To see the other types of publications on this topic, follow the link: Biophysics, Medical.
Dissertations / Theses on the topic 'Biophysics, Medical'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 dissertations / theses for your research on the topic 'Biophysics, Medical.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse dissertations / theses on a wide variety of disciplines and organise your bibliography correctly.
1
Studholme, Colin. "Measures of 3D medical image alignment." Thesis, King's College London (University of London), 1997. https://kclpure.kcl.ac.uk/portal/en/theses/measures-of-3d-medical-image-alignment(7e3dd0a9-6dc2-4ff0-8b9f-8fd513728ffb).html.
Full text
2
McAuley, Bernard. "Principles of a-Si:H photodiodes for medical X-ray imaging." Thesis, University of Surrey, 1998. http://epubs.surrey.ac.uk/843988/.
Full textAbstract:
In this thesis we assess the use of a-Si photodiodes for medical X-ray imaging. The design of an a-Si X-ray imager based on an active matrix, suitable for medical imaging is outlined. The key points in the design are highlighted, and the role of the a-Si photodiode is discussed. We outline the underlying physics of photodiodes, with particular attention to a-Si, and review the current literature. Based on this a model suitable for simulation has been developed. This model is able to replicate the thickness independence of a-Si diodes without resorting to an arbitrary charge at the p/i interface. Because individual pixels must be isolated, a certain fraction of any pixel will have to be contactless. This causes a considerable loss of signal. The possibility of retrieving this lost signal by using a lateral field was examined using the above model. Five structures were examined. (1) A basic photodiode with a longer top contact than the bottom contact. (2) A junction focussed photodiode where an addition junction contact is placed between the contacts on the bottom to induce a lateral field. (3) An insulated focussed photodiode where an insulated contact is placed between the contacts on the bottom of the diode to induce a lateral field. (4) A skewed photodiode, where the top and bottom contacts are deliberately misaligned to generate a lateral potential. (5) A skewed photodiode with additional insulating contacts on the top and bottom to improve the lateral potential. The focussing elements in these devices were show to have varying degrees of efficiency. It was noted that the current models for recombination would not be suitable for transient simulations. Also, as they neglect the presence of amphoteric defects it seems likely that they would underestimate the recombination. An examination of the current dangling bond models was undertaken with a view to using these in simulations. However, application of these models to the problem at hand revealed limitations in their use. A new approach was tried, using a transient analysis, but this was also found to be wanting. Finally, possible paths for future work are discussed, along with the apparatus constructed for measurements to corroborate the simulation results.
3
Levesque, Ives. "Quantitative magnetic resonance imaging of magnetization transfer and T2 relaxation in human white matter pathology." Thesis, McGill University, 2009. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=66751.
Full textAbstract:
The primary aim of this thesis is the reconciliation of two seemingly disparate quantitative magnetic resonance imaging (MRI) techniques proposed to characterize human brain white matter (WM) in health and disease. Quantitative magnetization transfer imaging (QMTI) and multi-component analysis of T2 relaxation (QT2) both attempt to quantify myelin content in vivo, but are based on fundamentally different models of WM. QMTI probes the macromolecular component of tissue using a two-pool model of magnetization transfer, while QT2 isolates the water signal from distinct micro-anatomical compartments. The specific objectives were to determine the interrelationship between measurements made with both techniques in the context of potential pathological changes associated with multiple sclerosis (MS), and to apply both to track WM changes in the acute phase of MS lesions. First, simulations were used to evaluate the theoretical sensitivity of each technique to the characteristics of a model of WM that incorporates four pools of magnetization, based on published in vitro measurements. Next, the experimental reproducibility of each technique was investigated, and the impact of certain basic variations in the data acquisition and analysis procedures was evaluated. In the final stage, both methods were applied longitudinally in vivo to assess the dynamic changes that occur in acute, contrast-enhancing lesions of MS. The theoretical results illustrate the sensitivity and limitations of QMTI and QT2 to specific pathology-inspired modifications of WM, and shed new light on the potential specificity of often-neglected QMTI parameters. The reproducibility of both techniques is acceptable for use in repeated clinical measurements, and QMTI has lower variability overall. The importance of corrections for magnetic field inhomogeneity in QMTI is demonstrated, and a simple optimization of the QMTI data acquisition is introducL'objectif principal de cette thèse est la réconciliation de deux techniques quantitatives d'imagerie par résonance magnétique, en apparence difféerentes, utilisées pour la caractérisation de la susbtance blanche du cerveau humain en santé ou affectée par la maladie. Les techniques d'imagerie quantitative par transfert de magnétisation (QTM) et d'analyse de la relaxation T2 par de multiples composantes (QT2) proposent toutes deux des mesures in vivo de la quantitée de myéline, mais à l'aide de modèles fondamentalement différents. D'un côté, l'imagerie QTM sonde la composante macro-moléculaire des tissues à l'aide d'un modèle à deux réservoirs pour le transfert de magnétisation. De l'autre, l'imagerie QT2 sépare les signaux acqueux provenant de compartiments micro-anatomiques distincts. Plus spécifiquement, cet ouvrage cherche à mieux comprendre l'interdépendance des mesures de ces deux techniques dans le contexte pathologique de la sclérose en plaques (SEP), pour ensuite les appliquer à l' étude de lésions aigues de SEP. En premier lieu, des simulations ont été effectuées pour évaluer la sensibilité de chaque technique aux caractéristiques d'un modèle plus complet de la substance blanche, qui découle de résultats in vitro publiés et incorpore quatre réservoirs de magnétisation. Ensuite, la reproductibilité de chacune des techniques a été évaluée; de plus, quelques variations élémentaires des méthodes d'acquisition et d'analyse des données examinées. En dernier lieu, les deux techniques ont été utilisées in vivo afin de mesurer les changements dynamiques des lésions aigues de SEP, présentant un hyper-signal rehaussée par un agent de contraste. Les résultats des simulations démontrent d'un point de vue théorique la sensibilité et les limites de chacune de ces technique aux changements dans la substance blanche. Ces résultats apportent égalem
4
Bell, David N. "Physical factors governing the aggregation of human platelets in sheared suspensions." Thesis, McGill University, 1988. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=75873.
Full textAbstract:
The effect of shear rate on the ADP-induced aggregation of human blood platelets in flow through tubes was studied over the full physiologically significant range. The extent of single platelet aggregation at 0.2 $ mu$M ADP in citrated platelet-rich plasma, PRP, was greatest at mean tube shear rate, G = 314 s$ sp{-1}$; however, aggregate size steadily decreased from G = 39.3 to 1800 s$ sp{-1}$. At 1.0 $ mu$M ADP the rate of aggregation increased up to G = 1800 s$ sp{-1}$ where virtually no unaggregated platelets remained after 43 s of flow, although, aggregate size was still limited by shear rate. A shear-dependent delay in the onset of aggregation and an increase in collision efficiency with time suggest the existence of a time and shear-dependency in the expression of bonds mediating aggregation. Greater aggregation of platelets from female donors than male donors was due to differences in the ionized calcium concentration, (Ca$ sp{2+}$), in the plasma of donors of different hematocrit when the chelating agent citrate is used as anticoagulant. At physiological (Ca$ sp{2+}$) aggregation was much greater in heparinized and hirudinized plasma than in citrated plasma and no sex difference was present. Aggregation in whole blood was much greater than in PRP due to a shear-dependent increase in the frequency of collision between activated platelets caused by the motion of red cells.
5
Carlini, Lina. "Photosensitization of InP/ZnS quantum dots for photodynamic therapy." Thesis, McGill University, 2012. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=106430.
Full textAbstract:
Photodynamic therapy (PDT) is a treatment that makes use of light and a photosensitizing drug to destroy malignant cells. Current clinically approved drugs suffer from many limitations; the most prevalent of these is due to the absorption coefficient of human tissues in the wavelength regime where these drugs are excitable. Semiconductor quantum dots (QDs) can overcome this drawback since they can be synthesized to become excited at any wavelength. The goal of this thesis is to explore the possibility of using core/shell Indium Phosphide/Zinc Sulfide (InP/ZnS) quantum dots (QDs) for photodynamic therapy applications. Electron paramagnetic resonance (EPR) spectroscopy and colorimetric assays were used to identify the nature of toxic species produced. From these findings, the physical mechanism by which these particles produce toxic species is discussed. It was found that InP/ZnS QDs produced superoxide anions and hydroxyl radicals, the levels of which depended on the ZnS shell thickness. Furthermore, the level of cellular uptake was studied in different cell lines using confocal microscopy. It was found that InP localized in the perinuclear region of all cell lines and that B16 melanoma cells showed the most efficient levels of uptake (2.5 times greater than the uptake from KB cells). Lastly, conjugation of InP QDs to the chemotherapeutic drug doxorubicin (Dox) was studied using flow cytometry and colorimetric assays. It was found that conjugation of Dox to InP led to enhanced levels of cell death; it is proposed that this was due to more efficient drug delivery by the conjugate. In summary, photosensitization processes in InP/ZnS QDs can be exploited for PDT applications; these particles also prove to be promising as a drug delivery agent. Despite this, photophysical processes of these QDs must be further explored to ameliorate their design for PDT.La thérapie photodynamique (TPD) est un traitement médical qui détruit les cellules cancéreuses en utilisant des photons de lumière, typiquement en forme de laser, afin d'activer des drogues photosensibles. Présentement, les médicaments approuvés pour usage clinique ont d'importantes limitations. Particulièrement, le coefficient d'absorption des tissus humains se retrouve dans la même gamme de longueur d'onde où les médicaments sont excitables; par conséquent, leur efficacité est compromise. Les nanoparticules de matériaux semi-conducteurs, appelées aussi points quantiques (PQs), ont l'habilité de surpasser cette limitation parce qu'ils peuvent être produits pour absorber la lumière à n'importe quelle longueur d'onde. L'objectif de cette thèse est donc d'évaluer la possibilité d'utiliser les PQs pour la TPD. Plus spécifiquement, les PQs composés d'un cœur de phosphure d'indium (InP) avec une coquille du sulfure de zinc (ZnS) ont été examinés. La spectroscopie par résonance paramagnétique électronique (RPE) et les tests colorimétriques ont été utilisés pour identifier la nature des espèces toxiques produites, ainsi que le mécanisme responsable de leur formation. Les résultats ont montré que les particules de InP/ZnS produisent des anions de superoxyde et des radicaux d'hydroxyle; la quantité des radicaux formés dépend de l'épaisseur de la coquille ZnS. En plus, la microscopie confocale a été utilisée pour évaluer l'ingestion intracellulaire des PQs par divers types de cellules. Ces images ont démontré que les PQs se concentrent dans le cytoplasme autour du noyau et que les cellules mélanomes de type B16 sont celles qui absorbent le plus (2.5 fois plus que les cellules KB). Finalement, les PQs ont été conjuguées à un agent chimiothérapeutique (doxorubicin (Dox)) et leur toxicité a été explorée par cytométrie en flux et des tests colorimétriques. La mort cellulaire a augmenté avec l'attachement de PQs, ce qui s'explique par une amélioration de la livraison intracellulaire de Dox. En conclusion, les PQs InP/Zn révèlent être des candidats prometteurs en tant que médicaments et agents de livraison pour la TPD, cependant certains éléments de leur structure restent à être améliorés.
6
Cohalan, Claire. "Cerebral blood volume changes during human neuronal activation: a comparative study of VASO and VERVE." Thesis, McGill University, 2009. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=66871.
Full textAbstract:
In this research, two techniques which measure hemodynamic changes during neuronal activation in humans were studied. The Vascular Space Occupancy (VASO) technique indirectly measures changes in total cerebral blood volume (CBV) by measuring the decrease in grey matter signal during activation, in images in which the blood signal is nulled. The Venous Refocusing for Volume Estimation (VERVE) technique measures changes in venous blood volume by exploiting the dependence of partially-deoxygenated blood's T2¬ on the refocusing interval τ180. Using a simultaneous visual and motor task, a (ΔCBV/CBVrest)total of 25.0 ± 13.9 % and a (ΔCBV/CBVrest)¬venous of 3.9 ± 1.6 % were measured using VASO and VERVE, respectively. Though the VASO technique has a high CNR and is simple to implement, its signal has contributions from many compartments other than grey matter. VERVE has fewer deleterious effects, but suffers from a higher power deposition. The activated regions in VERVE overlap better with BOLD activation than the VASO regions do, which, combined with VERVE's specificity to venous CBV changes, make it more appropriate in an investigation of the blood volume contribution to the BOLD signal.Deux techniques visant à mesurer les changements de volume sanguin cérébral durant l'activité neuronale sont étudiées. La première, Vascular Space Occupancy (VASO), mesure l'augmentation de l'ensemble du sang en mesurant la baisse du signal provenant de la matière grise, dans une image où la magnétisation du sang est nulle. La deuxième, Venous Refocusing for Volume Estimation (VERVE), mesure en particulier l'augmentation du volume sanguin veineux en exploitant la dépendance du T2 du sang partiellement deoxygéné sur l'intervalle de refocalisation τ180. Avec une tâche à la fois motrice et visuelle, un (ΔCBV/CBVrepos)totale de 25,0 ± 13,9 % et un (ΔCBV/CBVrepos)¬veineux de 3,9 ± 1,6 % ont été mesurés par VASO et VERVE, respectivement. La méthode VASO est facile à instrumenter, et jouit d'un ratio contraste-bruit plus élevé que VERVE, mais plusieurs compartiments autres que la matière grise contribuent à son signal. Moins d'effets gênants contribuent au signal de VERVE, mais celui-ci souffre d'un taux de puissance déposé élevé, parfois atteignant les limites imposées par la Commission Fédérale des Communications. Le volume activé de VERVE correspond mieux que le volume activé de VASO au volume activé de BOLD. Ce fait, et celui que VERVE mesure spécifiquement le volume veineux, prônent l'utilisation de cette technique dans une analyse de la contribution du volume sanguin au signal BOLD.
7
Xu, Ling Bin. "Commissioning of a GafChromic EBT film dosimetry protocol at the Ionizing Radiation Standards group of the National Research Council." Thesis, McGill University, 2009. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=67022.
Full textAbstract:
A GafChromic EBT film dosimetry protocol was established at the Ionizing Radiation Standards group of National Research Council. After a literature view, several aspects of EBT film dosimetry were investigated. The energy and radiation modality independence of EBT film was confirmed at the 2 % level. A calibration curve was established using a 32 point calibration curve described by a four-parameter polynomial. The darkening of EBT film is found to be significant after the first 24 hours, and up to 5 % darkening was observed over three months, which rules out the use of EBT film as an audit dosimeter. We confirmed the need for scanner uniformity correction and devised a single equation correction technique. The film homogeneity was found to be the dominant factor in dose measurement uncertainty. After establishing the film dosimetry protocol, the EBT film was used as a two-dimensional dosimeter in Monte Carlo benchmarking experiments.Un protocol dosimétrie utilisant du film Gafchromic EBT a été établi d'en le groupe des Étalons de rayonnements ionisants du Conseil national de recherches. Après une vue de la littérature, plusieurs aspects de la dosimétrie du film EBT ont été étudiés. L'indépendance de l'énergie et le tipe de rayonnement du film EBT a été confirmé avec une precision de 2%. Une courbe d'étalonnage a été établie en utilisant une courbe d'étalonnage de 32 point décrite par un polynôme a quatre paramètres. Le noircissement du film EBT a ete jugée significative après les premières 24 heures, et jusqu'à 5% a été observé au cours d'assombrissement de trios mois, ce qui exclut l'utilisation du film EBT comme un dosimètre audit. Nous avons confirmé la nécessité de faire un correction pour l'uniformité du scanner et concu une seule equation pour la correction. L'homogénéité du film a été le facteur dominant dans l'incertitude de la mesure du dose. Après avoir établi le protocole du film, le film EBT a été utilisé comme un dosimètre à deux dimensions pour des experiences de confirmation des techniques Monte Carlo.
8
Mawko, G. M. "Three-dimensional analysis of digital subtraction angiograms for stereotactic neurosurgery planning." Thesis, McGill University, 1989. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=74238.
Full textAbstract:
Geometric and tomographic methods of reconstructing three-dimensional cerebral blood vessels from two-dimensional digital subtraction angiograms are studied experimentally.Three-dimensional vessel geometry is reconstructed from center-line coordinates of corresponding vessel branches in both stereo and biplane angiogram pairs. The problem associated with finding corresponding vessel branches in biplane images was shown to be reduced by re-projection of stereoscopically reconstructed vessels. Results indicate that the limiting factor in reconstruction accuracy is the degree of vessel foreshortening in biplane image pairs.
An iterative algorithm ('Clean') is adapted to tomographic reconstruction of vessel cross-sections from a small number of views. Star-pattern artifacts in images initially formed by back-projection are removed by iterative deconvolution guided by 'a priori' object knowledge. This procedure is repeated for a set of two-dimensional sections that describe the three-dimensional vascular structure. Results show that there is sufficient detail in reconstructed sections to determine the location of vascular structures.
9
Herrmann, Marc. "Development of a microfluidic immunoassay platform for the rapid quantification of low-picomolar concentrations of protein biomarkers." Thesis, McGill University, 2008. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=21988.
Full textAbstract:
The sensitive and specific detection of proteins is at the center of many routine analyses in fundamental research, medical diagnosis, food quality control and environmental safety. The current gold standard for these applications remains the laborious and costly microwell plate ELISA. Over the last decade, new miniaturized devices have emerged: microfluidic systems that can drastically reduce the costs and the time of analysis. Many approaches and designs have been proposed. However, some recurrent difficulties remain that prevent the achievement of a system with the necessary balance between scientific performance, cost-effectiveness and user friendliness. These limitations include the complexity to maintain a constant flow rate in a simple and repeatable fashion, to mix solutions in a laminar flow regime, to control undesired surface effects, and to connect the chip to external pumping instruments. This thesis describes a novel microfluidic immunoassay platform that addresses the aforementioned issues while also achieving highly sensitive parallel measurements for the rapid quantification of protein biomarkers. The development of this platform followed three consecutive stages: (i) the establishment of an initial design for the simple manipulation of solutions in stop-flow mode, and the elaboration of strategies for mixing and for the simultaneous detection of parallel reactions, (ii) the introduction of the concept of Dual Network system, which removes the need for channel passivation against the non-specific adsorption of proteins, and (iii) the optimization of the critical assay parameters for the quantification of the cytokine TNF-alpha. The main attributes of the developed platform are also presented: the straightforward fabrication process, the simplified flow control, the enzymatically generated fluorescent signal, and the multi-purpose use of magnetic beads. These microbeads were utilized as functionalized substrate to capture the analyte, but also toLa détection sensible et spécifique de protéines se trouve au cœur d'analyses de routine dans la recherche fondamentale, le diagnostique médical, le contrôle qualité de la nourriture et la sûreté environnementale. Le standard actuel pour ces applications est toujours le coûteux et laborieux test ELISA en micropuits. Au cours de la dernière décennie, de nouveaux dispositifs miniaturisés ont fait leur apparition : des systèmes microfluidiques pouvant réduire de manière drastique les coûts et les temps d'analyse. Plusieurs approches et designs ont été proposés. Cependant, certaines difficultés récurrentes entravent toujours l'avènement d'un système possédant l'équilibre nécessaire entre la performance scientifique, le maintient de coûts bas, et la facilité d'utilisation. Ces limitations incluent la complixité de fixer une vitesse de flot constante de façon simple et reproductible, de mixer des solutions en régime laminaire, de contrôler les effets de surfaces indésireux, et de connecter la puce à des instruments de pompage externes. Cette thèse décrit une nouvelle plateforme d'immunoessais microfluidiques, qui adresse les problèmes mentionnés tout en réalisant des mesures hautement sensibles et en parallèle pour la quantification de biomarqueurs protéiques. Son développement a suivi trois étapes consécutives : (i) l'établissement d'un design initial pour la manipulation aisée de solutions en mode stop-flow, l'élaboration de stratégies de mixage et de détection simultanée de réactions parallèles, (ii) l'introduction du concept de système Dual Network, qui supprime la nécessité de passiver les canaux contre l'adsorption non-spécifique de protéines, et (iii) l'optimisation des paramètres critiques de l'essai pour la quantification de la cytokine TNF-alpha. Les attribues principaux de la plateforme sont également présentés : le procédé de fabrication rapide, le contrôle du flot simplifié, le signal$
10
Liu, Qian. "Structural insights into apoptotic regulation by BCL-2 family." Thesis, McGill University, 2010. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=95022.
Full textAbstract:
Myeloid cell leukemia 1 (MCL-1), an anti-apoptotic BCL-2 member, is active in the preservation of mitochondrial integrity during apoptosis. By collective data from nuclear magnetic resonance (NMR) spectroscopy and titration calorimetry, we revealed the selectivity of MCL-1 in binding BH3 ligands of interest to mammalian biology, and proved that the core domain of MCL-1 (cMCL-1) is necessary and sufficient for BH3 ligand binding. We characterized the in vitro protein-protein interaction between cMCL-1 and activated BID, which occurs in a very slow manner in solution but is otherwise similar to the interaction between cMCL-1 and BID-BH3 peptide. We also present the solution structure of complex cMCL-1:BID-BH3, which may greatly facilitate drug discovery studies of human tumor malignancies. BAK, a multi-region pro-apoptotic protein, directly mediates the mitochondrial outer membrane permeablization (MOMP). We completed a structural investigation of BAK by X-ray crystallography. We report two structures of BAK's homo-dimers, one zinc-mediated (cBAK) and one disulphide-bond-linked (cBAK-o). Their dimerizing sites locate closely at D160 and H164 in cBAK and C166 in cBAK-o, which allow them to compose a unique regulatory element to switch BAK's activity as suggested in mitochondria activity-testing assays. BAK is tightly regulated through protein-protein interactions by MCL-1. We characterize the conformational changes in BAK and MCL-1 using detergents to mimic the membrane environment, and studied their interaction in vitro. The non-ionic detergent IGEPAL and the zwitterionic detergent CHAPS have different effects on these two proteins, but both initiate the heterodimerization. The complex of MCL-1 and BAK can be disrupted by either a BID-BH3 peptide, which acts through binding to MCL-1, or a mutation in BH3 region of BAK (L78A), demonstrating the essential role of BAK's BH3 in its regulation by MCL-1. This thesis concludes with a hybrid model for BAK activation:La protéine MCL-1 (Myeloid cell leukemia 1), qui appartient à la classe de protéines anti-apoptotiques BCL-2, joue un rôle dans le maintien de l'intégrité mitochondriale durant l'apoptose. Les résultats obtenus par résonance magnétique nucléaire (RMN) et par titrage calorimétrique, nous ont permis de mettre en évidence la sélectivité de la protéine MCL-1 pour les ligands mammifères d'interêt biologiques qui contiennent le motif BH3 et nous avons ainsi démontré que le domaine central du facteur MCL-1 (cMCL-1) est nécessaire et suffisant pour cette interaction. Nous avons caractérisé in vitro l'interaction entre le domaine cMCL-1 et le facteur activé BID; cette interaction se produit lentement en solution mais est similaire à celle observée entre le domaine cMCL-1 et le peptide BID-BH3. De plus nous avons résolu la structure du complexe cMCL-1:BID-BH3, qui est une cible potentielle qui pourrait être à la base d'un criblage d'une banque de petites molécules dans le cas de tumeurs humaines malignes. BAK, une protéine pro-apoptotic modulaire, permet la perméabilité de la membrane externe de la mitochondrie: ce mécanisme est dénommé MOMP pour the mitochondrial outer membrane permeablization. Nous avons accompli l'étude structurale de la protéine BAK par cristallographie et diffraction de rayons X. Nous présentons deux complexes de la protéine BAK: un homodimère lié par une molécule de zinc (cBAK) et une qui contient un pont disulfure (cBAK-o). Le site de dimérisation se situe proche des résidu D160 et H164 pour cBAK et C166 pour cBAK-o, ce qui leur confère un élément de régulation unique pour moduler l'activité de BAK comme suggéré dans des essais d'activité mitochondriale. La protéine BAK est finement régulée grâce à son interaction protéine-protéine avec MCL-1. Nous avons caractérisé les changements conformations des facteurs BAK et MCL-1 à l'aide de détergents pour modéliser un environnement m
11
Alonso, Ortiz Eva. "Quantitative functional MRI based evaluation of caffeine's effects on brain physiology." Thesis, McGill University, 2012. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=106308.
Full textAbstract:
The blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) signal is one of the most recently developed imaging techniques used to identify localized changes in brain activity. The BOLD signal is a function of cerebral blood flow (CBF), the cerebral metabolic rate of oxygen consumption (CMRO2), and cerebral blood volume (CBV). Normally coupled changes in these physiological parameters during regional increases in neural activity will result in BOLD signal increases. This makes the BOLD signal useful as a tool for identifying areas of increased neural activity. Moreover, it can also be used to infer changes in neurophysiology as a response to certain stimuli in the healthy brain, in individuals with certain neurological conditions affecting the cerebrovasculature and under the effect of some types of drugs. There is a major challenge to be faced when using the BOLD signal to study neurophysiological changes that occur under the effect of certain drugs or in the case of neurovascular disease. Under these circumstances, the underlying physiology and normally coupled vascular/metabolic response to a stimulus will be altered. Consequently, changes seen in the BOLD signal during regional increases in neural activity may not be associated with the same neurovascular changes that would occur in the healthy brain. Caffeine is an example of a widely used drug which has been shown to elicit such changes in the neurophysiological state. Two experiments were performed on a group of healthy volunteers in order quantify the effects of caffeine on both baseline neurophysiology and the BOLD signal changes evoked during a visual stimulus. The first involved the measurement of the oxygen extraction fraction(OEF) by performing venous blood magnetic resonance (MR) relaxometry and the second, the measurement of the BOLD and CBF response to a visual stimulus. The results obtained demonstrate that after caffeine consumption there is an increase in baseline OEF (OEF0) and a decrease in baseline CBF (CBF0), but a non-significant change in baseline CMRO2 (CMRO2,0). The caffeine-induced change in the individual BOLD and CBF response to a visual stimulus was found to correlate negatively with individual caffeine-induced change in CBF0. However, the average percent change in visually evoked BOLD and CBF signals across all subjects remained unaltered following caffeine consumption, whereas the CMRO2 response to a visual stimulus was found to increase.L'effet BOLD (blood oxygenation level dependent) est l'une des plus récentes techniques d'imagerie par résonance magnetique (IRM) utilisée pour identifier les changements localisés d'activité cérébrale. Le signal BOLD varie en fonction de la circulation sanguine cérébrale (CBF), du taux métabolique cérébral de la consommation d'oxygène (CMRO2), et du volume sanguin cérébral (CBV). Les changements normalement-couplés de ces paramètres physiologiques lors d'une augmentation régionale d'activité neurale causeront une augmentation du signal BOLD. Cela rend le signal BOLD utile comme outil pour identifier les régions d'augmentation de l'activité neuronale. Deplus, le signal BOLD permet de déterminer quels changements neurophysiologiques suivent certains stimulus dans les cas suivants : le cerveau sain; le cerveau de personnes atteintes d'affections neurologiques affectant la cérébrovasculature; et le cerveau sous l'effet de certains types de médicaments. Un défi majeur se présente lorsque le signal BOLD est utilisé pour étudier les changements neurophysiologiques se produisant sous l'effet de certains médicaments ou en cas de maladie neuro-vasculaire. Lors de ce type d'utilisation, la physiologie sous-jacente et la réponse normalement-couplée vasculaire/métabolique à un stimulus est altérée. Par conséquent, les changements observés dans le signal BOLD au cours des augmentations régionales d'activité neuronale ne correspondent pas aux changements neurovasculaires qui se produisent normalement dans le cas du cerveau sain. La caféine est un médicament couramment utilisé qui a suscité de tels changements dans l'état neurophysiologique. Deux expériences ont été réalisées sur un groupe de volontaires sains dans le but de quantifier les effets de la caféine sur la neurophysiologie de base et les changements évoqués sur le signal BOLD lorsd'un stimulus visuel. La première expérience mesure la fraction de l'extraction d'oxygène (OEF) en effectuant de la relaxométrie par résonance magnetique sur le sang veineux. La deuxième expérience mesure la réponse du signal BOLD et CBFà un stimulus visuel. Les résultats montrent que, après la consommation de caféine il y a une augmentation de l'OEF, une augmentation de la réponse du CMRO2 au stimulus visuel, une diminution de la CBF de base (CBF0) et un changement non-significatif du CMRO2 de base (CMRO2,0). On observe une corrélation négative entre les changements générés par la consommation de caféine sur les réponses du signal BOLD et de la CBF au stimulus visuel et les changements générés par la consommation de caféine sur la CBF0. Néanmoins, en moyenne, la consommation de caféine ne génére aucun changement sur la réponse du signal BOLD et de la CBF au stimulus visuel.
12
Chen, Jing. "Cerebral venous blood volume: methodology for In Vivo measurement and implications for BOLD fMRI." Thesis, McGill University, 2009. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=40666.
Full textAbstract:
Changes in cerebral venous blood volume (DCBVv) is a critical component of the BOLD fMRI signal (instead of total DCBV), but its role has remained relatively unexplored, predominantly because measuring CBVv non-invasively is challenging. Motivated by this challenge, this thesis focuses on the development and use of the venous refocusing for volume estimation (VERVE) technique to non-invasively measure DCBVv. Driven by the substantial signal-to-noise (SNR) gain at high field, VERVE was re-designed for 3 T. This technique is strongly field-dependent through its reliance on venous blood transverse relaxation (T2) variations as a function of the Carr-Purcell Meiboom-Gill (CPMG) refocusing interval and blood oxygenation. To characterize this dependence, human whole blood T2 relaxometry was performed at 3 T. The results reveal significantly enhanced blood T2 dependence relative to 1.5 T, one best modelled as a diffusion process. In addition, human grey and white matter T2 relaxometry results support venous blood T2 variation being the predominant source of VERVE contrast at 3 T. The subsequent design of VERVE was based on the blood relaxometry results. Also, to minimize signal biases due to gradient-echo BOLD effects, greatly amplified at 3 T, a turbo spin-echo approach was adopted, further boosting SNR. VERVE was then used with arterial spin labeling (ASL) to assess the steady-state venous flow-volume relationship in humans under visual and sensorimotor stimulation. The results demonstrated a spatially-invariant flow-volume relationship characterized by a power-law coefficient (a) of 0.23, significantly lower than Grubb’s value of 0.38 (derived using total DCBV). The assumption of the latter in calibrated BOLD introduced a significant underestimation in cerebral oxygen metabolism changes (DCMRO2). Finally, the interactions giving rise to the controversial BOLD post-stimulus undershoot were examined with respect to the prevalent biomechanical, metabolic and neuronLes changements du volume sanguin cérébral veineux (DCBVv) est un élément essentiel du signal BOLD (par opposition à l’ensemble de DCBV). Pourtant, jusqu'ici le rôle du CBVv est resté relativement inexploré, et ce du aux difficultés liées aux mesures non-invasives du CBVv. Motivée par ce défi, cette thèse se rapporte sur le développement et l'utilisation de la méthode VERVE (refocalisation veineuse pour l’estimation du volume), qui permet l’estimation non-invasive de DCBVv. D’abord, l’augmentation importante du rapport signal-sur-bruit (SNR) aux champs magnétiques élevés a mené à réviser VERVE pour 3 T. Le contraste VERVE est basé sur les variations du temps de relaxation transversale (T2) sanguin veineux en fonction de l’intervalle de refocalisation Carr-Purcell Meiboom-Gill (CPMG) et de l’oxygénation sanguine. Pour caractériser cette dépendance, qui dépend fortement du champ magnétique, une étude relaxométrique du sang humain a été réalisé à 3 T. Les résultats indiquent que la dépendance du T2 sanguin est amplifiée de façon importante entre 1.5 T et 3 T. Un modèle de diffusion décrit le mieux cette dépendance. D’autre part, une étude relaxométrique de la matière grise et blanche a été réalisée, confirmant la dominance de l’effet T2 sanguin dans le contraste VERVE. La composition de VERVE se rapporte aux résultats relaxométriques sanguins. En plus, afin de minimiser l’effet de l’écho de gradient, amplifié à 3 T, une approche turbo spin-écho a été adoptée. VERVE est ensuite utilisée avec le marquage des spins artériels (ASL) pour mesurer les changements du CBVv et du débit sanguin cérébral (CBF) chez les sujets sains lors de stimulations visuelles et sensorimotrices. Les résultats démontrent une relation débit-volume invariante à travers le cortex, caractérisée par a = 0.23, inférieure à la valeur de Grubb (0.38, calculée a partir du CBV total). En employant cett
13
Meadley, Stacey. "Investigation of the structure of healthy and diseased human ascending aorta by multiphoton microscopy." Thesis, McGill University, 2009. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=66789.
Full textAbstract:
There have been relatively few examinations of the microstructure of the human ascending aorta and none relating it to the biochemical composition and the tissue mechanics. This study uses multiphoton microscopy, an innovative new tool in biological imaging, to study the structure of the two proteins elastin and collagen in the ascending aorta. Healthy and dilated ascending aortic tissue was examined at two regions, the inner curvature and outer curvature. Dilated aortas were classified by aortic valve type. The morphology of the fenestrations in the elastic laminae and the collagen fibers were quantified. The results show variation of microstructure by aortic valve type and also by region. Correlations between the microstructures and the biochemical composition and the tissue mechanics suggest that multiphoton microscopy could potentially be used for rapid determination of biochemistry and biomechanics of human ascending aortic tissue d uring surgery. This study demonstrates that vessel wall remodeling occurs with ascending aorta dilation.Peu d'études portent sur la microstructure de l'aorte ascendante humaine et aucune relative à la composition biochimique et à la mécanique des tissus ont été réalisées. Cette étude utilise la microscopie multiphotonique, un nouvel outil employé en imagerie biologique, afin d'étudier la structure de deux protéines, l'élastine et le collagène, dans l'aorte ascendante. Des tissus en santé d'aortes ascendantes dilatées ont été examinés dans deux régions, la courbure intérieure et extérieure. Les aortes dilatées ont été classées par type de valve, bicuspide ou tricuspide. La morphologie des fenestrations dans les lames élastiques de l'aorte ainsi que les fibres de collagène ont été quantifiées. Les résultats démontrent une différence dans les divers types de valve aortique et également dans les différentes régions analysées. Les corrélations entre la microstructure et la composition biochimique ainsi que la mécanique des tissus suggèrent que la microscopie multiphotonique pourrait être utilisée pour la détermination rapide de la biochimie et la biomécanique de l'aorte ascendante humaine lors de chirurgies aortiques. Cette étude démontre que le remodelage de la paroi se produit simultanément avec la dilatation de l'aorte ascendante.
14
Dumas, Eve-Marie. "Development of new imaging tools for environmental microbiology." Thesis, McGill University, 2010. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=95020.
Full textAbstract:
Environmental microbiology is a field that has been explored for years using tools which are limited in their ability to adapt to the environment studied. The goal of this thesis is to develop new tools for in situ imaging of microorganisms. The first of these tools is a class of photoluminescent probes for fluorescence microscopy. Many microscopic dyes have been used with light microscopes to label microorganisms, but the protocol of each of these techniques limits either the type of organism targeted or the type of environment that can be studied. Most of these probes also only work for a short time due to photobleaching or degrade if stored. An emerging class of fluorophores in the field of cellular and microbiology is the quantum dot (QD), a semiconductor nanoparticle which has recently been made biocompatible. The use of QDs as bacterial probe I studied here, and characterized by studying the particles' interaction with and cytotoxicity to several test organisms, both Gram positive and Gram negative. We find that QDs are toxic to most bacteria due, among other things, to their production of reactive oxygen species. However, this affect varies from one strain to another, suggesting the existence of resistance mechanisms. Although QDs are more toxic to Gram negative strains, electron transfer and depolarisation does not seem to be the source of the toxicity. QDs have a promising future in microbiology as both labeling and anti-microbial agents. In the second part of the thesis, a new microscopic technology was explored for field use: live in-line holographic microscopy. A custom, laser-based holographic microscope was used in a Mars analogue site in order to determine whether it was capable of surviving the harsh conditions and of providing valid data. We experimented in automating the system by combining it with an amphibious robot which was shown to be able to pull the holographic microscope while the latter was recording. Overall, these findingsLa microbiologie environnementale est une discipline qui a longtemps été explorée à l'aide d'outils qui sont limités par leur habileté à s'adapter à l'environnement. Le but de cette thèse est de développer de nouveaux outils pour l'imagerie de microorganismes in situ. Le premier de ces outils est une classe de sonde photolumineuse pour la microscopie fluorescente. Plusieurs teintures ont été utilisé avec des microscopes à lumière afin d'étiqueter des microorganismes, mais chacune de ces techniques est limitée par son protocole. Ces techniques peuvent soit seulement cibler certains types d'organismes, soit sont limitée au niveau de l'environnement étudié. De plus, La plupart de ces teintures sont blanchient par la lumière et ne peuvent être entreposée très longtemps. Les points quantiques (PQ), une nanoparticule semiconductrice qui est maintenant biocompatible, sont maintenant utilisés en microbiologie. J'ai explore ici, l'utilisation de PQs comme sonde bactérienne et les est caractérisée en étudiant leur interaction avec et la toxicité causée à plusieurs microorganismes. Nous avons démontré que la toxicité des PQs est causée, entre autre, par la libération d'espèces d'oxygène réactive. Cependant, l'effet observé varie selon la souche, suggérant l'existence d'un procédé de résistance aux PQs. Nous avons conclus que malgré le fait que les bactéries Gram négatives sont plus affectée par les particules que les Gram positives, le transfère d'électron et la dépolarisation ne sont pas en cause. Les PQs ont un futur prometteur en microbiologie entant que sonde et agent antimicrobien. Dans la seconde partie de cette thèse, l'utilisation d'une nouvelle technologie microscopique sur le terrain a été explorée. Un microscope holographique au laser modifié a été utilisé sur un site analogue à la planète Mars afin de s'assurer que l'instrument pouvait subir ces conditions extrêmes sans dommage et pouvait
15
Li, Cathy Shije 1974. "Function and regulation of histone deacetylase 4." Thesis, McGill University, 2006. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=98750.
Full textAbstract:
Histone acetyltransferases and histone deacetylases (HDACs) maintain dynamic acetylation and deacetylation of histories and other proteins in vivo, and are actively involved in the control of gene transcription and other nuclear processes. One mechanism by which functions of these enzymes are regulated operates through differential intracellular compartmentalization. HDAC4, -5, -7 and -9, the four members of class IIa, shuttle between the nucleus and the cytoplasm in a manner dependent on specific phosphorylation stimulated by several known kinases, and these deacetylases possess intrinsic nuclear import and export signals for dynamic nucleocytoplasmic trafficking. The ability to change their intracellular localization implies that class IIa HDACs have some potential functions in different subcellular compartments. To gain additional insights into this, I first focused on studying the function and regulation of HDAC4. As a result, I identified protein kinase D3 as a novel kinase for HDAC4 and found that this kinase physically interacts with HDAC4 and stimulates its nuclear export. Then I tried to purify protein complexes of RFXANK and ANKRA2, two homologous ankyrin-repeat proteins that are known to associate with HDCA4, using the tandem affinity purification (TAP) strategy. The results that I have obtained reveal a novel mechanism for regulating the nuclear export of HDAC4 and suggest that its cytoplasmic localization may also be indicative of potential cytoplasmic functions rather than just for simple sequestration from its nuclear targets.
16
Morcos, Marc. "Applications of deformable image registration: automatic segmentation and adaptive radiation therapy." Thesis, McGill University, 2012. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=106480.
Full textAbstract:
The contents of this thesis are best divided into two components: (i) evaluation of atlas-based segmentation and deformable contour propagation and (ii) adaptive radiation therapy using deformable electron density mapping. The first component of this thesis involves the evaluation of two commercial deformable registration systems with respect to automatic segmentation techniques. Overall, the techniques revealed that manual modifications would be required if the structures were to be used for treatment planning. The automatic segmentation methods utilized by both commercial products serve as an excellent starting point for contouring process and also reduce inter- and intra-physician variability when contouring. In the second component, we developed a framework for dose accumulation adaptive radiation therapy. By registering the planning computed tomography (CT) images to the weekly cone-beam computed tomography (CBCT) images, we were able to produce modified CBCT images which possessed CT Hounsfield units; this was achieved by using deformable image registration. Dose distributions were recalculated onto the modified CBCT images and then compared to the planned dose distributions. Results indicated that deformable electron density mapping is a feasible technique to allow dose distributions to be recalculated on pre-treatment CBCT scans.Le contenu de cette thèse est divisé en deux partis: (i) l'evaluation de la segmentation automatique basée sur des atlas anatomiques numériques et la propagation des structures déformables et (ii) la radiothérapie adaptative déformable utilisant la cartographie de la densité électronique. Le premier élément de cette thèse comprend l'evaluation de deux logiciels commerciaux par rapport aux techniques de segmentation automatique. Globalement, l'evaluation des techniques a démontré que des modifications manuelles seraient nécessaires si les contours créés par les logiciels devaient être utilisées cliniquement. Les méthodes de segmentation automatique utilisées par les deux produits commerciaux peuvent servir d'excellent point de départ pour le processus de contournage et aussi permettent de réduire la variabilité inter- et intra-médecin lors du contournage.Dans la deuxième parti, nous avons développé un processus pour l'accumulation de dose en radiothérapie adaptative. En enregistrant les images de planification de la tomodensitométrie (TDM) aux images de tomodensitométrie conique (TDMC), nous avons été en mesure de produire des images modifiées TDMC qui possédait des unités Hounsfield TDM en passant par l'enregistrement déformable des images utilisées. Les distributions de dose ont été recalculées sur les images de TDMC modifiées et ensuite comparées à la distribution de dose prévue. Les résultats indiquent que la cartographie déformable de la densité d'électronique est une technique adéquate pour permettre de recalculer les distributions de dose sur les images de TDMC.
17
Berman, Avery. "Development of a funtional magnetic resonance imaging simulator: deterministic simulation of the transverse magnetization in microvasulature." Thesis, McGill University, 2012. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=110687.
Full textAbstract:
Numerical simulations are invaluable in the development and understanding of magnetic resonance imaging (MRI) techniques. Motivated by the goal of understanding the behaviour of the functional MRI (fMRI) signal in brain tissue, this thesis employs a deterministic simulation technique in which the transverse magnetization and B0 inhomogeneity within a voxel are spatially discretized and the stochastic self-diffusion of water molecules is modelled as a Gaussian isotropic blurring of the transverse magnetization. While this simulation technique has existed since fMRI was in its infancy, its use has increased recently as investigators have attempted to quantitatively interpret the measured signal. Despite its recent popularity, thorough quantitative validation of the technique is lacking in the literature.With the development of quantitative fMRI techniques being the driving force, this thesis validates three-dimensional deterministic simulations of the MR signal with a focus on their application in cerebral microvasculature. Individual blood vessels are modelled by infinite cylinders with a realistic distribution of radii. Using a spin echo sequence, the effects of several simulation parameters are investigated.Validations ignoring the effect of diffusion show that the discretization of the voxel into subvoxels can be very coarse – up to 10 μm subvoxel widths – without adversely affecting the simulation outcomes. Simulations including diffusion are validated using an analytical solution to the Bloch-Torrey equation for comparison. In the presence of diffusion, subvoxel size is a key factor and it needs to be sufficiently small (~ 2 μm), depending on the rest of the simulation parameters, in order for the simulations to be accurate. Finally, as a proof-of-concept, it is shown that larger subvoxels can be used and still produce accurate simulations if the diffusion coefficient is scaled by a correction factor to produce the desired time series.Les simulations numériques sont d'une valeur inestimable pour le développement et la compréhension des techniques d'imagerie par résonance magnétique (IRM). Cette thèse, motivée par le but de comprendre le comportement du signal de l'IRM fonctionnelle (IRMf) dans le tissu cérébral, utilise une technique de simulation déterministe dans laquelle la magnétisation transversale et l'inhomogénéité B0 au sein d'un voxel sont spatialement discrétisées et l'auto-diffusion stochastique des molécules d'eau est modélisée par un flou gaussien isotrope de la magnétisation transversale. Bien que cette technique de simulation existe depuis les débuts de l'IRMf, son utilisation a augmenté récemment par des chercheurs tentant d'interpréter quantitativement le signal mesuré. Malgré sa popularité récente, une validation quantitative approfondie de cette technique est absente de la littérature.Ayant pour force motrice le développement de techniques d'IRMf quantitatives, cette thèse valide des simulations tridimensionnelles déterministes du signal IRM en mettant l'emphase sur leur application dans la microvascularisation cérébrale. Les vaisseaux sanguins individuels sont modélisés par des cylindres infinis avec une distribution de rayons réaliste. Les effets de plusieurs paramètres de simulation sont étudiées en utilisant une séquence écho de spin.Des validations ignorant l'effet de diffusion montrent que la discrétisation des voxel en sous-voxels peut être très grossière - jusqu'à des tailles de sous-voxels de 10 μm - sans détériorer les résultats de la simulation. Des simulations tenant compte de la diffusion sont validées à l'aide d'une solution analytique à l'équation de Bloch-Torrey. En présence de diffusion, la taille des sous-voxels est un facteur clé et doit être petite (~ 2 μm, dépendamment des autres paramètres de simulation) pour que les simulations soient précises. Enfin, comme preuve de concept, il est démontré que des simulations précises peuvent être obtenues avec des sous-voxels plus grands pourvu que le coefficient de diffusion soit multiplié par un facteur de correction pour produire la série temporelle désirée.
18
Curtis, James. "Whole Brain Isotropic Arterial Spin Labeling Magnetic Resonance Imaging in a transgenic mouse model of Alzheimer's Disease." Thesis, McGill University, 2009. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=32516.
Full textAbstract:
This thesis presents the design, implementation, and validation of a novel, arterial spin labeling (ASL) perfusion magnetic resonance imaging (MRI) pulse sequence to generate three-dimensional quantitative maps of cerebral blood flow (CBF) in mice at 7 Tesla with an isotropic 281μm resolution. ASL and anatomical scans were registered to a common template using an automated non-linear registration pipeline to allow for voxel-wise inter-scan and inter-subject comparisons of CBF. The technique was applied to the study of a transgenic mouse model of Alzheimer's Disease (AD) which demonstrates many of the characteristic features of cerebrovascular dysfunction present in AD. The technique resolved regions of significant difference between transgenic and wild-type mouse populations using voxel-wise- and region-of-interest-based analyses. These findings are the first to demonstrate the utility of perfusion MRI for population-based analysis of cerebrovascular pathophysiology in transgenic AD mice.Cette thèse présente la conception et la validation d'un nouveau séquence d'acquisition d'imagerie par resonance magnetique (IRM) pour la marquage des spins des arteres (ASL) pour créer des cartes parametrique en trois-dimensions de debit de sanguin cérébral (CBF) dans les souris à 7 Tesla. avec un résolution isotrope de 281 μm. Les volumes d'IRM anatomique et ASL ont été enregistrées avec un procedure non linéaire pour effectuer des comparaisons de CBF par-voxel entre les scans seriale et entre les animaux. La technique a été appliquée à l'étude d'un modèle de souris transgénique de la maladie d'Alzheimer (MA), qui démontre beaucoup de traits caractéristiques de dysfonctionnement cérébral qui sont présents dans la maladie d'Alzheimer. La technique résolu régions de différence significative entre les populations transgéniques et de type sauvage par les methodes d'analyse par-voxel et par-regions-d'intérêt. Ces résultats sont les premiers à démontrer l'utilité de l'IRM de perfusion au niveau de la population sur l'analyse de physiopathologie vasculaire cérébral dans les souris transgéniques MA.
19
Aldelaijan, Saad. "Reference dosimetry of HDR Ir-192 brachytherapy source using radiochromic film." Thesis, McGill University, 2010. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=95205.
Full textAbstract:
A protocol of establishing radiochromic film based reference dosimetry for high dose rate Ir-192 brachytherapy source was assessed and described. A comparison between calibration curves created in water and Solid Water are provided. Solid Water was shown to be a viable alternative to water in establishing calibration curve for Ir-192 radiation beam. A Monte Carlo correction factor was calculated to convert the dose to water into dose to Solid Water and the experimental methods that we performed agreed with the Monte Carlo results where the ratio (DSW/DW)Ir-192 was found to be 0.9808 ± 0.14% (1σ). EBT-2 GAFCHROMIC film model was also investigated for absorption properties and found to be a less sensitive than its predecessor (EBT-1) in terms of net change of absorbance, but that did not affect the dosimetric value that this film possesses. A dose error assessment method has been described for EBT-2 film model (and is applicable to other types as well) that can establish the time error constraints on the post-irradiation scanning time that will still provide an acceptable dose error for clinical applications if the protocol employing the shorter post-irradiation scanning time is implemented in the clinic. We show that for two post-irradiation scanning times of 30 minutes and 24 hours the 1% dose error can be granted if the scanning time window is less than ± 5 minutes and ± 2 hours, respectively. Performance of EBT-2 model was also evaluated in water and it was concluded that a suggested correction protocol is necessary for immersion times that exceed 2 hours. This correction was tested with the calibration curve created from water setup and found to be effective when compared to the dose-corrected calibration curve in Solid Water.Un protocole d'établir film radiochromique dosimétrie de référence en fonction de débit de dose élevé source Ir-192 curiethérapie été évalués et décrits. Une comparaison entre les courbes d'étalonnage créé dans l'eau et Solid WaterTM sont fournis. Solid WaterTM s'est révélée être une alternative viable à l'eau dans l'établissement de la courbe d'étalonnage pour les Ir-192 faisceau de rayonnement. Un facteur de correction de Monte Carlo a été calculé pour convertir la dose à l'eau en dose à Solid WaterTM et les méthodes expérimentales que nous avons réalisé d'accord avec les résultats de Monte Carlo où le ratio (DSW/DW)Ir-192 a été trouvé à 0.9808 ± 0.14% (1σ). EBT-2 modèle GAFCHROMICTM film a également été étudiée pour les propriétés d'absorption et jugé être un moins sensible que son prédécesseur (EBT-1) en termes de variation nette de l'absorbance, mais cela n'a pas d'incidence sur la valeur dosimétrique que ce film possède. Une méthode d'évaluation des doses d'erreur a été décrit pour le modèle EBT-2 film (et est applicable à d'autres types ainsi) qui permet d'établir les contraintes de temps d'erreur sur le post-irradiation temps de balayage, qui va encore donner une erreur de dose acceptable pour des applications cliniques, si le protocole emploie le plus court post-irradiation de numérisation temps est mis en uvre dans la clinique. Nous montrons que pour deux post-irradiation de numérisation fois de 30 minutes et 24 heures, la dose d'erreur de 1% peut être accordée si la fenêtre de temps de balayage est inférieure à ± 5 minutes et de ± 2 heures, respectivement. Performance de la EBT-2 modèle a également été évaluée dans l'eau et il a été conclu un protocole de correction proposé est nécessaire pour que les temps d'immersion supérieure à 2 heures. Cette correction a été testé avec la courbe de calibration créée à partir d'installation de l'eau et ont été jugés effic
20
Sarfehnia, Arman. "Water calorimetry-based radiation dosimetry in iridium-192 brachytherapy and proton therapy." Thesis, McGill University, 2010. http://digitool.Library.McGill.CA:8881/R/?func=dbin-jump-full&object_id=92297.
Full text
21
Abbott, Heather Elizabeth. "Comparisons of the factors influencing intrinsic radiosensitivity between two isogenic human ovarian carcinoma cell lines." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape2/PQDD_0021/MQ57080.pdf.
Full text
22
Sabet-Kassouf, Nilufar. "Preliminary studies on the structural characterization of aminoglycoside nucleotidyltransferase ANT(2")-la and spectinomycin kinase SpcN." Thesis, McGill University, 2014. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=121350.
Full textAbstract:
Aminoglycosides are broad-spectrum antibiotics that corrupt normal protein synthesis by acting on the coding and translocation mechanisms of the 30S ribosomal subunit. The most common mechanism of resistance to this class of antibiotics is enzymatic modification. There are three families of aminoglycoside modifying enzymes: the N-acetyltransferases (AAC), the O-phosphotransferases (APH), and the O-adenyltransferases (ANT). The focus of this thesis is on the APH and ANT families. Spectinomycin kinase (SpcN), also referred to as APH(9)-Ib, catalyzes the phosphorylation of spectinomycin exclusively, rendering it inactive. It shares its substrate specificity with APH(9)-Ia, for which the crystal structure has been described (Fong et al, 2010). Structural elements related to substrate binding remain largely conserved within the APH family, and the structural characterization of various APHs can provide valuable insight into structure-function relationships, such as substrate spectrum. Here, we report initial overexpression and purification methods for SpcN and explore solubilization methods to improve protein overexpression. Aminoglycoside nucleotidyltransferase (2”)-Ia (ANT(2”)-Ia) is among the most prevalent and widespread AMEs in North America (Ramirez & Tomalsky, 2010). It catalyzes the transfer of adenosine monophosphate to the 2” position of 4-6-disubstituted aminoglycosides, preventing binding to the 30S ribosomal subunit. Its clinical relevance makes it an important target for structure-based drug design. Previous studies of ANT(2”)-Ia were limited due to the formation of inclusion bodies during ANT(2”)-Ia overexpression (Ekman et al., 2001). Here, we report the increase in protein solubility and stability as a result of cleaving 50 extraneous amino acids from the N-terminus. Overexpression and purification of this construct yields 17 mg of soluble, stable, and active protein per liter of culture. We used heteronuclear single quantum correlation (HSQC) and HNCACB, CBCAcoNH triple resonance NMR experiments to characterize the protein. We sequentially assigned 144 of the 176 non-proline amide backbone residues of ANT(2”)-Ia. Titration analyses of ANT(2”)-Ia with tobramycin and ATP separately at 1:1 concentration ratios show unique global chemical shift perturbations for each, suggesting different binding pockets for both substrates.Les aminosides sont une classe d'antibiotiques à large spectre qui affectent l'efficacité de la synthèse protéique. Parmi les mécanismes de résistance contre cette classe d'antibiotique, l'inactivation enzymatique est le plus souvent fréquenté. Il existe trois classes d'enzymes capable d'inactiver les aminosides: les N-acetiltransferases (AAC), les O-phosphotransferases (APH), et les O-adeniltransferases (ANT). Cette thèse discutera les familles ANT et APH. Spectinomycin kinase (SpcN), aussi nommé APH(9)-Ib, catalyse la phosphorylation et l'inactivation de l'aminoside spectinomicin exclusivement. Il partage cette spécificité du substrat avec APH(9)-Ia, pour lequel la structure cristallographique à déjà été caractérisée (Fong et al., 2010). Étant donné que les éléments structurels reliés à la liaison du substrat et au site de reconnaissance sont largement conservés parmi les membres de la famille APH, les études sur la configuration tridimensionnelle des APH fournissent des informations importantes sur la relation entre structure et fonction, dont la spécificité du site de reconnaissance par exemple. Cette thèse explique les démarches prisent pour exprimer, solubiliser et purifier SpcN.L'aminoside nucleotidilstransferase 2"-Ia (ANT(2")-Ia) est parmi les enzymes de résistance contre les aminosides les plus souvent fréquentés (Ramirez & Tomalsky, 2010). Il catalyse le transfert de adénosine monophosphate à la position 2" des aminosides 4,6-bisubstituées, ce qui les empêchent de se lier au sous-unité 30S du ribosome. Son importance dans le milieu clinique fait en sorte qu'il et un cible intéressant pour la recherche et le développement d'antibiotiques basée sur les structures tridimensionnelles. À date, les études sur ANT(2")-Ia on été limitées par le fait qu'il s'exprime de façon non soluble (Ekman et al., 2001). Nos études, décrient dans cette thèse, propose une nouvelle forme soluble et active de ANT(2")-Ia qui serait la version plus physiologiquement exacte. Nous avons pu obtenir 17 mg de protéine pure, soluble et active à partir d'un litre de culture. Nous avons fait l'attribution séquentielle des déplacements chimiques des atomes de la chaîne principale par RNM en utilisant des expériences bi- et tri-dimensionnelles, dont HSQC et HNCACB et CNCAcoNH. Nous avons complété l'attribution de 144 des 176 résidus (excluant les prolines). Nous avons aussi fait des analyses de titration avec les substrats de ANT(2")-Ia, ATP et tobramicin séparément, à une concentration de 1:1. Ces analyses démontrent des perturbations globales des déplacement chimiques uniques pour chaque interaction, ce qui suggère que les sites de reconnaissances pour chaque substrat sont différents.
23
Roman, Horia Nicolae. "Smooth muscle molecular mechanics in the latch-state." Thesis, McGill University, 2014. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=121358.
Full textAbstract:
The latch-state is the capacity of smooth muscle to maintain force for long periods of time with low energy consumption. The prevalent theory to explain the latch-state suggests that if myosin gets deactivated (dephosphorylated) while attached to actin, it remains attached and maintains force. Other theories suggest that dephosphorylated and detached myosin can bind to actin to maintain force and that actin regulatory proteins participate in the force maintenance. All theories of the latch-state were based on measurements performed at the whole muscle level and were never confirmed at the molecular level. Verifying the latch-state theories at the molecular level was the main goal of this thesis.To further our understanding of the latch-state, the role of calponin in the binding of unphosphorylated myosin to actin was determined. The laser trap assay was used to measure the average force of unbinding (Funb) in the absence and presence of calponin. Calponin enhanced the Funb. Phosphorylation of calponin with Ca2+-calmodulin dependant protein kinase II, which detaches calponin from actin, decreased the Funb to the unregulated actin level. Performing the measurements at high ionic strength, which detaches calponin from myosin, had the same effect on the Funb. These later two measurements demonstrate that calponin enhances the Funb of unphosphorylated myosin to actin by crosslinking them together. Next, the effect of caldesmon on the Funb was studied; caldesmon enhanced the Funb. Because tropomyosin is known to potentiate biochemical and mechanical effects of caldesmon, its action on the Funb in combination with caldesmon was also measured. Tropomyosin enhanced the Funb on its own but had no synergistic effect with caldesmon. Phosphorylation of caldesmon with the extracellular signal-regulated kinase (ERK) decreased the Funb below the unregulated actin level. Because ERK phosphorylation of caldesmon occurs late in the contraction, this last result suggests a relaxation mechanism from the latch-state. Examination of the force traces revealed a visco-elastic behavior of myosin in the presence of ERK phosphorylated caldesmon which either prevents binding or promotes detachment from actin, thus leading to muscle relaxation. Finally, the ultimate molecular level demonstration of the latch-state requires dephosphorylation of myosin during molecular force measurements with a laser trap assay. However, addition of myosin light chain phosphatase cannot be done without disturbing the single molecule level mechanics measurements. Thus, a microfluidic device was designed and developed to allow the addition of chemicals to a molecular mechanics flow-through chamber without creating any bulk flow. A micro-channel chamber was created by standard photolithography on silicon wafers with the patterns transferred to polymethylsiloxane (PDMS). The chamber was then bound to a polycarbonate membrane which itself was bound to the molecular mechanics chamber. The micro-channels assured rapid distribution of the chemicals whereas the membrane assured efficient delivery but prevented bulk flow. The device was tested by injection of adenosine triphosphate to initiate the propulsion of actin by myosin. The proof of principle of this microfluidic device concludes this thesis.Le muscle lisse possède la capacité unique de maintenir une force élevée tout en consommant peu d'adénosine triphosphate (ATP); cette propriété est appelée 'latch-state'. La théorie la mieux connue pour expliquer cet état suggère que si la myosine est désactivée (déphosphorylation de sa chaîne légère) pendant qu'elle est attachée à l'actine, elle reste attachée et maintient la force. D'autres théories suggèrent que la myosine désactivée et détachée peut s'attacher à l'actine pour maintenir la force et que les protéines régulatrices de l'actine participent aussi à cet effort. Toutes les théories sur l'état 'latch' ont été extrapolées à partir de mesures réalisées sur la totalité du muscle sans jamais être confirmées au niveau moléculaire. Le but principal de cette thèse était de vérifier les théories de l'état 'latch' au niveau moléculaire. Afin de mieux comprendre l'état 'latch', le rôle de la calponine, dans l'attachement de la myosine non-phosphorylée à l'actine, a été déterminé. Des pinces optiques ont été utilisées pour mesurer la force moyenne de leur détachement (Funb) en l'absence et en présence de la calponine. La calponine a augmenté la Funb. La phosphorylation de la calponine avec l'enzyme protéine kinase II (Ca2+-calmoduline dépendante), qui a pour effet de détacher la calponine de l'actine, a diminué la Funb jusqu'au niveau de l'actine non-régulée. De plus, des mesures de force ont été réalisées à haute force ionique, détachant cette fois-ci la calponine de la myosine. Ceci a aussi diminué la Funb jusqu'au niveau de l'actine non-régulée. Ces résultats montrent que la calponine augmente la Funb de la myosine non-phosphorylée à l'actine par liaison croisée (myosine-calponine-actine). Ensuite, l'effet de la caldesmone sur la Funb a été étudié; la caldesmone augmente aussi la Funb. Puisque la tropomyosine est connue pour promouvoir les actions biochimiques et mécaniques de la caldesmone, son action sur la Funb en combinaison avec la caldesmone a aussi été mesurée. La tropomyosine augmente la Funb lorsqu'elle est seule mais n'a pas d'effet synergétique avec la caldesmone. La phosphorylation de la caldesmone avec la kinase régulatrice des signaux extracellulaires (ERK) a diminué la Funb en dessous du niveau de l'actine non-régulée. Ce dernier résultat suggère un mécanisme de relaxation à partir de l'état 'latch' étant donné que la phosphorylation de la caldesmone par ERK se produit tard dans la contraction. D'autre part, l'examen des traces de force a révélé un comportement viscoélastique de la myosine en présence de la caldesmone phosphorylée, ce qui semble soit prévenir l'attachement, soit promouvoir le détachement de l'actine, menant ainsi à la relaxation du muscle à partir de l'état 'latch'. Finalement, la démonstration ultime de l'état 'latch' au niveau moléculaire requiert la déphosphorylation de la myosine pendant les mesures de forces moléculaires faites à l'aide de pinces optiques. Cependant l'addition de la phosphatase de la chaîne légère de myosine ne peut se faire sans perturber les mesures de mécanique au niveau moléculaire. A cet effet, un appareil micro-fluidique a été conçu et développé pour permettre l'ajout de solutions biochimiques à la chambre de mesure de micromécanique sans créer de débit net. Des micro-canaux ont été créés par photolithographie sur substrats de silicium suivie d'un transfert des formes sur polymethylsiloxane (PDMS). La chambre des micro-canaux a ensuite été collée à une membrane de polycarbonate qui elle a ensuite été collée à la chambre de micromécanique. Les micro-canaux assurent la livraison rapide et uniforme tandis que la membrane assure le transfert efficace des produits biochimiques tout en empêchant un débit net. Le fonctionnement de l'appareil a été vérifié en injectant de l'ATP en présence d'actine et de myosine phosphorylée. La propulsion de l'actine par la myosine a été observée validant ainsi le principe de l'appareil microfluidique.
24
Mullins, Joel. "Evaluation of dose calculations and couch positional accuracy in the context of dynamic couch trajectories." Thesis, McGill University, 2014. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=123099.
Full textAbstract:
The Varian TrueBeam STx linear accelerator features a developer's mode in which treatment plans can be programmed that include patient couch motion during radiation delivery. The combination of synchronous couch/gantry trajectories with Varian volumetric modulated arc therapy (VMAT) optimizations, called RapidArc, can result in a treatment technique that has been designated Virtual Isocenter RapidArc (VIRA). Prior to its implementation, the accuracy of dose calculations in the Varian Eclipse treatment planning system, on which the RapidArc optimization depends, must be validated, as well as the positional accuracy of the TrueBeam patient couch. The dose calculation accuracy was evaluated extrinsically through the delivery of clinical dynamic multileaf collimator (DMLC) intensity modulated radiotherapy (IMRT) treatment plans as a function of source-to-surface distance (SSD) and measurement with ionization chamber and Gafchromic EBT3 film. Parameters intrinsic to dose calculations in Eclipse, the dosimetric leaf gap (DLG) and leaf transmission (LT), were also investigated for their dependence on SSD. The positional accuracy of the treatment couch was assessed through the generation of treatment plans with static couch/gantry, static couch/rotating gantry, and synchronous couch and gantry motion, with measurement of the real-time ionization chamber current positioned in a cylindrical phantom during radiation delivery. The relative agreement of ionization chamber measurements to Eclipse dose calculations for DMLC IMRT treatment plans decreased by 1.5±0.3% over SSDs in the range of 85 cm to 135 cm (less than 1.0% deviation from standard clinical reference conditions of 100 cm SSD). Gafchromic EBT3 film measurements were consistent with ionization chamber results, though noise in the film data at low doses resulted in large uncertainties. Measurements of DLG were independent of SSD, following corrections for geometric projection. LT showed a dependence on SSD of 0.09±0.02% over the SSD range investigated. The ionization chamber current measurements for synchronous couch and gantry rotation, analogous to the proposed VIRA technique, indicated a maximum deviation of 0.2 cm relative to treatment isocenter, equal to the deviation observed for the rotating gantry/static couch treatment, analogous to conventional VMAT delivery. These results indicate that the Varian TrueBeam and Eclipse maintain the necessary positional and dosimetric accuracy required for VMAT treatments involving dynamic couch trajectories.L'accélérateur linéaire TrueBeam STx de Varian possède un mode d'utilisation avancé où des plans de traitement peuvent être programmés pour inclure un mouvement de la table où repose le patient pendant le traitement. La combinaison des trajectoires synchronisés de la table de traitement ainsi que du gantry avec la plate-forme d'optimisation RapidArc pour la radiothérapie conformationnelle avec modulation d'intensité volumétrique (VMAT) produit une technique de traitement appelée RapidArc avec isocentre virtuel (VIRA). En vue de réaliser cette nouvelle technique, la justesse du calcul de dose dans la plate-forme de planification de traitements Eclipse, sur laquelle l'optimisation RapidArc dépend, doit être validée ainsi que la justesse du positionnement de la table de traitement. La justesse du calcul de dose fut évaluée de façon extrinsèque en comparant le résultat de la plate-forme RapidArc pour un plan de traitement de radiothérapie conformationnelle avec modulation d'intensité (IMRT) utilisant un collimateur multilames dynamique (DMLC) à des valeurs mesurés à l'aide d'une chambre d'ionisation ainsi que des films Gafchromic EBT3 en fonction de la distance entre la source et la surface (SSD) d'un phantôme. La dépendence sur SSD de deux paramètres instrinsèques au calcul de dose dans Eclipse, l'écart dosimétrique entre les lames (DLG) et la transmission des lames (LT) fut aussi étudiée. La justesse du positionnement de la table de traitement fut évaluée en produisant des plans de traitements avec la table et le gantry stationnaire, la table stationnaire et le gantry en mouvement ainsi qu'avec le mouvement synchronisé de la table et du gantry, tout en ayant une chambre d'ionisation positionnée dans un phantôme cylindrique durant la période d'irradiation. L'accord relatif entre les valeurs obtenus de la chambre d'ionisation et ceux d'Eclipse pour les plans DMLC IMRT est descendu de 1.5±0.3% en changeant le SSD de 85 cm jusqu'à 135 cm (moins de 1% de deviation des conditions de références clinique où le SSD est de 100 cm). Les valeurs obtenus à partir des films Gafchromic EBT3 sont en accord avec ceux de la chambre d'ionisation. Par contre, le bruit dans les données du film à basses doses a produit une grande incertitude. En corrigeant pour la projection géométrique, les valeurs du DLG ont été observé comme étant indépendantes du SSD. Le LT a démontré une dépendence sur le SSD de 0.09±0.02% sur la portée de SSD étudiés. Les valeurs de la chambre d'ionisation pour le mouvement synchronisé de la table de traitement et du gantry proposé pour la technique VIRA ont indiqué une déviation maximale de 0.2 cm relativement à l'isocentre du traitement. La même déviation fut observé pour le traitement où la table était stationnaire et le gantry était en mouvement, ce qui correspond aux traitements conventionnels VMAT. Ces résultats démontrent que l'accélérateur linéaire TrueBeam de Varian ainsi q'Eclipse maintiennent la justesse dosimétrique nécéssaire pour les traitements VMAT impliquant des trajectoires dynamiques de la table de traitement.
25
Chouinard, Julie. "Effets des LDL natives et oxydées sur l'évolution des propriétés biomécaniques des cellules endothéliales et imagerie des LDL par microscope à force atomique." [S.l. : s.n.], 2007.
Find full text
26
Khatchadourian, Rafael. "Monte Carlo simulations for neutron shielding in radiotherapy bunkers." Thesis, McGill University, 2013. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=119421.
Full textAbstract:
Photoneutrons generated in the linac head are a byproduct of the radiotherapy process and can be potentially harmful to clinical personnel. The lack of accuracy associated with analytical photoneutron shielding methods has generated much interest in the Monte-Carlo (MC) method as a more flexible and precise tool for radiotherapy bunker design. The purpose of this work was to use MC simulations to characterize photoneutron fluence, dose, and spectrum throughout various radiotherapy bunker configurations and for various room design features, such as the presence of a maze, a bulkhead, and the addition of borated polyethylene on the maze walls. Three existing rooms at the MUHC and two hypothetical doorless rooms were modelled with the MCNP5 code and using the Visual Editor GUI. The analytical spectrum of an 18 MV linac served as the point source of photoneutrons and was surrounded with a 10 cm radius tungsten sphere placed 100 cm above the isocenter. The next-event estimator variance reduction technique was used and simulations were performed with 20 million particle histories yielding un- certainties under 1%. Physical measurements were also attempted with bubble detectors and a He-3 neutron spectrometer. The latter was unsuccessful because of pulse pile-up caused by the Linac's pulsed mode of operation, whereas the former gave us qualitative information on neutron equivalent dose distribution in the maze and around the linac. Simulation results showed a marked decrease in neutron equivalent dose near the bunker entrance when maze walls are lined with BPE and when a bulk-head is added in the inner maze passage. It was found that the high thermal neutron cross-section of BPE was key in reducing the portion of thermal photoneutrons in the spectrum along the maze. The bulkhead was also useful in reducing photoneutron fluence entering the maze and hence reducing overall photoneutron dose near the entrance of the bunker. Future work will focus on validating simulations with accurate physical measurements and refining the MC code to make it more user friendly and flexible in reproducing bunker geometry.Les photoneutrons générés par le linac sont un produit secondaire de la radiothérapie et peuvent être nuisibles au personnel médical. Le manque de précision des équations analytiques pour le blindage contre les photoneutrons a accéléré le développement des méthodes Monte-Carlo (MC), qui sont considérées plus flexibles et précises pour le design des salles de radiothérapie. L'objectif de cette étude est d'utiliser les simulations MC afin de caractériser le flux, la dose, et le spectre des photoneutrons pour différentes configurations de salles de radiothérapie, telles que la présence d'un corridor, d'un bloc d'atténuation, et l'addition de borate de polyéthyléne sur les murs du corridor. Trois chambres du MUHC et deux chambres hypothétiques ont été modélisées avec le code MCNP5 et le logiciel Visual Editor. Le spectre d'énergie analytique d'un linac opérant à 18 MV a été utilisée comme source ponctuelle de photoneutrons. Ce point est entouré d'une sphére de Tungsténe de 10 cm de rayon positionnée 100 cm au dessus de l'isocentre. L'estimateur du prochain événement est la technique de réduction de variance qui a été utilisée et les simulations ont été effectuées avec 20 millions de particules résultant en des incertitudes inférieures à 1%. Des mesures physiques ont aussi été tentées à l'aide de compteurs à bulles et un spectrométre de neutrons à He-3. Ce dernier n'a pas eu de succés à cause de l'effet d'accumulation du signal pulsé. Les tests avec compteurs de bulles ont permis d'avoir une idée qualitative sur la distribution de la dose équivalente dans le corridor et autour du linac. Les résultats des simulations ont montré une diminution de la dose équivalente de neutron prés de l'entrée de la chambre quand les murs du corridor sont couverts de borate de polyéthyléne et quand un bloc d'atténuation est présent dans le passage de la chambre centrale vers le corridor. Il a été confirmé que la haute probabilité d'interaction des neutrons de basses énergies avec le borate de polyéthyléne est essentiel à la réduction de la portion de photoneutrons à basses énergies à travers le corridor. Le bloc atténuateur contribue aussi à la réduction du flux de photoneutrons entrant dans le corridor et réduit ainsi la dose totale à l'entrée de la chambre. La suite des travaux vise à mettre l'emphase sur la validation des simulations à l'aide de mesures expérimentales et sur le perfectionnement du code MC pour donner plus de flexibilité à l'utilisateur dans la reproduction des salles de radiothérapie.
27
Chambers, Kelley Ann. "Immune damage in irradiated mice: Contributions of differential radiosensitivity and apoptosis in mononuclear cells, and alterations in natural killer cell cytolytic potential." Thesis, University of Ottawa (Canada), 1997. http://hdl.handle.net/10393/10180.
Full textAbstract:
Damage to the immune system of exposed individuals renders the host susceptible to opportunistic infection and disease. The purpose of this investigation was to contribute to the understanding of mechanisms underlying depression of host immune responses following radiation exposure. Peripheral blood mononuclear cells (PBMC) of mice irradiated with 0-700 rad $\gamma$-whole body irradiation (WBI) were analyzed by flow cytometry (FCA). Natural killer (NK) cells and CD4+ T lymphocytes were selectively enhanced following radiation exposure, demonstrating radioresistance of these cell types over other PBMC, while B lymphocytes were dramatically radiosensitive. Dextran sulfate mobilization of mononuclear cells (MNC) from lymphoid tissues into the blood revealed that the same pattern of MNC loss had occurred throughout the lymphoid tissues. PBMC alterations reflected similar changes occurring in previous studies of splenic mononuclear cells $\{$1$\}$, and may promote immune dysregulation. The role of apoptosis in radiation-induced injury to the immune system in the low to intermediate dose range (0 to 400 rad) was investigated in PBMC. 25 rad induced apoptosis in PBMC above the unirradiated control within 2 hours post-irradiation; apoptosis induction increased with higher doses (100-400 rad). Additionally, the impact of ionizing radiation on NK cell function was assessed. 24 hours following radiation exposure, NK cytotoxicity against YAC-1 target cells was depressed by doses of 25 or 50 rad, with little change in the 100 to 400 rad range. By day 7, NK cytolytic potential was reduced or unaffected by doses lower than 200 rad, while a single exposure of 400 rad enhanced cytotoxicity. The results of this investigation have furthered our understanding of factors which may be important in the impairment of immune responses post-irradiation.
28
Casault, Sebastien. "Exact enumeration approach to solving transient diffusion problems applied to drug delivery." Thesis, University of Ottawa (Canada), 2007. http://hdl.handle.net/10393/27817.
Full textAbstract:
This is a study of drug delivery problems from hydrogels and it is mainly focused on the effects of the hydrogel's geometry on the behaviour of the release profile. Studying drug delivery also offers one the opportunity to delve into the physical mechanisms involved in the release process to better understand its theoretical implications. We can apply the well-developed theory of diffusion in order to understand many aspects of drug delivery. Thus, this thesis starts with a presentation of concepts and theories used in the following two articles (chapters). We go over the basic concept of drug delivery, followed by an introduction on diffusion. We then explain the ideas governing drug release and how we have modeled it. The tools used to generate our drug release platforms are presented followed by a discussion on characterizing the resulting drug release profiles.
This thesis is presented as a series of two articles that have been submitted to peer-reviewed scientific journals. The first article presents a novel combinatorial technique used to obtain controlled drug delivery profiles. We use an exact enumeration diffusion model in order to obtain our drug release profiles and test its validity by comparing these results with analytical theory and widely used empirical tools. By using a genetic algorithm, we then show that it is possible to tailor the drug delivery platform in order to get a specific functional form of the release profile.
The second article consists in testing two widely used empirical functions that are used in the literature to characterize drug release profiles. Several claims have been made regarding the interpretation of these functions and we have used our exact enumeration data to argue that although the functions fit the data relatively well on certain time scales, they do not necessarily convey reliable information about the mechanism of release.
Finally, we conclude with preliminary work that was done on a second optimization technique to be used in controlling drug delivery profiles. The Metropolis simulated annealing was used to further optimize the design of the drug release platform and was shown to be quite effective, albeit being computationally demanding.
29
Wang, Yin 1951. "Influences of membrane biophysical properties on the Metarhodopsin I to Metarhodopsin II transition in visual excitation." Diss., The University of Arizona, 1997. http://hdl.handle.net/10150/282520.
Full textAbstract:
Current biophysical studies of membrane proteins are centered on the relation of their structures to key biological functions of membranes in terms of lipid-protein interactions. The conformational transition of rhodopsin from Metarhodopsin I to Metarhodopsin II (Meta I-Meta II) is the triggering event for the visual process. Meta II is the activated form of the visual receptor and binds a signal transducing G protein (transducin), followed by two amplification stages which lead to generation of a visual nerve impulse. Herein, flash photolysis and surface plasmon resonance (SPR) spectroscopy techniques have been used to monitor the Meta I-Meta II transition of rhodopsin in various membrane recombinants. The flash photolysis experiments clearly show a substantial shift to the left of the Meta I-Meta II equilibrium for rhodopsin in egg phosphatidylcholine recombinant membranes. Investigation of the influences on rhodopsin function by non-lamellar forming lipids reveals a characteristic relationship between the Gibbs free energy change for the Meta I-Meta II equilibrium of rhodopsin and the intrinsic curvature of the lipid bilayer. Complementary SPR studies suggest a protrusion of the protein at the activated Meta II state which may be associated with exposure of recognition sites for the signal transducing G protein on the cytoplasmic surface of rhodopsin. All the experimental results obtained here are consistent with the hypothesis of a new flexible surface biomembrane model. The Meta II state is favored by a negative spontaneous curvature of the bilayer, corresponding to an imbalance of the lateral forces within the polar head groups and acyl chains. The mean curvature of membrane bilayer in the Meta II state reflects the small spontaneous curvature of the lipid bilayer in the vicinity of protein. Relief of the lipid curvature frustration in the Meta II state energetically couples the lipids to the photoexcitation of rhodopsin. Consideration of the various energetic contributions suggests the bilayer curvature free energy provides a reservoir of work in the modulation of rhodopsin function in the visual process. These studies that biophysical properties of the liquid-crystalline lipid bilayer are important in relation to protein function and may be relevant to the biomedical investigations of visual dysfunction.
30
Ye, Hongwei. "Development and implementation of fully three-dimensional iterative reconstruction approaches in spect with parallel, fan- and cone-beam collimators." Related electronic resource: Current Research at SU : database of SU dissertations, recent titles available full text, 2008. http://wwwlib.umi.com/cr/syr/main.
Full text
31
Kim, Kristin. "Characterization of calcium binding protein 1 (CaBP1/CD) expression and localization in the mouse brain." Thesis, University of Iowa, 2013. https://ir.uiowa.edu/etd/2545.
Full textAbstract:
Ca2+-binding proteins (CaBP) alter Ca2+ signals, triggering cellular processes such as gene transcription regulation in neurons. CaBP1/CD is a calmodulin (CaM)-like Ca2+ binding protein that may regulate neuronal functions through interactions with effectors such as voltage-gated Ca2+ (Cav) channels and inositol trisphosphate receptors (InsP3Rs). To gain insight into the potential cellular functions of CaBP1/CD, we analyzed the expression and localization of CaBP1/CD variants in mouse brain. Of the three CaBP1/CD splice variants that have been characterized (CaBP1-S, CaBP1-L, and caldendrin (CD)), CD was the major variant expressed in mouse brain by western blot and quantitative polymerase chain reaction. These results reflected the expression of CaBP1/CD since they were not reproduced in mice with targeted disruption of the gene encoding CaBP1/CD (CaBP1 knock-out). By immunoperoxidase labeling, CaBP1/CD was localized in multiple cell-types including pyramidal cells in the cerebral cortex and hippocampal CA3 neurons and inhibitory neurons in the cerebellum. In the cerebellum, CaBP1/CD was not detected in Purkinje neurons but strongly colocalized with voltage-sensitive Shaker-type potassium channel, Kv1.2, in the pinceau formation formed between basket cells and the Purkinje cell axon initial segment. We conclude that CaBP1/CD is expressed in a subset of principal neurons where it may regulate Ca2+ signaling and neuronal excitability.
32
Wang, Yi Zhen 1965. "Photoneutrons and induced activity from medical linear accelerators." Thesis, McGill University, 2004. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=81453.
Full textAbstract:
This study involves the measurement of the neutron equivalent dose ( NED) and the induced activity produced from medical linear accelerators. For the NED, various parameters such as the profile, field effects and energy responses were studied. The NED in a Solid Water(TM) phantom was measured and a new quantity, the neutron equivalent dose tissue-air ratio (NTAR), was defined and determined. Neutron production for electron beams was also measured. For the induced activity, comparisons were carried out between different linacs, fields and dose rates. The half life and activation saturation were also studied. A mathematical model of induced activity was developed to explain the experimental results. Room surveys of NED and induced activity were performed in and around a high energy linear accelerator room. Unwanted doses from photoneutrons and induced activity to the high energy linear accelerator radiotherapy staff and patient were estimated.
33
Zhang, Jing 1961. "System identification of bladder hydrodynamics." Thesis, McGill University, 1994. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=26440.
Full textAbstract:
Understanding bladder mechanics and the changes caused by bladder outlet obstruction is an important task in urology. In this work, bladder mechanics are examined in terms of bladder hydrodynamics: the relation between a perturbing volume applied to the bladder and the evoked pressure change. A PC-based experimental system was built which can generate a computer-controlled perturbation volume and measure volume and pressure signals.The bladders of six minipigs, three normal and three obstructed, were subjected to stochastic volume perturbations about different average volume levels and evoked pressure changes were measured. The hydrodynamic stiffness transfer function relating volume and pressure was calculated and described by a second-order, lumped parametric model having inertial, viscous and elastic terms. Estimates of the elastic constant (K) increased linearly with volume in both normal and obstructed animals. The rate of increase was substantially greater in the obstructed animals than in the normals. Consequently, this approach shows promise for distinguishing normal and obstructed bladder mechanics.
34
Veerassamy, Shalini. "Revisiting hemodynamic analysis of pulmonary edema after the onset of left ventricular dysfunction using a mathematical model of the cardiovascular system." Thesis, McGill University, 2000. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=31075.
Full textAbstract:
The aim of this project was to extend a mathematical model of the cardiovascular circulation, originally built by Burkhoff and Tyberg [6]. The model was implemented in Simulink and consists of 6 lumped vascular compartments interconnected by segments allowing unidirectional blood flow. A set of 6 differential equations describe changes in blood volume in the four systemic and two ventricular compartments as functions of time in terms of the pressure across each compartment and the resistances between them. The model was used to investigate why pulmonary venous pressure rises after the onset of left ventricular dysfunction. Special attention was given to the pericardial and peripheral resistance effects. Sensitivity analysis showed that our parameter values and ratios were more appropriate than those of Burkhoff and Tyberg [6]. We conclude that, although stressed volume has a fundamental role in raising the pulmonary venous pressure, contractile strength and systemic arterial resistance also contribute considerably.
35
Wang, Ping 1968 Feb 17. "Structure genomics of zebrafish granulins." Thesis, McGill University, 2004. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=81452.
Full textAbstract:
This study focused on the structural genomics of granulin/epithelin modules (GEMs). Expression, purification and NMR studies of 14 out of all known 19 zebrafish GEMs allowed an assessment of the degree of structural diversity in their C-terminal subdomains. Very interestingly, one well-folded zebrafish GEM was obtained, and its three-dimensional structure was determined with high accuracy using NOE, H-bond, dihedral angle and residue dipolar coupling constraints. Solution structure determination and 15N NMR relaxation measurements indicate that one unique proline residue of the zebrafish GEM may confer the well-structured and stable folding property of the stack of all four beta-hairpins in contrast to other members of the GEM protein family.
36
Ezzadeen, Hani. "Extraction and segmentation of MRI brain images." Thesis, McGill University, 2006. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=97949.
Full textAbstract:
Brain image segmentation is an active research in computer image analysis. The challenge lies in the fact that the brain anatomy is not identical for all normal subjects let alone subjects with abnormal tissue.In this thesis, we explain the research we have implemented to extract the brain from T1-weighted MRI images, and then segment the brain into the three prominent compartments (i.e. the cerebellum and the two hemispheres of the cerebrum). The brain extraction is implemented using morphological operations after thresholding. The brain segmentation, however, is implemented in two separate steps. The first step segments the two hemispheres by approximating the midsagittal surface using mainly Radon transform. The second step segments the cerebellum using an atlas-based contour as an initial contour for the gradient vector flow active contour algorithm.
Validation tests have been performed for the brain extraction and cerebellum segmentation methods.
37
Dumoulin, Serge O. "Motion mechanisms and cortical areas in human vision : psychophysics and fMRI." Thesis, McGill University, 2003. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=82860.
Full textAbstract:
Our visual world contains both luminance- (first-order) and contrast-defined (second-order) information. Distinct mechanisms underlying the perception of first-order and second-order motion have been proposed from electrophysiological, psychophysical and neurological studies. In this thesis psychophysical and human brain imaging (fMRI) experiments are described that support the notion of distinct mechanisms, but extend the previous studies by providing evidence for a functional dissociation and a relative cortical specialization for first- and second-order motion.Using psychophysical methods, a directional anisotropy was found for second-order but not first-order motion in peripheral vision. This anisotropy is interpreted as a functional dissociation implicating the second-order mechanism in optic flow processing.
Identification of early visual cortical areas is a prerequisite to any functional assessment of these visual areas. To this aim a novel human brain mapping method has been developed which automatically segments early human retinotopic visual areas. Unlike previous methods this procedure does not depend on a cortical surface reconstruction and thereby greatly simplifies the analysis.
In a combined psychophysical and fMRI study, distinct cortical regions, in occipital and parietal lobes, were preferentially activated by either first- or second-order motion. These results provide evidence for the idea that first-order motion is computed in V1 and second-order motion in later occipital visual areas. In addition the results suggest a functional dissociation of the two kinds of motion beyond the occipital lobe consistent with a role for the second-order mechanism in optic flow analysis.
38
Galiana, Laura. "Identification of ankle stiffness components in stroke patients." Thesis, McGill University, 2002. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=79230.
Full textAbstract:
The purpose of this study was to measure ankle stiffness in stroke patients using system identification, which provides an objective method of separating reflex and intrinsic stiffness components.We studied twelve (12) stroke patients with clinical evidence of ankle spasticity and compared them with nine (9) gender- and age-matched controls. Subjects lay supine with their foot attached to an electro-hydraulic actuator by a custom-fitted boot. Series of pseudo-random binary sequences were used to rotate the ankle. The position, torque, and EMG recorded during these perturbations were used to separate the reflex and intrinsic contributions of ankle stiffness.
The results of this study showed that ankle stiffness was increased in four (4) stroke patients, mostly due to the increased reflex stiffness component. Furthermore, the changes in reflex stiffness varied with position; ankle stiffness increased in these stroke subjects as the ankle was dorsiflexed. The reflex gain parameter explained the increased reflex stiffness.
39
Hauerstock, David. "Telemetric measurement of compressive loads in the sheep lumbar spine." Thesis, McGill University, 2000. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=30785.
Full textAbstract:
The goal of this study was to develop and validate a system for the telemetric measurement of in vivo compressive intervertebral loads in the sheep, and to measure these loads in a variety of activities.A miniature load cell and radio transmitter were implanted in the L3--L4 space of the spine. A total of four sheep were operated on; one was sacrificed five days after surgery, due to failure of the transmitter, and another was sacrificed after failing to ambulate for two weeks after surgery. The other two animals (average mass 67 kg) were kept for five weeks, during which a range of activities were performed, including standing, lying prone, walking/trotting, and jumping.
Results for a range of activities were as follows: in walking at 1.5 m/s, average maximum and minimum loads were 461 N and 256 N, respectively; in walking at 2m/s, average maximum and minimum loads were 684 N and 303 N, respectively; in standing, loads averaged 161 N; and in lying prone, loads averaged 212 N. The highest loads were recorded in jumping, where the peak load was 1290 N.
The results of this study demonstrate for the first time, to our knowledge, the magnitude of in vivo axial loads in the sheep lumbar spine. These findings have implications for the evaluation of studies which employ the sheep model to test spinal implants. As treatment methods for disc degeneration progress from the spacer and fusion approach to more sophisticated prostheses and tissue engineered disc replacements which preserve segmental mobility, such data will become even more important to the design, animal testing, and evaluation of implants.
40
Liang, Chen. "Design of miniature microscope objective optics for biomedical imaging." Diss., The University of Arizona, 2002. http://hdl.handle.net/10150/280105.
Full textAbstract:
The topic of this dissertation is on the design and construction of miniature microscope objective optics. The design of miniature microscope objective is both similar and different from conventional microscope objective. The design and construction of two miniature microscope objectives are presented in this dissertation. The first one is a high numerical aperture (NA), water-immersion objective and it is a part of a fiber confocal reflectance microscope (FCRM). The second one is a moderate NA dry objective and it is a part of a miniature microscope array (MMA). The capability, complexity and fabrication method of the two miniature objectives are different but they both share some similar design traits as result of their miniaturization. FCRM's miniature objective has a NA of 1.0 and it is designed to operate at near infrared lambda = 1,064 nm. It is 7 mm in outer diameter and 21 mm in length (measured from object plane to image plane). This kind of dimension is approximately 10 times smaller than a conventional microscope objective of similar caliber. Sub-micrometer resolution has been experimentally demonstrated with this miniature objective. MMA's miniature objective has a NA of 0.4 and it is designed to operate over the visible spectrum. It is 1.2 mm in diameter and 9.4 mm in length. The image quality of MMA's miniature objective is experimentally demonstrated to be comparable to the state-of-art commercial microscope objective.
41
Lee, Junwon. "The development of a miniature imaging system: Design, fabrication and metrology." Diss., The University of Arizona, 2003. http://hdl.handle.net/10150/289892.
Full textAbstract:
The topic of dissertation is on the development of a miniature imaging device named as multi-modal miniature microscope [a.k.a. 4M Device]. Generally speaking, the development of an optical imaging device involves three main processes: optical design, fabrication and metrology. They are interdependent and often comprise a feedback loop. This dissertation will address these three processes sequentially. The 4M device is miniature compound microscope consisting of miniature optics, electronic imaging device, and mechanical device. Every component is integrated on single silicon substrate. The main purpose of 4M device is to provide an imaging capability for the detection of pre-cancer without biopsy. It uses a novel optics called hybrid lens that is fabricated by using a grayscale photomask and photolithographic technique. The hybrid lens is made of sot-gel material and glass substrate. It has 1.2mm of diameter and its surface is conic. Given lens design constraints from the fabrication, the series of lens design for 4M device are implemented and presented. Each design delivers diffraction-limited imaging performance with N.A ranging from 0.4 to 0.7. The 4M device that is currently built has 0.4 of N.A. The imaging quality assessments of 4M device are also implemented in quantitative and qualitative ways. There are two instruments for imaging quality assessment: Multi-modal imaging testbed for entire imaging device and Shack-Hartmann wavefront sensor for individual element. The qualitative assessment includes multi-modal imaging experiments under different illumination modes. The object is a cervical cancer cell prepared by Dr. Kortum's Group at Univ. of Texas at Austin. The qualitative assessment includes the surface characterization and wavefront measurement of individual optics and the MTF measurement of entire device. The results of imaging quality assessment show the potential of 4M device for medical imaging device. They also explain the degradation of imaging quality.
42
Shue, Guay-Haur. "System models of skeletal muscle." Case Western Reserve University School of Graduate Studies / OhioLINK, 1995. http://rave.ohiolink.edu/etdc/view?acc_num=case1058448071.
Full text
43
Wang, Jeffrey Bond. "Modelling Mechanical Interactions Between Cancerous Mammary Acini." Thesis, Harvard University, 2015. http://nrs.harvard.edu/urn-3:HUL.InstRepos:14398530.
Full textAbstract:
The rules and mechanical forces governing cell motility and interactions with the extracellular matrix of a tissue are often critical for understanding the mechanisms by which breast cancer is able to spread through the breast tissue and eventually metastasize. Ex vivo experimentation has demonstrated the the formation of long collagen fibers through collagen gels between the cancerous mammary acini responsible for milk production, providing a fiber scaffolding along which cancer cells can disorganize. We present a minimal mechanical model that serves as a potential explanation for the formation of these collagen fibers and the resultant motion. Our working hypothesis is that cancerous cells induce this fiber formation by pulling on the gel and taking advantage of the specific mechanical properties of collagen. To model this system, we present a hybrid method where we employ a new Eulerian, fixed grid simulation known as the Reference Map Method to model the collagen as a nonlinear viscoelastic material coupled with a multi-agent model to describe individual cancer cells. We find that these phenomena can be explained two simple ideas: cells pull collagen radially inwards and move towards the tension gradient of the collagen gel, while being exposed to standard adhesive and collision forces. From a computational perspective, we hope that our work can serve as a generalizable framework for future theoretical studies of the mechanical interactions between a large number of cells and a dynamic environment.
44
Delorme, Sebastien. "Biomechanical analysis of ankle kinematics and ligament strain in snowboarding." Thesis, University of Ottawa (Canada), 2004. http://hdl.handle.net/10393/29096.
Full textAbstract:
Because snowboarders are known to injure their ankles more often than alpine skiers, it has been postulated that stiffer snowboard boots would provide better protection to the ankle ligaments than current soft boots do.
To test this hypothesis, we have measured the kinematics of the feet and lower legs of five snowboarders riding down a course of 10 gates on a ski hill using an electromagnetic motion tracking system. Results were obtained with each snowboarder wearing soft boots and stiffer step-in boots. The measurements were expressed in anatomically relevant rotations of the ankle joint complex.
Two models were developed to predict ligament strains from rotations of the ankle joint complex: (1) a statistical model using published ligament strain measured on cadaver specimens at various combinations of ankle rotations as an interpolation and extrapolation table to predict strains in two ankle ligaments at the rotations measured during the snowboarding trials; (2) a personalized 2-degrees-of-freedom kinematic model of the ankle joint complex, based on the Denavit-Hartenberg formulation of serial-link manipulators, to predict strains in flue ankle ligaments from the relative position of the shank and foot.
The experimental results showed that the left and right ankles are asymmetrically rotated, mostly in dorsiflexion, eversion and external rotation. Compared to step-in boots and bindings, soft boots and strap bindings allowed more rotation of the ankle joint complex and more strain in the anterior talofibular ligament, according to the statistical model. The kinematic model was not sensitive enough to detect differences in ligament strains between the 2 types of equipment. A functional determination of the axes of rotation of the talocrural and subtalar joints could further improve the predictions of this model.
This is the first known study to document experimentally the kinematics of snowboarding. It generally confirms the expectation that softer boats allow significantly wider ranges of ankle rotation and ligament strain.
45
Alsharief, Fahda Fawaz. "Role of Translation Initiation in Regulation of Epithelial Junctions and Cell Motility." VCU Scholars Compass, 2017. http://scholarscompass.vcu.edu/etd/5018.
Full textAbstract:
The integrity and barrier properties of intestinal epithelium are determined by specialized adhesive structures known as intercellular junctions; composed of adherens junctions (AJs), tight junctions (TJs) and focal adhesions that mediate cell-cell and cell matrix interactions, respectively. These two types of epithelial cell adhesions regulate each other during disruption and restitution of the epithelial barrier. Inflammatory cytokines such as interferon gamma (IFNγ) and tumor necrosis factor alpha (TNFα) are elevated during intestinal inflammation. The most notable effects of IFNγ and TNFα on intestinal epithelial homeostasis involve disruption of apical junctions and attenuation of cell migration. Although molecular mechanisms underlying these effects remain poorly understood, expressional downregulation of different adhesion proteins may play a major role in the cytokine-dependent disruption of the intestinal epithelial barriers. This thesis is based on the hypothesis that inhibition of the protein translation initiation machinery promotes the disruption of the intestinal epithelial barrier and attenuates epithelial restitution during mucosal inflammation. This study was focused on two eukaryotic translation initiation factors, eIF4G1 and eIF4G2, which play essential roles in the regulation of cap-dependent protein translation. Expression of both translation initiation factors was dramatically downregulated in model intestinal epithelial cell monolayers treated with IFNγ and TNFα in parallel to cytokine-induced disruption of the epithelial barrier. siRNA or shRNA-mediated downregulation of either eIF4G1, or eIF4G2 increased permeability of well-differentiated SK-CO15 intestinal epithelial cell monolayers and decreased expression of different adherens junction and tight junction proteins. Furthermore depletion of these translation initiating factors inhibits different modes of migration (wound healing and transfilter migration) of stem-cell like and well-differentiated intestinal epithelial cells. These findings suggest that eukaryotic translation initiation factors of the eIF4G family play unique roles in regulating integrity and restitution of the intestinal epithelial barrier. Downregulation of these translation initiating factors may mediate disruption of the intestinal epithelial barriers during mucosal inflammation.
46
Bussière, Marc R. "Monte Carlo study of relative depth doses at diagnostic energies." Thesis, McGill University, 1991. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=61182.
Full textAbstract:
This thesis is concerned with the creation, verification and implementation of a computer programme for simulating photon transport in diagnostic radiology. The programme is based on the Monte Carlo technique in which probabilistic problems are solved using random numbers. For this reason mathematical number generators along with a few standard tests which enable the randomness of the numbers to be evaluated are introduced. A discussion on sampling from probability distributions is presented with emphasis on the physical aspects of the Monte Carlo technique applied to low energy photon transport. The validity of the computer programme is established by comparisons with previously published Monte Carlo work, with predictions from an analytical photon transport model and with experimental measurements. The application of Monte Carlo simulations to specific radiographic problems are illustrated by the modeling of percent depth doses.
47
Audet, Chantal. "NMR-based radiation dosimetry using polymer solutions." Thesis, McGill University, 1990. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=59996.
Full textAbstract:
The spin-spin and spin-lattice relaxation times of protons on polymers, T$ sb{ rm 1p}$ and T$ sb{ rm 2p}$, respectively, have been used to probe the absorbed dose of irradiated polymer solutions in which radiation-induced changes in polymer molecular weight, M$ sb{ rm n}$, occur. The M$ sb{ rm n}$ dependencies of T$ sb{ rm 1p}$ and T$ sb{ rm 2p}$, and of the water proton T$ sb{ rm 1w}$ for solutions of poly(ethylene oxide) (PEO) in D$ sb2$O and H$ sb2$O are presented. T$ sb{ rm 1p}$ and T$ sb{ rm 1w}$ are independent of M$ sb{ rm n},$ and T$ sb{ rm 2p}$ varies with M$ sb{ rm n}$ according to a specific inverse power dependence until low M$ sb{ rm n}$ when T$ sb2$ saturation occurs. The dose dependence of T$ sb{ rm 1p}$ and T$ sb{ rm 2p}$ measured for dilute solutions of PEO in D$ sb2$O reflects the dependence of M$ sb{ rm n}$ on dose. A novel semi-empirical model is proposed for the dose dependence of T$ sb{ rm 2p}$ which incorporates the measured M$ sb{ rm n}$ power dependence of T$ sb{ rm 2p}$ into a theoretical expression of the dose dependence of the M$ sb{ rm n}$. This expression is based on previous bulk polymer work and has been modified to hold for polymers in solution. The model can be fitted well to the T$ sb{ rm 2p}$ data measured for different doses, and the values of the fitting parameters agree with those expected from independent measurements. Practical aspects of the NMR/polymer dosimetry technique are also addressed.
48
Campbell, Jennifer 1975. "Magnetic resonance diffusion tensor imaging." Thesis, McGill University, 2000. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=30809.
Full textAbstract:
Magnetic resonance imaging (MRI) can be used to image diffusion in liquids, such as water in brain structures. Molecular diffusion can be isotropic or anisotropic, depending on the fluid's environment, and can therefore be characterized by a scalar, D, or by a tensor, D, in the respective cases. For anisotropic environments, the eigenvector of D corresponding to the largest eigenvalue indicates the preferred direction of diffusion.This thesis describes the design and implementation of diffusion tensor imaging on a clinical MRI system. An acquisition sequence was designed and post-processing software developed to create diffusion trace images, scalar anisotropy maps, and anisotropy vector maps. A number of practical imaging problems were addressed and solved, including optimization of sequence parameters, accounting for flow effects, and dealing with eddy currents, patient motion, and ghosting. Experimental validation of the sequence was performed by calculating the trace of the diffusion tensor measured in various isotropic liquids. The results agreed very well with the quantitative values found in the literature, and the scalar anisotropy index was also found to be correct in isotropic phantoms. Anisotropy maps, showing the preferred direction of diffusion, were generated in human brain in vivo. These showed the expected white matter tracts in the corpus callosum.
49
Patrocinio, Horacio Jose. "Evaluation of backscatter factors for diagnostic X-ray beams." Thesis, McGill University, 1993. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=69520.
Full textAbstract:
This thesis proposes models for the calculation of upper and lower limiting values to the backscatter factor (BSF) that can be used to evaluate measured and modelled BSF values. The upper limit to the BSF is obtained from a Monte Carlo simulation of an infinite parallel beam incident on a semi-infinite phantom in which the dose contribution from all orders of photon scatter is considered. The lower limit is calculated using an analytical photon transport model which considers only the primary dose and the scatter dose from photons that have undergone a single scattering interaction in the phantom. A parametrization of the limiting values in terms of photon energy and irradiation field size is presented and comparisons are made with BSF's from the literature. To further illustrate the utility of the limiting BSF's, comparisons are also made with current TLD-measured BSF's and Monte Carlo simulations of the BSF.
50
Courteau, Pierre. "Electron arc therapy dose calculation using the angle-b concept." Thesis, McGill University, 1993. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=57004.
Full textAbstract:
A computer program was developed during the course of this work to calculate electron arc dose distributions with the angle $ beta$ concept. The angle $ beta$ uniquely describes the dependence of radial percentage depth doses an electron arc therapy on the nominal field width, isocenter depth, and virtual source-axis distance. The $ beta$ concept can be used in clinical situations to determine the field width when the isocenter depth and the required radial percentage depth dose are known. This thesis presents an overview of the physical properties of electron arc therapy and describes in detail the angle $ beta$ pseudo-arc technique used at McGill. A description of the algorithms used in the computer program is given the $ beta$ technique is compared to measurements and other calculation methods.