VictorJuiz/thesis huggingface dataset:
Investigation of molecular and cellular basis of leukemia mediated by tyrosine kinase chromosomal translocations

Leukemia is a malignancy of hematopoietic progenitors with poorly known etiology. Approximately 50% of all leukemias are associated with chromosomal translocations, which fuse two different genes, generating novel fusion proteins. Chromosomal translocations often involve transcription factors and tyrosine kinases. Bcr-Abl, the cause of chronic myeloid leukemia, is the best known example of chromosomal translocations, and represents a paradigm of tyrosine kinase fusions. Several other tyrosine kinase fusions have been described in various forms of leukemia including Tel-Jak2 and Tel-PDGFbetaR. Characterization of the mechanism of their actions and their downstream substrates has greatly enhanced our understanding of the molecular basis of leukemia. In the last part of the study, we sought to understand the molecular basis of the disease specificity downstream of three leukemogenic translocations: Bcr-Abl, Tel-PDGFbetaR and Tel-Jak2. Despite the differences in the fusion partners involved in each fusion, the three fusions are similar in the mechanism of ligand-independent activation and the substrates activated in the cytoplasm. Initially, we investigated the role of the Dok protein family downstream of a normal hematopoietic cytokine receptor, the Interleukin 3 receptor (IL-3R) and the Tel-Jak2 translocation. The Dok proteins represent adaptor proteins that can recruit a distinct set of signalling molecules. As such, they can modulate signals transduced from various cytokine receptors and growth-factor receptors, and effect changes in cell growth, adhesion and migration. Our study demonstrates that Dok-1, Dok-2 and Dok-3 are tyrosine-phosphorylated by the IL-3R, and can modulate cell migration and MAP kinases. On the other hand, expression of the Tel-Jak2 translocation results in constitutive phosphorylation of all three Dok proteins. Downstream of Tel-Jak2, Dok-3 can regulate the cytokine-independent growth and migration of cells. Importantly, we determined that the four carboxy terminal tyrosines of Dok-3 are critical in mediating the effects of Dok-3. We identified genes that are uniquely regulated by Bcr-Abl, Tel-PDGFbetaR and Tel-Jak2 as well as a subset of genes commonly regulated by all three proteins. Many of these genes represent novel substrates of these fusions, and given their involvement in regulating cell growth, migration and differentiation, further characterization of these genes would help us delineate the molecular basis of leukemogenesis.
Differential effect of 5-azacytidine treatment on cardiomyogenic differentiation and reparative capacity of varying bone marrow cell subpopulations

Objective. We evaluated the efficacy of bone marrow cells (BMC) versus mononuclear cells (MNC), each with or without 5-azacytidine (5-aza), on angiogenesis and myogenesis to determine whether 5-aza has differential effects on the ability to repair infarcted hearts. Methods. Female Lewis rats underwent coronary ligation 3 weeks before cell transplantation with 3 x 106 male donor BMC, MNC, BMC treated with 5-aza (5aza-BMC), 5aza-MNC or medium (Control). Two and 4 weeks after transplantation, we evaluated transplanted cell survival, vascular densities, regional perfusion and left ventricular (LV) function. Results. Cell survival decreased from 2 to 4 weeks, and was greatest in 5aza-BMC. Vascular densities and perfusion in the scar and border zone increased from 2 to 4 weeks, and was greatest in 5aza-BMC. Both 2 and 4 weeks after transplantation, LV ejection fraction (LVEF) was highest in 5aza-BMC. Conclusions. Pretreatment with 5-aza enhanced the survival, angiogenic and myogenic effects of BMC, but not of MNC.
A proposed fuzzy system modeling algorithm with an application in pharmacokinetic modeling

In this thesis, a new fuzzy system modeling algorithm is proposed to address some of the limitations of existing approaches. The new algorithm differs from existing ones in its approach to (i) input membership assignment; a new n-dimensional rule structure is proposed which does not assume an a priori shape for the fuzzy clusters and does not break the natural ties among the data vector; (ii) significant input determination; a fuzzy supervised learning approach is developed which assigns a significance degree to the input variables unlike the existing algorithms that classifies an input variable as either significant or not; (iii) degree of firing determination and inference; a k-NN based approach is developed since the existing algorithms are not applicable to the new n-dimensional antecedent structure proposed; (iv) fuzzy output clustering; problems with the well-known and widely referred FCM [3] algorithm are revealed and a new clustering algorithm is proposed. Furthermore, a Type 2 fuzzy system modeling, which is, based on interval-valued membership degrees rather than singleton membership degrees (as is with Type 1 modeling) is provided. The proposed algorithms (Type 1 and Type 2) are evaluated in terms of predictive performance and determination of the significance degrees in two different data sets and compared with other algorithms that exist in the literature. The first data set is a two-input single output nonlinear function prediction, which is used as benchmark in the literature. The second data set is from the clinical pharmacology field, namely pharmacokinetic modeling of lithium. The proposed algorithms are compared with different pharmacokinetic modeling approaches from the literature. The comparisons demonstrated that the proposed algorithms could be successfully applied in pharmacokinetic modeling. Overall results showed that the proposed fuzzy system modeling could effectively approximate nonlinear functions with simple fuzzy if-then rules, which does not assume a priori structure for the model. This is compatible with other recent research that demonstrates that fuzzy system modeling algorithms are universal approximaters. A theoretical result, which shows that the fuzzy containment property does not hold for continuous nonarchemedean De Morgan triples, is also included in the thesis.
"Vos qui concupiscitis" or "Ludus Filiorum Israel" :\ba critical edition

The poem which begins “Vos qui concupiscitis” is found in ten manuscripts written between the mid 14th century and the 16th century in England, Eastern and Central Europe. There is evidence to indicate that the poem was originally written in England in the 14th century and there is further evidence to indicate the poem can trace its origins to Cambridge. Corpus Christi Guild accounts in Cambridge record a Ludus Filiorum Israel in 1352–3 as well as a procession with masks in 1350–1 and there are indications that the poem fits this description. The poem presents a catalogue of biblical roles to be presented in procession, from Adam to St. John the Apostle. The descriptions of the figures were meant to be declaimed by a lector in a dramatic style similar to that which we find in the 15th century English Mummings of John Lydgate and his Procession of Corpus Christi. The descriptions of many of the figures mention their special relationship to Christ, either as a member of the “Tree of Jesse”, a prophet, or by their actions an allegory or type of Christ. The messianic characteristics of the poem place it in relationship to another earlier medieval biblical drama, the Procession of Prophets. “Vos qui concupiscitis” appears to have had a clerical origin and heritage and may have served as an important instruction for young students on biblical history, Christian prophecy and mores. Sometime early in its textual history the poem appears to have split into two parallel but nevertheless similar textual traditions; one of English origin (α) and another of Central and Eastern European (β). The α tradition appears to be the elder of the two. The β tradition appears to be a metrical refinement of α. The critical edition of “Vos qui concupiscitis” presents the texts and translations of both traditions with a critical apparatus that documents the textual variants. The text versions are labeled α and β. Explanatory Notes following the two texts document the sources, textual notes, and editorial commentary. Finally, an index to proper names and moral exempla follow the Explanatory Notes.
Educators collaborating across cultures in a computer mediated communications environment

This study sought to understand how teachers from different cultures, i.e., Canada and England, learned to collaborate in a computer mediated communications environment. Groups of teachers formed groups through a face-to-face meeting and then worked together in a CMC environment to design common learning experiences for their students. Insights into how the process of collaboration developed in CMC were gained through a qualitative case study in which data were collected through interviews, email dialogue, a survey, and the researcher's journal and field notes. Analysis of the case data showed that: (1) the newly formed groups, working in a CMC environment, worked through a series of group functioning stages, (2) teachers in the Project thought it was important to know the group members well and that face-to-face interaction helped with this, (3) the newly formed groups working in a CMC environment were influenced by the new collaborative relationship as well as the computer technology and therefore required additional time to complete tasks, (4) easy access to computers for emailing was necessary, (5) the groups of teachers collaborating in a CMC environment successfully collaborated to create a product, (6) establishing situations in which groups of teachers collaborate through CMC can effect change in the teaching/learning environment, (7) differences between educational issues and structures imposed on individual group members impacted on group members' ability to collaborate in CMC, and (8) the extent to which cultural diversity manifests itself was unresolved due to the similarities of the English and Canadian cultures. Slight differences in holidays impacted somewhat on the flow of email dialogue. The implication for change endeavours is that collaboration in a CMC environment can be an effective change strategy. Teachers in the two case studies emerged from the Project with confidence in their abilities to collaborate in a CMC environment and to continue to, through this medium, productively create/design learning experiences for their students. Participants found it difficult to work in a CMC environment. Their work demanded careful planning and extensive support.

Keywords: Telecommunication
Computer conferencing
Multimedia systems
Information technology, Computer-assisted instruction
Information retrieval
Child support obligations of step-parents in Canada

This thesis is an exploration of the child support obligations of step-parents in Canada. Step-parents are becoming more common in today's family law as more marriages break down and new relationships form. In many jurisdictions, there is no or very little legal recognition of step-parents. In Canada, however, there is broader legal recognition of de facto parent-child relationships, with the result that, step-parents may in many circumstances be liable for child support when their relationship with the children's biological parent breaks down. Canada currently has thresholds to determine parental status and how much support is required if the step-parent is held to stand in the place of a parent. This thesis will explore why many step-parents find these obligations unfair as discretion and uncertainty surrounds this area of law. Is reform needed in the Canadian model before other jurisdictions can add elements of the Canadian model into their own?
Nineteenth century physiology in the making: introducing West European experimentalism to the Russian context

The dissertation is a study of the rise of laboratory science in nineteenth-century Russia. It explores the cross-national scientific connections, which emerged anew after the Crimean war, in the context of the 1860s reforms in Russia and of the development of ‘scientific medicine’ in Germany. The thesis focuses on the signal role played by the military in the development of the first in Russia teaching-research laboratories at the St. Petersburg Medico-Surgical Academy. It explores how experimental and teaching practice and its methodology and instrumentation was disseminated from Germany to Russia, and how the innovative techniques and the improved apparatus introduced by I. M. Sechenov and I. F. Cyon into physiological research and teaching contributed to the growth of physiology into a modern scientific discipline. It also discusses the difficulties associated with doing laboratory sciences in Russia by foreground of Sechenov's professional moves, and allows us to picture contrasts in the attitudes and potentialities of War Ministry and Ministry of Education for the introduction of the laboratory. Sechenov's blood gases and salt solution research and the reception of his methodology are placed within the context of the debate on the solution theory between D. I. Mendeleev and Wilhelm Ostwald's school in Germany. Thus the thesis outlines the changes Russian scientific culture underwent during the “golden age” of its development in the second half of the nineteenth century wrought by the state, industrial, and military interests.
Visualizing voice locations: Amplifying the effects of spatial audio with simple displays

The purpose of this dissertation is to understand how displays of voice locations enhance the benefits of spatialized audio communication. While existing literature suggests visualizations of voice locations aren't beneficial, earlier investigations have only examined small, familiar audio spaces. This work extends previous research by investigating the benefits of visualizing voice locations in more complex, unfamiliar audio spaces, where identification is more difficult. An exploratory study compared the benefits of low-fidelity spatialization to those previously demonstrated for high-fidelity techniques in audio-only interfaces. This study confirmed the subjective benefits of spatialization and demonstrated that knowledge of voice locations aided listeners in disambiguating similar voices. Based on these findings, three additional studies were conducted. In the second and third studies, the utility of visualizing voice locations was examined in comparison to non-spatialized and spatialized audio-only environments for a voice identification task across audio spaces of differing complexity and familiarity. These studies demonstrated that visualizing voice locations improved identification performance, particularly in audio spaces with more voices. The fourth study investigated how the relative scale of auditory and visual displays affected voice identification performance. This study demonstrated that increasing the distribution of voice locations, both for the auditory and visual display components, improved voice identification. This research produced a number of notable contributions. This was the first set of experiments to examine how audio space complexity and visual and auditory display scale affect the voice identification-related benefits of visualizing voice locations, establishing a novel methodology for evaluating voice identification performance across a variety of display conditions. Experimental findings demonstrated that visualizations of voice locations support the accurate identification of unfamiliar voices, particularly in larger, complex audio spaces. These findings also showed that the relative scale of both the auditory and the visual display components affect the identification of unfamiliar spatialized voices. Finally, this research led to the formulation of design guidelines to aid practitioners in developing display interfaces that better support voice-identification. Future studies could evaluate how the benefits of visualizations are affected by further increases in audio space complexity, as well as how spatialized audio/visual displays affect other aspects of remote collaboration.
State aids in the European Union for the pharmaceutical industry: developing a solution to plaguing issues

Describes the Internal Market and the methods used to achieve it. Examines the techniques utilized by the European Union institutions in attempting to achieve a single market for pharmaceutical products. Discusses the limited effect of the Transparency Directive and of parallel trade in facilitating the attainment of a single market for pharmaceuticals. Explains the inefficiencies created by the promotion of parallel imports of pharmaceuticals; inefficiencies very specific to the pharmaceutical industry because pharmaceutical pricing competence remains at the national level. Highlights judicial inadvertence to these specific inefficiencies in interpreting Articles 30, 81 and 82 of the Treaty establishing the European Community by presenting recent jurisprudence of the European Union courts. Argues that the use of state aids to fund the research and development activities of the pharmaceutical industry could effectively minimize the parallel importation of pharmaceuticals and assist in harmonizing national pharmaceutical price control policies.

Keywords: Subsidies, European Union countries
Pharmaceutical industry, European Union countries
Effects of folate deficiency on endothelial cell biology: Folate deficiency induces profound effects on global patterns of gene expression in vascular endothelial cells

Folate deficiency is an independent risk factor for atherosclerotic cardiovascular disease. The hypothesis that folate deficiency directly affects endothelial cells has never been tested. To better understand how folate deficiency elicits changes in vascular wall homeostasis, we characterized an in vitro model of endothelial cell folate deficiency using human umbilical vein endothelial cells (HUVECs). We conducted global gene expression analysis to address the effects of folate deficiency on endothelial cell gene expression. Severe folate deficiency, induced the classic response of reduced cell growth induced, by an intra S-phase cell cycle arrest, and increased cell volume. Primary endothelial cells were found to be sensitive to physiological levels of folate at a concentration of 40 nM (within the normal range in humans) and respond by exhibiting an inflammatory response as evidenced by the changes in expression of IL-8, CXCL1, ICAM1, COX-1 and COX-2. These changes are characteristic of the activated endothelium.
Exact calculation and estimation in children in grades three to eight: relations to working memory

The development of calculation and estimation skills and the contribution of cognitive competencies such as memory to these skills are not well understood. The present study compared double-digit estimation and calculation in 60 children from grades three to eight. Presentation format (horizontal vs. vertical) and complexity (carry vs. no-carry) were manipulated for both types of math problems. The relations of these math skills to verbal and visual spatial memory were examined. Calculation and estimation showed grade related changes, but children were slower and less accurate at estimation than calculation across grades. Complexity affected problem solving accuracy. In general, visual spatial working memory was related to estimation. For calculation, verbal working memory was related to vertical carry problems, and verbal short term memory was related to no carry problems. Results are discussed with reference to theories about the development of numerical skills and their relations to memory.
Charge injection properties of Alq3based devices

The role of LiF in improving the charge injection in Al/Alq3 based OLEDs is investigated by making and testing the current-voltage characteristics of a series of single carrier devices. It is found that thinner layers of LiF ( sim;2A) have a greater impact than thicker layers and that LiF has a much greater impact at the top organic/Al interface than at the bottom interface, due to differences caused by the deposition sequence. Charge transport is found to be injection limited, but doesn't quite fit the thermionic emission theory. When used with Ag electrodes, LiF has a blocking effect. Electrically poling Al/LiF/Alq3/LiF/Al devices at -15V results in negative differential resistance peaks in the IN characteristics. These peaks can be erased and reformed and are used as the basis for a new injection model. LiF also improves electron injection in devices having C60 in place of Alq3, through the formation of ohmic contacts.
Preparation and properties of lipid bilayers supported on spherical hydrogel beads

Lipid bilayers supported on micron-sized spherical polyHEMA beads were prepared. The lipobeads coatings consisted of 100% DMPC, DMPC/cholesterol (70/30) or DMPC/DMPG (1:1). Coating of the beads was established by fluorescence microscopy, of a fluorophore-labeled lipid. The thermotropic phase behavior of the lipobead coating was similar to that of lipids in the absence of HEMA, based on 1H NMR studies. Cholesterol broadened the phase transition temperature of the lipids. 31P NMR under fast MAS conditions in the presence of a chemical shift reagent, Praseodymium (III), demonstrated that only a single bilayer was wrapped around each hydrogel bead. The successful coating of the hydrogel beads with lipid has opened many doors to future studies with applications to better understanding of membrane structure and functions, drug delivery; targeted drug release and NMR based diffusion studies in lipid bilayers.
Granular segregation dynamics in a rotating drum

Heterogeneous granular mixtures tend to segregate by size when tumbled in a partially filled, horizontal rotating drum. After a few drum rotations the small grains move towards the axis of rotation and form a buried radial core, which, after several hundred drum rotations, splits into axial bands. This process can display complex, oscillatory wave dynamics during the transient before segregation saturates. In this thesis, we report on measurements of the axial transport of grains in the radial core, the dynamics of the axial segregation process, and the oscillatory wave transient. We show experimentally that two fields, the concentration and dynamic angle of repose, whose coupling was theoretically postulated, do not evolve as predicted, which falsifies a recent model. We also report that the axial transport of small grains in the radial core is subdiffusive. This does not depend on grain type or rotation rate. We show that the self-mixing of monodisperse grains is as well a subdiffusive mixing process. Lastly, we find that the growth rate scaling of the axial segregation pattern increases as a function of drum diameter and grain size ratio. None of these findings are accounted for by any theoretical model of this system.
Determining the nature and location of emission sources contributing to Toronto aerosol

This work examined the chemical character and geographic origins of Toronto particulate matter smaller than 2.5 microns (PM2.5). PM2.5 has been linked with increased human morbidity and mortality in Ontario. The influence of local emissions, long range transport of air, and atmospheric chemical processes on the seasonal and diurnal behaviour of PM2.5 mass number concentrations, and chemical composition variation via real-time mass spectrometry of individual aerosol particles was studied. Toronto PM 2.5 levels were found to be affected by anthropogenic activities like traffic and construction, and natural processes like forest fires and intercontinental dust transport. Nine distinct emission sources contributing to Toronto PM 2.5 were identified by use of the novel use of single particle data. The importance of the Midwestern United States and Southern Ontario as Toronto PM2.5 source regions was confirmed and evidence for a relationship between local smog advisories and Toronto organic nitrate aerosol discovered.