VictorJuiz/thesis huggingface dataset:
Molecular mechanisms of the homeobox gene HOX11 in B cell lymphomagenesis

The HOX11 homeobox gene was originally identified at the recurrent t(10;14)(g24;q11) translocation breakpoint, a chromosomal abnormality observed in 5-7% of T cell acute lymphoblastic leukemias (T-ALLs). HOX11-transgenic mice (IgHmu-HOX11Tg) that express HOX11 in the B cell compartment develop B cell lymphomas with extended latency. To identify the additional genetic events required prior to the onset of malignant lymphoma, we performed a proviral insertional mutagenesis screen and identified and validated multiple targets involving genes associated with the chromosome segregation machinery. This suggested that HOX11-expressing cells are prone to chromosome instability. Accordingly, relative to control cultures, incidences of micronuclei formation and numerical chromosomal abnormalities were significantly elevated in primary IgHmu-HOX11Tg B cell cultures following treatment with spindle poisons. The accumulation of aneuploid karyotypes in the IgHmu-HOX11Tg B cell cultures correlated with aberrant bypass of the mitotic spindle assembly checkpoint. To fully validate the synergistic collaboration of HOX11 overexpression and the targets identified in the proviral mutagenesis screen, the role of the Ubr1 gene, the most frequently targeted locus, in cooperating with HOX11 was assessed. Diminished expression of Ubr1 by siRNA-knockdown in HOX11-expressing T-ALL cell lines, K3P and SIL, and in HOX11-3T3 cultures, correlated with elevated incidences of micronuclei formation. Moreover, IgHmu-HOX11 Tg/Ubr1-/- double mutant mice and observed a mild acceleration of lymphomagenesis and B lymphocytes from IgHmu-HOX11Tg/Ubr1 -/- mice also revealed a marked increase in propensity for accumulation of aneuploid karyotypes relative to control cultures. Elevated expression of mitotic regulators, cyclin B1, cyclin A and cdc20, was detected in IgHmu-HOX11Tg B cells and was speculated to play a role in facilitating abrogation of mitotic arrest. To fully assess the relevance of cyclin B1 upregulation in HOX11-associated chromosome instability, mutants were generated which mimicked a constitutively phosphorylated HOX11 protein (HOX11 T47E) incapable of cyclin B1 activation. HOX11 T47E mutants remained capable of inducing micronuclei formation and bypass of mitotic arrest. Collectively, these results indicate a cooperativity of spindle assembly checkpoint gene deregulation and elevated HOX11 expression in promoting lymphomagenesis vis-a-vis the abrogation of spindle checkpoint control and the induction of chromosome instability in a cyclin B1-independent manner.
Interhelical interactions of transmembrane segments 9 and 10 in the cystic fibrosis transmembrane conductance regulator

Mutations in the membrane domain of the cystic fibrosis transmembrane conductance regulator (CFTR) are the cause of CF disease. To determine how these various mutations alter CFTR structure and function, we have performed SDS-PAGE shift analysis, circular dichroism, and tyrosine fluorescence spectroscopy on wild type and CF-phenotypic mutants of the transmembrane (TM) hairpin of CFTR TM9-10. Various interhelical interactions were detected: mutants A 1006E and V 1008D's non-native hydrogen bond potential partner were confirmed respectively; and a salt bridge and hydrogen bond network was elucidated among R 1030, D993 and Y 1032. Studies of more than 20 mutant CFTR TM9-10 hairpin constructs revealed that the method of SDS-PAGE gel shift analysis is more sensitive to the removal of interhelical interactions near the loop region of TM hairpins than to other TM positions. The results show that various CF-phenotypic mutants can significantly alter the wt hairpin structure, and thereby produce aberrant CFTR function.
Blood transfusion and colorectal cancer in the leukoreduction era: Outcomes and appropriateness

We assessed the relationship between transfusion and colorectal cancer (CRC) outcomes, as well as the appropriateness of perioperative transfusion, in patients who had curative resections for colorectal adenocarcinoma between Sept. 1999 and Dec. 2002 at a tertiary centre. Patients were followed until Dec. 2005 to estimate overall survival (OS) and disease-free survival (DFS). Transfusion appropriateness was assessed using hospital guidelines. Among 301 patients, 29.9% were transfused. OS was shorter in transfused patients (3-yr OS: 68.9 vs. 91.3%, log rank p
157-nm radiation induced bragg gratings in silica optical waveguides

This thesis reports the first detailed study of Bragg grating writing using 157-nm radiation. The 7.9-eV photon from the 157-nm laser is attractive for inducing strong index changes in germanosilicate and fused silica. Fiber Bragg gratings were written in standard telecom fiber (SMF-28), with index modulation of ∼1.7 × 10−4 in hydrogen-free SMF-28. The gratings have good long-term stability, and sidelobe suppression of 17 dB without apodization. The index modulation improves to ∼6 × 10−4 and Δn∼1.8 × 10−3 in hydrogen-loaded SMF-28. Bragg gratings were fabricated in pure fused silica holey fiber, yielding Δn∼1.4 × 10−3 at 90 kJ/cm2 fluence exposure, and offered good cladding mode suppression. Bragg gratings were also written within silica-on-silicon planar waveguides and buried waveguides in fused silica blocks. The results demonstrate an alternate laser source for writing fiber Bragg gratings not requiring photosensitivity enhancement in germanosilicate waveguides, and is practical for writing gratings in pure fused silica holey fiber.
Craniofacial effects of neurocranial surgery in isolated sagittal synostosis

Background. Isolated sagittal synostosis (ISS) is characterized by premature sagittal suture fusion and distorted neurocranium. To restore neurocranial morphology, most ISS patients undergo corrective surgery. Objectives. To investigate whether neurocranial surgery in ISS patients has a significant effect on form or growth of the face or cranial base. Methods. Three-dimensional CT-scans were obtained for pre- (n=48) and post-operative (n=21) ISS patients, and controls (n=25). Basicranial and facial landmarks were collected from CT reconstructions and analyzed using Euclidean distance matrix analysis. Subsamples of age-matched patients were used to identify differences in morphology and growth. Results. Surgery has no statistically significant (p≤0.05) effect on the morphology of the face however differences in facial position were seen. Untreated basicranial subsets displayed the most statistically significant morphological and growth differences when compared to the controls. Conclusion. Surgery in ISS patients has minimal effect on facial development, however it does aid in normalizing basicranial morphology.
Detailed space-time-level analysis of miocene hydrothermal Zn-Ag-Au mineralization and alteration, Virginia Area, Huancavelica, Central Peru

The Virginia area is associated with the Mesozoic Condorsinga limestones, upper section of the Pucara Group, which were intruded by different pulses of Miocene dioritic subvolcanic and rhyolitic to dacitic volcanics. The Late Oligocene-Early Miocene microcrystalline dioritic subvolcanic intrusions were emplaced as shallow stocks and dikes, and produced an extensive and apparently barren green garnet skarn alteration. The fluids trapped in garnets show trapping temperatures between 182 ± 26°C and 234 ± 48°C, salinity between 13 ± 9 and 19 ± 7 eq.wt% NaCl and depths of trapping between 77 and 281 metres. Later Miocene porphyritic rhyolitic to dacitic Caudalosa volcanics were emplaced after and altered the previously formed rocks including the subvolcanic intrusions. The hydrothermal fluids generated during the Caudalosa volcanism produced Zn mineralization hosted by the bottom unit of the volcanics, which comprises carbonate-altered skarn-bearing volcanic breccias; and Au mineralization in a high sulfidation epithermal system hosted by the top units of the volcanics.
Transcriptional profiling of xenografts as a model system for classification of lung cancer

Lung Cancer is the leading cause of cancer deaths and can be classified as either small cell (SCLC) or non-small cell lung cancer (NSCLC). NSCLC is further divided into squamous (SQCC), adeno (ADC) or large cell carcinoma (LCC). The aim of this project was to use xenograft tumors as a model for identification of candidate biomarkers for molecular classification of non-small cell lung cancer. Expression profiles from xenograft tissue from 10 (ADC and SQCC) lung cancer cell lines were derived using oligonucleotide arrays. This data was then analyzed using Cluster and Treeview and SAM analysis. It was found that the xenografts clustered according to histopathological typing. Altogether the expression of 333 genes was upregulated in either ADC or SQCC. Expression levels of twelve of the genes were confirmed by real time RT-PCR. We also found gene expression levels clustered cell lines separately from the xenografts. An in silico analysis of the transcription profiles of primary lung tumors available in public domain reveals that 45 of the distinguishing 333 genes also were differentially expressed in primary ADC or SQCC. It is concluded that lung cancer cell line xenografts are useful models for the study of gene expression in lung cancer.
Modelling of blood flow through mechanical heart valves using large eddy simulation

A majority of heart valve replacement procedures use bi-leaflet mechanical heart valves (MHV). Although these valves function adequately, they require constant anticoagulant therapy to prevent thrombus (clot) formation. Thrombus formation is primarily due to platelet activation, which is caused by nonphysiological flow conditions through MHVs. Blood flow in MHVs can be turbulent, and thus there is a need to better understand both laminar and turbulent flow through MHVs. In this work, a code for the solution of the two-dimensional Navier-Stokes equations has been extended to include the Streamline Upwind/Petrov Galerkin (SUPG) method and Large Eddy Simulation (LES) for modelling turbulent flows using the constant co-efficient Smagorinsky model. Different numerical tests have been performed to evaluate the validity of the numerical code. Results from the unsteady turbulent simulation agree qualitatively with computational and experimental studies, indicating that turbulence affects the flow field in the vicinity of the heart valve and should be addressed when modelling blood flow in MHVs.
Development of an outer cortical bone model for the investigation of bone/implant healing

Cortical bone is an important site for the early stabilization of endosseous implants, the regenerative capacity of which is not well understood. To study peri-implant cortical bone healing in the absence of marrow cavity tissues, and hence the true regenerative capacity of cortical bone, a rat femur model was developed in which "cortical plate" implants were tied to chiselled non-medullary canal-penetrating defects on the outer cortex. Tensile testing following sample retrieval at 1-, 3-, and 5-week endpoints showed that implants that had received a nanomaterial calcium phosphate treatment exhibited enhanced fixation with the cortical bone, compared to untreated implants. Fractured bone tissue, indicating bone-bonding, was observed by FESEM on post-tensile testing implants as early as the 1-week endpoint, mediated through a non-collagenous interfacial cement line matrix. Further, BSEI and histology analyses showed that peri-implant cortical bone healing isolated from marrow cavity tissues could occur by both contact and distance osteogenesis.
The influence of design-relevant parameters on multiple object tracking performance

The research was motivated by the need to anticipate the attentional demands and design factors that are involved in planned display applications for Global Situation Awareness. This motivation led to the following question: What are the practical design parameters that influence performance in multiple-object tracking? A pilot study and three experiments, involving a total of 82 participants, were used to investigate this question, employing adaptations of the Sears and Pylyshyn (2000) multiple-object tracking task. Perceptual speed, as measured by the 'Hidden Patterns Test' (HPT), was used to evaluate experimental participants' combined Executive Working Memory (EWM) and Visuospatial Working Memory (VWM) capacity. In Experiment 1, employing object speeds from 4 to 8 degrees per second, participants with high HPT scores, responded faster than participants with medium and low scores. These differences were insensitive to increased numbers of targets (3 to 4) and distractors (4, 8 and 12). Response time decreased for high HDP scoring participants only, over a sequence of 8 blocks of a5 trials per block, but with no reduction in tracking accuracy. Tracking accuracy for targets decreased with increasing numbers of distractors and was higher for high HDP scoring participants. Two design recommendations are identified for global situation awareness displays involving tracking multiple moving objects: (1) minimize display complexity (the number of displayed moving objects and background map clutter) and (2) reduce task complexity (e.g. map referencing) to enhance multiple-object tracking performance and message handling complexity to reduce mental workload. The research also supported the use of personnel selection as a method of obtaining a sufficient level of MOT performance based on differences in working memory capacity for map scales of 1:10,000 and below, and viewing distances of less than 50 cm, where object speeds are likely to be high relative to the field of view presented in the map. Finally, the research also demonstrated the value of practice in developing skill with tasks in global situation displays involving multiple-object tracking. In Experiment 2, with object speeds reduced to 1-4 degrees per second, a high clutter background map, reduced response time but did not affect tracking accuracy. Response time and tracking accuracy were not influenced by differences at HDP pattern scores. A secondary task involving referencing the behavior of a moving object relative to a feature on the map reduced both response time and tracking accuracy. Experiment 3 involved the addition of a secondary task that loaded phonological working memory. The addition of the secondary message retention task, at two levels of difficulty, did not affect tracking response time or tracking accuracy but increased mental workload.
Predisposing factors to formation of cleft lip and palate: inherited craniofacial skeletal morphology

The objective of this study was to identify inherited craniofacial morphologic features in individuals at risk for cleft of the lip and/or palate. Thirty-three pairs of Caucasian monozygotic twins (17 males, 16 females), discordant for CLP (15 cases), CL (10 cases) and CP (8 cases), aged from 3 to 18 years, were collected from five craniofacial centers (U.S. & Canada). The non-cleft twin of each set was compared to a control individual matched by age and sex from the Burlington Growth Center, Ontario. Postero-anterior and lateral cephalograms were traced and digitized using a computer custom analysis. Descriptive statistics, t-tests and ANOVA were used to test 40 variables. The pooled CL(P) non-cleft twins were significantly different from the controls in the nasal width, cranial base length, cranial base width/length ratio and maxillary width/length ratio. It was concluded that these factors may predispose to the formation of the cleft lip and palate.
Cyclooxygenase-2 knockdown in colon cancer by RNA interference

Overexpression of COX-2 is observed early in colon cancer. Treatments with COX-2 specific NSAIDs, were shown to reduce polyp size and number in FAP patients with a predisposition to colorectal adenoma and cancer. However, the use of COX-2-specific NSAIDs in colon cancer patients has recently revealed increased cardiovascular risks. These harmful side effects may be the result of COX-dependent or COX-independent mechanisms. RNA interference (RNAi) is a method of post-transcriptional gene silencing intrinsic to cells. This thesis explores strategies to specifically downregulate COX-2 expression in colon cancer cells using NSAID treatments and the novel method of RNAi. In HT29 colon cancer cells, COX-2 siRNA treatment for 72 hours resulted in endogenous COX-2 protein knockdown by 60%. Endogenous COX-2 mRNA knockdown corroborated protein results by exhibiting a knockdown of 55% in these same cell lines with independent treatments. Taken together, COX-2 knockdown can be achieved through RNAi in COX-2-expressing cell lines. Such methods of COX-2-specific knockdown may have better potential to be used for chemopreventive measures in the future.
Understanding team learning in a multiprofessional health care setting

The aim of this research is to determine how team-learning activities occur among team members in the multiprofessional context of an academic health care organization. I use a qualitative case study approach to describe the characteristics embedded in the daily interactions of a well-established team of experts from various health professions providing team focused healthcare in a peritoneal dialysis unit. The two broad themes of this thesis reflect team-learning characteristics and activities: First, the nature of the team within an aspiring learning organization and second, the nature of team learning activities focusing on the use of knowledge. These themes are not isolated, but rather are intermingled and represent the learning and functioning of this single well-established multiprofessional healthcare team. Findings support the key point, the role of leaders is crucial in the outcome of teams learning to work together. There are recommendations for healthcare organizations moving towards becoming learning organizations.

Keywords: Group work in education
Medical education
Organizational learning
Evaluating the hyperactivity/inattention sub-scale of the National Longitudinal Survey of Children and Youth (NLSCY)

Objective. To validate the National Longitudinal Survey of Children and Youth (NLSCY) parent-report Hyperactivity/Inattention Scale (NLSCY H/I scale) for use in non-clinical populations. Method . Using logistic regression, the association of the parent-report NLSCY H/I scale is evaluated against Ritalin use, emotional disorder; and impaired school, peer or family functioning in NLSCY sub-sample of 10498 observations, representing 2,360,300 school-age children in 1994/95. Threshold scores with equivalent false negatives and false positives were identified. Using analogous threshold in the nearly-identical precursor scale, the association of a high scale-score with DSM IV diagnosis of ADHD is measured in a clinical sample of 32 case-control pairs. Results. The parent-report NLSCY H/I Scale is associated with Ritalin use [OR = 16.21(95%CI:11.21--23.45)] and emotional disorder [OR = 16.87 (11.31--25.16)]. The analogous precursor scale is associated with diagnosis of ADHD [OR = 16.24 (1.95--135.30)]. Conclusion. The parent-report NLSCY H/I Scale is a valid indicator of ADHD in non-clinical populations.
Globotriaosylceramide (Gb3) expression and membrane presentation: implications for the hemolytic uremic syndrome and human immunodeficiency virus infection

The binding of verotoxin 1 (VT1), verotoxin 2 (VT2) and monoclonal anti-Gb 3 (38.13) to a series of globotriaosylceramide (Gb3) analogues and to structures within the human kidney were compared. These studies indicate a marked heterogeneity of Gb3 expression within renal glomerular tissue and differential binding of VT1, VT2, and anti-Gb3 revealed two distinct phenotypes in the adult. These ligands recognize unique carbohydrate epitopes on the Gb3 sugar and minor chemical derivatization of VT1B can induce subtle changes in Gb3 recognition to significantly affect tissue binding. This histological heterogeneity in human renal glomerular Gb3 expression likely plays a significant, perhaps cholesterol-dependent, role in determining pathology following infection with verotoxin-producing E. coli. Separate studies showed that activation of peripheral blood mononuclear cells, but not T cell lines, with phytohemagglutinin (PHA)/interleukin-2 (IL-2) increases overall glycolipid content and induces Gb3 synthesis that is thought to enable HIV envelope fusion with host cell membranes.
No longer crying in the wilderness: Canadian evangelical organizations and their networks

This dissertation establishes that Canadian evangelicals are no longer, if they ever were, completely isolated from each other and from the communities in which they operate. It explores how networks among evangelical churches influence the functioning of those same churches and their relationship with other organizations in the local community. It does this by examining the nature and structure of the networks evangelical churches are involved in, in one geographical location. It establishes who these evangelicals are, and how and why they interact with each other, and with other organizations in the local community. I conclude that there is significant diversity within the local Protestant religious community; that interconnections among churches can relate to organizational similarity but just as often, cross-denominational, theological, and size boundaries; that reasons for interaction are often functional, rather than based on characteristic similarity; and finally, that direct connections are relatively sparse but indirect connections are plentiful. These conclusions establish that different types of Protestant churches do not line up in two distinct camps opposite in focus in all situations.

Keywords: Church buildings, Canada
The processing-structure-properties relationship of beta (BCC) titanium for orthopedic applications

Beta titanium alloys are being investigated for orthopedic applications due to their lower moduli of elasticity, consequently reducing possible stress shielding effect which leads to bone loss adjacent to integrally-bonded implants. In the present study, cyclic four-point bending fatigue testing was conducted to study fatigue behaviour (initiation + significant crack growth) of a beta titanium alloy, Ti-12Mo-6Zr-2Fe (TMZF) and Ti-6Al-4V, an alpha + beta alloy prepared with sintered titanium porous coatings. Results showed that the Ti-6Al-4V alloy required greater number of cycles for observable fatigue crack initiation compared with the TMZF alloy. The characteristics of the cracks observed in both materials were similar as they all initiated at the particle-substrate sinter neck and developed transgranularly along certain crystallographic planes. The greater number of cycles to develop detectable fatigue cracks in Ti-6A1-4V alloys was believed to be due to the stronger crack propagation resistance of the lamellar alpha + beta structure. Keywords: Beta Titanium, Fatigue, Cyclic four-point bending, Porous coating, Sintering, Orthopedic implants.