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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
381

Development of molecular diagnostic system for detection of hepatitis B virus in blood donations

Fun, Sze-tat., 范思達. January 2003 (has links)
published_or_final_version / Medical Sciences / Master / Master of Medical Sciences
382

The isolation and characterization of phages with lytic activity against Mycobacterium avium subspecies paratuberculosis, and their application using Bioluminescent Assay in Real-Time Loop-mediated isothermal amplification assay for rapid detection

Basra, Simone 10 January 2013 (has links)
The goal of this project was to incorporate bacteriophage with Bioluminescent Assay in Real-Time Loop-mediated isothermal amplification (BART-LAMP) for the rapid detection of Mycobacterium avium subspecies paratuberculosis (MAP). As the causative agent of Johne’s Disease, there are no rapid detection methods that are suitable in specificity and sensitivity. A screening assay for phage isolation was developed, and over 400 samples were screened for the isolation of a bacteriophage against MAP. One novel Mycobacterium phage was isolated and characterized using transmission electron miscroscopy, host range studies, restriction enzyme digestion, and pH and temperature stability. It was sequenced, annotated, and underwent an in silico protein analysis. No pathogenic or lysogenic genes were detected, and it was found to be related to Gordonia phage GTE2. BART-LAMP was applied to the detection of the isolated phage using purely extracted DNA and crude phage lysate, showing that phages could be detected successfully. / Beef Cattle Research Council; Agriculture and AgriFood Canada through Growing Forward initiative
383

Mechanisms behind growth of castration-resistant prostate cancer bone metastases

Jernberg, Emma January 2013 (has links)
Background: The first-line treatment for patients with advanced prostate cancer (PC) is androgen deprivation therapy. This therapy is initially effective, but after some time tumors relapse, predominantly within the bone, and are then termed castration-resistant prostate cancer (CRPC). The majority of CRPC tumors show androgen receptor (AR) activity despite castrate levels of circulating testosterone. AR activity could be caused by several mechanisms including; intratumoral androgen synthesis, AR amplification, AR mutations and expression of AR splice variants. The mechanisms controlling CRPC growth in the clinically most relevant metastatic site, the bone, are not fully identified. The purpose of this thesis was therefore to explore AR expression and possible mechanisms behind CRPC growth in PC bone metastases in order to find mechanisms that could be targeted for treatment and/or predict response to certain therapies. Materials and Methods: We have examined hormone-naïve and CRPC bone metastases samples obtained from patients at metastasis surgery, non-malignant and malignant prostate samples obtained from patients at radical prostatectomy, and PC cell lines cultured in vitro. Analysis has been performed using RT-PCR, whole-genome expression arrays, immunohistochemistry, western blotting, FISH, copy number assays and gene ontology analysis. Functional studies have been made by protein overexpression and knock-down in PC cells in vitro and effects studied by evaluation of cell viability, migration, and invasion. Results: We found that high nuclear AR immunostaining (presumed to reflect high AR activity) in bone metastases from CRPC patients was associated with a particularly poor prognosis, while no difference in AR staining was observed between hormone-naïve and CRPC metastases. Further, expression of AR splice variants (AR-V7, AR-V567es) was associated with a high nuclear AR immunostaining score and shown to be increased in CRPC compared to hormone-naïve bone metastases. High levels (levels in the upper quartile) of AR splice variants in CRPC bone metastases was related to disturbed cell cycle regulation and short patients survival. No differences in steroidogenic enzyme levels were detected between CRPC and hormone-naïve bone metastases. Higher levels of enzymes involved in late steps of androgen synthesis (adrenal gland steroid conversion) were observed in bone metastases than in non-malignant and/or malignant prostate tissue, while the enzyme levels in earlier steps (de novo steroidogenesis) were lower in bone metastases. A subgroup of metastases expressed very high levels of AKR1C3, indicating that this group may have an induced capacity of converting adrenal-gland derived steroids into more potent androgens. This was not associated to CRPC but merely with the advanced stage of metastasis. High protein levels of AR splice variants were found in bone metastases with low AKR1C3 levels, while metastases with high AKR1C3 levels primarily contained low AR variant levels. Furthermore, about half of the CRPC bone metastases showed androgen receptor gene amplification which was associated with co-amplification of YIPF6, and a gene expression pattern that pointed at decreased osteoclast activity, and consequently decreased bone resorption. Conclusions: The majority of CRPC bone metastases show high nuclear AR immunostaining that seems to be associated with a particularly unfavorable outcome after metastasis surgery. Subgroups of CRPC bone metastases could be identified according to presence of AR amplification and expression levels of AKR1C3 or AR splice variants, which might have clinical relevance for treatment of PC patients. / <p>Författaren är även publicerad med efternamnet Hörnberg.</p>
384

Roles of EEF1A2 & PTK6 in breast cancer

Fida, Mariam January 2011 (has links)
Eukaryotic Translation Elongation Factor 1 Alpha (EEF1A) exists as two forms with different tissue specificities and encoded by separate loci: eEF1A1 on 6q13 and eEF1A2 on 20q13.3. eEF1A1 is ubiquitously expressed whereas eEF1A2 expression is normally limited to the heart, brain and skeletal muscles. eEF1A proteins are GTP-binding proteins that recruit an amino-acylated tRNA to the ribosome during the elongation phase of protein translation. eEF1A2 mRNA and protein are highly expressed in 50–60% of primary human breast tumors and metastases but not in normal breast epithelium. Since it is also overexpressed in 30% of primary human ovarian tumors, transforms rodent fibroblasts and increases their tumorigenicity in nude mice, eEF1A2 is considered to be a potential human oncogene. The mechanism of eEF1A2 expression is yet to be determined. Studies showed no gene mutation and no correlation between locus amplification or methylation and gene expression. Phosphate Tyrosine Kinase-6 (PTK6) is also located on 20q13.3. It is 48kb upstream of EEF1A2. PTK6 is a non-receptor tyrosine-kinase that is normally expressed in epithelial linings, prostate, skin and oral epithelium but it is not detected in the normal human mammary epithelium. PTK6 has been found to be expressed in many breast cancer cell lines and in approximately 60% of primary human breast tumors but it has not been detected in normal human breast tissue nor in fibroadenomas. Like other tyrosine kinases, PTK6 phosphorylates and activates downstream substrates that would be predicted to lead to increased transcriptional activity and therefore mediates proliferation of breast cancer cells. PTK6 is considered a prognostic marker of metastasis-free survival in breast cancer independent of the classical markers of tumor size, lymph node involvement and HER2 status. The aim of this project was to characterize for the first time the genomic region containing the two mentioned breast cancer oncogenes and understand their various roleswhether they act in tandem or independently in breast tumorigenesis. Immunohistochemistry was performed on tissue microarrays from 300 breast cancer patients to detect the expression levels of eEF1A2 and PTK6. Tumors that showed a high co-expression were analyzed for the genes’ copy number. An increased copy number of PTK6 was detected but not of eEF1A2 nor of adjacent genes on the 20q13.3 amplicon. To understand the effect of EEF1A2 expression on other genes, microarray analysis was performed on NIH-3T3 cells stably transfected with EEF1A2. Many upregulated genes were associated with different types of cancers. This was further confirmed by real-time PCR. However, when the NIH-3T3 cells were transiently transfected with EEF1A2, the genes that were upregulated in the microarray study showed no change in expression. In conclusion, EEF1A2 and PTK6 act independently and each acts through a different mechanism in breast tumorigenesis.
385

TRPA1 CHANNELS IN COCHLEAR SUPPORTING CELLS REGULATE HEARING SENSITIVITY AFTER NOISE EXPOSURE

Velez-Ortega, Alejandra C 01 January 2014 (has links)
TRPA1 channels are sensors for noxious stimuli in a subset of nociceptive neurons. TRPA1 channels are also expressed in cells of the mammalian inner ear, but their function in this tissue remains unknown given that Trpa1–/– mice exhibit normal hearing, balance and sensory mechanotransduction. Here we show that non-sensory (supporting) cells of the hearing organ in the cochlea detect tissue damage via the activation of TRPA1 channels and subsequently modulate cochlear amplification through active cellshape changes. We found that cochlear supporting cells of wild type but not Trpa1–/– mice generate inward currents and robust long-lasting Ca2+ responses after stimulation with TRPA1 agonists. These Ca2+ responses often propagated between different types of supporting cells and were accompanied by prominent tissue displacements. The most prominent shape changes were observed in pillar cells which here we show possess Ca2+-dependent contractile machinery. Increased oxidative stress following acoustic overstimulation leads to the generation of lipid peroxidation byproducts such as 4-hydroxynonenal (4-HNE) that could directly activate TRPA1. Therefore, we exposed mice to mild noise and found a longer-lasting inhibition of cochlear amplification in wild type than in Trpa1–/– mice. Our results suggest that TRPA1-dependent changes in pillar cell shape can alter the tissue geometry and affect cochlear amplification. We believe this novel mechanism of cochlear regulation may protect or fine-tune the organ of Corti after noise exposure or other cochlear injuries.
386

Outcomes of an audiologic rehabilitation programme for working adults with hearing impairment who do not wear amplification

Grosskreutz, Jessica Susanne Gabriele January 2013 (has links)
Hearing impairment is a chronic health condition that affects increasingly younger age groups. Prevalence rates in the working population are estimated to be between four and nine percent when defined by audiometric loss, and between 30 – 40% when using self-report of hearing problems. Hearing impairment can limit and threaten the social functioning of the affected person. It interferes with oral communication, causing activity limitations and participation restrictions. Additionally, a stigma is attached to hearing loss that can lead to feelings of embarrassment, guilt, anxiety and social exclusion. The stigma also poses a threat to the identity of the hearing impaired person who, in return, manages this threat by concealing or disclosing their hearing impairment depending on the social implications. As a consequence, help–seeking is delayed by a considerable amount of time. Although proven to be an effective intervention, amplification is often rejected by working adults. Another available effective intervention is participating in audiologic rehabilitation (AR) programmes. These programmes focus on stigma reduction and communication strategies. Most existing programmes target an elderly population that had been fitted with hearing aids. No programme for working adults who do not wear amplification is published in the literature. The new AR programme “See it! Hear it! Say it!” had been designed for adults who do not wear amplification and previously trialled in the USA. The purpose of this study was to evaluate the short and mid-term outcomes of a version adapted for the New Zealand context, specifically changes in health related quality of life (HRQoL) and cognitive anxiety. Thirteen participants in two groups participated in the study. The design was a quasi–randomised pre-test/post-test/follow-up test with waitlist design. Outcomes were measured with the International Outcome Inventory – Alternative Interventions (IOI-AI), the Hearing Handicap Inventory for Adults (HHIA), the Cognitive Anxiety Scale (CAS) and a non-standardised online questionnaire. Results demonstrated statistically significant differences between pre-group and follow-up assessment outcomes. Effect sizes ranged between 0.606 and 2.114. Participants reported implementing communication strategies in a number of adverse listening environments. These findings provide evidence that the New Zealand specific version of “See it! Hear it! Say it!” is effective in improving HRQoL and reducing cognitive anxiety.
387

Seismic response of Little Red Hill - towards an understanding of topographic effects on ground motion and rock slope failure

Büch, Florian January 2008 (has links)
A field experiment was conducted at near Lake Coleridge in the Southern Alps of New Zealand, focusing on the kinematic response of bedrock-dominated mountain edifices to seismic shaking. The role of topographic amplification of seismic waves causing degradation and possible failure of rock masses was examined. To study site effects of topography on seismic ground motion in a field situation, a small, elongated, and bedrock-dominated mountain ridge (Little Red Hill) was chosen and equipped with a seismic array. In total seven EARSS instruments (Mark L-4-3D seismometers) were installed on the crest, the flank and the base of the 210 m high, 500 m wide, and 800 m long mountain edifice from February to July 2006. Seismic records of local and regional earthquakes, as well as seismic signals generated by an explosive source nearby, were recorded and are used to provide information on the modes of vibration as well as amplification and deamplification effects on different parts of the edifice. The ground motion records were analyzed using three different methods:comparisons of peak ground accelerations (PGA), power spectral density analysis (PSD), and standard spectral ratio analysis (SSR). Time and frequency domain analyses show that site amplification is concentrated along the elongated crest of the edifice where amplifications of up to 1100 % were measured relative to the motion at the flat base. Theoretical calculations and frequency analyses of field data indicate a maximum response along the ridge crest of Little Red Hill for frequencies of about 5 Hz, which correlate to wavelengths approximately equal to the half-width or height of the edifice (~240 m). The consequence of amplification effects on the stability and degradation of rock masses can be seen: areas showing high amplification effects overlap with the spatial distribution of seismogenic block fields at Little Red Hill. Additionally, a laboratory-scale (1:1,000) physical model was constructed to investigate the effect of topographic amplification of ground motion across a mountain edifice by simulating the situation of the Little Red Hill field experiment in a smallscale laboratory environment. The laboratory results show the maximum response of the model correlates to the fundamental mode of vibration of Little Red Hill at approximately 2.2 Hz. It is concluded that topography, geometry and distance to the seismic source, play a key role causing amplification effects of seismic ground motion and degradation of rock mass across bedrock-dominated mountain edifices.
388

amplification Raman stimulée de signaux hyperfréquences sur porteuse optique

Keïta, Kafing 20 July 2006 (has links) (PDF)
Ce travail vise à l'élaboration d'un système d'amplification faible bruit de signaux hyperfréquences sur porteuse optique. Nous avons mené une étude expérimentale de l'amplification Raman dans des fibres optiques monomodes à 1550nm. La configuration contra-propageante -la moins bruitée- permet d'atteindre des gains nets de plus de 25dB, elle s'est aussi montrée plus performante en termes de RIN (relative intensity noise) qu'un EDFA commercial. Une analyse théorique de l'amplification Raman a été conduite dans le domaine spectral afin de quantifier le transfert de RIN de la pompe vers le signal. L'analyse a montré une décroissance de ce transfert à hautes fréquences que l'on considère un laser de pompe monochromatique faiblement modulé ou, à l'opposé, pseudo-incohérent. Par contre, à basses fréquences, le laser de pompe monochromatique faiblement modulé apporte un excès de bruit qui n'est pas présent avec la pompe pseudo-incohérente. Ce type de source de pompe peut donc présenter un intérêt tout particulier pour le développement d'amplificateurs Raman faible bruit pour les liaisons opto-hyperfréquences. Une autre piste envisagée est la réduction du bruit d'émission spontanée amplifiée. Nous avons étudié les moyens à mettre en œuvre pour parvenir à diminuer ce bruit. L'utilisation de deux lasers de pompe de même puissance présentant un faible décalage spectral (devant la largeur de la transition Raman) doit permettre d'atteindre ce résultat. Les descriptions holographique, "optique non linéaire" ou quantique de la diffusion Raman bifréquence indiquent que pour une réduction effective du bruit d'émission spontanée, il faut que les deux pompes soient opposées en amplitude.
389

Combinaison de faisceaux mutuellement incohérents par amplification paramétrique optique

Tropheme, Benoit 10 December 2012 (has links) (PDF)
L'objectif de cette thèse est d'étudier une technique de combinaison cohérente de faisceaux : l'amplification paramétrique optique (OPA) à multiple pompes. Cette technique permet de transférer instantanément l'énergie de nombreuses pompes en un unique faisceau signal sans stockage d'énergie, et ainsi s'affranchissant d'effets thermiques dans le milieu amplificateur. Ceci peut s'avérer intéressant pour combiner l'énergie de multiples lasers à fibre et réaliser l'amplification à forte cadence de lasers très énergétiques ou d'impulsions à spectre large. A l'aide d'un code de calcul général et d'une étude expérimentale utilisant comme cristal non linéaire du BBO ou du LBO, nous calculons dans un premier temps la localisation des pompes autour du signal à amplifier, ainsi que les tolérances angulaires correspondantes qui déterminent la criticité d'alignement d'une telle configuration. Nous nous intéressons ensuite aux mécanismes de recombinaisons parasites entre une pompe et l'idler correspondant à une autre pompe. Après avoir démontré expérimentalement que ces recombinaisons peuvent dégrader les caractéristiques spatiales et spectrales du signal amplifié, nous montrons qu'il est possible d'éliminer ces risques de couplages néfastes en écartant suffisamment les pompes entre elles. Une modélisation originale de l'OPA multi-pompes suggère de relier ces phénomènes parasites aux effets des réseaux résultant des interactions entre les différentes pompes. La dernière partie présente l'expérience d'OPA à 5 pompes qui nous a permis d'atteindre un rendement de transfert énergétique des pompes vers le signal de 27%, et obtenir ainsi un signal plus énergétique que chaque pompe prise séparément.
390

Etudes expérimentales des propriétés dispersives de structures photoniques à base de micro-résonateurs pour la réalisation de fonctions optiques

Trebaol, Stephane 19 October 2010 (has links) (PDF)
La caractérisation de résonateurs de facteurs de surtension très élevés (> 10^8) est difficilement réalisée à partir des méthodes expérimentales conventionnelles en régime stationnaire. Nous proposerons une méthode hybride spectrale/temporelle permettant la mesure du facteur de surtension global et la discrimination, de manière univoque, des facteurs Q_0 intrinsèque et Q_e extrinsèque du dispositif. Par cette simple mesure, nous déterminons le régime de couplage et les propriétés dispersives de micro-cavités. Dans un second temps, nous présenterons différentes architectures à base de cavités couplées actives donnant accès un à degré de liberté supplémentaire quant au contrôle de la dispersion. Nous étudierons successivement le phénomène de transparence induite pour la réalisation d'états de lumière lente puis la dispersion induite dans le cas de deux et trois cavités. Dans ce dernier cas, la modulation des pertes intrinsèques mène à un contrôle actif du facteur de qualité de la structure. La démonstration expérimentale de ce principe montre la possibilité d'ingénierie du facteur Q par l'utilisation de structures photoniques artificielles actives.

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