VictorJuiz/thesis huggingface dataset:
G-protein coupled receptor modulation of N-methyl-D-aspartate channel activity

Almost all excitatory synaptic transmission in the central nervous system (CNS) is mediated by the neurotransmitter glutamate. At CAI synapses glutamate-gated ion channels (AMPARs and NMDARs) are important for fast excitatory synaptic transmission and long-term synaptic plasticity. The activity of these ionotropic receptors, and hence the strength of synaptic transmission, is modulated by a variety of post-translational modifications. Growing evidence demonstrates that the post-synaptic response can be altered when other membrane receptors (such as G-protein coupled receptors--GPCR--and receptor tyrosine kinases) are activated. We report here, that activation of D4 dopamine receptors (a GPCR) acts to depress synaptic transmission by inhibiting NMDA channel activity in CAI pyramidal neurons. This effect involves the "transactivation" of a receptor tyrosine kinase, which in turn activates a PLC-IP3R-Ca 2+-calmodulin cascade that enhances [Ca2+]i-dependent inactivation of NMDA receptors. In contrast to these results, activation of metabotropic glutamate receptor-5 (a GPCR) potentiates NMDA receptor currents. This enhancement results from an IP3R/PKC/Pyk2/Src signalling cascade that depends upon co-incident mGluR5 and NNMAR activity. Moreover, we find that co-activation of NMDARs and mGluR5 under low intracellular calcium buffering conditions induces a long-lasting enhancement of excitatory synaptic transmission (i.e., LTP). The dopaminergic and glutamatergic systems have contrasting effects on synaptic transmission, yet they use similar signaling molecules. How such differences occur is unclear, but may involve kinase specific isoforms or the contribution of calcium from different sources. Our findings have the potential to account for the aetiology of several neurological disorders (e.g., stroke, Parkinson's disease, schizophrenia, attention deficit disorder and epilepsy) associated with improper glutamatergic and dopaminergic signalling in the CNS.
A game of cat and mouse, the bullying and teasing experiences of children with cerebral palsy

An exploratory qualitative study was undertaken to determine how ten children, aged 8 to 13, with a diagnosis of Cerebral Palsy describe and experience peer teasing and bullying at school. Seven themes emerged in girls' and boys' descriptions of their experiences of victimization: a two-tiered definition of bullying, the type of abuse endured, negative reactions and emotions, pointing the blame, their failing support systems, friends, and a disabled child as a bully. These themes support the idea that children with physical disabilities experience and interpret bullying similarly to children without disabilities, however both their learning disabilities and the adults' reactions clearly made it difficult for them to deal with their struggles at school. The situations improved for children who were seen by adults to whom they turned, as requiring help, whereas those who were not believed or were ignored continued to experience victimization. This study illuminates the need for professionals and parents to acknowledge the bullying and teasing claims children with physical disabilities make. Without their assistance children will continue to be victimized. Increased education and awareness of peer victimization is essential for anyone dealing with children with disabilities. The study's limitations, the implications for social work practice and future research are discussed.
Holocene and recent sedimentation record from glacier-fed Mud Lake, British Columbia, Canada

Mud Lake, a proglacial lake in the Monashee Mountains of British Columbia, Canada, consists of two sub-basins. Settling from suspension dominates contemporary sediment delivery to the western sub-basin, while gravity flow deposits (slumps and turbidites) dominate in the eastern sub-basin. Deposits in the western sub-basin are couplets of coarse, light coloured laminae alternating with thinner, finer grained and dark coloured laminae and are inferred as carved. The majority of suspended sediment is currently delivered through overflow events during late spring and early summer. A multiple regression model including mean daily temperature in winter, mean daily precipitation in spring, total winter precipitation and mean daily March temperature explains 55% of the observed variation in varve thickness since 1929 AD (Ã = 0.05). Glacial activity in the Mud Lake watershed, as indicated by varve thickness, shows no consistent trend since 1820 AD. Thick deglacial and early post-glacial sediments account for over 65% of infill thickness and contain thick, coarse-grained Bouma-type sequences.
The interaction of district interventions with organizational learning processes in schools and school districts

This study examined the interaction of district interventions with organizational learning processes at the school and district office level. Three research questions guided this study: What is the nature of district interventions in schools? How do district interventions interact with organizational learning processes at the school and district level? What are the reasons for variations in schools' learning from district interventions? This qualitative multi-case study was guided by a conceptual framework developed from a review of literature on school districts, organizational intervention, and organizational learning. District intervention was conceptualized in nine categories of intervention: educational policy, accountability and monitoring, information and feedback, district improvement and strategic planning recruitment and professional development, process facilitation, provision of models and information for school improvement, structural interventions, and cultural/organizational learning interventions. Organizational learning processes were conceptualized as routine and non-routine learning in four dimensions--organizational dialectic, knowledge, task, and learning approach. Potential variables which might mediate the interaction of district interventions with organizational learning processes were also identified through a review of literature. Data for this study were collected at the district office and three schools in one school district in Ontario, Canada. The sample district was chosen because of its involvement in a number of district interventions, including a school and district monitoring intervention in partnership with the Centre for Leadership Development, OISE/UT. For this intervention, the school district had adopted the survey instruments and organizational learning perspective presented in 'Making Schools Smarter' (Leithwood & Aitken, 1995). A major focus of this study was to examine how the monitoring intervention, and other district interventions, interacted with organizational learning processes at the school and district level. Data were collected through semi-structured interviews, document analysis, and observation. The findings of this study were presented in four case studies (district office and three schools) using description, causal networks, and tables to display evidence of organizational learning and to analyze the variables which mediated the interaction of district interventions with organizational learning processes. In addition, a cross-case analysis of data identified main themes and patterns, and synthesized the mediating variable categories across cases and across the four dimensions of organizational learning. (Abstract shortened by UMI.)
Compliance with environmental policies in China, the role of state capacity

The goals of this study are twofold. First, I seek to provide a clear and effective definition of state capacity that enables us to predict whether governments are likely to enforce policy effectively. Second, I examine whether variation in state capacity does indeed predict compliance with government policies. I focus on environmental policy in China to test the usefulness of my conception of state capacity and its consequences. The study employs two analytical approaches. First, relying on quantitative methods, I evaluate the state capacity of ten representative Chinese provinces and their compliance with the environmental policies dictated by the central government of China. This method involves assessing provincial adherence to centrally dictated water quality standards and effluent discharge controls. The results point to the existence of a positive correlation between provincial capacity and relative compliance. The second analytical approach is qualitative in nature. This allows me to move beyond the observed correlation to investigate whether there is a causal relationship between state capacity and compliance. The qualitative analysis involves a detailed assessment of policy compliance in one sample province, Jiangsu. In this case, I evaluate the capacity of municipal governments and the compliance of factories under their jurisdiction. The results point to the central role of state capacity in compliance with policies. The results also point to the importance of factors other than state capacity. Analyses based on the state capacity model will only be accurate if preceded by an assessment of the policies to be enforced. Specifically, the analysis must determine whether the policies have the potential to result in significant change. In addition, the commitment of the government to the policy must be assessed. Governments with substantial capacity will direct it to certain policy goals but not to others. This research provides a state capacity model that can effectively predict government policy implementation and enforcement. Future research should address the relevance of the model in developing countries around the globe and in domains other than environmental policy.
Interaction between mesangial cell signaling and cytoskeletal function and high glucose in response to endothelin-1 and mechanical stretch

In diabetes, glomerular mesangial cells (MCs) are transformed into a sclerotic phenotype. This is due to the direct effect of high glucose, mechanical stretch due to raised intraglomerular pressure, and autocrine growth factors such as transforming growth factor ß1 (TGF-ß1), angiotensin II (ANG II) and endothelin-1 (ET-1). Activation of protein kinase C (PKC) and mitogen-activated protein kinases (MAPKs) has also been implicated. The loss of afferent arteriolar smooth muscle cell contractility in high glucose, leading to intraglomerular hypertension, is mimicked by the vascular smooth muscle cell-like MCs. The purpose of these studies was to: (1) determine the role of PKC isozymes in ET-1-stimulated MC contraction; (2) identify the mechanism of high glucose-induced loss of MC contractile responsiveness to ET-1; and, (3) examine the interaction of high glucose and mechanical stretch on MC PKC and MAPK signaling. In 5.6 mM normal glucose (NG), ET-1 stimulated MC contraction, ' in situ' PKC activity, and the membrane and particulate translocation of PKC-Ã, -[delta], -[epsilon], but not PKC-ßI, -ßII or -[zeta]. In 30 mM high glucose (HG), MCs did not respond to ET-1, despite normal translocation of PKC-isozymes. This was not due to altered Ca2+ signaling or ETA receptor expression. HG increased basal myosin light chain (MLC 20) phosphorylation, but this was not PKC-dependent. HG stimulated F-actin disassembly and the membrane accumulation and activity of PKC-[zeta]. Pretreatment for 24 h with a PKC-[zeta] inhibitor (ZI) restored PKC-[zeta] activity, MC size, F-actin assembly and the contractile responsiveness to ET-1, suggesting that HG-induced MC dysfunction is mediated by PKC-[zeta]-dependent cytoskeletal disorganization and not altered signaling. HG for 48 h enhanced 5 min stretch-induced ERK1/ERK2 activation but not p38, in MCs subjected to 15% stretch on fibronectin. Stretch-induced activation of MAPKs required an intact cytoskeleton and was ß1 integrin-dependent, but was independent of PKC, tyrosine kinase, Ca2+, PI3-kinase or 'src' kinase. Dephosphorylation of ERK1/ERK2 but not p38, was diminished in HG following inhibition of cellular kinases by ATP depletion. This implies reduced phosphatase activity in HG. Enhanced MC ERK1/ERK2 signaling in response to the combined effects of mechanical stretch and HG may contribute to the pathogenesis of diabetic nephropathy.
Leaching, hydration and physical-mechanical properties of spent chromated copper arsenate (CCA)-treated wood-cement composites

With the rapidly increasing amount of the spent chromated copper arsenate (CCA)-treated wood, measures should be taken to recycle it in a more practical, economic and environmentally friendly manner. One promising approach is to use this material as furnish in wood-cement composites, but a better understanding of the interaction between treated wood and cement is needed. This thesis was mainly focused on: (1) Considering the effects of hot water extraction, CCA retention and wood/cement ratio on wood-cement compatibility, by hydration characteristic measurement, x-ray diffractometer (XRD) analysis and strength test. (2) Attempting to increase physical-mechanical properties of cementbonded particleboard (CBPB) made from spent CCA-treated wood, by adding silica fume and adjusting water/cement ratio. (3) Studying the leaching properties of CCA-treated wood-cement composites; finding the origin of leachable CCA components and considering the effect of FeSO4, silica fume, accelerators, water/cement ratio, wood/cement ratio, CCA retention and hydration time on the leaching properties of CCA-treated wood-cement composites. (Abstract shortened by UMI.)
Regulation of the mevalonate pathway by dietary fat and cholesterol in mammary cancer development

Dietary lipids have been implicated in breast cancer development but their precise role and molecular mechanisms of action are poorly understood. The objective of this investigation was to examine in rodent models a mechanism by which dietary polyunsaturated fatty acids (PUFAs) and cholesterol could regulate mammary tumorigenesis. The hypothesis is that mevalonate synthesis mediates the effects of dietary PUFAs and cholesterol on mammary tumorigenesis. 3-Hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase is the rate limiting enzyme in cholesterol biosynthesis that catalyzes the formation of mevalonate which is essential for cell proliferation. Dietary cholesterol was found to increase serum cholesterol and inhibit the development of rat mammary tumors while oxidized cholesterol abrogated both of these effects. Dietary cholesterol decreased mevalonate synthesis in the mammary glands but not in mammary tumors. Mevalonate is also a precursor of isoprenoids that are required for the function of growth regulatory proteins such as H-Ras. Cholesterol inhibited the development of mammary tumors initiated by either 7,12-dimethylbenz[a]anthracene or N-methyl-N-nitrosourea, carcinogens that give rise to tumors with different frequencies of H-ras mutations. Thus, inhibition of mevalonate synthesis may be a mechanism by which cholesterol inhibits tumorigenesis, but the effects are independent of H-ras mutations. The objective of the second part of this work was to determine whether a decrease in mevalonate synthesis could explain the known inhibitory effects of n-3 PUFAs on experimental mammary tumorigenesis. Compared to n-6 PUFAs, n-3 PUFAs decreased mevalonate synthesis in rat mammary glands while increasing the levels of a protein and mRNA transcript with some homology to the low-density lipoprotein receptor (LDL-R). n-3 PUFAs decreased mammary gland HMG-CoA reductase activity and protein levels in wild-type but not LDL-R-deficient mice, suggesting that the LDL-R is required for n-3 PUFAs to decrease mevalonate synthesis in the mammary gland. The changes in HMG-CoA reductase activity observed in these experiments are in agreement with changes in mammary tumorigenesis suggesting that this biochemical pathway may mediate the effects of dietary cholesterol and fat on cancer development. Understanding how lipids regulate breast cancer development may lead to mechanism-based strategies to prevent this disease.
Listen to the (in)mate, a life history, readers theatre (re)presentation of women in Ecuador jails accused of drug trafficking

This thesis, presented in a readers theatre format, is grounded in life history and arts-informed research perspectives. Aimed to reach diverse audiences, the readers theatre script offers an alternative modality to present explanations for women's involvement in the illegal drug trade in Ecuador, South America. Individual life history interviews with seven women accused of drug trafficking are represented in a minimally staged conversation. In a dramatic mode, through scenes and acts, the script momentarily merges women's childhood and family experiences, spousal relationships and child care with their knowledge, or absence of knowledge, and experience in the illegal drug trade. Relevant social science literature provide thesis readers and script audiences with a contextual backdrop to the women's accounts of their lived experience. The inmates' narratives are staged against the background provided by low income households headed by women, "war on drugs" inspired legislation, and Ecuador's political and economic crisis.
After the Fact, Contemporary Feminist Fiction and Historical Trauma

During the 1980s and 1990s, novels dealing with past traumatic experiences in both the public and private spheres appeared with some regularity. These works depict historical atrocities, including slavery and genocide, as well as varying forms of interpersonal violence, and notably childhood sexual abuse. They draw on the growing body of interdisciplinary research and theory which has come to be known as trauma studies, an area of concern heavily inflected by psychoanalytic approaches to memory and narration. Many trauma novels take the form of historical fiction, narrated in the first-person by fictional or fictionalized survivors whose accounts bear witness to the need for violent actions to be admitted into public consciousness. This dissertation proposes that concerns about the construction of identities, chiefly in terms of gender, race, and sexuality, have been grafted onto past events, creating a testimonial and explicitly feminist form of fiction authored by women writers from a range of cultural backgrounds. These novels frequently deal with women survivors, highlighting the relationships between narration, gender, and trauma. The works I examine--Margaret Atwood's 'Alias Grace', Nora Okja Keller's 'Comfort Woman', Joy Kogawa's 'Obasan ', Edwidge Danticat's 'The Farming of Bones' and Julia Alvarez's 'In the Time of the Butterflies'--stress that both trauma and recovery have collective as well as individual dimensions. These novels are explicitly pedagogical, teaching lessons about historical events and emphasizing the need for an ethical engagement with the past. They make claims on readers to function as the receivers of painful and complicated stories, in order to assist in the creation of historical memory. These five Canadian and American novels respond to recent questions raised in a variety of disciplines and contexts about the nature of historical storytelling. With the exception of Margaret Atwood's 'Alias Grace', they counter the dominance of postmodern approaches to historical recreation, focussing instead on the significance of telling apparently transparent, if not always verifiable, truths about the past. These works are acutely interested in the telling of trauma as a socially constructed and meaningful act, one requiring the active participation of both a witness and an engaged listener. Reciting accounts of trauma, and listening to these horrifying narratives, are the primary activities depicted by the novels I study.
Efficient support for IS-IP guaranteed service in an IP-ATM internetwork

The Guaranteed Service (GS) has been proposed to support emerging real-time TCP/IP internet applications with the most stringent QoS demands. In this thesis, we investigate efficient support for GS sessions in an IP-ATM internetwork. We obtained results on the effect of ATM networks on the leaky bucket based characterization of GS flows, which is a very important issue in resource allocation. We also investigated schemes to account for the ATM subnet to the RSVP mechanism in supporting GS sessions. Based on the establishment of a tighter upper bound on GS packet delay, we propose the Combined-Server (CS) scheme, which is very efficient in terms of service rate requirement, buffer requirement at downstream routers, lowest worst-case delay supportable, and multiple ATM subnet handling capability. We also investigated some implementation issues. The CS scheme, together with the recently reported ISAC signaling, provides efficient support for GS sessions in an IP-ATM internetwork.
The development and application of a solid phase technology, a route to no carrier added technetium 99m radiopharmaceuticals

A solid phase labelling process was developed to produce a no-carrier-added (NCA) formulation of technetium-99m radiopharmaceuticals which eliminates an undesirable purification step. Three peptidic N$\sb3$S technetium ligands were covalently attached to several polymeric matrices. The supports were functionalized with maleimide followed by thioether bond formation with the free thiols of the N$\sb3$S ligands. The loading of each was determined by amino acid analysis (AAA) and each was labelled with technetium-99m. The NCA products released from the supports were analysed by HPLC to give radiochemical purities as high as 99.7% and by dose calibrator to give recovered radiochemical yields as high as 81% with a dependance on the polymer type and the loading of the peptidic ligands. AAA indicated the products were essentially carrier-free. The technology was then applied to the streptavidin-biotin system to show that a NCA formulation of a $\sp{\rm 99m}$Tc labelled biotin molecule (RP488) improves binding to streptavidin-agarose conjugated beads in vitro and gives higher in vivo localisation at subcutaneously injected streptavidin-agarose beads in a rat model. The development and application of this solid-phase labelling process demonstrate it to be successful and an important advancement in rsdiopharmaceutical formulation.
A hierarchical community of experts

The unsupervised extraction of high-level representations from data is a difficult problem. Many hierarchical graphical models have been proposed to solve this problem, but all suffer from representational difficulties or problems in generalizing the architecture to multiple layers. A multilayer graphical model is proposed that avoids the difficulties of earlier models. The model combines binary and linear stochastic units in a novel way: The binary units gate the outputs of the linear units. Inference is intractable, so a Markov chain Monte Carlo approximation scheme called Gibbs sampling is used. Normal Gibbs sampling requires that the Markov chain reach equilibrium before samples are used for learning. It is shown that "brief" Gibbs sampling can be used for learning, where the samples are used even though the Markov chain is far from equilibrium. Simulations demonstrate that the network can extract high-level representations from some small but interesting data sets.