VictorJuiz/thesis huggingface dataset:
Immobilization and characterization of oligonucleotides on functionalized substrates

The effective immobilization of DNA and RNA oligomers onto a substrate is a crucial component in the biosensor development process. This thesis presents the development of strategies for nucleic acid attachment and the subsequent surface characterization using X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), and radiochemical assay. A 31-mer of the viral messenger RNA transcript (TAR) was physisorbed onto a cation-activated mica surface and characterized in solution, using tapping-mode AFM (TM-AFM). The subsequent binding of a Tat protein-derived peptide to the TAR-RNA was observed, and comparison was made with the single-step physisorption of the TAR-Tat complex, formed a priori in solution. A volume distribution analysis showed a greater number of large particles in the sequentially formed complex, suggesting non-specific binding of peptide to the surface-bound RNA strand. Cationic (DMTAP) and zwitterionic (DMPC) lipid bilayers on mica were employed as alternate supports for adsorption of TAR and the TAR-Tat complex. Incorporation of TAR into cationic bilayer vesicles prior to bilayer fusion was found to be the optimal method of attaching TAR to the lipid surface. This allowed for the subsequent introduction of the Tat peptide, and demonstrated the capability of the method to study biomolecular interactions. The covalent attachment of oligonucleotides onto surfaces is advantageous as it can yield more stable and reproducible films. Mica and silicon were used as substrates for self-assembled monolayers (SAMs) of functionalized silanes which could be employed for oligonucleotide immobilization. A bifunctional silane, 1-(thiotrifluoroacetato)-11-(trichloro-silyl)-undecane (TTU), was synthesized and used as a one component system or in combination with spacer silanes to construct reactive surfaces. The silane films were characterized using contact angle, XPS and AFM measurements. Thiol-modified oligonucleotides (25-mers and 18-mers) were attached to the silanes directly, through disulfide bond formation and via homo-bifunctional linkers. Quantitation was performed using radiochemical analysis. The effects of linker on attachment density were determined. Solvent effects were studied and it was determined that dimethyl sulfoxide (DMSO) was an effective solvent for immobilization with optimal specificity. The hybridization efficiency of the covalently attached oligonucleotides was quantified with radiochemical methods, and was determined to be approximately 20%.
A systematic cell size screen in Saccharomyces cerevisiae and characterization of the Start inhibitor Whi5

Cell size homeostasis requires the precise coordination of growth and division. In the budding yeast Saccharomyces cerevisiae, these processes are coordinated by a critical cell size threshold, which is exerted in late G1 phase immediately prior to Start. At Start, cells irrevocably commit to a subsequent round of cell division. The construction of a complete set of sim;6000 yeast strains deleted for every open reading frame allowed us to systematically identify abnormally large (lge) or small (whi) mutants with potential roles in cell size homeostasis. This screen identified over 40 novel components involved in setting the critical cell size threshold at Start. In particular, we found that ribosome biogenesis plays a crucial role in cell size determination; this pathway appears to be evolutionarily conserved. From this screen I further characterized the novel Start repressor Whi5. Entry into S-phase is driven by two heterodimeric transcription factors, SBF and MBF; Whi5 represses S-phase entry by directly binding to SBF and MBF, inhibiting their activation. I found that Whi5 is phosphorylated by all forms of cyclin-Cdc28 activity and that phosphorylation of the Whi5-SBF complex in late G1 phase results in the elimination of Whi5 activity by two mechanisms: Whi5 dissociation from SBF/MBF, and subsequently, nuclear export of Whi5 by the exportin Msn5. Efficient phospho-dependent export of Whi5 by Msn5 depends upon a threshold level of phosphorylation. Upon the release of Whi5, the RNA PolII holoenzyme and general transcription factors are recruited to and activate SBF/MBF-regulated promoters. My data demonstrate that Whi5 links cyclin-Cdc28 activity to S-phase entry. Upon the elimination of Cdc28 activity in late anaphase, Whi5 is dephosphorylated by Cdc14, allowing for its import by the importin Kap121 and subsequent G1-phase repression of SBF/MBF. Whi5 is functionally analogous to members of the retinoblastoma tumor suppressor protein (pRB) family in mammalian cells. Like Whi5, pRB-family members repress E2F transcription factors until the reactivation of CDK activity, and phosphorylation of pRB-family members by cyclin-CDK complexes in late G1 phase eliminates pRB-mediated repression. Thus, the identification of Whi5 unifies G1-S control in eukaryotes.
Analysis of semantic classes: Toward non-factoid question answering

The task of question answering (QA) is to find the accurate and precise answer to a natural language question in some predefined text. Most existing QA systems handle fact-based questions that usually take named entities as the answers. In this thesis, we focus on a different type of QA---non-factoid QA (NFQA) to deal with more complex information needs. The goal of the present study is to propose approaches that tackle important problems in non-factoid QA. We proposed an approach using semantic class analysis as the organizing principle to answer non-factoid questions. This approach contains four major components: (1) Detecting semantic classes in questions and answer sources; (2) Identifying properties of semantic classes; (3) Question-answer matching: exploring properties of semantic classes to find relevant pieces of information; (4) Constructing answers by merging or synthesizing relevant information using relations between semantic classes. We investigated NFQA in the context of clinical question answering, and focused on three semantic classes that correspond to roles in the commonly accepted PICO format of describing clinical scenarios. The three classes are: the problem of the patient, the intervention used to treat the problem, and the clinical outcome. We built explicit connection between text summarization and identifying answer components in NFQA and constructed a summarization system that explores a supervised classification model to extract important sentences for answer construction. We investigated the role of clinical outcome and their polarity in this task. We identified an important property of semantic classes---their cores. We showed how cores of interventions, problems, and outcomes in a sentence can be extracted automatically by developing an approach exploring semi-supervised learning techniques. Another property that We analyzed is polarity, an inherent property of clinical outcomes. We developed a method using a supervised learning model to automatically detect polarity of clinical outcomes. We used rule-based approaches to identify clinical outcomes and relations between instances of interventions in sentences.
Designing constraint informed handheld-supported literacy innovations for struggling readers

An important area for research investigation involves the design of literacy innovations for struggling readers that harness both pedagogical and technological features of the learning environment, such that students are engaged in deep understanding of complex texts. This thesis describes a design research study that builds upon the highly effective cognitive strategy approach of reciprocal teaching and extends to other literacy activities in order to explore how handheld computers may support and augment struggling readers' exploration and understanding of difficult texts. Informed by a cognitive work analysis methodology, this design research study considers how human-technological interactions can be best designed to overcome a multitude of constraints found within complex educational settings that might otherwise impede the success of innovative approaches to literacy.

Keywords: Educational psychology
Cognitive psychology
Educational technology
An examination of response latency as an indicator of cognitive strategy in the beagle dog

For a decade our lab has been developing a canine model of human aging and cognition. To date response accuracy has provided the only measure of cognition. Few animal models have examined the utility of response latency (RL) as an indicator of cognitive impairment, despite numerous indications in the human literature that aging causes response slowing. In a series of experiments the RLs of young and aged dogs (Canis familiaris) were examined across a variety of cognitive tasks, including a spatial task (3-DNMP) and several discrimination and reversal tasks. The first experiment examined how acquisition of the 3-DNMP spatial task influenced RL. Robust age effects were found: Compared to their aged counterparts, young animals responded slower, made fewer errors and displayed RLs that were sensitive to increases in task difficulty. These RL differences reflected the utilization of age-specific response strategies. Young animals applied a cognitive strategy, while aged animals applied a stimulus response strategy. The second experiment examined the influence of extensive training on RL. The dogs were given spatial or non-spatial cognitive training prior to two consecutive 3-DNMP training periods. Initially, RL age difference were absent, however when the task difficulty level was raised significant RL age differences emerged. Aged animals continued to respond fast and inaccurate compared to young animals, which continued to reflect the age-specific response patterns in Experiment 1. Prior training also influenced performance; aged dogs with extensive spatial training outperformed aged dogs with non-cognitive training. The third experiment examined the stability of RL across several cognitive tasks: Strong correlations emerged indicating that fast responding animals responded fast across all of the cognitive tasks, but within an animal RL was longer on the more difficult tasks. Thus, individual factors as well as task specific factors contributed to the observed RLs. Finally, the fourth experiment examined the utility of RL as an indicator of therapeutic efficacy following long-term dietary antioxidant supplementation and enrichment. Antioxidant fed and enriched aged animals outperformed control animals by the third testing year: They displayed slower RLs and increased accuracy. Together, the results indicated that both treatments facilitated better performance in aged dogs.
Social science research in Canada and federal government information policy: the case of Statistics Canada

The effects of information policy on use and users of government information by focusing on social science researchers' use of information from Canada's central statistical agency, Statistics Canada. Two literature reviews cover social scientists' use of statistics, and government information policy. A multi-method approach is used to examine the effects of specific Canadian federal government restraint and cost-recovery initiatives of the mid-1980s which applied to government information. Statistics Canada's response to these initiatives is revealed using case study methodology. Bibliometric research objectively documents policy effects on social science researchers' use of statistics sources by examining a sample of 360 articles published from 1982 to 1993 in 21 Canadian social science research journals in Economics, Education, Geography, Political Science and Sociology. Examination of citations, tables, and text in the sampled articles reveals extent of use of statistics from Statistics Canada and other governmental and nongovernmental sources, both Canadian and foreign, over a period before and after policy implementation. A survey of authors of sampled articles supplements the bibliometric findings. Results of the case study show that Statistics Canada sought to recover costs and achieve greater revenues through higher prices and increasing electronic data dissemination. Bibliometric analysis shows there was no significant change over time in use of statistics from Statistics Canada or any other governmental or nongovernmental source. The use of Statistics Canada paper products declined significantly. The survey reveals that social science researchers are unhappy with the price increases, but have not changed the statistics sources they use as a result. The movement of statistical information into electronic formats is well received, though more respondents (in 1995) still used paper products than electronic ones. Possible explanations for these findings are proposed. Alternative effects of increased prices and format changes are suggested which might be examined in future research. Additionally, the implications of the research findings in relation to these social scientists and the agencies involved in information and management are discussed as potential topics for further research.

Keywords: Social sciences, Research
Social sciences, Canada
Information policy, Canada
Online information services, Canada
Information services, Canada
Statistical services
Political support among adolescents in post-communist hybrid regimes

The collapse of communism has triggered the rise of hybrid regimes falling somewhere between democracy and dictatorship. A critical issue in these societies is how to ensure citizen support for the new political order. Drawing upon Easton's work, this study distinguishes three objects of political support: the regime, incumbent authorities, and political community. Institutional theories argue that incumbent job performance is vital to political support in post-communist societies. Political socialization theory, in contrast, attaches the greatest importance to the role of socialization agents, including schools and the mass media. While scholars have tested these hypotheses using survey data on voting-age citizens, scant research concentrated on the political attitudes of adolescents in Eastern Europe. To address this oversight, this dissertation analyzes the effects of political socialization and incumbent performance on political support among 13-16 year old adolescents in Russia and Ukraine. A distinguishing characteristic of this cohort of citizens is that it has grown up without any firsthand experience with the communist regime. The empirical analysis is based on an original survey of 1,814 adolescents in spring-fall 2005. Several important findings emerge from the study. First, the results demonstrate how different agents of political socialization influence the magnitude of political support among adolescents. Specifically, the analysis finds that open classroom climate fosters democratic support, but weakens national pride among students. In addition, exposure to news media has a stronger impact on trust in political incumbents than trust in occupants of order-related institutions. Second, the results reveal that satisfaction with incumbent performance is positively associated with regrets about the demise of the Soviet Union among Russian adolescents, whereas the reverse trend is observed in Ukraine. Furthermore, the results unequivocally show that the east-west regional cleavage has a profound influence on the political attitudes of Ukrainian respondents. This dissertation contributes to comparative politics literature in several ways. First, the research expands our understanding of political socialization processes in non-democracies. Second, the study reveals that the effects of incumbent performance are contingent on the national context. Finally, the analysis illuminates how regional divisions influence political attitudes of adolescents in a divided society.
The role of Ptc1 and Ptc2 in epidermal development, homeostasis and tumorigenesis

Hedgehog signaling plays a crucial role in the development and patterning of various tissues in vertebrates and invertebrates. In vertebrates, Patched1 (Ptc1) and Patched2 (Ptc2) encode the receptors for the secreted signaling molecule, Shh. Ptc normally acts as a negative regulator of the Shh signaling pathway. When Shh is available to interact with Ptc, the pathway is activated resulting in the expression of target genes such as Ptc1 and Gli1. Interestingly, Ptc genes are expressed in a complimentary expression pattern in developing skin suggesting that they might possess distinct functions. Ptc1 has been shown to be a tumor suppressor but the role of Ptc1 in skin development has not been elucidated. Furthermore, the role of Ptc2 in development and tumorigenesis has not been determined. Ptc1, Ptc2 and Ptc1;Ptc2 mutants have been generated and analyzed to determine the unique and overlapping functions of Ptc1 and Ptc2. I have shown that Ptc2 is dispensable for embryogenesis, viability and reproduction, but required for adult epidermal homeostasis. Normal hair follicles could develop in the absence of Ptc1, but adults lacking normal Ptc1 function displayed epidermal hyperplasia and late-onset skin tumors. In Ptc1;Ptc2 double mutants epidermal development was greatly compromised. These mutants lacked hair follicles and a stratified epidermis, revealing the overlapping functions of Ptc genes. My data also unveiled that normal Ptc function is required in regulation of the epidermal progenitor cell population and uncovered c-myc as a novel target of Shh signaling in the adult epidermis. In conclusion, my study demonstrated the unique as well as overlapping roles of Ptc genes in epidermal development, homeostasis and tumorigenesis.
Development and validation of singlet oxygen luminescence-based photodynamic therapy dosimetry

Photodynamic therapy (PDT) is an emerging treatment for cancer and other conditions. PDT relies on the combined action of light, photosensitive drugs and molecular oxygen to generate reactive oxygen species, the most important of which is widely believed to be singlet oxygen (1O2). 1O2 rapidly oxidizes surrounding biomolecules in tissue, resulting in the photodynamic effect. 1O2 is known to undergo luminescence at 1270 run, a fact that is routinely verified in simple solutions. In biological tissues, the probability of 1O2 luminescence falls to approximately 10-8 due to the dense intracellular environment and drastically reduced 1O2 lifetime. As such, measurement of 1O2 luminescence in cells in vitro or in tissues in vivo has never been reliably demonstrated in the past. The design and experimental validation of a spatially-resolved 1O2 luminescence detection system (i.e. a 1O2 imager) is also presented, as well as a technique for determining the ground-state molecular oxygen concentration based on 1O2 kinetics. Future work includes animal tumor dose-response studies, evaluation of novel photosensitizing compounds, and design of a clinical dosimetry system. (Abstract shortened by UMI.)In this work, a study is presented in which 1O2 luminescence was measured for the first time during PDT of leukemia cells in vitro and normal rat tissue in vivo using a novel, near-infrared sensitive photomultiplier tube. Measurement of the kinetics of the photosensitizer and of 1O2 in these environments was also possible. Studies that demonstrate that this luminescence correlates strongly with PDT treatment response in cell suspensions and in the skin of normal mice sensitized with Amino-leveulinic acid induced protoporphyrin IX (ALA-PpIX) are also presented. These studies confirm the likely role of 1O2 in porphyrin based PDT, and are encouraging for the prospect of development of a clinical 1O2 luminescence PDT dosimetry system.
Anatomical phenotyping of the mouse with magnetic resonance imaging

Modern biomedical research depends heavily on mouse models of human disease and development. The prominent role of mice in the laboratory highlights the need for tools that assess their biological, physiological and anatomical status. These mouse characterization tasks are very similar to those required in assessment of human disease. Consequently, biomedical research stands to benefit from recent technological developments for clinical diagnosis. Adaptation of these techniques to the mouse scale enables direct comparison of human and mouse diseases as well as alternative and improved means of mouse characterization. This thesis therefore describes advances in high throughput MR imaging and analysis techniques. Specific emphasis is placed on developments for anatomical phenotyping. The thesis introduces mouse MRI by reviewing recent progress from the literature, including the description of high throughput multiple mouse MRI (MMMRI). Next, a MMMRI acquisition protocol is presented that was designed for anatomical visualization with T2-weighting. It is shown to produce high resolution images of the brain simultaneously in four live mice. Subsequently, artifacts were observed in some MMMRI images and determined to result from a peculiar gradient hardware imperfection. The nature and elimination of these artifacts is demonstrated. The final development in the thesis is an automated analysis methodology that improves anatomical analysis efficiency. This simplification was achieved computationally by pooling data and assessing anatomical differences between groups of mice. Together, these developments enable simpler and more powerful studies of mouse biology and its relation to human diseases. Medical imaging has revolutionized diagnosis and staging of many human ailments and promises similar reforms in mouse studies. Imaging permits non-invasive and repeatable assessment for longitudinal experiments and three-dimensional visualization of anatomical features. Magnetic resonance imaging (MRI) is one well-established modality known largely for its excellent soft tissue contrast. In order to take advantage of this feature in mouse research, certain modifications to standard clinical practices are warranted. Most notably, the clinical philosophy of individualized patient treatment must be altered so that large groups of mice can be accommodated in each study. Systematic acquisition of images and efficient analysis of data are essential to making mouse MRI studies practical.
Between cultural rights of minorities and human rights of women: state obligations in the context of delegated jurisdiction

What kind of obligations does international human rights law impose upon states when they consider accommodating minority groups' customary or religious legal traditions by granting them a degree of autonomous jurisdiction? In particular, what to do with traditions that discriminate against minority women? One way to approach this question is to examine state obligations under the ICCPR and the CEDAW in relation to the prohibition of discrimination against women in general and in the context of cultural rights of minorities in particular. The central finding of this thesis is that both conventions impose severe restrictions on the kind of legal traditions that states can legitimately accommodate. Furthermore, the ICCPR and the CEDAW require that state parties take positive measures to combat in-group discrimination. Accordingly, international human rights law should be taken into account in designing and modifying legal-institutional solutions in the field of multicultural accommodation arrangements involving delegated jurisdiction.

Keywords: Minorities, Legal status, laws, etc
Women's rights
Sex discrimination against women, Law and legislation