VictorJuiz/thesis huggingface dataset:
Mechanisms of gene regulation in the undifferentiated intestinal epithelium

Analysis of gene expression and regulation in undifferentiated intestinal epithelial cells may provide information useful in the understanding of development, differentiation and pathogenesis in the intestinal epithelium. The intestinal epithelium is a unique tissue in which to study molecular aspects of development and differentiation. During development, regional and cell-specific differences in gene expression are established during a period of rapid cellular expansion, cytodifferentiation and morphogenesis, and then maintained despite continuous cell proliferation and migration-associated differentiation in the adult tissue. Most intestinal pathologies, including carcinogenesis, derive from primitive, undifferentiated progenitor cell types whose patterns and mechanisms for regulating gene expression are poorly understood at present. This thesis is the result of an attempt to increase our knowledge in this area by studying the regulation of P-glycoprotein, a membrane transporter mediating the multidrug resistant phenotype in a variety of tumours, and OCI-5/Glypican 3, a proteoglycan involved in the Simpson-Golabi-Behmel overgrowth syndrome, in primitive intestinal epithelial cells. Analysis of P-glycoprotein isotype expression in the intestinal epithelium identified expression of Class II P-glycoprotein transcript in undifferentiated intestinal cell types. The promoter region of the Class I gene was characterized and an enhancer element identified which functions specifically in undifferentiated intestinal epithelial cells. Characterization of OCI-5 expression in the same type of intestinal cells revealed induction by changes in cell shape associated with confluence. Isolation of the OCI-5 promoter identified positive and negative promoter regions conserved across species. Confluence-dependent induction was mediated by the release of a block to transcriptional elongation. These studies have identified novel mechanisms for gene regulation in the undifferentiated intestinal epithelium. Insight into the normal biology ot primordial intestinal cells will provide a basis for future study of the changes which result in lineage commitment and lead to disease.
Bristol fashion, the maritime culture of Bristol, 1650-1700

Most literature dealing with early modern seamen assume that these men were segregated from the rest of society. Yet, little research into the nature of seafarer's connections to their communities has actually been done. This thesis offers an examination of Bristol seamen between 1650 and 1700. In this specific example we discover that the image of the "Jack Tar," so often applied to early modern seafarers, does not hold true, at least for the Bristol example. Bristol seamen had strong ties to other members of the maritime community, but their links were not exclusive to their fellow seafarers. Their occupational sub-culture was suffused with associations based on family ties, religious affiliation, ethnicity, friendship and neighbourhood. In this they were little different from other men and women of the period. The women of the maritime community were important in keeping open the lines of communication between their husbands and the local community while the men were at sea. The "occupational widowhood" which resulted from their husband's extended absences gave these women a degree of freedom not allowed to other women. To some it proved a boon, to others a bane. While traditional bonds and the presence of their wives provided continuity and stability in their port lives, the labour of Bristol's merchant seamen was undergoing an evolution between 1650 and 1700. This transformation mirrored other changes occurring in the larger community of the city. The consolidation of trans-Atlantic trade which had altered the membership of the city's economic elite began to influence the make-up of crews on Bristol ships. As seamen's wages fell, trade increased and the educational standards needed for masters rose, the social make-up of mariners and sailors began to change. This resulted in a greater degree of social distance between mariners and sailors.
Implementation issues in the introduction of computers into the Iranian education system

This study investigated the introduction of computers into the Iranian educational system, the rationale for introducing the Computer Studies course, and most importantly, the implementation process. The first main focus of the study was to identify the factors and conditions that were important in the computer implementation process. The second focus was to examine how these factors relate to models of implementation of innovation, particularly to Fullan's model which was used as the theoretical framework, and to examine the strengths and weaknesses of his model as applied to the situation of Iran and other developing countries. Participants were samples of different groups involved in the innovation, namely policy makers, principals, teachers, computer lab managers, students and parents. The data collected consisted of questionnaires, semi-structured interviews, policy documents and on-site observations in Iranian high schools in Isfahan (one of the largest Iranian cities). The high rate of questionnaire returns and interview participation demonstrated the participants' interest in cooperating to improve the computer education in Iranian high schools. The results of the study confirm that the identified implementation issues in using computers in Iranian schools were similar to those in other developing countries, e.g., lack of hardware, software and maintenance, lack of trained people, lack of clarity about the objectives, motivational problems, gender inequity in relation to using computers, and the programming language used as well as the little educational software that was available was in English and culturally inappropriate. The findings also indicated that certain characteristics of the Iranian situation that strongly influenced the implementation process are not emphasized, or overlooked in the theoretical assumptions of the more common models of implementation derived from experience in western industrialized countries. On the basis of these findings, the researcher offered suggestions both for additional elements to be considered in formulating theories of implementation for developing countries and for measures to be taken by national authorities such as those in Iran for coping with technological change in schools. The study was innovative in that it examined the role of situational factors, in particular factors of traditional societies in transition: socio-economic, socio-cultural factors and political stability, in the implementation of technological change. The data provided substantial evidence for the importance of socio-cultural and socio-economic factors in the implementation of the Computer Studies course. However, political stability was not dealt with in-depth and needs more research. Any implementation model should take into consideration the role of situational factors in a given society.
Teacher intervention within dramatic play

This study examines the dramatic play of five year olds when one of the active participants is their teacher, and considers the place of dramatic play in a school setting. The teacher-researcher investigated the dramatic playing in a kindergarten environment using a qualitative methodology. The data was collected by observing and recording the events and dialogue in a journal. An examination of the recorded events revealed that dramatic playing is a learning medium that five year olds use to explore ideas which results in their growth as learners. The teacher as a participant is an intervention agent who supports the development of dramatic play initiated by five year olds. This thesis reveals that dramatic playing can provide educators with an environment in which they can intervene in role while observing the children and assessing possible areas of development and exploration. Within this context, a teacher can participate in the children's social, cognitive and aesthetic development. Dramatic play often is chosen by five year olds to experiment and explore ideas and concepts. By supporting the children's choice of dramatic play, the teacher can observe the players' development through integrated learning. Large blocks of time, a variety of materials, and books to be read aloud representing many genres are resources that a teacher can use to enhance dramatic playing. "Being as if" and "what if" are two characteristics of dramatic playing that promote problem solving. The players, as others, can pose questions, try out ideas, and analyze, reflect, modify and extend responses. In creating texts, the children reinforce and develop language strategies and skills. Dramatic playing gives the teacher a context in which he/she can be a participant as well as an observer of young children's learning.
Psychological sequelae of minor motor vehicle accidents, vulnerability and protective factors

This study examined the psychological sequelae of minor motor vehicle accidents (MVAs). One hundred adult volunteers were assessed for symptoms of depression, anxiety, intrusion and avoidance resulting from the minor MVA using standardized measures. It was hypothesized that a group of victims of minor MVAs would report severe psychological symptoms regardless the minor nature of their accidents and that the group with severe symptoms would differ from the group with minimal symptoms in the intervening variables. It was also predicted that the hostility received in the recovery environment would have a more significant relationship to psychological symptomatology than the support received. Twenty-five percent of the sample reported severe depression and 47% reported severe anxiety. Significant levels of post traumatic stress were reported by 65% of the participants involved in minor MVAs. Results indicate that the experience of the MVA as threatening to the victim's life is a factor which increase vulnerability for higher psychological symptomatology after minor MVAs. Significant patterns of relationships among the different symptom severity groups and the pre-MVA, MVA and post-MVA variables were found using MANOVA. Individuals with a tendency to experience negative affects were found to be at risk to develop severe levels of anxiety and depression following a minor MVA but this vulnerability was not found to have an effect on the severity of post-traumatic symptoms. Results suggest that the exposure to previous traumatic events do not predispose MVA victims to higher symptomatology after a minor MVA but that previous experiences of traumatic events in which there has been a death threat may have a vulnerability effect. This vulnerability effect may be related to reactivation of traumatic memories. The incidence of severe symptomatology after a minor MVA was comparable to results of research involving severely injured MVA victims, suggesting that the severity of the injury in a MVA may not play an essential role in the development of psychological symptoms, instead, subjective factors such as fear for one's life and environmental factors such as hostility in the recovery environment, may play a more significant role in the severity of symptomatology. Hostility received in the recovery environment accounted for more of the psychological symptom variance of the MVA sample than the support received. The findings of the current research point to the impact of negative relationships in the post-MVA environment and to the detrimental effects of a hostile family environment in the development of severe psychological symptoms. Social support was not found to be a protective factor for symptom severity. The lack of importance of support as a protective variable for psychological symptoms after minor MVAs in the context of the significant importance of hostility as a vulnerability factor is perhaps the most interesting finding of the present study.
Hydrocarbon yield of pyrolytic graphite due to low-energy hydrogen irradiation

Recent developments with gaseous divertors in tokamaks have led to prospects of less energetic ion bombardment (10's of eV) in the divertor region. Previous low-energy results indicate that an H-ion induced chemical erosion process is occurring which is distinct from that observed for high impact energies (300 eV-3 keV). Furthermore, there is some discrepancy in the literature as to the magnitude of the isotopic effect due to H$\sp+$ and D$\sp+$ impact at these low energies. In the present experiments, mass spectrometry in the residual gas is used to perform a systematic study of hydrocarbon formation rates as a function of pyrolytic graphite temperature (300-1000 K) and ion energy (10-200 eV) for mass-analysed H$\sp+$ and D$\sp+$ beams (10$\sp{18}$ ions/m$\sp2$s). This provides a unique opportunity to also investigate isotopic effects. The results can be used to optimize operating conditions in a tokamak fusion reactor. The present results indicate that, as the ion impact energy is reduced, there is a reduction in the maximum chemical yield (Y$\sb{\rm m}$) and that broadening of the temperature dependence for hydrocarbon formation does, in fact, lead to significant erosion for low-energy impact at room temperature. These room-temperature methane and total chemical yields display maxima at about 50 eV and decrease as the ion energy is further reduced. Within experimental errors the isotopic effect on the chemical yield was not significant and was generally less than a factor of 1.7. Furthermore, there was strong evidence for changes in the dominating erosion mechanism(s) as the ion energy was reduced below 100 eV. A semi-empirical model has been developed, based on previously identified atomistic processes, with some modifications and additional processes incorporated. In general, this model agrees very well with the present results for methane production due to H$\sp+$ and D$\sp+$ impact. The additional processes, which account for the kinetic effects of the energetic particles, can be used to explain many of the observed erosion features.
The canine as an animal model of human aging and dementia, a behavioral and neurobiological analysis

Behavioral and neuroanatomical techniques were used to study a canine model of aging. Pound source and beagle dogs ranging in age up to 15 years, were tested on a battery of cognitive tasks. All dogs were tested for reward and object approach learning, which contained elements of procedural learning. Dogs were also tested for object and odor discrimination and reversal, object and spatial delayed non matching to sample (DNMS) and landmark discrimination learning. Open field activity and human interaction tests measured noncognitive behaviors. Tissue from a subset of dogs was examined to determine the relationship between cognitive decline and neuropathology as a function of age. Age-dependent cognitive changes were dependent upon: (1) task; (2) breed and/or source; and (3) individual differences. The pattern of cognitive deficits in pound source dogs differed from beagle dogs; aged pound source dogs, but not beagles, were consistently impaired on tasks sensitive to frontal lobe function. A subpopulation of pound source dogs was deficient on tasks sensitive to medial temporal lobe function. Aged beagles, but not pound source dogs, were impaired on procedural learning tasks. In all tasks, some aged dogs performed as well as younger dogs and others were impaired relative to their age-matched peers. Noncognitive behaviors also varied as a function of age and breed but were independent of changes in cognitive function. Quantification of beta amyloid accumulation, present in diffuse senile plaques, revealed an association between neuropathology and cognition that depended upon: (1) breed; (2) task and (3) brain structure. Pound source dogs accumulated significantly more amyloid than similarly aged beagle dogs. Procedural learning task performance did not predict amyloid pathology in either the entorhinal or prefrontal cortices. Tasks containing elements of declarative learning, including object discrimination, reversal, and spatial DNMS were correlated with amyloid pathology in both brain structures in pound source dogs. We could dissociate amyloid accumulation within entorhinal and prefrontal cortex, in beagle dogs, based upon spatial DNMS and visual discrimination learning scores, respectively. Our results suggest that aged dogs show a pattern of cognitive deficits and neuropathological changes that parallel those seen in aged humans and Alzheimer's disease.
Regulation of IFN-Ã expression

The biology of interferon-alpha (IFN-$\alpha$) proteins has best been studied for their induced expression in response to virus infections and their antiviral activities. IFN-$\alpha$ proteins also have potent antiproliferative activities and as such, they are involved in normal cell growth regulation. There is mounting evidence that loss of function or dysregulation of the IFN system may contribute to the pathogenesis of a number of human illnesses. In order to better study the expression of IFN-$\alpha$ genes, a PCR-based approach using consensus IFN-$\alpha$ primers was developed which can detect all 14 members of the IFN-$\alpha$ gene family. Using this approach, IFN-$\alpha$ subtypes were observed to be differentially regulated in response to particular forms of stimuli and in different cell types. For example, three IFN-$\alpha$ subtypes, IFNA1, IFNA2 and IFNA8, accounted for over 80% of the IFN-$\alpha$ mRNA induced in the promonocytic cell line, U937, but less than 50% of the IFN-$\alpha$ mRNA in peripheral blood mononuclear cells (PBMCs). Further studies on the regulation of IFN-$\alpha$ expression in U937 cells revealed that there are distinct forms of IFN-$\alpha$ inducibility in response to particular combinations of "priming" agents and specific inducers. The induced production of IFN-$\alpha$ proteins in U937 cells stimulated with lipopolysaccharide (LPS) or phorbol 12-myristate 13-acetate (PMA) was strictly dependent on pretreatment or "priming" of the cells with IFN-$\alpha$ or IFN-$\gamma.$ Finally, IFN-$\alpha$ induction in U937 cells was determined to require the activity of the dsRNA-dependent protein kinase, PKR. Loss-of-function phenotypes in U937 stable transformant cell clones were generated by overexpression of an antisense PKR transcript or a trans-dominant negative PKR gene. Both types of PKR-deficient cells exhibited impaired induction of IFN-$\alpha$ and IFN-$\beta$ genes, as well as reduced abilities to restrict virus replication. In summary, these results indicate that IFN-$\alpha$ genes are differentially responsive to particular forms of stimuli and that PKR plays a central role in regulating the expression of the IFN-$\alpha$ gene family.
Tandem queues attended by a moving server

Optimization analysis of tandem queues attended by a moving server with holding and switching costs are the main concern in this research. First, as basic models, two-stage tandem queues attended by a moving server are analyzed to find the optimal policies in the first and the second stages in a two-stage tandem queue. It is shown that the optimal policy in the second stage which minimizes the total discounted and long run average holding and switching costs is a greedy and exhaustive policy. Considering greedy and exhaustive policy for the second stage, three different service policies: (i) static, (ii) semi-dynamic (gated-limited) and (iii) dynamic (double-threshold) policies are defined for the first stage of a two-stage tandem queue, an $M/G\sb1 - G\sb2/1$ queue, to respectively deal with situations that (i) no information, (ii) partial information, or (iii) complete information about the number of customers in the system are available. To obtain the optimal static, gated-limited and double-threshold policies, three different models are developed and it is shown that the optimal gated-limited policy is almost independent of the arrival rate if switchover times are zero. For N-stage tandem queue $M/G\sb1 - G\sb2 -{\cdots}-G\sb{N}/1,$ greedy and exhaustive policies downstream of stage 2 are defined and then three different models are developed to find the optimal static, gated-limited and double-threshold policies which minimize the total average holding and switching costs in these queues. Also, optimal policies in N-stage tandem queues with batch arrivals, $G\sp{(x)}/G\sb1-G\sb2-{\cdots}-G\sb{N}/1$ queues, are studied through a new operational tool which reveals the properties of greedy and exhaustive policies and establishes two efficient and accurate heuristic algorithms to obtain the optimal policy. Finally, U-shaped lines which are actually tandem queues attended by moving servers are reviewed and a general definition and classification scheme are presented which organize the previous research and lead to the potential for further research on these lines. Then, by decomposing U-shaped lines into tandem queues attended by a moving server, the effects of switching costs and switchover times on some types of these lines are analyzed.
Molecular analysis of the signaling and transport differences of the B cell antigen receptors of the IgM and IgD classes

Two major membrane immunoglobulin (mIg) isotypes, mIgM and mIgD, are expressed on the B cell surface. Despite their homologous structures, identical antigen specificity and similar functions in B cell activation and antigen presentation, they do differ in certain aspects of signal transduction and intracellular transport mechanisms. Study of a B lymphoma line that phenotypically resembles immature B cells and coexpresses exogenous mIgD and endogenous mIgM molecules has revealed that the two isotypes can mediate opposite growth regulatory signals within the same cell. A detailed analysis of the early biochemical events initiated by the two mIgs has been conducted, and the results indicate that their signaling mechanisms are similar in many aspects but dramatically differ in the regulation of a novel SHP-1 tyrosine phosphatase-associated tyrosyl phosphoprotein, pp44. mIgM signaling, which leads to cell death, induces the association of SHP-1 and pp44, while mIgD signaling does not lead to such an association, and does not induce cell death. This observation has been extended to several other cell lines, and the correlation between mIg-mediated cell death and pp44/SHP-1 association is established. Further experiments suggest that pp44 is a surface membrane glycoprotein, which once tyrosine phosphorylated, is able to engage several signaling proteins. pp44 tyrosine phosphorylation, however, is negatively regulated by SHP-1. Therefore, pp44 represents a novel target of SHP-1 in B cell antigen receptor (BCR) signaling and may play a role in determining its signaling outcome. mIgM and mIgD also differ in their transport mechanism. While both bind to a heterodimer of Ig-$\alpha$ and Ig-$\beta$ in vivo, only mIgM requires Ig-$\alpha/\beta$ for surface expression. Mutagenesis studies were performed and results indicate that the differential dependence on Ig-$\alpha/\beta$ for surface expression lies in the transmembrane region residues of the mIg heavy chains. Furthermore, the roles of Ig-$\alpha/\beta$ and an ER chaperone, calnexin, in the transport of these wildtype and mutant mIgs were studied in detail to elucidate some of the molecular events governing mIg surface expression.