VictorJuiz/thesis huggingface dataset:
Physical and genetic analysis of the human chromosome 14 long arm subtelomeric region at 14q32.33 going to 14qter

The human immunoglobulin heavy chain gene cluster (IGH) is located at 14q32.33, near the long arm telomere of chromosome 14. Physical maps suggested that 14qter might be some distance from IGH. Human subtelomeric regions are the sites of increased recombination and have a male to female recombination ratio that is higher than elsewhere in the genome. My goal was to complete the map of distal 14q, to develop genetic markers for 14qter, and to examine recombination in this subtelomeric region. Initially, 13 DNA markers were used to characterize naturally occurring terminal deletions, to refine the physical map and determine if deletion breakpoints were near 14qter. Two markers, previously mapped distal to IGH, were mapped proximal to IGH. The breakpoint of a ring chromosome was mapped to a 350 kb interval within IGH, representing the smallest region of distal monosomy 14q reported to date. Somatic cell hybrid lines were next used to map IGH variable region (VH) segments that previously were not placed within IGH. Four NotI DNA fragments, representing eleven VH segments, mapped to chromosomes 15 and 16. Two yeast artificial chromosomes (YAC) containing functional human telomeres were mapped to the telomeric end of IGH. A VH segment at the distal ends of the YACs was sensitive to nuclease Bal31 digestion of human DNA, demonstrating that these represent the 14q telomere. The physical map of IGH was completed and extends to within 25 kb of the telomere. Polymorphic markers were cloned from the distal part of IGH, approximately 90 and 200 kb from the telomere. Haplotypes of these markers were constructed for use as a highly polymorphic genetic marker which will be useful for anchoring genetic maps. Linkage analysis using the 40 pedigree CEPH reference panel revealed increased recombination within this region. Recombination was not significantly higher in males than in females, indicating that this region differs from other human subtelomeric regions.
Immune response against the p53 tumor suppressor gene product: Clinical studies and molecular mechanisms

In this study the immune response against the p53 tumor suppressor protein was investigated. The development of quantitative immunoassays for measuring p53 antibody titers in serum allowed the performance of an extensive study for p53 autoantibody generation in 1392 patients with 13 different malignancies. Patients with colon and ovarian cancer develop antibodies against p53 with higher frequencies than patients with other types of tumors. Analysis of serum samples from blood donors and healthy volunteers demonstrated the high specificity of this test ($>$98%). Serum p53 autoantibodies are indicators of unfavorable outcome in ovarian and breast cancers, but have no prognostic value in colon cancer. p53 antibody titers fluctuated with time in parallel with other conventional tumor markers, reflecting changes in disease status. Based on this observation I suggest that monitoring cancer patients with serum p53 may have clinical utility, especially in those whose tumors do not produce conventional tumor markers, like CEA or CA-125. Further, p53 autoantibodies were present in the ascites fluid of 20% of ovarian cancer patients. p53 protein was detected in the ascites fluid of 7% of these patients. This is the first identification of p53 protein in a biological fluid. p53 antibodies were found more frequently in sera of patients with tumors expressing high levels of p53 protein (p = 0.05). However, not all patients with tumors overexpressing p53 developed p53 antibodies, and not all p53 antibody-positive patients had p53 overexpression in their tumors. p53 antibody-positive patients did not have higher frequency of p53 gene mutations than p53 antibody-negative patients. The former were associated with a Tyr substitution in the protein product. These studies on the immunological and molecular aspects of p53 autoantibody generation in cancer contribute to the better understanding of this immune reaction of the host against cancer, and offer possibilities for cancer monitoring and possibly diagnosis.
A deep imaging survey of brightest cluster galaxies

A deep imaging survey of brightest cluster galaxies (BCGs) has been completed. We present results of B and R band surface photometry for 25 BCGs, many of which have been classified as "cD" galaxies. Data were obtained using a large format CCD (2048 x 2048 pixels) and 0.9 m telescope. This arrangement was capable of imaging the enormous spatial extent of these objects. The isophotes of the BCGs were modeled with elliptical contours, and used to produce a set of surface brightness profiles. Fits of the profiles showed that the Sersic (1968) law best described our data. Two-component models of the "cD" profiles also showed a good agreement between the models and the data. Parametrisations of our profiles have yielded two distinct classes of BCGs based upon the amplitude of their effective radii, $r\sb{e}.$ The large $r\sb{e}$ BCGs are called diffuse BCGs, and are similar, but not identical, to the classical definition of a cD. The parent clusters of our diffuse BCGs coincides with the list of clusters with flat, faint-end luminosity functions (Lopez-Cruz 1997), suggesting that the two properties may be related. We present a model in which the growth of these galaxies is governed by the destruction of dwarf galaxies within the cluster. The remaining BCGs form a class of objects with a different formation history, possibly linked to the merging of several large galaxy units early in the cluster collapse. The colour profiles have shown that there are detectable blueward colour gradients in BCGs, in agreement with the data seen in ordinary ellipticals. We have confirmed that BCGs are aligned with their parent clusters by estimating the orientations of these clusters from their distribution of galaxies. This alignment suggests that cluster formation and BCG formation are linked, and is predicted from formation mechanisms of both types of BCGs.
Towards a formal account of diagnostic problem solving

Automated diagnosis has long been a problem of interest to the artificial intelligence community. To the practitioner, artificial intelligence holds the promise of addressing difficult problems in automated diagnostic problem solving. To the formalist, diagnostic problem solving embodies many of the fundamental challenges of artificial intelligence within a broad range of application domains. This thesis investigates formal representation and reasoning issues that underlie diagnostic problem solving. We assert that an investigation of diagnostic problem solving must address testing and repairing, in addition to the task of diagnosis. Further, we argue that a comprehensive account of diagnostic problem solving requires reasoning about action and change. Providing such an account presents at least two fundamental challenges: first, a knowledge representation scheme must be devised to capture the interrelationship between actions and the state and behaviour of a system; second, formal characterization of the tasks involved in diagnostic problem solving must be defined. This thesis proposes the predicate calculus and the situation calculus as logical languages for explicating the representation and reasoning issues involved in diagnostic problem solving. Using the language of the situation calculus, we propose a knowledge representation scheme that enables us to integrate a representation of actions with the representation of the behaviour of a static system. In doing so, we provide a semantically justified closed-form solution to the frame and ramification problems for a class of state constraints that occurs commonly in many application domains. With a representation in hand, we present a logical characterization of the task of diagnosis for behaviourally static systems whose state can be affected by actions which occur in the world. Integrating a theory of action into our representation provides for a broad definition of diagnosis. In addition to conjecturing what is wrong with a system, we employ actions both as observations to project what may be wrong with a system, and as diagnoses to explain what happened to cause observed behaviour. In diagnostic problem solving, testing is required to discriminate a space of candidate diagnoses. Using the language of the predicate calculus we study formal issues related to testing, including test design, test generation and the conclusions that can be drawn from the outcome of a test. Finally, we introduce the problem of achieving tests and repairs, characterizing these tasks as instances of the planning problem in the language of the situation calculus.
Identification and characterization of human hematopoietic stem cells using gene transfer and the novel SCID transplantation assay

The absence of preclinical repopulation assays for primitive human hematopoietic cells has hindered the development of stem cell gene therapy. Current human gene therapy trials employ gene transfer methods optimized using surrogate in vitro colony-forming cell (CFC) and longterm culture-initiating cell (LTC-IC) assays and by inference from studies on other mammalian species. In this thesis, we report the identification and characterization of a novel human hematopoietic cell, capable of repopulating the bone marrow (BM) of nonobese diabetic mice with severe combined immunodeficiency (NOD/SCID), namely the SCID-repopulating cell (SRC). Human BM or cord blood (CB) cells were infected with retroviral vectors and subsequently transplanted into NOD/SCID mice. Whereas CFC and LTC-IC were efficiently transduced with retroviruses, SRCs were transduced rarely, establishing that SRC are biologically distinct from most CFC and LTC-IC. Moreover, characterization of the cell surface phenotype indicated that SRC are exclusively CD3$\sp+$CD38$\sp-$ in contrast to CFC and LTC-IC that are mostly found in the CD34$\sp+$CD38$\sp+$ fraction after multiparameter flow sorting, confirming the distinct character of SRC. In combination with various data obtained in the past decade, these analyses provide the strongest evidence that SRC defines a novel human hematopoietic cell that is more immature than any other cell type detected to date. The inefficient infection of SRC was consistent with the low level of gene marking reported in primates and human gene therapy trials. This inability to infect the most primitive human repopulating cells, in contrast to most CFC and LTC-IC, highlights the need for appropriate pre-clinical models that will predict the outcomes of human clinical trials. As described in chapter 3 of this thesis, primitive BM cells from $\beta$-thalassemia major and sickle cell anemia (SCA) patients can engraft and proliferate in the BM of immune-deficient mice. The BM of transplanted mice contained the entire erythroid lineage from BFU-E to mature erythrocytes expressing human $\gamma$-, $\beta$- or $\rm\beta\sp{s}$-globin as in the original donor. Moreover, human erythroid cells from mice transplanted with SCA bone marrow showed characteristic sickling under reducing conditions in an in vitro assay. This system can thus be used to evaluate gene transfer efficiency into primitive human cells, longevity of expression, expression in the appropriate lineage, and correction of the disease phenotype.
Solvothermal synthesis, characterization and mode of formation of aluminophosphate chains, layers and frameworks

The solvothermal synthesis of aluminophosphates is described, using organic amine additives ranging from primary to quaternary to cyclic. A tetraethylene glycol solvent led to a series of novel aluminophosphate crystal structures, denoted UT-n, where UT denotes University of Toronto and n denotes structure type. Of the eight structures that were discovered to date, two are one-dimensionally extended chains, five are two-dimensional layers and one is a three-dimensional framework. For all, the inorganic architecture is anionic and is charge-balanced by occluded alkylammonium template molecules. The chain and layered structures each contain an extensive hydrogen bonding network between the terminal oxygens of the phosphate groups and the ammonium hydrogens. A series of alkylammonium phosphate structures were also discovered, which contain layers of phosphate molecules separated by interdigitated or bilayers of alkylammoniums. The aluminophosphate and phosphate solids were characterized by a variety of techniques, including VT-PXRD, TGA, MS, SEM and solid state NMR. Many interesting results were found, such as a topotactic anionic framework to neutral framework transformation. The data also showed an unprecedented aluminophosphate chain to layer solid state transformation, where both end products were previously synthesized and fully solved UT-n crystal structures. This is followed by a new model for the mode of formation of aluminophosphates, which points out previously unrecognized structural aspects and is based on experimental evidence. The model involves a crystallizable chain precursor, which on hydrolysis, rearrangement and condensation, leads to a theoretically infinite number of possible chain types. These chains connect together and thereby account for the architectures, dimensionality and observed structural trends of potentially all known and theoretical aluminophosphate chains, layers and frameworks. Examples of each will be given. Finally, changing the template molecule to an amphiphilic n-alkylamine (C$\sb{\rm n}$H$\sb{\rm 2n+1}$NH$\sb2$) resulted in a series of novel mesolamellar aluminophosphates (MLA's). The phase(s), crystallinity and morphology of the resultant product were found to be highly dependent on carbon chain length. For n = 8 to 12, a series of remarkable surface morphologies were discovered. After the characterization of the MLA materials, a preliminary mode of formation will be described, involving an alkylammonium phosphate liquid crystal phase.
Les mémoires de la vie de Henriette-Sylvie de Molière de Mme de Villedieu, une esthétique de désordre

L'oeuvre de Mme de Villedieu, que la critique actuelle a redecouverte apres trois siecles d'oubli, et notamment un roman, les Memoires de la vie des Henriette-Sylvie de Moliere, nous aident a reconsiderer le jugement trop souvent global et hatif que l'on porte sur l'epoque de Louis XIV ainsi que la vision monolithique trop longtemps entretenue sur la litterature classique. Plus encore, une lecture tres attentive du texte fermement replace dans son contexte politique, social et litteraire contribue a mettre en lumiere toute sa saveur et son originalite. Au lieu de se conformer a l'esthetique que nous appelons maintenant 'classique', une esthetique compatible avec la vision politico-sociale de Louis XIV, Mme de Villedieu pratique deliberement une esthetique du desordre qui exprime ce meme desordre que Louis XIV esperait enrayer. Ce qui conduit le lecteur a s'interroger sur l'ordre social: naissance, position sociale, reputation, condition de la femme, egalite des sexes et statut de l'individu dans la societe. Batarde et veuve, Sylvie, le personnage central feminin, est doublement marginale dans une societe patriarcale hierarchisee. C'est une femme qui ecrit, et ce faisant s'approprie du pouvoir. Mme de Villedieu prete a sa narratrice un reseau de techniques textuelles qui ont pour but la desorientation ou le depaysement du lecteur. Elle construit l'ambiguite afin de transmettre au lecteur son experience personnelle du desordre du vecu. L'esthetique du desordre exige que le lecteur s'engage dans une lecture active, qu'il ressente a son tour le desordre du vecu. Il ne se livre pas a une activite purement intellectuelle, mais aussi, surtout, a une activite emotionnelle et viscerale. Ou se situent les forces ou les causes de ce desordre? Partout et nulle part, dans les espaces qui separent deux moments d'ordre, dans le vide. Les Memoires de Sylvie expriment, fetent meme, la liberte du desordre. Dans ce roman qui surprend par son originalite et sa vivacite, Mme de Villedieu met en vedette une 'instigatrice du desordre' qui perturbe l'ordre social par sa naissance et sa conduite. Le fait qu'elle ecrit au lieu de se taire la rend encore plus "extravagante".
Equity, efficiency and the second best in dynamic policy analysis

A general framework for dynamic policy analysis in the second best is presented. The framework is characterized by a parsimonious social welfare functional, an independent positive model of the economy, second-best constraints on lump-sum redistribution, market failures, and inter-regional trade equilibrium. Chapter one reviews the literature regarding market-based vs. social discounting in cost-benefit analysis. The major arguments in favour of market discounting are analyzed and found to be inappropriate in the context of the second best. Alternative techniques to account for the opportunity cost of public finance and ensure the efficiency and feasibility of policy are reviewed. Chapter two is concerned with the choice of a dynamic social welfare functional. The familiar isoelastic form is adopted with a number of changes designed to make it conform better with common principles of equity, particularly anonymity. Two decision rules are derived from the isoelastic welfare functional for use in cost-benefit analysis: one a standard welfare change measure, and the other the present value of dollar benefits which relies upon the social rate of discount. Since both decision rules require information on the distribution of a project's net benefits, consistency of policy analysis requires the use of a common analytical framework, rather than a common social rate of discount. Chapter three demonstrates the application of the second-best framework by estimating the optimal control of greenhouse gas emissions in a four-region model of the world. To date, most economic research on policies to control global warming has been limited to internalizing the greenhouse externality in a positive model of the economy. In contrast, chapter three determines the optimal policy by constrained welfare maximization. Control paths of emissions and equivalent carbon taxes (permit prices) are estimated, as well as paths of side payments (permit allocations) to compensate poorer regions for their abatement efforts. The effect of the second-best framework is to give much higher levels of emissions abatement than most previous research. Emissions reductions are on the order of four times higher than results from positive models, and equivalent carbon taxes at are least fourteen times higher.
Ontario's mandated school councils, public willingness to serve and factors influencing that willingness, a case study

This study investigated the response, in one school community, of 310 parents and 36 non-parents (businesspersons, professionals, community workers, and other citizens), to the Ontario government's school council initiative. As an exercise in participatory democracy, the initiative can be typified as an example of the form of democracy outlined by de Tocqueville (1835/1990). Oldfield (1990) described this as civic republicanism and established three criteria for its practice: democracy must be an activity not a status; it must empower those who practice it; it must provide sufficient motivation to engage citizens. Through the use of a questionnaire, interviews, and discussion groups, the study examined the willingness of those who participated to serve as members of a secondary school council and their reasons for that willingness, relating these reasons to Oldfield's criteria. Surprisingly, although the parents exhibited a positive attitude towards the potential value they perceived to be inherent in the notion of a school council, they did not appear to be willing to support the initiative by actually serving as members of the council. They cited lack of time, personal insecurity, and a reluctance for running in an election as major factors inhibiting their participation. Apathy was not a significant factor in this issue. The non-parents also displayed a positive attitude towards the notion of a school council but, unlike the parents, indicated greater interest in serving as members. Apparently the government's initiative, although providing activity and empowerment, did not, at the time of the study, supply sufficient motivation for parents who were, for the most part, motivated solely by their narrow concern with educational opportunities for their children. Non-parents, on the other hand who had no children in the school, responded more favourably since they were moved by a broader range of motivational influences. The study concludes by making several recommendations to administrators about the necessity of understanding the nature of their communities and of providing appropriate motivation for enthusiastic voluntary participation from parents.
Regulation of SPARC expression and function during early embryonic development

Migratory and signalling pathways require the interplay of extracellular and cell-surface molecules which govern many aspects of cell differentiation and tissue morphogenesis. The extracellular matrix glycoprotein SPARC is expressed by many tissues as they undergo rapid proliferation, differentiation, and morphogenesis. In vitro studies have also demonstrated that SPARC interferes with cell-substratum interactions and modulates cell-cycle progression. The present study examines the role that SPARC plays during the embryonic development of Xenopus laevis. In situ hybridization and immunohistochemistry were used to examine the relationship between SPARC localization and important developmental events. SPARC expression was abundant, though transient, within the early axial mesoderm, particularly the notochord and the somites. The spatial-temporal localization of SPARC within the somites paralleled the presence of gap junctions which are believed to play a role in the electrical coupling of pre-innervated Xenopus somites. A lack of correlation between SPARC transcript expression and protein localization was observed within the neural tube. The effects of ectopic SPARC expression on early developmental events was examined. Ectopic introduction of SPARC RNA, protein and peptides resulted in a number of shared developmental phenotypes, most prevalent of which was a reduction on embryonic axis. A peptide representing the EF-hand related calcium-binding domain of SPARC produced the most dramatic and dose-dependent effects. Though exterior morphological criteria suggested that gastrulation was not affected, resultant headless or axis-reduced embryos indicated that important events, such as cell-cell signalling, may have been affected. Other SPARC peptides which displayed potent effects on cellular activities in vitro had no effects on early development. The regulation of SPARC was also examined. SPARC expression by ectodermal animal cap cells required cell-cell interaction. Mesoderm inducers, such as activin, elevated SPARC expression within intact animal cap explants. Xenopus genomic sequences were identified and analysis revealed that the intron-exon organization of the $5\sb{\rm F}$ regulatory region of Xenopus SPARC was similar to that of mammalian SPARC. Though overall similarity between Xenopus and mammalian regulatory sequences was very low, several individual regulatory elements were conserved. The overall importance of proper SPARC expression and function during early development is discussed.