Thèses : « Investigative factors »

1

Pearson, Sally Jennifer. « Factors influencing the disclosure of child sexual abuse in investigative interviews ». Thesis, University of Leeds, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.396561.

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Richardson, Beverley A. « Factors which affect the recruitment of Blacks into the teaching profession : an investigative study ». DigitalCommons@Robert W. Woodruff Library, Atlanta University Center, 1990. http://digitalcommons.auctr.edu/dissertations/2811.

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The purpose of this study was to investigate relationships and differences among the dependent variable of the intent to pursue a career in teaching and the independent variables of opportunities for career advancement, the perceived image of the teaching profession, financial resources available for initial teacher training, expected salary, incentives and benefits, ability to motivate, student discipline problems, and teacher competency tests. Participants in this study (N=150) included high school students who attend different Georgia public schools, and college students who were within their first three years of study in Atlanta University Center schools. Data were secured using the Teaching Interest Survey, developed by the researcher. The design used for this research was nonparametric statistics which included the use of descriptive statistics and Chi Square Contingency. The 0.05 level of significance was used to test the null hypothesis. The major findings for this study were: (a) no significant relationship exists between the intent to pursue a career in teaching and the perceptions of the following: opportunities to advance, image of the teaching profession, expected salary, incentives and fringe benefits, ability to motivate students to learn, discipline problems, and teacher competency tests; (b) a significant relationship was found to exist between the intent to pursue a teaching career and available financial resources for initial training; (c) perceptions of the professional image of teaching were influenced by home town size; (d) the higher the level of education, the more positive the perception of teaching; and (e) perception of teaching as a profession is positively influenced when one has a favorite teacher. The following recommendations were made: (a) early recruitment/intervention programs for young Black students should be incorporated in schools; (b) organizations should be reactivated or created for teacher recruitment; (c) additional resources for initial teacher training should be made available; (d) teachers and organizations should lobby legislators for salary increases; (e) partnerships should be created between school systems and colleges; and (f) a parent volunteer program should be incorporated in schools.

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Raman, Nair R. « An investigative and evaluative study of factors affecting quality of agricultural and farm information services in Kerala ». Diss., University of Kerala, 2004. http://www.keralauniversity.edu/.

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Agriculture is not only a country’s backbone of food, livelihood and ecological security systems, but is also the very soul of its sovereignty. In Kerala population density is high and land is scarce. To achieve sustainable advancement in quality of human life, meeting the domestic food requirement is to be given foremost priority in development plans. As the area of cultivation cannot be increased and growth of population cannot be controlled growth in food production is to be achieved by qualitative improvement in farming. This requires improvements in material inputs, farming techniques, storage technology and research. Effective integration of these factors is tied closely to adequate information flow, which can be ensured only by an efficient information system for agricultural education, research, extension and development. So evaluation and improvement of existing information services is very crucial for sustainable agricultural growth. The study evaluates the existing information resources, facilities, services, possibilities for resource sharing, accessibility of external sources, and the factors that affect the quality and efficiency of information services in agricultural sector. Coverage is limited to the State of Kerala. Sample consist 105 institutions of different levels, and information users consisting of 426 scientists and 220 farmers. Different sets of questionnaires and interview schedule were used to elicit information. The study found that agricultural research conducted at various institutions in the region at huge public expense has generated knowledge for improving production. Along with these huge collections of acquired content is also stored in the sector. But when a farmer, an extension worker, a scientist or an administrator needs information it is not easily accessible. The study found that agricultural sector fails to effectively bank on information resources available due to the lack of an information system and network. Recommends an Agricultural and Farm Information System for Kerala. Suggests a model plan for a computer communication network for resource sharing between the agricultural institutions in the State, which will also ensure, smooth flow of results of research down to the grassroots level to achieve maximum productivity in agriculture.

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Hall, Susan Rebecca. « Assessing emotional distress in abused children during videotaped investigative interviews : The effect of risk and protective factors ». Diss., The University of Arizona, 2001. http://hdl.handle.net/10150/280419.

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Social science research shows that many maltreated children suffer adverse psychological consequences, but less evidence exists to identify which children may be more or less at risk for such effects. In addition, some negative effects may be compounded when abused children interact with the criminal justice system. While public policies and procedures have been modified to address these issues (e.g., courtroom accommodations), little research has assessed which children would benefit most from them. To fill these needs, the present study: (a) tested the concurrent criterion validity of a new clinical-forensic assessment tool, the Videotaped Interview Trauma Assessment List (VITAL), a behavioral observation instrument that, when fully validated, can be used with other methods to assess emotional distress, risk/protective factors, and need for courtroom accommodations in allegedly abused children, and (b) assessed how risk and protective factors affected allegedly abused children's emotions and behaviors during actual investigative interviews. The results from the present study lend support to the concurrent criterion validity of the VITAL, because it functionally measured the children's existing emotional state and assessed the impact of interviewers' questions/statements on children's emotions/behaviors. Results were consistent with prior research on investigative interviewing and risk/protective factors. Specifically, the investigative interviews were generally an uncomfortable experience for the children; however, the presence of one or more sources of social support resulted in statistically significantly lower internalizing ratings (i.e., sadness, anxiety, embarrassment, withdrawal). Similarly, non-offending parental support tended to result in lower internalizing and depression ratings. While ratings of children's internalizing or externalizing emotions/behaviors were not affected by the majority of risk factors proposed in prior research (i.e., higher frequency of abuse, threat or use of force, closer relationship between the alleged abuser and the child, higher degree of intrusiveness of sexual abuse, less time in rapport, and family dysfunction), some trends were indicated (e.g., longest duration of alleged abuse tended to result in the most externalizing behavior, higher number of investigative interviews tended to result in higher internalizing and lower positive ratings). Future validity research on the VITAL is recommended because behavioral instruments are virtually absent in psycho-legal child maltreatment research and practice.

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Alkatheeri, Ayman. « An investigative study on the relationship between organizational factors and knowledge management effectiveness in UAE public organizations : the case study of Abu Dhabi ». Thesis, University of Wolverhampton, 2018. http://hdl.handle.net/2436/622073.

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This study examines the relationship between organizational factors (Culture, Structure, Strategy and Technology) and Knowledge Management Effectiveness (KME) in Abu Dhabi public organizations. The literature indicates that these factors are widely used to explore KME in construction organizations, but little analysis has been undertaken for UAE public construction companies. The government of Abu Dhabi regulates eight different construction organizations. This study obtained 414 samples from the considered organizations. An empirical research with quantitative methods was undertaken. First, a comprehensive literature reviewed enabled the derivation of three hypotheses, which were then verified through a quantitative survey of the eight organizations. A questionnaire was administered to 414 active department managers, supervisors and employees of Abu Dhabi public organizations whose job description indicated responsibility for KME implementation. Descriptive statistical analysis was used to evaluate the organizational factors and KME of the considered organizations. Ordered logistic regression was used to assess the influence of the organizational factors on KME, and factor analysis was used for the extraction of the significant dimensions of these factors. Ordered logistic regression was used to explore the relationships between the significant dimensions found in these factors and KME. It was discovered that there is significant relationship between organizational factors and KME, but only a few dimensions have significant impacts. Therefore, a model was subsequently developed for the improvement of KME in Abu Dhabi public organizations consisting of significant areas and dimensions of factors impacting on KME, which was developed in a group discussion conducted with senior and middle management leaders from the considered organizations, who were responsible for implementing knowledge management. This model was then validated in Abu Dhabi public organizations and the results indicate the areas and factors of Abu Dhabi public organizations' knowledge management leaders that need to be strengthened to improve KME performance.

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Flanders, Judith Ann. « An investigative study of the relationship between single- sex/coeducational school transition and sex role identity and achievement motivational factors / ». Connect to resource, 1992. http://rave.ohiolink.edu/etdc/view.cgi?acc%5Fnum=osu1265288158.

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Costello, Rachel Elizabeth. « Union and Nonunion Employment : An Investigative Study of Factors in the Employment Setting that May Influence the Development of Burnout ». ScholarWorks, 2011. https://scholarworks.waldenu.edu/dissertations/1004.

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The primary goal of this two-phased, sequential mixed-methods study was to discover whether union affiliation is associated with a lower occurrence of burnout in factory workers by comparing union and nonunion workers. The objective was to determine levels of burnout in union and nonunion employees as well their perception of social support in the workplace. The theoretical synthesis consisted of conservation of resources theory and the theory of reasoned action. The Oldenburg Burnout Inventory (OLBI) and the Quality of Worklife Questionnaire were used to identify the characteristics of the workplace (job demands and job resources) and the level of burnout. Quantitative results confirmed the presence of burnout in both sample populations. Regression results for union participants identified both poor management and increased in job demands as significant predictors of burnout. Conversely, regression results for nonunion participants pointed to poor management only as a significant predictor of burnout. Qualitative descriptive and explanatory thematic results provided additional contextual support for the quantitative findings - specifically, that both union and nonunion participants identified management as a primary concern. In addition, union participants also identified manpower and support as primary concerns in the work environment. The findings point to the negative consequences of burnout for the employer and employee and to areas of concern that need to be addressed in the employment setting. Implications for positive social change include the development of programs to minimize the development of burnout and increase an employee's organizational commitment.

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Boateng, Joyce. « An investigative study assessing the success factors and hindrances in the effective resource mobilisation for a municipal entity in the Eastern Cape ». Thesis, Stellenbosch : Stellenbosch University, 2013. http://hdl.handle.net/10019.1/95630.

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Thesis (MBA) -- Stellenbosch University, 2013.
Resources are the heartbeat of an institution. Without adequate resources, an institution will fail to implement its mandate and will also face problems as a going concern that could eventually lead to its collapse, thereby failing the hopes and aspirations of the people it claims to serve. An institution must develop a conscious effort to mobilise its resources by including this aspect in its business strategy and prioritising it. Ntinga O.R. Tambo Development Agency has been established to implement the LED strategy of the O.R. Tambo District Municipality. As a municipal entity this Development Agency is prohibited from trading to realise additional funding and depends solely on grants from the District Municipality, which are on the decline. Registering the entity as a state-owned company (SOC) would allow it to trade to generate revenue and be eligible to collaborate with investors in developing self-sustaining communities. Improving the socio-economic status of any community requires the development of capital infrastructure. Sustainable community development can only be achieved if proper processes are in place to facilitate an all-inclusive community participation process that allows the communities to decide on programmes that will improve their livelihoods and also take their cultural beliefs into consideration. Communities must be empowered to take decisions that affect their future and they must be consulted at the project initiation stage through to its implementation and finalisation. The community programmes that are implemented must be informed by community needs assessments that are properly undertaken and will utilise community resources to meet unmet needs. Successful community programmes are those that are embraced by the communities. Performance monitoring systems are important to assess the attainment of set objectives so that the programme’s impact on the socio-economic status of the communities can be evaluated. Management is responsible for mobilising resources. However, successful resource mobilisation requires the involvement of the board of directors and the establishment of a resource mobilisation advisory council, with its members being well connected. A lean resource mobilisation structure should be maintained and populated when the need arises. Good governance and clean audit reports are catalysts for successful resource mobilisation and all governance structures must be in place to ensure that fraud and theft are limited. Continuous risk assessments are critical in curbing fraud and theft. Relationship management with funders is important. It entails the development of trust and respect. Some funders will invest in a programme based on the common values they share with the organisation. The organisational culture must visibly display the shared values that are lived by all of the organisation’s employees. Resource mobilisation efforts should not rely solely on one income stream, but should be a combination of a number of efforts, from strategic partnerships in the form of public-private partnerships, to property management. An institution must be creative and innovative in adapting its operations in an environment that is ever-changing especially its agility in responding to constant changes in funding institutions’ requirements. Non-compliance with donor funding requirements and investor funding conditions is a barrier to resource mobilisation efforts. Lack of properly qualified personnel to manage investor and donor funding, which could lead to mismanagement of funds, erodes investor confidence in an institution.

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Mruk, Karen. « Small Molecule Investigation of KCNQ Potassium Channels : A Dissertation ». eScholarship@UMMS, 2012. https://escholarship.umassmed.edu/gsbs_diss/621.

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Voltage-gated K+ channels associate with multiple regulatory proteins to form complexes with diverse gating properties and pharmacological sensitivities. Small molecules which activate or inhibit channel function are valuable tools for dissecting the assembly and function of these macromolecular complexes. My thesis focuses on the discovery and use of small molecules to probe the structure and function of the KCNQ family of voltage-gated K+ channels. One protein that obligatorily assembles with KCNQ channels to mediate proper assembly, trafficking, and gating is the calcium sensor, calmodulin. Although resolution of the crystal structures of calmodulin associated with isolated peptide fragments from other ion channels has provided some insight into how calmodulin interacts with and modulates KCNQ channels, structural information for calmodulin bound to a fully folded ion channel in the membrane is unknown. In Chapter II, I developed an intracellular tethered blocker approach to determine the location of calmodulin binding with respect to the KCNQ ion-conducting pathway. Using distance restraints from a panel of these intracellular tethered blockers we then generated models of the KCNQ-calmodulin complex. Our model places calmodulin close to the gate of KCNQ channels, providing structural insight into how CaM is able to communicate changes in intracellular calcium levels to KCNQ channel complexes. In addition to pore blockers, chemical modification of ion channels has been used to probe ion channel function. During my initial attempt to chemically activate KCNQ channels, I discovered that some boronates modulate KCNQ complexes. In Chapter III, the activating derivative, phenylboronic acid, is characterized. Characterization of activation by phenylboronic acid showed that it targeted the ion conduction pathway of KCNQ channels with some specificity over other voltage-gated K+ channels. The commercial availability of thousands of boronic acid derivatives provides a large class of compounds with which to systematically dissect the mechanisms of KCNQ gating and may lead to the discovery of a potent activator of KCNQ complexes for the treatment of channelopathies. All of the electrophysiological studies presented in this thesis were conducted in Xenopus oocytes. Unexpectedly, during the studies described above, the quality of our Xenopus oocytes declined. The afflicted oocytes developed black foci on their membranes, had negligible electric resting potentials, and poor viability. Culturing the compromised oocytes determined that they were infected with multi-drug resistant Stenotrophomonas maltophilia, Pseudomonas fluorescens and Pseudomonas putida. Antibiotic testing showed that all three species of bacteria were susceptible to amikacin and ciprofloxacin, which when included in the oocyte storage media prevented the appearance of black foci and resulted in oocytes that were usable for electrophysiological recordings. This study provides a solution to a common issue that plagues many electrophysiologists who use Xenopus oocytes. Taken together, these findings provide new insights into activation of KCNQ channel complexes and provide new tools to study the structure-function relationship of voltage-gated K+ channels.

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Mucavele, Simao. « Factors influencing the implementation of the new basic education curriculum in Mozambican schools ». Thesis, Pretoria : [s.n.], 2008. http://upetd.up.ac.za/thesis/available/etd-04272009-095504.

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Harrington, Kimberly Stacy. « Intranuclear Trafficking of RUNX/AML/CBFA/PEBP2 Transcription Factors in Living Cells : A Dissertation ». eScholarship@UMMS, 2003. https://escholarship.umassmed.edu/gsbs_diss/104.

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The family of runt related transcription factors (RUNX/Cbfa/AML/PEBP2) are essential for cellular differentiation and fetal development. RUNX factors are distributed throughout the nucleus in punctate foci that are associated with the nuclear matrix/scaffold and generally correspond with sites of active transcription. Truncations of RUNX proteins that eliminate the C-terminus including a 31-amino acid segment designated the nuclear matrix targeting signal (NMTS) lose nuclear matrix association and result in lethal hematopoietic (RUNX1) and skeletal (RUNX2) phenotypes in mice. These findings suggest that the targeting of RUNX factors to subnuclear foci may mediate the formation of multimeric regulatory complexes and contribute to transcriptional control. In this study, we hypothesized that RUNX transcription factors may dynamically move through the nucleus and associate with subnuclear domains in a C-terminal dependent mechanism to regulate transcription. Therefore, we investigated the subnuclear distribution and mobility of RUNX transcription factors in living cells using enhanced green fluorescent protein (EGFP) fused to RUNX proteins. The RUNX C-terminus was demonstrated to be necessary for the dynamic association of RUNX with stable subnuclear domains. Time-lapse fluorescence microscopy showed that RUNX1 and RUNX2 localize to punctate foci that remain stationary in the nuclear space in living cells. By measuring fluorescence recovery after photobleaching, both RUNX1 and RUNX2 were found to dynamically and rapidly associate with these subnuclear foci with a half-time of recovery in the ten-second time scale. A large immobile fraction of RUNX1 and RUNX2 proteins was observed in the photobleaching experiments, which suggests that this fraction of RUNX1 and RUNX2 proteins are immobilized through the C-terminal domain by interacting with the nuclear architecture. Truncation of the C-terminus of RUNX2, which removes the NMTS as well as several co-regulatory protein interaction domains, increases the mobility of RUNX2 by at least an order of magnitude, resulting in a half-time of recovery equivalent to that of EGFP alone. Contributions of the NMTS sequence to the subnuclear distribution and mobility of RUNX2 were further assessed by creating point mutations in the NMTS of RUNX2 fused to EGFP. The results show that these point mutations decrease, but do not abolish, association with the nuclear matrix compared to wild-type EGFP-RUNX2. Three patterns of subnuclear distribution were similarly observed in living cells for both NMTS mutants and wild-type RUNX2. Furthermore, the NMTS mutations showed no measurable effect on the mobility of RUNX2. However, the mobility of RUNX proteins in each of the different subnuclear distributions observed in living cells were significantly different from each other. The punctate distribution appears to correlate with higher fluorescence intensity, suggesting that the protein concentration in the cell may have an effect on the formation or size of the foci. These findings suggest that the entire NMTS and/or the co-regulatory protein interaction domains may be necessary to immobilize RUNX2 proteins. Because RUNX factors contain a conserved intranuclear targeting signal, we examined whether RUNX1 and RUNX2 are targeted to common subnuclear domains. The results show that RUNX1 and RUNX2 colocalized in common subnuclear foci. Furthermore, RUNX subnuclear foci contain the co-regulatory protein CBFβ, which heterodimerizes with RUNX factors, and nascent transcripts as shown by BrUTP incorporation. These results suggest that RUNX subnuclear foci may represent sites of transcription containing multi-subunit transcription factor complexes. RUNX2 transcription factors induce expression of the osteocalcin promoter during osteoblast differentiation and to study both RUNX2 and osteocalcin function, it would be helpful to have transgenic mice in which OC expression could be easily evaluated. Therefore, to assess the in vivo regulation of osteocalcin by RUNX protein, we generated transgenic mice expressing EGFP controlled by the osteocalcin promoter. Our results show that EGFP is expressed from the OC promoter in a cultured osteosarcoma cell line, but not in a kidney cell line, and is induced by vitamin D3. Furthermore, the OC-EGFP transgenic mice specifically express EGFP in osteoblasts and osteocytes in bone tissues. Moreover, EGFP is expressed in mineralized bone nodules of differentiated bone marrow derived from transgenic mice. Thus, these mice produce a good model for studying the in vivo effects of RUNX-mediated osteocalcin regulation and for developing potential drug therapies for bone diseases. Taken together, our results in living cells support the conclusion that RUNX transcription factors dynamically associate with stationary subnuclear foci in a C-terminal dependent mechanism to regulate gene expression. Moreover, RUNX subnuclear foci represent transcription sites containing nascent transcripts and co-regulatory interacting proteins. These conclusions provide a mechanism for how RUNX transcription factors may associate with subnuclear foci to regulate gene expression. Furthermore, the OC-EGFP transgenic mice now provide a useful tool for studying the in vivo function and regulation of osteocalcin by RUNX proteins during osteoblast differentiation and possibly for developing therapeutic drugs for treatment of bone diseases in the future.

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Alamares, Judith G. « Newcastle Disease Virus Virulence : Mechanism of the Interferon Antagonistic Activity of the V Protein and Characterization of a Putative Virulence-Specific Antibody to the Attachment Protein : a dissertation ». eScholarship@UMMS, 2008. https://escholarship.umassmed.edu/gsbs_diss/372.

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Newcastle disease virus (NDV) is a member of the genus Avulavirus of the Paramyxoviridaefamily of enveloped negative-stranded RNA viruses. The virus causes respiratory, neurological, or enteric disease in many species of birds, resulting in significant losses to the poultry industry worldwide. Strains of the virus are classified into three pathotypes based on the severity of disease in chickens. Avirulent strains that produce mild or asymptomatic infections are termed lentogenic, whereas virulent strains are termed velogenic. Strains of intermediate virulence are termed mesogenic. The envelope of NDV virions contains two types of glycoproteins, the hemagglutinin-neuraminidase (HN) and fusion (F) proteins. HN mediates three functions: 1) virus attachment to sialic acid-containing receptors; 2) neuraminidase activity that cleaves sialic acid from progeny virions to prevent self-aggregation; and, 3) complementation of the F protein in the promotion of fusion. Though it is widely accepted that cleavage of a fusion protein precursor is the primary determinant of NDV virulence, it is not the sole determinant. At least two other proteins, HN and the V protein, contribute to virulence. The V protein possesses interferon (IFN) antagonistic activity. The long-range goal of these studies is to understand the roles of HN and V in the differential virulence patterns exhibited by members of the NDV serotype. The first aim is to compare the IFN antagonistic activity of the V protein from a lentogenic and a mesogenic strain of the virus. The results of this study demonstrate that the V protein of the mesogenic strain Beaudette C (BC) exhibits greater IFN antagonistic activity than that of the lentogenic strain La Sota. Hence, the IFN antagonistic activities of the two V proteins correlate with their known virulence properties. Comparison of the C-terminal regions of La Sota and BC V proteins revealed four amino acid differences. The results demonstrate that the IFN antagonistic activity of La Sota V increases when any one of these residues is mutated to the corresponding residue in BC V. Conversely, the IFN antagonistic activity of BC V decreases when any one of these four residues is mutated to the corresponding residue in La Sota V. However, no single residue accounts for the difference in IFN antagonistic activity between the two V proteins. Also, analysis of La Sota V and BC V proteins with multiple mutations in these positions revealed that the four residues are collectively responsible for the difference in the IFN antagonistic activity of the two V proteins. Finally, characterization of chimeric La Sota/BC V proteins showed that the N-terminal region also contributes to the IFN antagonistic activity of V. Contrary to an earlier report, results described here demonstrate that the NDV V protein does not target STAT1 for degradation. However, both La Sota and BC V proteins target interferon regulatory factor (IRF)-7 for degradation and promote the conversion of full-length IRF-7 to a lower molecular weight form (IRF-7*). This is the first demonstration that IRF-7 is targeted by a paramyxovirus V protein. The amount of IRF-7* decreases in a dose-dependent manner in the presence of a proteasome inhibitor, suggesting that IRF-7* is a degradation product of IRF-7. Furthermore, the BC V protein promotes complete conversion of IRF-7 to IRF7*, whereas the La Sota V protein does so less efficiently. Again, this is consistent with the difference in IFN antagonistic activity of the two V proteins, and in turn, with their virulence. The second aim is to characterize an HN-specific monoclonal antibody called AVS-I. A previous study suggested that AVS-I recognizes an epitope that is conserved in lentogenic strains and raises the possibility that this epitope may colocalize with a determinant of virulence in HN. To further characterize antibody AVS-I and the epitope it recognizes, we (i) determined its specificity for several additional strains of the virus, (ii) mapped its binding to HN in competition with our own antibodies, (iii) determined its functional inhibition profile, and (iv) isolated and sequenced an AVS-I escape mutant. The results demonstrate that AVS-I binds to a conformational epitope at the carboxy terminus of HN. This suggests that this region of HN may define a determinant of virulence. However, it was also shown that AVS-I, which was previously thought to be specific for avirulent strains of NDV, actually recognizes individual mesogenic and velogenic strains. In conclusion, the data presented in this dissertation contributes to a greater understanding of the molecular basis for NDV virulence and may aid in development of antiviral strategies and generation of recombinant NDVs suitable for use in cancer and gene therapy.

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Heneghan, John F. « M₁ Muscarinic Modulation of N-Type Calcium Channels : A Dissertation ». eScholarship@UMMS, 2006. https://escholarship.umassmed.edu/gsbs_diss/255.

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The influx of calcium through N-type calcium channels (N-current) affects a myriad of neuronal functions. These include the triggering of synaptic release of neurotransmitter, adjustment of membrane potential and changes in gene transcription. N-channels are highly modulated proteins, so that N-current is attenuated or potentiated in response to environmental changes. In turn, the modulation of N-current has a direct effect on the downstream events, making the N-channel a focal point in neural signaling, and its modulation a mechanism for short term plasticity. The modulation of N-current by M1 muscarinic receptors (M1Rs) is of particular interest for several reasons. The M1R is instrumental in both cognition and memory formation as indicated by studies using either pharmacological agents aimed at M1Rs or knockout animals lacking M1Rs. Clinically, the M1R is an important target in the treatment of Alzheimer’s disease. Thus, like the N-channel, the M1R is an important element of neural signaling. Moreover, the stimulation of M1Rs affects N-current by through signaling pathways which despite being studied for decades, are not completely understood. For my dissertation I have investigated of M1R signaling on N-current using electrophysiological recordings of N-current from freshly dissociated neurons and from HEK cells expressing N-channels and M1Rs. Asking how one receptor affects one type of calcium channel would seem to be a simple question. However, the answer has many facets. Since M1Rs have multiple downstream effects and N-channels are highly modulated proteins, stimulation of M1Rs initiates several different pathways which modulate N-current. This thesis aims to unravel some of the complexities of the interactions of two vital components of neuronal signaling. Here I present the results of studies elucidating three different actions of M1signaling of N-current modulation. The first study I present here examines the effect of N-channel subunit composition on modulation of N-current. The stimulation of M1Rs in superior cervical ganglion (SCG) neurons elicits a distinct pattern of modulation; inhibiting N-current elicited by strong depolarizations and enhancing current elicited by lesser depolarizations. Thus M1Rs cause two simultaneous modulatory effects on N-current; increasing voltage sensitivity and decreasing overall conductance. I found the expression of the N-channel’s β subunit (CaVβ) determines the observed effect. Specifically when the isoform CaVβ2a is expressed M1 stimulation elicits enhancement without inhibition. Conversely, when CaVβ1b, CaVβ3, or CaVβ4 are expressed M1 stimulation elicits inhibition with out enhancement. These results fit a model in which both the enhancing and inhibiting effects of M1stimulation occur in all channels, but typically inhibition dominates. CaVβ2a blocks inhibition unmasking latent enhancement. Moreover, using mutants and chimeras I found palmitoylation of CaVβ2a at the N-terminus plays a key role in blocking inhibition. My findings predict the expression and localization of different CaVβ isoforms would dramatically alter modulation of N-current and thus may represent a previously unrecognized form of plasticity. The inhibition of N-current by M1Rs is controversial. It has been proposed recently that inhibition is directly attributable to the depletion of phosphatidylinositol-4,5-bisphosphate [PtdIns(4,5)P2] during M1 stimulation. However, in our lab, we have found arachidonic acid (AA) release, which occurs subsequent to PtdIns(4,5)P2 hydrolysis, is both necessary and sufficient to elicit inhibition. Therefore, in a second study, I tested the effect of CaVβ expression on N-current during exogenous AA application and found a pattern of modulation identical to M1R stimulation. Furthermore, I took part in a collaborative project identifying the AA producing enzyme, diacylglycerol lipase (DAGL), to be a necessary component of the inhibitory pathway elicited by M1Rs. These findings provide increased evidence for AA release being a key factor in the M1R stimulated pathway of inhibition. Moreover, these discoveries identify the expression of CaVβ2a and use of specific DAGL inhibitors as a molecular and pharmacological strategy to block inhibition of N-current, respectively. These tools allow the dissection of downstream effects of M1R stimulation, so that other modulatory effects may be observed. The phosphorylation of N-channels by protein kinase C (PKC) blocks inhibition of current brought on by G-protein β and γ subunits (Gβγ) binding directly to the channel. Relief of Gβγ inhibition by other means has been identified as a mechanism of short term plasticity. M1Rs are known to simulate PKC, but a connection between M1Rs and PKC phosphorylation of Nchannels had not been demonstrated. I hypothesized that PKC stimulation may be occluded by other downstream effects of M1Rs. Therefore in a third study, I used a pharmacological approach on SCG neurons to dissect the PKC activating pathway from the other downstream effects of M1 stimulation. I observed modulation of N-current indicating a loss of Gβγ&#; inhibition, thus consistent with PKC phosphorylation of channels. This conclusion reveals another aspect of M1 modulation, which can function as a means of short term plasticity.

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Paquette, Sara Montminy. « Evasion of LPS-TLR4 Signaling as a Virulence Determinate for Yersinia pestis ». eScholarship@UMMS, 2009. https://escholarship.umassmed.edu/gsbs_diss/458.

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Yersinia pestis, the gram-negative causative agent of plague, is a master of immune evasion. The bacterium possesses a type three secretion system which translocates Yop effector proteins into host immune cells to inhibit a number of immune and cell signaling cascades. Interestingly, this apparatus is not expressed at low temperatures such as those found within the flea vector and is therefore neither in place nor functional when the bacteria are first transmitted into a mammalian host. However, the bacterium is still able to avoid activating the immune system, even very early during infection. When grown at 37°C (human body temperature) Y. pestis produces a tetra-acyl lipid A molecule, which is antagonistic to the human Toll like receptor 4/MD2, the major lipopolysaccharide recognition receptor. Although tetra-acyl lipid A binds this receptor complex, it does not induce signaling, and in fact inhibits the receptors interaction with other stimulatory forms of lipid A. The work undertaken in this thesis seeks to determine if the production of tetra-acyl lipid A by Y. pestis is a key virulence determinant and was a critical factor in the evolution of Y. pestis from its ancestral parent Yersinia pseudotuberculosis. By examining the enzymes involved in the lipid A biosynthesis pathway, it has been determined that Y. pestis lacks LpxL, a key enzyme that adds a secondary acyl chain on to the tetra acyl lipid A molecule. In the absence of this enzyme, Y. pestis cannot produce a TLR4 stimulating form of lipid A, whereas Y. pseudotuberculosis does contain the gene for LpxL and produces a stimulatory hexa acyl lipid A. To determine if the absence of LpxL in Y. pestis is important for virulence, LpxL from E. coli and Y. pseudotuberculosis were introduced into Y. pestis. In both cases the addition of LpxL led to bacterium which produced a hexa-acylated lipid A molecule and TLR4/MD2 stimulatory LPS. To verify the LpxL phenotype, lpxL was deleted from Y. pseudotuberculosis, resulting in bacteria which produce tetra-acylated lipid A and nonstimulatory LPS. Mice challenged with LpxL expressing Y. pestis were found to be completely resistant to infection. This profound attenuation in virulence is TLR4 dependent, as mice deficient for this receptor rapidly succumb to disease. These altered strains of the bacterium also act as vaccines, as mice infected with Y. pestis expressing LpxL then challenged with wild type Y. pestis do not become ill. These data demonstrate that the production of tetra-acyl lipid A is a critical virulence determinant for Y. pestis, and that the loss of LpxL formed a major step in the evolution of Y. pestis from Y. pseudotuberculosis. These bacterial strains were also used as tools to determine the contributions of different innate immune receptors and adaptor molecules to the host response during Y. pestis infection. The use of LpxL expressing Y. pestis allowed identification of the innate immune pathways critical for protection during Y. pestis infection. This model also established that CD14 recognition of rough LPS is critical for protection from Y. pestisexpressing LpxL, and activation of the IL-1 receptor and the induction of IL-1β plays a major role in this infection as well. The lipid A acylation profile of gram negative bacteria can have a direct and profound effect on the pathogenesis of the organism. This work illustrates a previously unknown and critical aspect of Y. pestis pathogenesis, which can be extended to other gram-negative pathogens. The greater detail of the contributions which different host adaptor and receptor molecules make to the overall innate immune signaling pathway will allow a better insight into how gram negative infections progress and how they are counteracted by the immune system. Alterations of the lipid A profile of Y. pestis have important implications for the production of vaccines to Y. pestis and other gram negative pathogens. Taken together, this work describes a novel mechanism for immune evasion by gram negative bacteria with consequences for understanding the immune response and the creation of more effective vaccines, both of which will decrease the danger posed by this virulent pathogen.

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Vaidya, Harsh Jayeshkumar. « Investigation of transcriptional regulation of Foxn1 in fetal thymic epithelial progenitor cells ». Thesis, University of Edinburgh, 2016. http://hdl.handle.net/1842/21697.

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The thymus in mice and humans originates from the third pharyngeal pouch endoderm. This process is divided into early Foxn1-independent stages and later Foxn1-dependent stages. Foxn1 is indispensible for the differentiation of thymic epithelial progenitor cells (TEPCs) as the development of thymus in Foxn1 mutant mice is arrested around E12.5. The transcriptional changes associated with the developmental of the thymus are poorly understood. In particular, the transcriptional regulation of Foxn1 in the developing thymic rudiment has not been definitively identified. Recently, Pax1, Pax9, Tbx1, and E2Fs have been implicated in transcriptional regulation of Foxn1. However, with the exception of E2Fs, evidence regarding their direct involvement in regulating Foxn1 expression is missing. Therefore, the aims of this thesis were to study the transcriptional regulation of Foxn1 through identification of its regulatory regions and studying the transcriptional changes associated with the developing thymus. These aims were addressed through the use of chromatin-immunoprecipitation technique combined with next-generation sequencing and gene expression analyses of the developing TEPCs. The data presented in this thesis identified H3K4me3 and H3K27ac marked Foxn1 promoter and five H3K4me1 and H3K27ac marked putative enhancer regions. The combination of gene expression analyses and transcription factor binding sites within the above regions suggested Ets1, Isl1, Foxc1, Nfia, Nfib, Srf, Foxo1, Nfatc2, Ing4, Foxa2, Hes1, E2Fs, and p53 as candidate transcriptional regulators of Foxn1. Nfatc2 appears also to be a target of Foxn1 that could play an important role in thymus development by regulating a large set of genes. Comparison of wild type and Foxn1 null thymus showed that Foxn1 could act as positive regulator of Pax1 and negative regulator of Gata3 and Eya1, genes important for third pharyngeal pouch development. The comparison of transcriptome of E10.5 and E11.5 third pharyngeal pouch cells and E12.5 TEPCs showed that genes involved in tissue development are downregulated while those involved in antigen presentation, a process important for thymus function, are upregulated during development. These results also demonstrated a decrease in the activity of transcription factor network involving Hox genes and an increase in the activity of a network involving Nfkb, Rela, and Irf genes. Analysis of signalling pathways suggested that the NFκB signalling pathway could be important for thymus development after E12.5 while TGFβ signalling pathway appeared to be detrimental to Foxn1 expression in thymic epithelial cells. Together, I identified several transcription factors that could be involved in transcriptional regulation of Foxn1 in TEPCs, several genes that could be a target of FOXN1, changes in transcription factor network and signalling pathways associated with the developing thymic rudiment.

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Staines, Zoe Renee. « Knowledge management in criminal investigation : empirical examination and re-conceptualisation of dean's investigative thinking styles ». Thesis, Queensland University of Technology, 2013. https://eprints.qut.edu.au/64111/1/Zoe_Staines_Thesis.pdf.

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This thesis explored the current state of knowledge management in policing. A psychometric instrument was created and validated for use within police agencies as a means of facilitating the capture and transferral of critical investigative knowledge. The aim is to ensure that investigative expertise is not lost when detectives retire or leave the service. Improved knowledge management strategies that rely on this psychometric instrument can lead to greater efficiency and effectiveness in criminal investigation.

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Hing, Benjamin. « Investigating differential regulation of BDNF promoter IV activity by upstream polymorphic evolutionary conserved regions : implications for mood disorders and cognitive disfunction ». Thesis, University of Aberdeen, 2011. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=185597.

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Major depressive disorder (MDD) and bipolar disorder (BD) are psychiatric diseases that affect behavior and impair cognition. A gene important to these disorders is the brain derived neurotrophic factor (BDNF) which is involved in processes controlling neuroplasticity. Previous studies have suggested that BDNF expression levels have to be finely regulated for normal mental health and cognition. This study therefore aimed to identify cis-regulatory elements that regulate BDNF promoter IV (BP4), which plays a role in mood and cognition, and investigated how polymorphisms in these cis-regulatory elements might alter BP4 activity contributing to MDD and BD. BP4-LacZ transgenic mice and primary neuron cultures were used to show that BP4 was active in the hippocampus, cortex and amygdala and responded to PKC, KCl and Wnt signaling activation. Using comparative genomics, two highly conserved regions were identified, BE5.1 and BE5.2, which contain the rs10767664 and rs12273363 polymorphisms respectively. Reporter gene assays in primary cultures derived from these brain structures showed that BE5.1 and BE5.2 were responsible for “filtering” or “gating” the effects of different combination of activated signal transduction pathways on BP4. Thus, BE5.1 increased BP4 response to forskolin in cortical cultures while abolishing BP4 response to PMA in hippocampal cultures. Similarly, BE5.2 permitted BP4 response to KCl and combined forskolin and PMA treatment, but not individual forskolin and PMA treatment nor LiCl in cortical cultures. Significantly, the minor allele of rs12273363, which has been associated with MDD and BD susceptibility, acted as a more potent repressor of BP4 response to neuron depolarization by KCl and PKA/PKC activation in different primary cultures. The possible relevance of these findings to the role of altered BDNF expression in MDD and BD are discussed.

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Mufti, Ahmad. « Investigation of the association of novel genetic factors on von Willebrand factor (VWF) plasma levels ». Thesis, University of Sheffield, 2016. http://etheses.whiterose.ac.uk/12945/.

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Background: von Willebrand factor (VWF) is a large multimeric plasma glycoprotein. It plays an important role in haemostasis by promoting platelet adhesion and aggregation at sites of blood vessel damage and by binding to and prolonging the half-life of coagulation factor VIII (FVIII). VWF is synthesised in endothelial cells where it undergoes post-translational modifications including glycosylation and multimerisation. VWF levels vary considerably in the normal population and several factors have been associated with this variation including ABO blood group and age. However, known factors only account for ~65% of variation in level. Previous studies suggest that other genetic loci, including VWF, FUT3 and CLEC4M also influence VWF level. Aims: To identify genetic factors that influence VWF plasma level in the normal population and to investigate the mechanisms by which these genetic factors influence VWF level. Methods: DNA samples and phenotypic data (including VWF levels, age, gender and ABO blood group) were available for ~1100 healthy individuals (HC). Analysis was conducted on VWF, FUT3, FUT5, FUT6 and CLEC4M. In silico analysis was used to identify variants predicted to affect expression or activity. Variants of interest were then genotyped in HC and their association with VWF level was investigated. In vitro studies were used to investigate the effect of these variants on VWF protein and mRNA expression, exon splice enhancer (ESE) motifs, splicing and mRNA half-life. Results: Investigation of 111 single nucleotide variants (SNV) in VWF identified 11 with significant association with VWF plasma level, of which c.2385T > C and c.2365A > G had been reported in previous studies. In vitro analysis showed that both were associated with increased protein, mRNA level and mRNA half-life. Investigation of variants in FUT3, FUT5 and FUT6 showed that only FUT3 c.202T > C was significantly associated with VWF plasma level. Investigation of CLEC4M confirmed the association of a 23 amino acid variable number of tandem repeats (VNTR) with VWF plasma level. Conclusion: Variants within and outside VWF are found to be significantly associated with VWF plasma level through interfering with protein or mRNA levels. These factors were shown to have an additive effect and can be considered as risk factors for bleeding or cardiovascular disease.

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Saylor, Laurie. « Investigating the relationship between metamemory and memory performance predictions ». Thesis, Georgia Institute of Technology, 1990. http://hdl.handle.net/1853/28772.

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Barbarà, Molinero Alba. « Investigating the factors influencing professional identity on first-year university students : an exploratory study ». Doctoral thesis, Universitat Rovira i Virgili, 2015. http://hdl.handle.net/10803/401741.

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Considerant que la Identitat Professional actua com a mediadora de la decisió d’escollir un determinat camí professional, la present tesi té com objectiu contribuir en el coneixement sobre aquest fenomen, en l’àmbit universitari, mitjançant la construcció d’un marc conceptual integratiu dels factors que incideixen en el procés de construcció de la Identitat Professional dels estudiants universitaris de primer any. En primer lloc, s’han identificat els diferents factors que influeixen en la Identitat Professional, a través d’una revisió de literatura exhaustiva i d’un estudi qualitatiu amb estudiants universitaris de Turisme i Geografia, emprant Focus Groups. Amb els factors identificats, s’ha creat un marc conceptual inicial. En segon lloc, s’ha construït i validat un nou instrument que ens permet mesurar aquests factors (Condicionals Externs, Condicionals Personals, i Condicionals d’Experiència Educativa). En tercer lloc, s’ha analitzat la influència que exerceixen aquests factors en la força de la Identitat Professional dels estudiants, mitjançant múltiples anàlisis de regressió jeràrquica. Finalment, en quart lloc, amb la informació obtinguda, s’ha construït un marc conceptual final. Aquest integra els múltiples factors que influeixen en la Identitat Professional dels estudiants de primer de grau, així com, la influencia exercida per cadascun d’ells, considerant, per separat, els graus, les disciplines i la mostra global. D’aquest estudi es deriven múltiples implicacions per a la universitat en els àmbits de reclutament i d’orientació professional.
Considerando que la Identidad Profesional actúa como mediadora de la decisión de escoger un determinado camino profesional, la presente tesis tiene como objetivo contribuir en el conocimiento sobre este fenómeno, en el ámbito universitario, mediante la construcción de un marco conceptual integrativo de los factores que inciden en el proceso de construcción de la Identidad Profesional de los estudiantes universitarios de primer año. En primer lugar, se han identificado los diferentes factores que influyen en la Identidad Profesional, a través de un revisión de literatura exhaustiva, y de un estudio cualitativo con estudiantes universitarios de Turismo y Geografía, usando Focus Groups. Con los factores identificados, se ha creado un marco conceptual inicial. En segundo lugar, se ha construido y validado un nuevo instrumento que nos permite medir estos factores (Condicionales Externos, Condicionales Personales y Condicionales de Experiencia Educativa). En tercer lugar, se ha analizado la influencia que ejercen dichos factores en la fuerza de la Identidad Profesional de los estudiantes, mediante múltiples análisis de regresión jerárquica. Finalmente, en cuarto lugar, con la información obtenida, se ha construido un marco conceptual final. Éste integra los múltiples factores que influyen en la Identidad Profesional de los estudiantes de primero de grado, así como, las influencia ejercida por cada uno de ellos, considerando, por separado, los grados, las disciplinas y la muestra global. De este estudio se derivan múltiples implicaciones para la universidad en los ámbitos de reclutamiento y orientación profesional.
Taking into account that Professional Identity acts as a mediator to the decision to choose a specific professional path, the present thesis aims to contribute to the knowledge about this phenomenon, in the Higher Education context, through the construction of an integrative conceptual framework of the factors that affect the process of Professional Identity construction of the first-year university students. Firstly, the different factors that influence Professional Identity has been identified, through an exhaustive literature review and a qualitative study with university students from Tourism and Geography, using Focus Groups. Secondly, a new instrument that let to measure these factors (External Motivation Conditionals, Personal Motivation Conditionals, Educational Experience Conditionals) has been constructed and validated. Thirdly, the influence that the identified factors exert on student’s Professional Identity strength has been analysed by using multiple hierarchical regression analyses. Finally, fourthly, with the gathered information, a final conceptual framework has been constructed. This integrate the multiple factors that influence first-year university student’s Professional Identity, as well as the influence exerted by each of these factors, considering, separately, the bachelor degree, the disciplines and the whole sample. From this research, multiple implications for the university, in areas such as recruitment and counsellor guidance, arise

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Aidar, Lucas D. « An investigation into the major influences upon sustainable lifestyle choices in Australia ». Thesis, Griffith University, 2020. http://hdl.handle.net/10072/393195.

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Current human activity is unsustainable in terms of planetary boundaries and citizens and governments in industrialised nations, such as Australia, may need to assume greater responsibility and shift towards more sustainable behaviours and lifestyles. There has been a plethora of research aimed at developing policies which foster more sustainable behaviours and consumption. However, the effectiveness of promoting specific behaviours has been questioned by some authors who argue that encouraging more comprehensive changes in people’s behaviour and time use in the form of sustainable lifestyles may provide a more effective approach to achieving ‘sustainability’ (Backhaus, Breukers, Mont, Paukovic, & Mourik, 2013; Defra, 2011; Shirani, Butler, Henwood, Parkhill, & Pidgeon, 2015; Task Force on Sustainable Lifestyles, 2010). Under the assumption that lifestyle changes may be critical in effecting such a transformation, the aim of this research was to identify the key psychological and behavioural factors that characterise and influence different lifestyle choices in Australian societies. The primary research methodology has been based on an on-line survey. Key explanatory variables adopted were drawn from the Theory of Planned Behaviour, Norm Activation Model, New Ecological Paradigm scale and from the broader literature on sustainable living. The main dependent variable of focus was self-identified commitment to sustainable living (measured on a 4-point Likert scale). The sample consisted of 1,002 participants that were broadly representative of the adult Australian demographic in age, gender and living location. The main findings of this work relate to people’s beliefs about sustainable living, social identities, social norms, and feelings of moral obligation to live more sustainably. Firstly, the notion of a ‘sustainable lifestyle’ is not tied to a fixed definition and can be interpreted somewhat differently by different segments in society. This represents an opportunity for policy makers to reposition inhibiting beliefs such as ‘sustainable living is too expensive or difficult’ towards more ‘attractive’ beliefs about this lifestyle. Further, sustainable lifestyles have potentially strong ties to social identities. Hence, sustainable living may need to be positioned in a manner that minimises inter-group conflicts in social identity formation. Minimising inter-group conflicts can be approached by influencing social norms related to sustainable living (for instance, by ‘normalising’ this lifestyle into a mainstream concept using social marketing techniques). Given the empirical findings of this research, we provide some policy suggestions on how to influence social norms and identities so that sustainable lifestyles might become more appealing to a wider range of individuals in society. Feelings of moral obligation to live more sustainably were not shown to be correlated with the survey respondents’ awareness of worsening environmental conditions. Hence, motivational policies – that are guided by a ‘positive psychology’ perspective – may represent worthwhile avenues to influencing individuals to feel more responsible and morally obliged to (want to) adopt sustainable lifestyles. These ‘motivational policies’ may also be actioned via people’s social identities and social norms. For instance, people are more likely to be influenced by others in their ‘ingroup’ (e.g. their shared social identity group, such as political orientation). Hence, messages aimed at encouraging more sustainable living, which originate from other ingroup members (for instance, members of the same political identity) have the potential to be more well-received by certain segments in society. Lastly, ‘sustainability’ is a broad concept that can be interpreted in different ways. As such, to indicate somewhat more narrowly what this study was referring to in discussions of ‘sustainability’ and ‘sustainable lifestyles’, the degrowth scenario was used as the overarching theoretical platform. Degrowth emphasises the importance of reducing material consumption (one of the behaviours investigated in this research) and argues that ‘technology fixes’ may be insufficient to achieving a sustainable scenario. Degrowth also advocates for a temporary and controlled economic contraction as a precursory step to a ‘steady state’ economy. Lastly, the literature on degrowth was used in this study to help validate the argument that encouraging a wide-spread adoption of sustainable living in Australia (through policy interventions) is a likely ‘necessity’ for sustainability.
Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Environment and Sc
Science, Environment, Engineering and Technology
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Curran, Julie M. « An investigation of genetic variation in the clotting factors fibrinogen and factor XIIIa in athero-thrombotic disease ». Thesis, University of Oxford, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.301801.

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Eames, Hayley. « The Interferon Regulatory Factor 5 (IRF5) interactome : investigating the role of co-factors in regulation of inflammation ». Thesis, Imperial College London, 2013. http://hdl.handle.net/10044/1/29848.

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Interferon Regulatory Factor 5 (IRF5) is a key transcription factor that regulates inflammatory responses by acting as a mediator of macrophage plasticity. IRF5 is expressed at high levels in pro-inflammatory (M1) macrophages where it drives expression of characteristic M1 markers, such as IL-12p40, IL-12p35 and IL-23p19, and inhibits expression of typical markers of anti-inflammatory (M2) macrophages, like IL-10. In this way, IRF5 polarises macrophages towards a pro-inflammatory phenotype. There are two modes of IRF5 activity: 1) direct binding to Interferon Stimulated Response Element (ISRE) sites in the DNA, and 2) indirect recruitment via protein- protein interactions. IRF5 can be indirectly recruited via interactions with the RelA subunit of Nuclear Factor kappa B (NFκB) at multiple inflammatory loci genome- wide, including Tnf. This suggests protein-protein interactions between the two factors are of great importance for driving inflammatory gene expression. My research shows the IRF Association Domain (IAD) of IRF5 and the Dimerisation Domain (DD) of RelA form an interaction interface between the two proteins. I have identified a short peptide, a region of IRF5 IAD sequence, that can bind to RelA, and hypothesise this peptide could block IRF5-RelA interactions, potentially dampening expression of inflammatory mediators co-regulated by these two factors. I have also identified a novel co-factor of IRF5: Krüppel Associated Protein 1 (KAP1) by a proteomic screen consisting of affinity purification coupled to mass spectrometry. The IRF5-KAP1 complex is present in M1 macrophages, and absence of KAP1 in this cell type results in prolonged TNF secretion, suggesting that KAP1 is important for 'switching off' Tnf gene expression. Further investigation showed KAP1 is important for regulation of a heterochromatin (H3K9me3) environment downstream of the Tnf locus. By understanding the IRF5 interactome, we hope to unravel and potentially manipulate the determinants of IRF5's key role in inflammation in a cell-type and activity-specific manner.

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Martin, Christopher School of Biomedical Engineering UNSW. « Investigation of exogenous growth factors ; platelet derived growth factor, insulin-like growth factor binding protein and fibroblast growth factor, and their influence on in vivo bone repair ». Awarded by:University of New South Wales. School of Biomedical Engineering, 2006. http://handle.unsw.edu.au/1959.4/30405.

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This research investigated if exogenous growth factors (GFs), in particular platelet derived growth factor (PDGF), has an in vivo effect on the healing response of normal healthy bone. The research was orientated to study whether a clinical beneficial effect could be demonstrated. To achieve this two animal models were utilised, namely, a rabbit tibial osteotomy model and an ovine tibial defect and porous implant ingrowth model. The rabbit model comprised of a unilateral V-shaped tibial osteotomy, stabilised with an absorbable intramedullary pin and figure-of-eight tension band suture, with a 3 week survival period. The GFs tested in this model were 3 concentrations of PDGF, a single dose of insulin-like growth factor binding protein (IGF-BP) and a combination of the two. Each osteotomy was injected with a single bolus of collagen (control) or collagen containing GF (treatment) during surgery. After sacrifice tibiae were CT-scanned in situ, harvested and subject to 4-point bend testing. The callus, underlying bone and contralateral bone's greyscales and mechanical testing results were used for comparative analysis. The ovine model consisted of implanting 6 small rectangular shaped titanium alloy porous implants and one empty defect bilaterally in sheep's tibiae, for 4 and 6 weeks. The sheep were injected with tetracycline bone marker at 2 week intervals. The model's characteristics and any positional effects were initially investigated. Followed by an investigation into the influence of various exogenous GFs on the healing response and ingrowth characteristics of bone into the porous implants. The GFs investigated were PDGF, IGF-BP and fibroblast growth factor impregnated into the porous implants in a collagen carrier. Comparative analysis was done on results from 3-point bend testing of the bone/implant interface, image analysis to quantify percentage of bone, from scanning electron microscopy images of implant sections and confocal microscopy images of tibial defect sections. Analyses indicate that the GFs investigated have a direct and quantifiable positive in vivo effect. The more significant finding is that the growth factors have a potent systemic effect. These results were confirmed by both the sheep porous bone plug model and the rabbit tibial osteotomy model used within this research.

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Shaw, Gregory John Information Technology &amp Electrical Engineering Australian Defence Force Academy UNSW. « An investigation into the performance of different group communication modes : using soft systems methodology to investigate factors ». Awarded by:University of New South Wales - Australian Defence Force Academy. School of Information Technology and Electrical Engineering, 2007. http://handle.unsw.edu.au/1959.4/38733.

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This thesis has two distinct research threads. One thread examines the effectiveness of technology support on the performance of focus groups. Unlike previous research, the work described in this thesis addresses the fundamental issue that groups are social systems, and that comprehensive measurement of the effectiveness of group activities requires assessment of both the task-oriented and social aspects of the group activity. In this research, four different communication modes are used to compare group effectiveness. The second research thread in this thesis is the use of Systems Thinking, and specifically Soft Systems Methodology (SSM), as the framework for inquiring into the effects of technology support on group effectiveness. The strategy in this thesis for developing and evaluating hypotheses extends the general descriptions and guidance in the literature on using SSM for hypothesis testing. Systems thinking also provides the basis for examining the prevailing ???profile deviation??? view that the better the fit between the group task and the technology support the greater the group performance. Using the six perspectives of fit developed by Venkatraman (1989), the most common GSS models and other models developed to examine Task-Technology Fit (TTF) are analysed. The results show that group performance models are most often tested from a ???profile deviation??? perspective and TTF models developed from a profile deviation perspective claim to have predictive and descriptive validity for assessing the level of group performance. To assess whether an SSM based approach can improve the predictive and/or descriptive analysis of the impact of technology support on group work, a field experiment was conducted at the Australian Defence Force Academy. Twenty focus groups of officer cadets assessed their military training program using a GSS in one of four communication modes. The results showed little predictive or descriptive support for the profile deviation perspective of TTF when measuring the group???s overall effectiveness, task effectiveness, participant satisfaction or group relations. The alternative ???gestalt??? perspective, operationalised in this research by using SSM, provided a more comprehensive approach to examining the effectiveness of technology support for group work.

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Ruark, William Lennie. « A question of religion : an investigation of architecture of resistance ». Thesis, Georgia Institute of Technology, 1994. http://hdl.handle.net/1853/23113.

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Shonk, David Knight. « An investigation into the therapeutics of architecture ». Thesis, Georgia Institute of Technology, 1990. http://hdl.handle.net/1853/21736.

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Boz, Burcak. « An Investigation Of Seventh Grade Students ». Phd thesis, METU, 2009. http://etd.lib.metu.edu.tr/upload/3/12611276/index.pdf.

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The purpose of this study was to identify seventh grade students&rsquo
computational estimation strategies and factors associated with these strategies. A case study was conducted with five students. They were selected among 116 seventh grade students from a public elementary school in Aegean region. Two sessions of clinical interviews were carried out with each participant. In the first interview session, the Computational Estimation Test, which was consisted of 15 estimation questions, was administered to students with requesting explanations of solving procedure. In the second interview session, students answered to semi-structured questionnaire prepared by the researcher to understand their feelings and thoughts on estimation. The results of the study indicated that students used three kinds of computational estimation strategies, which were reformulation, translation, and compensation. Reformulation was the most used types of estimation and by all interviewees. It was divided into four sub-strategies, which were observed during the interviews, among them rule based rounding was the most preferred one. The most sophisticated strategy was compensation, which was used least frequently by the participants. The other kind of computational estimation strategy was translation, which means changing the operation for handling the questions more easily. Translation strategy was used students who performed well in number sense. Based on interviews and observations, there were some cognitive and affective factors, which were associated with the specified strategies. Number sense and mental computation were two sub categories of the cognitive factors. Besides these cognitive factors, confidence in ability to do mathematics, perception of mathematics, confidence in ability to do estimation, perception of estimation and tolerance for error, which were identified as affective factors, played important role for strategy selection and computational estimation. Good number sense may lead to use of multiple representations of numbers and use of translation strategies. Moreover, mental computation ability may enable students both to conduct reformulation and use compensation strategy easily. Interviewees who had both high confidence in ability to do mathematics and low confidence in ability to do estimation, preferred exact computation and more rule dependent estimation strategies, like rule based rounding. Low tolerance for error may influence students&rsquo
answers, in order to produce them in a narrow interval. Additionally, perception of estimation may lead students recognize estimation as useful and use of variety of computational estimation strategies. According to data analysis, feelings and thoughts about computational estimation may influence interviewees&rsquo
strategy usage, such as students, who had negative feelings on estimation and thoughts about mathematics wanted exactness, generally preferred exact computation process and did not use diverse computational estimation strategies. Students who had poor in number sense and mental computation could not conduct computational estimation strategies. Therefore, the research study may lead to better understanding of students&rsquo
perspectives on computational estimation. With understanding used strategies, and related factors are affecting computational estimation strategies, it might be produce effective instructional designs for teaching computational estimation.

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Kieliszewski, Cheryl A. « Twisted Metal : An Investigation into Observable Factors that Lead to Critical Traffic Events ». Diss., Virginia Tech, 2005. http://hdl.handle.net/10919/29859.

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The purpose of this research was to explore traffic event severity relationships, evaluate the potentiality of a hazardous event, and develop a framework of observable event factors. Data was collected from three regions in Virginia, each assumed to exemplify a unique driving environment due to amount of traffic and infrastructure characteristics. In combination, a broad spectrum of site, traffic, and driver performance variables were accounted for. Observational techniques of surveillance, incident reporting, and inventorying were used to collect site, traffic, and driver data. This effort resulted in 368 observed traffic events that were evenly distributed among the three regions that represented metropolitan, mid-sized city, and town/rural driving environments. The 368 events were evaluated for severity and contributing variables where 1% of the events were non-injury crashes, 10% were serious, near-crashes, 24% were near-crashes, and the remaining 65% were serious errors with a hazard present. Exploratory analyses were performed to understand the general relationship between event severity levels. Binary logistic regression analyses (Î± = 0.05) were performed to further scope predictor variables to identify traffic event characteristics with respect to severity level, maneuver type, and conflict type. The results were that 69 of 162 observed predictor variables were valuable in characterizing traffic events based on severity. It was found that variables could be grouped to create event severity signatures for crashes, serious near-crashes, and near-crashes. Based on these signatures, it was found that there is a trend between severity levels that included a propensity for problems with straight path maneuvers, lateral and longitudinal vehicle control, and information density within the driving environment as contributing to driver error and hence crashes and near-crashes. There were also differences between the severity levels. These differences were evident in the degree of control the driver appeared to have of the vehicle, type of control regulating the driving environment, and type of road users present in the driving environment. Modifications to roadway evaluative techniques would increase awareness of additional variables that impact drivers to make more informed decisions for roadway enhancements.
Ph. D.

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Elbasir, Mahmoud Hassan. « An investigation of factors affecting the adoption of e-payment system in Libya ». Thesis, De Montfort University, 2015. http://hdl.handle.net/2086/11420.

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Electronic payment systems (EPS) have received considerable attention from researchers and business owners worldwide, because of their potential to support economic development and growth. Despite the significant contribution of the growth in EPS to the ability to complete transactions via the Internet, Libya lags significantly behind developed countries in its adoption of EPS. This research focuses on factors affecting EPS adoption and use in Libya, explaining how they positively or negatively affect Libyan customers and organisations‟ willingness to adopt EPS. Data was collected via semi-structured interviews with different stakeholders, including consumers, organisational staff (e.g. Telecommunications Companies, Banks, the Ministry of Telecommunication and Informatics, etc.), and strategic decision-makers (e.g. the Under-Secretary of the Ministry of Communications, Director of Islamic Banking at Bank of Republic). The research implements Grounded Theory methods (GT), in particular the Straussian approach, to analyse, explore, and investigate the socio-organisational, technical, political, and economic factors affecting the adoption of EPS in Libya, and importantly the relationship between these factors. It discusses the impact of the factors identified, from both organisational and consumer perspectives, highlighting the factors and issues that need to be overcome to support successful adoption of EPS. The findings confirm that, for consumers and organisations alike, economic factors (e.g. perceived benefits, cooperation with existing entities, mutuality of stakeholders, Internet costs, standard of living, marketing businesses, awareness, withdrawal control, XX feasibility studies on EPS implementation, Islamic banking services and competition) are the core factors influencing the system‟s adoption. Furthermore, the findings revealed three new and significant factors of relevance to Libya, including standard of living, post coding and the unstable political situation in the country. These represent a unique contribution to the body of knowledge, illustrating the attitude of the Libyan people toward Internet usage, and current obstacles to EPS adoption. The use of substantive GT, in particular the Straussian approach, for data collection and data analysis in the field of EPS adoption, and the assessment of organisational and consumer attitudes, is unique to this research to the best of the researcher‟s knowledge. Thus, the research embodies a substantial contribution to the body of knowledge. The interpretive analysis of data using a Straussian approach has permitted the researcher to attain a deep understanding of the socio-organisational, economic, political, and technical factors affecting adoption of an E-payment system in Libya, as implemented by different stakeholders: Consumers, and Organisational. The benefits that the adoption of EPS in Libya will bring, include facilitation of online transactions, the availability of more secure websites, easier payment and access to the global markets. Furthermore, detailed recommendations are also being offered to assist decision-makers in the development and introduction of EPS in Libya, i.e. including the Communications and Informatics Ministry, which is hoped will advise internet service providers and companies to discount the cost of using the internet for limited bandwidths, in order to insure everyone access to the internet, and EPS.

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Barth, Timothy. « INFLUENCE MAP METHODOLOGY FOR EVALUATING SYSTEMIC SAFETY ISSUES ». Doctoral diss., University of Central Florida, 2006. http://digital.library.ucf.edu/cdm/ref/collection/ETD/id/3271.

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"Raising the bar" in safety performance is a critical challenge for many organizations. Contributing factor taxonomies organize information on why accidents occur. Therefore, they are essential elements of accident investigations and safety reporting systems. Organizations must balance efforts to identify causes of specific accidents with efforts to evaluate systemic safety issues in order to become more proactive about improving safety. This research successfully addressed two problems: (1) limited methods and metrics exist to support the design of effective taxonomies, and (2) influence relationships between contributing factors are not explicitly modeled within a taxonomy. The primary result of the taxonomic relationship modeling efforts was an innovative "dual role" contributing factor taxonomy with significant improvements in comprehensiveness and diagnosticity over existing taxonomies. The influence map methodology was the result of a unique graphical and analytical combination of the dual role taxonomy and influence relationship models. Influence maps were developed for several safety incidents at Kennedy Space Center. An independent assessment was conducted by a team of experts using the new dual role taxonomy and influence chain methodology to evaluate the accuracy and completeness of contributing factors identified during the formal incident investigations. One hundred and sixteen contributing factors were identified using the influence map methodology. Only 16% of these contributing factors were accurately identified with traditional tools, and over half of the 116 contributing factors were completely unaddressed by the findings and recommendations of the formal incident reports. The new methodology is being applied to improve spaceport operations and enhance designs of future NASA launch systems.
Ph.D.
Department of Industrial Engineering and Management Systems
Engineering and Computer Science
Industrial Engineering and Management Systems

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Dang, Yushe. « Investigation of immunoregulatory factors from human decidua ». Thesis, University of Surrey, 1996. http://epubs.surrey.ac.uk/843370/.

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During normal pregnancy, the fetus is not rejected by the maternal immune system despite bearing paternal MHC antigen. It has been proposed that this is due to the local production of immunoregulatory factors by the maternal decidua. This study was designed to investigate immunosuppressive factors derived from early human decidua. In the first part of the study, assays were standardised in order to monitor the immunoregulatory activity of factors derived from human decidua. These included mitogen induced lymphocyte proliferation, mixed lymphocyte culture, and the proliferation of human monocytic and T lymphoid cell lines. Using these assays, two fractions from the FPLC separation of the 10-100 KDa crude decidual supernatant with immunosuppressive activity have been identified and partially characterised. One contained molecules of 183 KDa under non-reducing SDS-PAGE analysis, and 70 and 29 KDa under reducing conditions (large molecular weight fraction; LMWF). Another had molecules of 7-14 KDa under non-reducing conditions (small molecular weight fraction; SMWF). Both of them inhibited mitogen-induced lymphoproliferation and the mixed lymphocyte reaction. In addition they inhibited the growth of a monocytic cell line (Mono Mac 6), but not that of a T lymphoblastic cell line (Jurkat E6.1). The suppression of cellular growth by the LMWF, but not the SMWF, was due to the arrest of the cells in the G0/G1 phase of the cell cycle. Neither fraction affected the expression of MHC class II on Mono Mac 6 cells. The decidua-derived suppressive factors showed some similarity to human transforming growth factor type beta (hTGFbeta), but their activity could not be eliminated by neutralising antibodies to hTGFbeta1 and (32. In contrast to the decidua factors, hTGFbeta1 was able to significantly suppress the expression of MHC class II molecules. In addition, acidification of LMWF decreased their suppressive activity, whereas others have shown that similar treatment of TGFbeta isolated from decidua enhanced its activity. Although some similarity to human decidua-associated protein hDP200 could be demonstrated with LMWF, lgG-like molecules could not be demonstrated in the latter. A low molecular weight protein with immunosuppressive activity-PP14- has been demonstrated in human decidua. Despite similarity, the SMWF clearly showed a distinct M.w distribution pattern to PP14 when analysed by Western blot. This suggests that SMWF was not PP14. In the final part of the study, the supernatants of decidual mononuclear cell cultures (non-fractionated or fractionated) were used to investigate the cells which may produce the factors. The preliminary results suggest that non-leukocytic decidua cells are unlikely to be responsible for the activity. Either T lymphocytes or NK cells are the more likely source, as the suppressive activity was largely increased in populations enriched for these cells, and concanavalin A enhanced their suppressive activity. However, the precise cellular source of these factors needs to be elucidated further.

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Sohi, Jasloveleen. « Investigation of factors regulating parathyroid cell proliferation ». Thesis, McGill University, 1994. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=55530.

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Parathyroid glands are responsible for maintaining normal extracellular calcium concentrations through their release of PTH. Calcium and 1,25-(OH)$ rm sb2D sb3$ have been demonstrated to be potent regulators of PTH and CgA synthesis and release. Primary cultures of quiescent bovine parathyroid cells proliferate in response to high concentrations of serum. Next, I examined the role of c-myc in the proliferation of the PT-r cell line, which was cloned from rat parathyroid cells. In order to study the role of c-myc in PT-r cell proliferation more precisely, I used antisense RNA technology to inhibit c-myc mRNA.
In summary, my studies have shown that parathyroid cells respond to selected growth factors. This proliferative response involves increased expression of c-myc, c-fos, c-jun and PTHrP. 1,25-(OH)$ rm sb2D sb3$ inhibits the expression or c-myc, and cell proliferation is inhited. The differentiated parathyroid cell expresses high levels of CgA and PTH. However, during proliferation these high levels are not sustained.

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Hudson, R. J. « Investigating the factors influencing RDX shock sensitivity ». Thesis, Cranfield University, 2012. http://dspace.lib.cranfield.ac.uk/handle/1826/7501.

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The shock sensitivity of RDX (cyclotrimethylenetrinitramine) is dependent upon factors including crystal size, morphology, internal defects, surface defects and HMX content. With the arrival of reduced sensitivity RDX (RSRDX) and the drive towards insensitive munitions (IM), understanding what influences sensitivity has become a significant topic within energetic materials research. During the RS-RDX international Round Robin Study (R4) the parameters which influence sensitivity were investigated, however large discrepancies were seen between different laboratories so the results were inconclusive. The objective of this work is to clarify how crystal properties and the manufacturing process affect RDX sensitivity. In this study the same RDX lots as those from the R4 were examined. Optical microscopy showed that internal defect content varied widely and was affected by the manufacturing process. A good correlation between sensitivity and defect quantity was seen for RDX lots produced by the same method. Likewise, microscopic examination also showed a large range of morphologies which was influenced by method of production. Scanning electron microscopy also showed that surface defects were approximately correlated to shock sensitivity, however general surface roughness agreed better with sensitivity than the number of specific defects such as cracks and holes. The mechanical properties of the RDX samples were investigated using nanoindentation. This showed a good correlation between the quantity of internal defects and modulus of elasticity, hardness and creep. There was also a good agreement between these parameters and sensitivity. Rheological analysis of RDX/polyethylene glycol suspensions indicated a good agreement between the rheological properties of the suspension and crystal morphology. This method could form a basis for a new testing method for RDX morphology. Differential scanning calorimetry demonstrated that crystal size influenced decomposition rate. The melting endotherm onset temperature and energy was correlated with HMX quantity.

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Rudkin, Justine K. « Investigating the virulence factors of Staphylococcus aureus ». Thesis, University of Bath, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.601682.

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Staphylococcus aureus is an important human pathogen and is a common cause of hospital -associated infections. It has the ability to cause a wide range of diseases, facilitated by a plethora of virulence factors. Resistance to antibiotics has played an important role in the recent evolution of this bacterium, allowing it to persist in the face of antibiotic treatment. The ever- increasing levels of resistance to multiple classes of antibiotics, has earned MRSA the name "superbug". However this antibiotic resistance comes at a biological cost. The aim of this thesis were to examine the negative effect of the methicillin resistance encoding type II SCCmec element on cytotoxicity and investigate the lack of an effect caused by the type IV SCCmec element We found that; The type II SCCmec element is implicated in the reduced cytotoxicity of type Il HA-MRSA. Expression of the mecA gene from the SCCmec element is directly responsible for this effect. High levels of mecA expression are required to produce the loss of cytotoxicity . Loss of cytotoxicity is caused by a lack of Agr quorum system activity. The cell wall of highly resistant type Il HA-MRSAs prevent quorum system signalling. Reduced cytotoxin expression in type IJ HA-MRSAs leads to reduced virulence in a murine model of sepsis. The relatively low level of mecA expression from the type IV element explains the maintenance of cytotoxicity in type IV CA-MRSAs. By increasing the level of mecA expression in type IV CA-MRSA we can reduce cytotoxin production. By addition of sub-inhibitory concentrations of oxacillin to the growth environment of type IV CA-MRSAs we can reduce cytotoxicity and reduce infection related morbidity in an invertebrate model of infection.

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Banting, Esme. « Investigating the psychological factors associated with obesity ». Thesis, University of Oxford, 2017. https://ora.ox.ac.uk/objects/uuid:ac7e230e-a4ec-40c6-a34f-045ee6693b89.

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Obesity is one of the most serious public health challenges of the 21^st century, associated with a range of adverse physical, psychological, social and economic consequences. The aetiology of obesity is complex; however, the psychological factors associated with overweight and obesity remain poorly understood. The first paper critically appraises evidence for three of the most developed psychological theories of obesity. Based on these findings, literature from the fields of emotion regulation and attachment are reviewed, and a novel developmental theory of obesity based on an integration of these theoretical constructs is proposed. Recommendations for future research based on a theoretical framework of emotion regulation are made, and implications for clinical practice including a focus on enhancing caregiver sensitivity are highlighted. The second paper explores the applicability of an established cognitive model of Bulimia Nervosa (BN) and binge eating to an overweight and obese sample. Findings support the relevance of cognitive aspects of the model in an overweight and obese sample, and highlight the potential role of early attachment relationships in the formation of cognitions that make an individual vulnerable to overweight and obesity in later life. Theoretical and clinical implications based on the established cognitive model are considered. Limitations include reliance on self-report and the correlational nature of analyses used. Recommendations for future research with larger, more representative samples to address these limitations are made. Overall, this dissertation makes a unique contribution to the psychological understanding of overweight and obesity, which has the potential to enhance treatment outcomes and suggests useful avenues for further research.

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Clementi, Eric Michael. « An investigation of highway influences on architecture ». Thesis, Georgia Institute of Technology, 1987. http://hdl.handle.net/1853/23982.

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GATNE, KALPAK PRAKASH. « EXPERIMENTAL INVESTIGATION OF DROPLET IMPACT DYNAMICS ON SOLID SURFACES ». University of Cincinnati / OhioLINK, 2006. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1163531264.

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MacIntosh, Caroline Gabrielle. « Investigation of the 'anorexia of ageing' ». Title page, contents and summary only, 2000. http://web4.library.adelaide.edu.au/theses/09PH/09phm15187.pdf.

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Includes bibliographical references (leaves 349-421) Addresses some of the mechanisms which may potentially contribute to the physiological anorexia of ageing, as suggested by previous animal and human studies.

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McSweeney, Andrew S. « An exploratory investigation of the implementation of Lean in a UK automotive plant ». Thesis, University of Bradford, 2017. http://hdl.handle.net/10454/16004.

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This thesis reflects upon several decades of research into Lean Production systems, highlighting the need for further investigation using an empirical study of exemplar implementations of Lean. The initial point of departure is an analysis of the current views of Lean based on a detailed literature review. The resulting Views of Lean Table provides a framework for the investigation of an exemplar Lean operation, viz the Nissan Sunderland Plant, widely regarded to be one of the most productive automotive plants in Europe. The exploratory nature of this investigation, and unique opportunity for access, argued for the use of an inductive single case study as an appropriate research approach. A four phase approach was used to; a) identify views of Lean, b) gain an initial understanding of the Nissan Production Way at the Nissan Sunderland Plant, b) acquire a detailed description of the Nissan Production Way and c) to assess the level of intrinsic motivation amongst employees. The primary objective of this research is to establish whether our current knowledge of Lean sufficiently encapsulates the concept’s many facets. Detailed semi-structured interviews with Nissan Production Way experts revealed that Nissan Sunderland Plant’s production system uses a large number of elements in contrast to the relatively narrow list of ‘Lean’ elements cited in the Views of Lean Table. In contrast to academic theory there was a focus on extrinsic motivation with low intrinsic motivation offset by the plant’s continuous fight for survival and ‘whatever-it-takes’ attitude. In practice Lean is viewed as an overarching philosophy with a toolkit encompassing a wide range of tools which are used when they are suitable for the task in hand.

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Craig, Robert George. « Promoting a career in engineering : an investigation of factors influencing career decision-making in New Zealand ». Thesis, Curtin University, 2012. http://hdl.handle.net/20.500.11937/2313.

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This thesis reports on survey research, conducted on a sample of Year 12 students within New Zealand who attended school in the Greater Auckland region during Autumn 2009. The survey gathered data in order to assess the students’ knowledge, attitudes, and the perceived influences on those attitudes, towards engineering as a career or field of study. The purpose of the research was to better understand factors that may influence Year 12 New Zealanders’ career decisions, especially with respect to careers in engineering, with a view to recommending to stakeholders how enrolment into Bachelor of Engineering programs might be increased.Schools were selected using stratified random sampling, and their Principals were approached through a strategy of emails, telephone calls, and by local personal contact. The students were surveyed via an online questionnaire, administered by school teachers and/or careers personnel, and conducted within school hours. A total of 292 students from 9 schools within the Greater Auckland region took part, and a variety of statistical techniques was used to analyze their responses.The New Zealand students were assessed as having a good knowledge of the benefits and demands of a career in engineering, and a positive attitude towards many of the suggested traits of engineering careers. Contradictions were found between the students’ perceived influences on their career choices, and the patterns of their response choices to a number of the survey questions. Statistically significant relationships were also found between the gender and ethnic background of the survey sample, the students’ attitudes towards careers in general and towards careers specifically in engineering, the influences on those attitudes, and the students’ selection of engineering as a career or field of study.Conclusions were drawn based on the research findings, and recommendations made as to how enrolment into Bachelor of Engineering programs might be increased. The recommendations formulated are directed to practitioners within the engineering profession and also to advisors within the education sector. Recommendations for additional research are then made.

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Hui, Man-ning, et 許文寧. « Investigating the role of SOX9 in human neural stem cells ». Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2013. http://hdl.handle.net/10722/193481.

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Neural stem cells (NSCs) exist in both embryonic and adult neural tissues and are characterized by their self-renewal capacity and multipotency that contribute to the generation of three major cell types in the vertebrate central nervous system (CNS):neurons, oligodendrocytes and astrocytes. The tremendous therapeutic potential of NSCs to treat the neurodegenerative diseases and repair brain injuries has provoked intensive study in the molecular regulation of their induction, maintenance and differentiation. Previous study reported that Sox9, a member of high-mobility-group(HMG) containing SoxE transcription factors family, plays important roles in regulating the formation and maintenance of NSCs in both mouse and chick CNS, as well as the cell fate switch between neuronal and glial. Whether it plays similar roles in human NSCs (hNSCs)is still unknown. My RT-qPCR analysis showed that SOX9is expressed at a basal level in human embryonic stem cells (hESCs) and up-regulated upon commitment into neural lineage and maintained at a high level in hESCs-derived hNSCs. I therefore hypothesized that SOX9 might also be involved in the induction, maintenance and differentiation of hNSCs. To test this, two stable hESC lines(HES2)were generated with each constitutively expressing short hairpin RNA (shRNA) against SOX9andGL2 Luciferase (Luc, as control) respectively. Upon neural induction, SOX9-knock-down(KD) hESCs were able to commit neural lineage and differentiate into NSCs/neurospheres (NSPs), however, these NSCs exhibited reduced multipotency and glial marker (GALC, CD44) expressions but enhanced self-renewal compared to the shLuc NSCs. Hence, SOX9 is required for both the induction and maintenance of multipotent hNSCs. Strikingly, extensive TUJ1+ neurites and advance groupings of these neurites into bundles were observed in SOX9-KD NSPs after three days and seven days neuronal differentiation respectively, suggesting premature neurogenesis as a result of SOX9 ablation. In addition, RT-qPCR analysis revealed down-regulated expression of NSC marker HES1but induced proneural basic helix-loop-helix transcription factor MASH1in shSOX9-1208 NSCs. The inhibitory role of HES1 on the expression and functions of MASH1 has been reported to be essential for the timely generation of neurons. Hence, ablation of SOX9 is likely to relieve the inhibition on MASH1activity via down-regulated HES1expression and leads to early neuronal differentiation. Expression of the potent neurite blocker NG2 was also found to be reduced in SOX9-KD NSCs which may explain the extensive neurite network observed. Altogether, similar to previous studies in mouse NSCs, SOX9 is also required for the induction and maintenance of hNSCs. However, this study further reveals a putative novel role of SOX9 in preventing premature neuronal differentiation by regulating the expressions of HES1 to counteract MASH1 function and NG2 to control neurite outgrowth.
published_or_final_version
Biochemistry
Master
Master of Philosophy

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Hegde, Nagaratna Shridhar. « Investigating the molecular mechanism of thiostrepton inhibition of FOXM1 activity ». Thesis, University of Cambridge, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.609983.

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Notari, Mario. « Investigation of the biological role of iASPP in vivo ». Thesis, University of Oxford, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.589601.

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The p53 family of transcription factors, which comprises the products of the TP53, TP63 and TP73 genes, is at the hub of different signalling pathways that determine the fate of a cell. In vitro, the p53 family posses a tumour suppressive function. However, in vivo, although p53-deficient mice develop spontaneous tumours, p73 and p63 KO animals show defects in neuronal and epidermal development, respectively. The ASPP family of proteins also consists of three members: ASPP 1, ASPP2 and iASPP. They are evolutionarily conserved binding partners and specific regulators of p53-, p63- and p73- mediated apoptosis in vitro. In contrast to ASPPl and ASPP2, the biological significance of iASPP in vivo and the possible interaction with p53 family members remains unclear, and it is the subject of this study. To investigate the role of iASPP in vivo, a transgenic mouse model was generated in which iASPP expression is controlled by the Cre/loxP recombination system. Deletion of iASPP resulted in the development of a cardiocutaneous disorder which displayed features of Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC), defects in hair follicle position and impaired epithelial stratification. iASPP loss resulted in a sudden, premature and arrhythmic mode of death of all iASPP mutant mice. iASPP deficiency induced p53-dependent apoptosis in embryonic hearts and dilation of the right ventricle, however, the inactivation of p53 alleles only rescued the fibro-fatty deposits present in iASPP KO hearts. Mechanistically, iASPP locates at the polar ends of cardiomyocytes where it matches the location of other proteins known to be involved in the etiology of ARVC and in maintaining the integrity of intercalated discs. Loss of iASPP also resulted in increased differentiation of primary keratinocytes both in vitro and in vivo. Consistent with this, iASPP bound p63 and inhibited the transcriptional activity of both T Ap63a and T Ap63α and ΔNp63 in vitro, and regulated the expression level ofp63-regulated genes such as envoplakin. These results demonstrate that iASPP prevents cardiocutaneous disorder through its ability to inhibit p53-induced apoptosis and to influence the integrity of intercalated disc. Moreover, iASPP is also an important regulator of p63 and is involved in controlling epithelial stratification in vivo.

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Green, Darren Michael. « Investigation of factors affecting skin penetration in vitro ». Thesis, Cardiff University, 2006. http://orca.cf.ac.uk/55436/.

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When desirable retardation of skin penetration of toxic compounds such as pesticides and chemical warfare agents was evaluated using model permeants, retardation was observed under certain conditions, but was not predictable. It was concluded that generic penetration modulation was not a realistic goal. Investigations into skin surface sampling techniques highlighted the difficulties of minimising variability, and comparison of in vitro tape stripping with published in vivo data for a clobetasol propionate cream demonstrated the significance of formulation inhomogeneity. Determination of orally administered doxycycline in the stratum corneum using in vivo skin surface biopsies suggested that it was unlikely that this technique could be of value for most orally administered drugs. Evaporative loss of volatile permeants, such as fragrances, during skin penetration studies makes it impossible to achieve full mass balance. Direct capture of evaporating material was occlusive and significantly affected the amount that permeated through the skin membranes. A simple novel method was therefore developed to allow estimation of evaporative loss under the experimental conditions. Pre-study skin water permeability coefficient (Kp) is frequently used as a membrane integrity check and it is generally assumed that skin of higher water permeability will be of higher permeability for subsequently applied compounds, regardless of differing physiochemical properties. However, it was shown that Kp did not correlate with subsequent test compound permeation for twelve compounds of moderate to high lipophilicity.

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Tollan, Clare Josephine. « Investigation of factors controlling cutaneous circulation in flaps ». Thesis, University of Glasgow, 2012. http://theses.gla.ac.uk/3164/.

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The aim of this research was to investigate the blood supply to the lower abdomen. This is a commonly used donor site for autologous reconstruction following breast cancer and the flap of tissue used is based on the deep inferior epigastric circulation (DIEP flap) or the superficial inferior epigastric circulation (SIEA flap). A pilot study investigated the feasibility of assessing the vascular territory of multiple blood vessels in the lower abdomen, and also observed the timing of changes in skin blood supply after free flap transfer. Further studies included sampling using microdialysis catheters, from different areas of the flap, around the theoretical time of opening of choke vessels between angiosomes. Manipulation of skin blood flow was initially investigated using capillary malformations as a model, observing current clinical use of EMLA and AMETOP topical anaesthetic pre-laser treatment.

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Mutiso, Lori A. « Factors Influencing Depression in Men : A Qualitative Investigation ». UKnowledge, 2015. http://uknowledge.uky.edu/nursing_etds/15.

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The purpose of this qualitative descriptive study is to describe men’s experiences of depression in order to provide direction for future research of the screening, diagnosing, and treatment of men's depression. Previous research indicates that men experience different depressive symptoms than women, and there is a possibility that men's depression is not being adequately captured by current screening standards, which would theoretically lead to a large number of men with unrecognized, undiagnosed, and untreated depression. If this is the case, this may explain the disproportionately low number of men diagnosed with depression compared to women, in contrast to the disproportionately high number of men who complete suicides. There is a need in the literature for descriptions of depression experienced by men in order to determine the adequacy of current psychometric screening tools and approaches to treatment which are currently in practice. This qualitative study seeks to begin to fill in this gap in the literature. Key findings indicate that intentionally and unintentionally hide their feelings of depression, and that men experience anger as an early sign of depression. In addition, men often do not recognize their distress as depression until someone else suggests they seek professional help; and men use various methods of distraction to cope with their distress, including excessive working, sleeping, eating, TV watching, and alcohol consumption. Recommendations for further research are discussed.

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Griffith, S. Jayne. « An investigation of psychosocial factors in back pain ». Thesis, University of East Anglia, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.267468.

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The thesis describes a number of qualitative and quantitative studies in the investigation of psychosocial risk factors for back pain and absenteeism. A study of information processing 'biases' was completed comparing three diagnostically different chronic pain groups. Back pain and arthritis patients devote greater processing resources towards illness information than healthy controls. Development of a pain schema is suggested to be related to the personal meaning of pain. A further cross sectional investigation of psychosocial factors associated with back pain in a care assistant population was conducted. Work factors including perception of physical strain and job satisfaction; psychological factors such as pain beliefs, emotionality and family pain history and measures of pain in the last month were assessed. Results found that people reporting back pain had significantly lower job satisfaction, were older and worked significantly longer as care assistants than those reporting a mixture of pain symptoms. Reporting of general pain symptoms and absenteeism was also investigated. This was followed by a longitudinal study of care workers at risk of back pain. Negative emotionality and job satisfaction were identified in a logistic regression as being significant predictors of back pain at six months. High negative emotionality scores at baseline were significantly correlated with high numbers of pain symptoms at follow-up. Difficulties in conducting longitudinal risk research are discussed. The development of the pain schema was investigated by distributing word stem tasks to a variable pain population at baseline and follow-up. People reporting three or more pain symptoms and high pain frequencies were more likely to give higher pain sensory completions. At follow-up, as number of pain symptoms increased over six months so did the number of pain affective responses. The final study was a qualitative investigation of the meaning of back pain in thirty two care assistants using semi structured interviews. Findings suggest that patients delay seeking treatment when they perceive high susceptibility of back pain in the iii working environment, low severity of back pain and few benefits of treatment. Such findings are further discussed within the principals of the Health Belief Model (Becker, 1974).

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Westacott, Mark Conway. « An investigation of psychological factors underlying auditory hallucinations ». Thesis, University of East Anglia, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.296872.

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Al-Saidan, S. M. H. « An investigation of some factors affecting transdermal permeation ». Thesis, Robert Gordon University, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.354972.

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Thèses sur le sujet « Investigative factors »

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