Apoptosis induced by ionizing radiation (IR) has been considered to be mediated predominantly via the intrinsic apoptotic pathway; however, we found that IR-induced apoptosis was significantly attenuated in NSCLC cells when caspase-8 was depleted using RNA interference (RNAi), suggesting involvement of the extrinsic apoptosis pathway. Moreover, overexpression of wild-type FLIP, but not a mutant form that cannot bind the critical death receptor adaptor protein FADD, also attenuated IR-induced apoptosis, confirming the importance of the extrinsic apoptotic pathway as a determinant of response to IR in NSCLC. Importantly, when FLIP protein levels were down-regulated by RNAi, IR-induced cell death was significantly enhanced. The clinically relevant histone deacetylase (HDAC) inhibitors vorinostat and entinostat were subsequently found to sensitize a subset of NSCLC cell lines to IR in a manner that was dependent on their ability to suppress FLIP expression and promote activation of caspase-8. Entinostat also enhanced the anti-tumor activity of IR in vivo. Therefore, FLIP down-regulation induced by HDAC inhibitors is a potential clinical strategy to radio-sensitize NSCLC and thereby improve response to radiotherapy. Overall, this study provides the first evidence that pharmacological inhibition of FLIP may improve response of NCSLC to IR.

Neoliberal Capitalism, Social Reproduction Crisis, Gender Implications and Forms of Resistance: The case of Greece

Neoliberal capitalism and its accompanied austerity measures has had a profound effect on social reproduction throughout Europe. Social reproduction, ie, the process that makes it possible for individuals, families, and society to reproduce itself – is in crisis. The concept of social reproduction utilized in this presentation is framed within the feminist and Marxist tradition. Historically, social reproduction was met through both waged and unwaged work with women playing a predominant role either as waged, predominantly public sector, workers (social workers, teachers, carers, nurses, etc) or as unpaid workers (unpaid carers: mothers, wives, etc.) but now both forms of work are destabilized and undermined. Thus, the crisis in social reproduction. Within this crisis women’s unequal position is further undermined but at the same time progressive women and men are organizing to present alternatives forms of social reproduction. This presentation by utilizing the case of Greece will first outline the neoliberal processes that have caused the crisis in social reproduction. Second, it will present the consequences of social reproduction by highlighting the gender implications. Third, it will discuss the reorganization of social reproduction which is taking place outside the logic of capitalist society and is manifested through the creation of solidarity health clinics and pharmacies, communal kitchens, creation of various forms of bartering etc. This presentation will argue that these forms present glimpses of another society , a society based on principles of solidarity and cooperation. A society worth fighting for. And finally the presentation will conclude by discussing at which level can this crisis be resolved and the role of the social work profession.

Monsters Take to the Streets! Monstrous Street-Art as Pedagogy of Resistance to Post-Olympic Regeneration in Hackney Wick?

This chapter explores geographies of gentrification and resistance in relation to the monstrous through the lens of street-art in post-Olympic London. It takes as a geographic case study Hackney Wick, which has for a long time been a bastion of alternative and creative living due to cheap rents in large, ex-industrial warehouse spaces. The artistic sociality of the area is imbued within its landscape, as prolific street artists have adorned ex-industrial warehouses and canal-side walls with graffiti and murals. Since the announcement of the 2012 Olympic Games, the area has been a site of intense political and aesthetic contestation. The post-Olympic legacy means that the area has been earmarked for redevelopment, with current residents facing the possibility of joining thousands already displaced by the games. The anxiety of dispossession is reflected by monstrous characters and sinister disembodied teeth, eyes and fingers embedded within the landscape, painted by local artists. Using geographically sensitive mobile and visual methodology to document the landscape and artwork, the chapter analyses and interprets the monstrous themes using a range of theorists including Mikhail Bakhtin, Georges Bataille and Nick Land. I argue that monstrous street-art lays visible claim to public territory for aesthetic purposes at odds with the visions of redevelopers and the needs of capital. Whilst street-art and graffiti do not fit easily within frameworks of organized political resistance or collective social movements, they operate as a kind of epistemological transgression that triggers transformative affects in the viewer. This creates conditions for pedagogies of resistance to gentrification by expressing and mobilizing political affects such as anger and anxiety, raising awareness of geographical politics, and encouraging the viewer to question the status quo of the built environment.

Status of resistance to phosphine in insect pests of stored products in Vietnam

In response to numerous reports of failures to control insect pests of stored products with phosphine in Vietnam, a national survey for resistance to this key fumigant was undertaken in 2009–2011. Data from a more limited survey undertaken by the authors in 2002 in northern Vietnam are also presented. Samples collected in the 2002 survey (Sitophilus oryzae, n=8; Tribolium castaneum, n=8) were tested using a full dose- response assay, while for the 2009–11 survey, F1 generations were tested for resistance with two discriminating dosages of phosphine to detect frequency of weak and strong resistance phenotypes. Compared with a susceptible reference strain, in 2002, resistance to phosphine was indicated in six T. castaneum samples but only two of S. oryzae. Resistance factor, however, did not exceed 2.8-fold in T. castaneum and 1.7 in S. oryzae indicating relatively low frequency and weak expression of resistance. In 2009–11 survey, 176 samples were collected from a range of food and feed storages along the supply chain and from all major regions of Vietnam (125 sites). Rhyzopertha dominica and S. oryzae were the most common species found infesting stored commodities. Resistance was detected at high frequency in all the species. Weak and strong resistance phenotype frequencies were, respectively: Cryptolestes ferrugineus (37 and 58%, n=19), R. dominica (1.5 and 97%, n=65), S. oryzae (34 and 59%, n=82) and T. castaneum (70 and 30%, n=10). Strong resistance phenotype was detected in all the major regions and all parts of the supply chain but frequency was the highest in central storages and animal feed establishments. The increase in frequency and strength of resistance to phosphine in the eight years between the two surveys has been rapid and dramatic. The survey demonstrates the threat of resistance to grain protection in Vietnam and highlights the need for training of fumigators, and the development and adoption of phosphine resistance management tactics nationally.

Investigations into the mechanism of orotidine 5'-monophosphate decarboxylase: Sources of substrate destabilization and transition state stabilization

Orotidine 5′-monophosphate decarboxylase (OMPDC) achieves a rarely paralleled rate acceleration, yet the catalytic basis prompting this enhancement have yet to be fully elucidated. To accomplish decarboxylation, OMPDC must overcome the high energy barrier due to the localized anionic charge of the intermediate. Mechanistic studies employing enzyme mutagenesis and product or intermediate analogues were used to investigate possible transition state stabilization by a carbene resonance structure. Viability of the carbene structure depends upon a key hydrogen bond between O4 of the substrate and the amide backbone of a conserved serine or threonine. Substitution of the conserved residue with Pro resulted in a kcat/KM of 1 M-1s-1; deletion of the FUMP O4 resulted in a product analogue that does not undergo H6 exchange or inhibit decarboxylation. Hence, indirect evidence reveals the O4-backbone interaction plays an important role for binding and catalysis. OMPDC likely has honed multiple mechanisms to attain its remarkable catalysis. The successful crystallizations of OMPDC a decade ago sparked hypotheses that structure and sequence conserved residues induced productive strain on the substrate-enzyme complex. Here, we demonstrate a new source of stress: a hydrophobic pocket adjacent to the OMP carboxylate that exhibits kinetic parameters characteristic of substrate destabilization. Substitution of these residues with hydrophilic side-chains, by providing hydrogen-bonding partners, decreased kcat by 10 to 10^4–fold. The same substitutions display very little change in the rate of product H6 exchange, supporting that this hydrophobic pocket affects the substrate-enzyme complex before the transition state. We also provide evidence that hydrophilic residues can insert water molecules into the pocket with detrimental effects to catalysis.