VictorJuiz/thesis huggingface dataset:
Role of post-transcriptional fibronection gene regulation in vascular neointimal formation. Modulation by nitric oxide

Closure of the ductus arteriosus, (DA) at term requires prenatal formation of intimal cushions, by a process of smooth muscle cell (SMC) migration into the subendothelium as observed in occlusive vascular disease. Migration of DA SMC in culture depends on increased fibronectin synthesis regulated by a post-transcriptional mechanism involving interaction of a microtubule-associated protein, LC-3, with an AU-rich element (ARE) in the 3′-untranslated region of fibronectin mRNA. In this thesis, we establish a critical role for post-transcriptional upregulation of fibronectin in DA intimal cushion formation in the intact animal. Fetal lamb DAs transfected in utero (90 days) with plasmid encoding decoy RNA to sequester fibronectin mRNA binding protein, LC-3, show inhibition of fibronectin mRNA translation and, at term (145 days), lack of intimal cushion formation with increased lumenal patency. Since NO is implicated in post-transcriptional gene regulation and DA physiology, we investigated its mechanistic role in LC-3-dependent fibronectin synthesis. NO production was 7-fold higher in DA versus aortic SMC associated with increased nNOS expression. The NOS inhibitor L-NMMA decreased fibronectin synthesis by ∼45–50%, whereas the NO donor, SNAP increased DA fibronectin synthesis ∼1-fold without affecting mRNA levels. Immunoblotting revealed that SNAP increased and L-NMMA reduced membrane-associated phosphorylated LC-3 involved in mRNA translation. RNA gel mobility shift assays demonstrated NO-dependent LC-3 binding to fibronectin mRNA ARE. Since TNF-α induced iNOS and fibronectin expression is implicated in vascular disease, we investigated whether an NO-dependent post-transcriptional mechanism was involved. TNF-α induction of fibronectin synthesis in coronary artery SMC correlated with enhanced NO production, was abrogated by the NO synthase inhibitor, L-NMMA, and reproduced with the NO donor, SNAP. TNF-α had no effect on fibronectin mRNA levels but increased LC-3 expression and LC-3-ARE binding in an NO-dependent manner. These data demonstrate a critical role for post-transcriptional upregulation of fibronectin in DA intimal formation, show that this process is regulated by NO, and extend this paradigm to the mechanism of TNF-α mediated occlusive vascular disease.
Participatory design of mobile phone software for seniors

We describe one of the first case studies involving older people (ages 55-86) as co-designers of software for mobile phones. A participatory design team consisting of five older women and a computer scientist met nine times over a period of six months. A software design was created and refined through a blend of group meetings and one-on-one sessions. Based on paper prototypes and participant opinions gathered from these sessions, we present Recall---a software customization that the team developed. We reflected on the process of participatory design with seniors and tested some usability dimensions of the software itself. We present the results of the reflection and testing as themes, integrated analyses, and guidelines for involving seniors in software design. To be successful, participatory software design with seniors requires a clear shared purpose, careful participant selection and meeting structuring, and significant investment in mutual learning activities.
Fractal characteristics of vascular structure and modeling of blood flow in three dimensions

Three-dimensional data of arterial trees in mouse and rat kidneys are obtained using high-resolution computed tomography (microCT). The performance of the General Electric MS8 microCT scanner and different vascular contrast agents are evaluated. Fractal relationships are observed for vessel diameter and conductance but not for segment length. Branching is found to be asymmetric for large vessels but becomes symmetric at smaller scales. The advantages of volume ordering over previous vessel ordering schemes are demonstrated and results are compared with theoretical expectations. The microCT data reveals a fully connected vascular tree with vessels down to 44 mum in mice and 76 mum in rats. Subtree conductances and blood flow in this structure are predicted based on extrapolating segment conductances down to the capillary level. It is the first model of blood flow in a complete organ that is based on the actual three-dimensional geometry of the vascular tree. Subsequent experiments to measure perfusion and vascular structure in the same organ are proposed to validate the model. Validated three-dimensional models of vascular systems are needed to eventually understand and be able to model the development, function, and pathology of complete organs and organisms. They will serve as gold standards for less sophisticated models. This thesis improves our understanding of blood flow physiology in tree-like, arterial vascular systems of complete organs such as the kidneys, lungs, and heart. Models of blood flow and experimental data of kidney morphology are presented based on the concept of volume ordering. A perfused volume of tissue is assigned to each segment within the vascular tree. This volume serves as a measure of scale and defines the volume order number of the segment. The dependence of vascular parameters such as vessel diameter and conductance on scale is examined and termed 'fractal' if it follows a power law as a function of scale. A theoretical, non-geometric model, which assumes fractal vessel segment conductance and scale-independent branching asymmetry, is introduced that produces perfusion heterogeneities similar to experimental observations in sheep hearts.
Measuring impairment consequences in adult patients with dysphagia

Clinician experts, caregivers and patients agreed on the importance of three impairment complications, namely pulmonary, nutrition and psychology. These consequences were included in the new impairment outcome index for adult patients with dysphagia. However, there were differences in perceptions among the three participant groups. Clinicians and caregivers attributed more relevance to the biomedical consequences of pulmonary and nutrition impairment, but patients prioritized in the reverse order with psychology most important. Patient's perceptions themselves also varied according to their recovery trajectory. The prevailing issue for acute patients was illness anxiety or more specifically the 'fear' of choking to death, while for the chronic patients the focus became depression and embarrassment. Dysphagia is a common disorder associated with impairment complications and even death. The overall purpose of this thesis was to develop a new tool that measures impairment status at a point in time in individual adult patients with dysphagia. The new tool was to (a) be simple in nature and feasible for use in all clinical settings and with both in and outpatients; (b) have parts for patient self-administration as well as clinician administration; and (c) be adjustable to address specific impairments. Its items were selected to capture the comprehensive meaning of impairment secondary to dysphagia from the perspectives of clinicians, patients and caregivers. The research next developed a comprehensive item inventory for the new tool. The tool is based on a well-defined conceptual framework specifically targeting the three impairment consequences in individual adult patients with dysphagia, namely pulmonary, nutrition-hydration and psychological impairment. For each impairment the tool addresses current status and risk, thus forming six separate but complementary subscales. Together the six subscales consist of 84 items (20 pulmonary, 18 nutrition-hydration, 46 psychology) that measure current impairment status and 40 items (24 pulmonary, 5 nutrition-hydration, 11 psychology) that measure increased risk for poor impairment. This tool will be important to clinicians because it will be the first to allow them to track impairment complications in their patients and to assess whether their interventions are beneficial in reducing or eliminating these complications.
Leaders helping teachers helping students: the role of transformational leaders in building teacher efficacy

Regardless of how well a centrally-driven reform is designed, it is only when teachers and school leaders have both the will and the capacity to implement reforms, in a conducive situation, that progress is made. At the core of this process of leaders building teachers' will and capacity is the concept of “teacher efficacy.” This dissertation described the relationship between school leadership (based on a model of transformational leadership) and teacher efficacy, in the implementation of large-scale reform. The conceptual framework proposed a relationship between leadership practices and student achievement, with two intervening variables: leadership practices were believed to have an influence on teacher efficacy, which in turn influenced teacher practices, which had an impact on student achievement. This research considered two different views of transformational leadership: both leaders' views of their own practices, and teachers' views of their leaders' practices. The research concerned the implementation of the National Literacy and Numeracy Strategies in elementary schools in England, and was based on surveys of teachers and headteachers in the early stages of implementing these reforms. Data were collected from 2374 teachers, and 417 headteachers and schools. Teachers reported moderate levels of self-efficacy in the implementation of these Strategies. They also saw moderate levels of transformational leadership practices in their leaders. These findings were not surprising in light of other research. The observed modest influence of transformational leadership practices on teachers' efficacy beliefs, however, called into question the expected relationship between these two variables. The thesis concluded that other factors had a stronger influence on building teacher efficacy in this instance—other factors such as the climate of reform overload, the lack of professional engagement in the reform efforts, and perhaps most importantly, the centralized nature of the reform initiative. It seemed likely that more effective leadership practices could have made a difference, but the highly centralized source of the reforms had made it difficult for leaders to become engaged in the process. Further research was recommended to assess the evolution of teachers' efficacy beliefs in the English reform effort, and to further explore the relationship between leadership and teacher efficacy.

Keywords: Educational leadership
School administrators
Teacher effectiveness
Teaching
Teachers
Educational change
Towards an understanding of local autonomy in Judaea between 6 and 66 CE (Roman Empire)

It is generally taken for granted that the authority of Judaean leaders was limited by the Romans from 6--66 CE to the extent that Jewish officials required Roman permission before carrying out such important functions as capital punishment and convening for official judicial purposes. This thesis examines the three critical pieces of literary evidence on which such a determination rests. An analysis of Josephus' Antiquities 20.202 leads to the conclusion that no restriction on the freedom of a high priest to convene a court in capital cases applied prior to 62 CE. An examination of John 18:31 within the context of the Gospel determines that the author introduced his assertion regarding a restriction on the use of capital punishment by Judaean leaders only in order to explain why it was necessary for Pilate to be involved in Jesus' death. Finally, explicit descriptions within the Gospels of official Judaean involvement in the arrest and death of Jesus can be adequately explained as both theologically necessary and strategically advantageous for the survival of the messianic sect. As a result, it makes sense to believe that the Judaean leaders were able to function autonomously in carrying out all the provisions of Jewish law from 6--66 CE, with no limitation on the freedom to assemble officially or carry out capital punishment before 62 CE.
SPARC is required for basal lamina stability by mediating type IV collagen deposition during embryonic development of Drosophila melanogaster

SPARC is a Ca2+-binding ECM glycoprotein whose modular organization is strikingly conserved in metazoa. In all organisms examined, SPARC is a single copy gene whose expression is first detected after zygotic activation of the genome. In Drosophila, SPARC (dsparc) is first expressed at cellularization and becomes enriched in mesoderm and endoderm during gastrulation. By mid-embryogenesis dsparc is expressed by macrophages, which also express other basal lamina components such as Laminin and Type W collagen. Basal laminae are multifunctional, extracellular matrix sheets that promote cell adhesion, migration, differentiation and survival. The dSPARC-enriched basal laminae surround the gut, CNS and overlie the epidermis. An imprecise excision of a P element located within a gene adjacent to the dsparc locus generated a dSPARC RNA null mutant that is embryonic lethal. In dsparc mutant embryos, synthesis of Type IV collagen by macrophages is observed but no Type IV collagen is detected in basal laminae. In Type IV collagen mutant embryos, dSPARC expression by macrophages is dramatically reduced and dSPARC is absent from basal laminae, suggesting that the secretion and assembly of dSPARC and Type IV collagen in basal laminae are interdependent. While the secretion and assembly of Laminin, Perlecan and Nidogen along tissue surfaces appears unaffected in dsparc mutant embryos, the distribution of Laminin becomes discontinuous by late embryogenesis. Moreover, the presence of collapsed tracheae and cuticle holes indicate a loss in tissue integrity. Transgenic expression of dSPARC by macrophages in dsparc mutant embryos restores Type IV collagen association with basal laminae, providing tensile strength to the Laminin network. While the transgenic dSPARC expression by macrophages rescues the tracheal and epidermis defects caused by tissue instability, embryonic lethality is still observed. Defects in dsparc mutant embryos are also observed prior to macrophage deposition of basal lamina components, indicating biological functions for dSPARC unrelated to its role in basal lamina function.
Evidence for enhanced transsulfuration as a mechanism underlying lower hyperhomocysteinemia in patients undergoing home nocturnal hemodialysis

A cross-sectional study of patients (n=33) receiving three different modes of hemodialysis was conducted to examine whether or not lower plasma total homocysteine concentrations ([tHcy]) observed in patients on home nocturnal hemodialysis (HNHD) (6-8 hours/session, 5-7 nights/week) could be explained by increased homocysteine (Hcy) losses in dialysate fluid. Patients on HNHD had significantly lower plasma [tHcy] compared to patients on in-center nocturnal hemodialysis (INHD) (6-8 hours/session, 3 nights/week) and on standard hemodialysis (SHD) (4 hours/session, 3 times/week) and lower plasma total cysteine concentrations ([tCys]) compared to patients on SHD. Patients on HNHD had significantly greater weekly dialysate Hcy losses vs SHD but not INHD and significantly markedly higher dialysate Cys losses than both patients on SHD and INHD. These results suggest that increased dialysate removal of Hcy alone does not explain the lower plasma [tHcy]. Instead this study raises the possibility that Hcy metabolism is enhanced through increased transsulfuration in patients on HNHD.
Morphological correlates of long-term plasticity in the rat neocortex

Discovering the neural mechanisms underlying learning and memory is a critical issue within neuroscience. Synaptic plasticity is a likely candidate for mediating many forms of learning and memory---especially in the neocortex. Since this region's unique electrophysiological properties may play a unique role in learning and memory, knowledge of how synaptic number and structure change in the neocortex may be critical to understanding the link between synaptic structure and function. Towards this understanding, a meta-analysis (study 1) assessed several paradigms of behavioral plasticity, revealing consistent changes associated with enhanced neocortical activity, including increases in bouton size, multisynaptic terminals, axospinuous synapses, and vesicular content. Moreover, opposite changes (i.e., decreased bouton size, multisynaptic terminals, axospinuous synapses, and vesicular content) followed the deprivation of cortical activity. Given this a priori hypothesis for associating cortical synapse activity with morphology, manipulation of these activity levels (study 2) was conducted to verify whether analogous findings would be observed in a single population. Long-term potentiation (LTP) was induced in 6 chronically-implanted Long-Evans hooded rats and induction of long-term depression (LTD) was attempted in 6 additional rats. Six implanted rats served as controls. The induction of LTP resulted in an increase in cortical volume per neuron restricted to the region immediately adjacent to the potentiated site (upper Layer V), reflecting an increase in the number of excitatory axospinuous synapses per neuron. The induction of LTD failed, so these animals were treated as low-frequency stimulation controls. Surprisingly, these animals also produced an increase in cortical volume per neuron restricted to Layer V, caused by an increase in the number of excitatory axospinuous synapses. Thus, it seems that both high- and low-frequency stimulation fail to produce changes in morphology of Layer II/III synapses, despite the implication of synaptogenesis in this layer for behavioral plasticity. Although results are consistent with previous data reporting synaptogenesis following hippocampal LTP and (perhaps) cerebellar LTD, it is unclear how these low-frequency effects fit. Although multiple interpretations are possible, the results call into question any direct and simple relationship between changes in behavioral activity and synaptic plasticity.
Cutaneous wound healing with methacrylic acid-co-methyl methacrylate beads

Methacrylic acid-co-methyl methacrylate (MAA) beads have been shown to induce angiogenesis. The mechanism underlying this response remains unclear. The purpose of this thesis was to develop a wound healing model for evaluation of the mechanism(s) whereby MAA beads induce angiogenesis and to evaluate the impact of MAA beads on the wound healing response. Mice were utilized to test two different models, artificial skin grafting and diabetic wound healing. In the first model, MAA beads seeded into the collagen matrix of artificial skin did not improve graft vascularization. In the second model, topical application of MAA beads to wounds created in diabetic mice stimulated angiogenesis and promoted wound closure. MAA beads did not affect the number of macrophages within the wound however the angiogenic effect may involve a change in phenotype. Wound tissue was further analyzed by flow cytometry to quantify individual sub-populations of cells and permit subsequent analyses using gene microarrays.
Measuring hope: is hope related to problem solving and criminal behaviour in offenders?

In the context of hope theory (Snyder, Harris, Anderson, Holleran, Irving, Sigmon et al., 1991), criminal offending can be described as choosing inappropriate pathways and a lowered sense of agency for desired outcomes. Researchers (e.g., Chang, 1998) have also found that individuals with low hope have inferior problem solving skills, which undoubtedly potentiate criminal behaviour. However, despite theoretical shifts in criminal treatment and corrections (i.e., movement toward strength-based, offender-focused programming), the assessment for recidivism risk has largely failed to incorporate dynamic, psychological risk factors such as hope. Thus, this study investigates the nature of hope in offenders in relation to their problem solving abilities and risk for recidivism. The results indicate that hope is indeed related to problem solving skills and risk for reoffending. The data are discussed in terms of the usefulness of hope in treatment approaches for offenders and incorporating the construct in assessments of risk for recidivism
Predicting long-term airflow obstruction and obliterative bronchiolitis after allogeneic marrow transplantation

Allogeneic marrow transplantation (BMT) may cause obstructive pulmonary function test (PFT) abnormalities associated with obliterative bronchiolitis (OB). In a retrospective cohort of 434 BMT patients transplanted between 1980 and 1997, three models of OB post BMT (linear and logistic regression and recursive partitioning—RP) were used to identify risk factors and develop a predictive index. Diagnostic accuracy of the models was compared. OB was defined as an absolute decrease of 0.1 in one second forced expiratory volume/forced vital capacity (FEV1/FVC) measured on PFT. Based on the concordance index, there is no significant difference between models (RP 0.68, linear 0.69, logistic 0.71). All models had low positive predictive values (0.16–0.20) and positive likelihood ratios (1.6–2.0). Risk factors included chronic graft versus host disease, BMT before 1987, busulfan conditioning and increased age. None of the models was clearly superior and more work is required in predicting post-BMT OB.
Domain characterization of human BRCA1

The first human breast and ovarian cancer susceptibility protein (BRCA1) is a tumour suppressor with an N-terminal RING domain and two tandem BRCA1 C-terminal (BRCT) domains. Although the structures of the two evolutionarily conserved termini have been solved, the structure of the poorly conserved central region remains unknown. To investigate this central portion, twenty-one overlapping protein fragments were designed to collectively encompass the central region. The structures of the soluble and intact fragments were characterized with nuclear magnetic resonance spectroscopy, circular dichroism spectroscopy and limited trypsin proteolysis. All of the protein fragments assayed appeared to be largely disordered. Gel electrophoretic mobility shift assays revealed that six of the fragments bound DNA, allowing the mapping of the published DNA binding region to a higher resolution. The lack of structure in the central region supports a model in which BRCA1 acts as a scaffolding protein for interactions with signalling proteins and DNA.
Surfactant treatment of silt size particles

This study looks at modifying the surface chemistry of silt sized particles using surfactants, to potentially reduce the frost susceptibility of silty soils. Cationic and anionic surfactants are used to treat silt sized glass beads and mine tailings. The behaviour of the surfactant treated and untreated particles is examined using sedimentation, capillary rise, direct shear, and saturated permeability tests. The sedimentation and capillary rise tests are sensitive to changes in surface chemistry, and there exists a relationship between the behaviour exhibited in these two tests. The direct shear and permeability tests on low density specimens show no noticeable effect of altering the particles' surface chemistry. Information about the hydrophobicity/hydrophilicity of the particles can be inferred from the sedimentation rate, final sedimentation volume, and the rate of capillary rise. The effect of treating the particles depends on the type and concentration of surfactant, and the type of particles.