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1
Paul, Clémence. "Fractionnement du dioxygène lors des processus biologiques : application à la reconstruction de la productivité passée de la biosphère." Electronic Thesis or Diss., université Paris-Saclay, 2024. http://www.theses.fr/2024UPASJ002.
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La composition isotopique du dioxygène piégé dans les bulles d'air des carottes de glace peut être utilisée pour reconstituer la productivité globale de la biosphère dans le passé ainsi que pour documenter l'évolution du cycle de l'eau aux basses latitudes. Le travail de cette thèse a été d'améliorer l'interprétation du δ18O de l'O2. Pour cela, nous avons affiné la détermination des différents coefficients de fractionnement associés au cycle de l'oxygène au niveau de la biosphère terrestre, c'est-à-dire pendant les processus de respiration et de photosynthèse. Afin de quantifier ces coefficients de fractionnement, nous avons développé un nouveau dispositif expérimental qui repose sur un système de chambres biologiques fermées multiplexées dans lesquelles tous les paramètres environnementaux sont contrôlés, stabilisés et mesurés. Ces chambres biologiques fermées ont un volume de 120 L permettant d'étudier un système « plante + sol ». La première étape a été de développer un prototype avec une seule chambre biologique et de faire une première étude sur la fétuque. Ensuite, un deuxième développement a permis de travailler sur plusieurs chambres biologiques via un système multiplexé. Nous avons aussi développé un instrument de spectrométrie optique (SARA-O2) afin de mesurer en continu la concentration et composition isotopique de l'O2 pendant les expériences en chambres multiplexées. Ceci remplace la mesure par spectrométrie de masse d'échantillons prélevés dans les chambres de façon manuelle. Ce système a permis d'étudier les coefficients de fractionnement pour plusieurs plantes (fétuque, bananier, laurier, maïs). Nous avons notamment mis en évidence un fractionnement isotopique associé à la photosynthèse terrestre. Les fractionnements biologiques trouvés lors de ces expériences ont finalement été intégrés dans des calculs globaux de composition isotopique du dioxygène de l'air et comparés aux mesures effectuées sur la dernière déglaciation. Ceci permet de conclure que les variations passées de δ18O de l'O2 dans l'atmosphère sont principalement liées aux variations du cycle hydrologique aux basses latitudes<br>The isotopic composition of oxygen trapped in air bubbles in ice cores can be used to reconstruct the global productivity of the biosphere in the past, as well as to document the evolution of the water cycle at low latitudes. The aim of this thesis was to improve the interpretation of δ18O de l'O2. Thus, we improved the determination of the various fractionation coefficients associated with the oxygen cycle at the level of the terrestrial biosphere, i.e. during the processes of respiration and photosynthesis. To quantify these fractionation coefficients, we have developed a new experimental set-up based on a system of multiplexed closed biological chambers in which all environmental parameters are controlled, stabilized and measured. These closed biological chambers have a volume of 120 L, enabling us to study a "plant + soil" system. The first step was to develop a prototype with a single biological chamber and carry out an initial study on fescue. This was followed by a second development, enabling us to work on several biological chambers via a multiplexed system. We also developed an optical spectrometry instrument (SARA-O2) for continuous measurement of O2 concentration and isotopic composition during multiplexed chamber experiments. This replaces manual mass spectrometry measurements of samples taken from the chambers. This system has enabled us to study fractionation coefficients for several plants (fescue, banana, laurel, maize). In particular, we highlighted isotopic fractionation associated with terrestrial photosynthesis. The biological fractionations found in these experiments were finally integrated into global calculations of the isotopic composition of atmospheric oxygen, and compared with measurements taken during the last deglaciation. This led to the conclusion that past variations in the δ18O of the O2 in the atmosphere are mainly linked to variations in the hydrological cycle at low latitudes
2
Alfvén, Tobias. "Bone and kidney effects from cadmium exposure : dose effect and dose response relationships /." Stockholm : Karolinska Univ. Press, 2002. http://diss.kib.ki.se/2002/91-7349-341-4.
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Kafrouni, Marilyne. "Relation dose-effet et optimisation de la dosimétrie en radiothérapie interne sélective du carcinome hépatocellulaire." Thesis, Montpellier, 2019. http://www.theses.fr/2019MONTT007/document.
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La radiothérapie interne sélective (RTIS), en plein développement ces dernières années, constitue une alternative thérapeutique pour les cancers primaires et secondaires inopérables du foie. Le principe repose sur l’administration intra-artérielle de microsphères chargées d’yttrium-90 avec pour objectif la destruction des cellules tumorales par l’irradiation.L’activité d’yttrium-90 à administrer au patient est actuellement généralement prescrite à partir d’approches semi-empiriques ou peu personnalisées, faciles à mettre en place cliniquement. De nouveaux outils sont aujourd'hui disponibles semblables à ceux utilisés en radiothérapie externe. Leur utilisation encore peu répandue nécessite un retour d'expérience clinique pour mettre en avant leurs bénéfices et guider l'application clinique. Par ailleurs, le traitement RTIS est précédé d'une étape de simulation. Des différences inhérentes à cette procédure en deux temps (type de particules utilisées, modalité d’imagerie, modifications de flux vasculaires, etc.) existent et pourraient potentiellement conduire à des écarts dosimétriques entre la planification et le traitement. C’est dans ce contexte que s’inscrit le projet de cette thèse qui porte sur l'optimisation de la dosimétrie pour le traitement du carcinome hépatocellulaire par RTIS.Les doses délivrées au cours de 42 traitements par microsphères de résine réalisés entre 2012 et 2015 au CHU de Montpellier, ont été rétrospectivement calculées à l’échelle du voxel sur un logiciel de dosimétrie dédié (PLANET Dose, DOSIsoft, Cachan). Les doses délivrées ont été calculées pour le volume tumoral et le volume de foie sain définis anatomiquement, à partir de l’imagerie post-traitement TEP aux microsphères d’yttrium-90. Ce travail a mené à deux études complémentaires. La première analyse a consisté à confronter les données dosimétriques recueillies (doses moyennes, histogrammes dose-volume) à la réponse tumorale, la toxicité hépatique et la survie du patient. Les résultats obtenus, en accord avec ceux de la littérature, ont confirmé l’existence d’une relation dose-effet en RTIS. La deuxième étude a mis en évidence les limites du modèle BSA (body surface area pour surface corporelle) qui avait été utilisé pour planifier l’activité à administrer, à prédire la dose délivrée et par conséquent l’efficacité du traitement. L’absence de considérations dosimétriques et de prise en compte de l’hétérogénéité de distribution, de ce modèle ont notamment été discutées. Ces deux études ont ainsi souligné l'intérêt de planifier l'activité d'yttrium-90 à administrer en se basant sur des données dosimétriques individualisées.Une troisième étude a été conduite sur une population de 23 patients atteints de CHC, traités par microsphères de verre traités entre 2015 et 2018 au CHU de Montpellier. L’objectif a été de comparer les dosimétries prédictives et post-traitement calculées à l’échelle du voxel. Les résultats cliniques obtenus ont été appuyés par des expérimentations sur fantômes physiques (simple et anthropomorphique). Une bonne corrélation a été montrée, mettant en avant la valeur prédictive de la dosimétrie de planification. En revanche, un écart significatif a été observé et semble lié en partie à la quantification de l’imagerie TEP à l’yttrium-90. De plus, il a été montré que le geste radiologique peut influencer la distribution de particules et donc de dose, d’où la nécessité d’une reproductibilité aussi parfaite que possible entre les deux étapes<br>Selective internal radiation therapy (SIRT) is a growing therapeutic alternative for unresectable primary and secondary liver cancer. The principle is based on the intra-arterial administration of yttrium-90 loaded microspheres for tumor cell destruction through irradiation.Yttrium-90 activity to be administered to the patient is, at the moment, usually prescribed using semi-empirical or barely personalized approaches that can be easily clinically implemented. New tools, similar to the ones used in external beam radiotherapy, are available today. These tools, which are not yet widely spread, require clinical feedback to show their benefits and guide the clinical application. Besides, a simulation stage is always performed before SIRT treatment itself. This two-step procedure implies differences (in terms of particles used, imaging modality, vascular flow modifications, etc.) that could potentially lead to dose deviations between planning and treatment. The thesis project comes within this scope, dealing with dosimetry optimization for hepatocellular carcinoma SIRT.Delivered doses during 42 treatment procedures performed between 2012 and 2015 at Montpellier University Hospital, were retrospectively calculated at the voxel level using a dosimetry dedicated software (PLANET Dose, DOSIsoft, Cachan). Two complementary studies were carried out from this work. The first one analyzed dose data (average dose, dose volume histograms) versus patient follow-up including tumor response, liver toxicity and patient survival. The results obtained are consistent with the other teams, confirming the dose-effect relationship in SIRT. The second study highlighted the limitations of the BSA (body surface area) model that was used for activity planning. In particular, the limitations of this model to predict delivered dose and consequently treatment efficiency were quantitatively demonstrated. The lack of dosimetry and heterogeneity distribution considerations were also discussed. These two studies emphasized the interest for yttrium-90 activity planning based on individualized dose data.A third study was conducted on a population of 23 patients treated between 2015 and 2018 at Montpellier University Hospital. The aim was to compare predictive and post-treatment dosimetry calculated at the voxel level. The clinical results were supported by phantom (simple and anthropomorphic) experimentations. A good correlation was observed highlighting the predictive value of dosimetry planning. However, a significant deviation was noticed and seems to be partly related to yttrium-90 TEP quantification. In addition, it was also noted that the radiological gesture can affect particle distribution and consequently dose distribution, this is why reproducibility as perfect as possible is required between the two stages
4
Rostand, Neil. "Modélisation compacte de l'effet des radiations naturelles des dispositifs sub-28nm pour des applications automobiles et aéronautiques." Thesis, Toulouse, ISAE, 2019. http://www.theses.fr/2019ESAE0035.
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L’objectif de cette thèse était le développement de modèles SET (Single Event Transient) et TID (Total Ionizing Dose) pour les MOSFETs de technologies fortement intégrées, reposant notamment sur la technologie SOI. Ces modèles devaient respecter les standards de la modélisation compacte afin d’assurer leur utilisation dans les simulateurs de circuits SPICE (ELDO, SPECTRE, PSPICE …) tout en assurant la justesse du contenu physique. Le langage d’implémentation est alors le Verilog-A. En 1A, l’investigation physique des SET a été effectuée à l’aide de simulations TCAD. Cette tâche a supporté le développement d’un premier modèle physique SET (validé par la TCAD) adapté aux technologies BULK.En 2A, le modèle physique a été rendu compact et implémenté en Verilog-A. Ce travail a nécessité le développement d’une méthode d’implémentation faisant appel à la considération d’un circuit électrique équivalent au phénomène SET. Le modèle ainsi implémenté en SPICE a été capable de prédire l’occurrence de SEUs (Single Event Upset) dans les mémoires et des erreurs plus fonctionnelles dans les registres à décalage. En parallèle, l’investigation physique du TID a été effectuée à l’aide simulations TCAD. Par ailleurs, les effets TID ont été modélisés et implémentés dans le modèle standard compact LETI – UTSOI décrivant le fonctionnement des transistors FDSOI. Le modèle a été validé à l’aide de simulations TCAD et a été utilisé pour extraire les paramètres TID sur des MOSFETs FDSOI irradiés au CEA/DAM.En 3A, un modèle compact SET pour technologies fortement intégrées (reposant sur la technologie SOI) a été développé. Ce modèle prend en compte l’amplification bipolaire inhérente à ce type de structure ainsi que la morphologie 3D de la charge générée par la particule ionisante. Des validations TCAD de ce modèle ont été effectuées. Par ailleurs, ce modèle SET a été interfacé avec le simulateur multi-physiques MUSCA SEP3 afin d’estimer le risque SEE sur des matrices mémoires FDSOI. L’apport du modèle SET a été mis en évidence dans la fiabilité de cette estimation<br>The purpose of the PhD was to develop "Single Event Transient"(SET) and "Total Ionizing Dose" (TID) models for sub-28nm MOS technologies. These models have been developed according to standards of compact modeling in order to be used into SPICE simulators (ELDO, SPECTRE, PSPICE ...) while main physical features are taken into account. The implementation has been done in Verilog-A langage.During the first year, SET physical investigation has been done performing TCAD simulations. It supported model development of SET applied to BULK technologies. During the second year, this model has been turned into a compact model and implemented in Verilog-A, which required the development of an implementation method involving equivalent electrical circuit. The resulting model has been able to predict "Single Event Upsets" (SEUs) in memories and functional errors in shift registers. Moreover, physical investigation of TID has been performed through TCAD simulations of FDSOI MOSFETs. TID effects have been included into standard FDSOI transistor model LETI-UTSOI. The model has been validated through TCAD simulations and has been used to extract TID parameters on experimental devices irradiated in CEA/DAM. The third year has been partly dedicated to SET model development for very integrated technologies (relying on SOI technology).This model takes bipolar amplification into account as well as 3D charge deposit morphology induced by the ionizing particle. TCAD validations have been performed in order to validate the model. Moreover, this model has been included into multi-physics simulator MUSCA SEP3 in order to assess SEE risk in FDSOI memory matrix. it has been found that the physical features the model is able to model can influence reliability of this assessment
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Morency, Catherine-Ève. "Effets de l'estradiol et de la progestérone sur le contrôle respiratoire en situation hypoxique chez le raton nouveau-né et impacts à long terme." Thesis, Université Laval, 2006. http://www.theses.ulaval.ca/2006/23851/23851.pdf.
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Sutton, Akil K. "Displacement Damage and Ionization Effects in Advanced Silicon-Germanium Heterojunction Bipolar Transistors." Thesis, Georgia Institute of Technology, 2005. http://hdl.handle.net/1853/7217.
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A summary of total dose effects observe in advanced Silicon Germanium (SiGe) Heterojunction Bipolar Transistors (HBTs) is presented in this work. The principal driving froces behin the increased use of SiGe BiCMOS technology in space based electronics systems are outlined in the motivation Section of Chapter I. This is followed by a discussion of the strained layer Si/SiGe material structure and relevant fabrication techniques used in the development of the first generation of this technology. A comprehensive description of the device performance is presented.
Chapter II presents an overview of radiation physics as it applies to microelectronic devices. Several sources of radiation are discussed including the environments encountered by satellites in different orbital paths around the earth. The particle types, interaction mechanisms and damage nomenclature are described.
Proton irradiation experiments to analyze worst case displacement and ionization damage are examined in chapter III. A description of the test conditions is first presented, followed by the experimental results on the observed dc and ac transistor performance metrics with incident radiation. The impact of the collector doping level on the degradation is discussed.
In a similar fashion, gamma irradiation experiments to focus on ionization only effects are presented in chapter IV. The experimental design and dc results are first presented, followed by a comparison of degradation under proton irradiation. Additional proton dose rate experiments conducted to further investigate observed differences between proton and gamma results are presented.
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Rossouw, Maria Susanna. "Validation of endpoints as biomarkers of low-dose radiation damage." Thesis, Cape Technikon, 2004. http://hdl.handle.net/20.500.11838/1461.
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Thesis (MTech (Biomedical Technology))--Cape Technikon, Cape Town, 2004<br>The need for radiobiological research was bom from the discovery that high doses of
radiation could cause cancer and other health effects. However, recent
developments in molecular biology uncovered the effects of low doses of radiation on
different biological systems and as a result new techniques have been developed to
measure these effects.
The aim of this study was thus to validate biomarkers of initial DNA strand breaks,
micronucleus formation, and the different pt ;ases of apoptosis as biological indicators
of low-dose radiation damage. Furthermore, the difference in response of blood cells
to different qualities and doses of radiation was investigated by irradiating cells with
low- and high-LET radiation simultaneously.
Blood from one donor was irradiated with doses between 0 and 4 Gy gamma- and
neutron radiation. The alkaline single-cell gel electrophoresis (comet) assay was
performed on different cell preparations directly after irradiation for the detection of
initial DNA strand breaks. Radiation-induced cytogenetic damage was investigated
using the cytokinesis-blocked micronucleus assay while different features of
apoptosis were investigated by measuring caspase activation, enzymatic DNA
fragmentation, and cellular morphology.
The comet assay was sensitive enough to detect DNA strand breaks above 0.25 Gy
and showed that the Iymphocyte isolation process induced some endogenous
damage in cells, detected by the formation of highly damaged cells and hedgehogs in
isolated cell preparations only.
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Ferraro, Rudy. "Development of Test Methods for the Qualification of Electronic Components and Systems Adapted to High-Energy Accelerator Radiation Environments." Thesis, Montpellier, 2019. http://www.theses.fr/2019MONTS118.
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Le Grand collisionneur de hadrons (LHC), le plus grand et le plus puissant au monde, a démarré en 2008 et constitue la dernière étape du complexe des accélérateurs du CERN. Le LHC consiste en un anneau de 27 kilomètres d'aimants supraconducteurs permettant d'accélérer deux faisceaux jusqu'à 7 TeV avant de les faire entrer en collision à 14 TeV dans l'une des cinq expériences de contrôle du résultat de la collision. Le LHC a notamment permis la découverte du boson de Higgs et d'autres particules baryoniques prédites par le modèle standard. L'environnement de rayonnement du LHC et de ses lignes d'injection est composé de différentes particules sur un large spectre d'énergies, du niveau GeV jusqu'au niveau meV (par exemple le neutron thermique). L'équipement électronique fonctionnant dans un environnement de rayonnement aussi rude, principalement basé sur des composants commerciaux prêts à l'emploi (COTS), peut subir des défaillances induites par des effets de rayonnement. La criticité de l'équipement peut être très élevée, dans le meilleur des cas, la défaillance d'un système de contrôle peut conduire à une chute du faisceau, ce qui peut drastiquement rendre le faisceau disponible pour la science et dans le pire des cas, la défaillance d'un système de sécurité peut conduire à la destruction d'une partie de la machine. La nouvelle mise à niveau du LHC prévue pour 2025, le LHC à haute luminosité (HL-LHC) atteindra une luminosité annuelle cinq fois supérieure à celle de la version actuelle du LHC. Par conséquent, les niveaux de rayonnement générés par le fonctionnement de la machine vont également augmenter considérablement. Avec des niveaux de rayonnement aussi élevés, un nombre important de systèmes commerciaux seront exposés à des niveaux de rayonnement auxquels ils ne peuvent résister. Cela impliquera soit de concevoir des systèmes plus robustes et tolérants à base de COTS, soit de remplacer préventivement les systèmes avant leur fin de vie utile. Ainsi, alors qu'au cours des années précédentes, les effets singuliers (EEI) étaient la principale cause de défaillance, à l'avenir, l'effet cumulatif du rayonnement deviendra également une préoccupation majeure. Bien qu'un effort considérable ait été fait dans le passé sur le processus de qualification contre les défaillances induites par les SEE, le processus de qualification pour les effets cumulatifs du rayonnement est resté pratiquement inchangé. L'objectif de ces travaux était donc d'étudier comment la Radiation Hardness Assurance (RHA) du CERN pourrait être améliorée pour répondre à ce nouveau défi et s'assurer qu'aucune défaillance de système n'aura d'impact sur les opérations du LHC. Plusieurs activités ont été menées à cet effet : (i) l'étude des particularités de l'environnement radiatif du LHC et de son impact sur les composants et les systèmes qui y sont exposés, (ii) l'étude de l'adéquation des méthodes de qualification actuelles et le développement d'approches adaptées aux besoins du CERN et (iii) l'étude des méthodes fiables pour estimer la durée de vie des systèmes<br>The Large Hadron Collider (LHC), the largest and most powerful in the world, started in 2008 and is the last stage of CERN's accelerator complex. The LHC consists in a 27-kilometer ring of superconducting magnets allowing to accelerate two beams up to 7 TeV before colliding them at 14 TeV in one of the five experiments monitoring the result of the collision. The LHC allowed notably the discovery of the Higgs boson and other baryonic particles predicted by the standard model. The radiation environment of the LHC and its injection lines is composed of different particles over a large spectrum of energies, from GeV level down to meV level (e.g. thermal neutron). The electronic equipment operating in such a harsh radiation environment, mostly based on Commercial Off The Shelf (COTS) components, can experience failures induced by radiation effects. The criticality of the equipment can be very high, in the best case, the failure of a control system can lead to a beam dump, which can drastically the availability of the beam for science and in the worst case, the failure of a safety system can lead to the destruction of part of the machine. The new upgrade of the LHC planned for 2025, the High Luminosity LHC (HL-LHC) will achieve an annual luminosity five time higher than the current version of the LHC. Consequently, the levels of the radiation generated by the operation of the machine will also drastically increase. With such high radiation levels, a significant number of COTS-based systems will be exposed to radiation levels they cannot withstand. This will imply to either design more robust tolerant COTS-based systems and/or substitute preventively systems before their end of life. Thus, while in the previous years the Single Event Effects (SEEs) where the dominant cause of failure, in the future, cumulative radiation effect will as well become a major preoccupation. While a huge effort has been done in the past on the qualification process against SEE-induced failures, the qualification process for cumulative radiation effects, remained mostly unchanged. The aim of this work was, therefore, to investigate how the CERN’s Radiation Hardness Assurance (RHA) could be improved to respond to this new challenge and ensure that no system failures will impact the LHC operations. This involved several activities; (i) the study of the particularities of the LHC radiative environment and its impact on the components and systems exposed to it, (ii) the study of the suitability of current qualification methods and the development of approaches adapted to CERN’s needs and (iii) the study of reliable system lifetime estimation methods
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Erekson, David McConkie. "Scheduled Healing: The Relationship Between Session Frequency and Psychotherapy Outcome in a Naturalistic Setting." BYU ScholarsArchive, 2013. https://scholarsarchive.byu.edu/etd/4037.
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The dose-effect relationship in psychotherapy has been examined extensively, but few studies have included session frequency as a component of psychotherapy "dose." Those studies that have examined the effects of session frequency have indicated that it may affect both the total amount of recovery and the speed of recovery. No studies were found examining the clinical significance of this construct in a naturalistic setting. The change trajectories of 16,003 clients were examined using multi-level modeling and including session frequency as a fixed effect. Of these clients, subgroups were identified that were scheduled approximately once a week or approximately once every two weeks. These groups were compared to each other for differences in speed of recovery and clinically significant change. Results indicated that more frequent therapy was associated with steeper recovery curves. When comparing groups scheduled once a week to those scheduled once every two weeks, more clinically significant gains were identified in those attending once a week, and more significant deterioration was identified in those attending once every two weeks. These findings are discussed in light of the existing literature and the implications for future psychotherapy research and clinical practice.
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Jaillet, Cyprien. "Modifications du glycome endothélial vasculaire dans le contexte d'une irradiation à forte dose." Thesis, Paris 6, 2017. http://www.theses.fr/2017PA066021/document.
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La radiothérapie constitue l’un des principaux traitements pour l’éradication des cancers. Cependant, elle présente un risque d’effets secondaires aux tissus sains environnant la tumeur. Dans ce processus, le système vasculaire et plus particulièrement l’endothélium jouent un rôle clé. Les cellules endothéliales activées favorisent le recrutement chronique des thrombocytes et des leucocytes, contribuant ainsi aux effets secondaires. D’autre part, dans les maladies inflammatoires, les glycanes exprimés à la surface des cellules endothéliales sont modifiés et influencent le recrutement des cellules immunitaires. Dans cette étude, nous avons évalué la modification des glycanes endothéliaux en réponse à une irradiation à forte dose, et étudié les effets fonctionnels de ces modifications sur le recrutement des leucocytes en utilisant un modèle de cellules endothéliales (HUVECs) in vitro. Nos résultats apportent les premières preuves d’une modification du glycome des cellules endothéliales en réponse à l’irradiation. Les N-glycanes hautement mannosylés, les O-glycanes et les motifs sialylées sont surexprimés. Parallèlement, le glycocalyx endothélial semble subir une dégradation. Nous avons évalué l’effet fonctionnel des modifications glycanique des cellules endothéliales irradiées sur l’adhésion d’une lignée de monocyte (THP-1). Nos résultats montrent que l’adhésion radio-induite est en partie due à la surexpression endothéliale des N-glycanes hautement mannosylés. Nous avons aussi évalué le glycome sur un modèle de souris irradiées et sur des pièces opératoires de patients traités par radiothérapies. Nos résultats de transcriptomiques sur la souris suggèrent l’existence de modifications glycaniques radio-induites in vivo. L’intégration de la composante glycanique permet de porter un regard nouveau sur le continuum d’évènement qui conduit aux lésions tissulaires radio-induites. A l’avenir, l’étude du glycome pourrait ouvrir de nouvelles pistes thérapeutiques pour une meilleure prise en charge des effets secondaires de la radiothérapie<br>Radiotherapy is one of the main treatments against cancers. However, it presents a risk of adverse effects for the normal tissues surrounding the tumors. The vascular network and especially the endothelium are considered as main targets to limit normal tissue damages and prevent side effects of radiotherapy. Activated endothelial cells are involved in the chronic recruitment of thrombocytes and leukocytes, resulting in tissue complications. On the other hand, in inflammatory diseases, the glycans expressed on the surface of endothelial cells are modified and lead to immune cells recruitment. We sought to evaluate changes in endothelial glycome in a context of exposure to high dose of radiation, and studied the functional consequences on the recruitment of leukocytes. In vitro, the characterization of the glycome was performed on a primary endothelial cell model (HUVEC). Our results provide the first evidences of an endothelial modification of the glycome after exposure to ionizing radiation. We report an overexpression of high mannose N-glycans, O-glycans and syalilated motifs. At the same time, endothelial glycocalyx appeared to be damaged by exposure to radiation. Next, we evaluated these radiation-induced modifications of endothelial glycans on monocyte adhesion. We show that the radiation induced adhesion was mediated by overexpression of high mannose N-glycans. We also investigated changes in glycome in an irradiated mouse model of enteropathy and in resections of patients treated with radiotherapy. In mice, a transcriptomic study suggests changes in glycans following radiation exposure. Collectively, these findings on glycome changes provide a new perspective of the continuum of events leading to normal tissue complications. In the future, the study of the glycome should open new therapeutics opportunities for better management of tissue damages induced by radiation
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Brucoli, Matteo. "Total ionizing dose monitoring for mixed field environments." Thesis, Montpellier, 2018. http://www.theses.fr/2018MONTS093/document.
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La mesure de la dose ionisante est aujourd'hui une tâche cruciale pour une large gamme d'applications fonctionnant dans des environnements de rayonnement sévères. Dans le contexte de l'amélioration de la luminosité du grand collisionneur de hadrons (LHC), la mesure des niveaux de rayonnement le long du complexe d'accélérateurs du CERN va devenir encore plus difficile. A cet effet, une connaissance plus détaillée du champ de rayonnement dans le tunnel de l'accélérateur et ses zones adjacentes devient nécessaire pour définir les exigences d'installation, de déplacement ou de blindage de l'électronique sensible au rayonnement. Dans l’objectif d’améliorer la mesure de la dose absorbée par les systèmes exposés au champ de rayonnement mixte généré par l’accélérateur, des investigations sur des nouveaux dosimètres ont été menées.Dans le cadre de cette recherche, deux dispositifs ont été étudiés et caractérisés pour être utilisés comme dosimètres et éventuellement pour compléter l'utilisation du dosimètre au silicium actuellement utilisé au CERN, à savoir le RADFET (RADiation-sensitive Field Effect Transistor) : un NMOS commercial et un ASIC (Application-specific Integrated Circuit) nommé FGDOS. Les dispositifs ont été sélectionnés selon deux approches opposées : d'une part, la réduction des coûts permettrait d'augmenter la densité des capteurs déployés. En conséquence directe, une carte des doses plus détaillée serait obtenue pour les grands systèmes distribués comme le LHC. D'autre part, la dosimétrie peut être améliorée en déployant des détecteurs plus sensibles, ce qui permettrait de mesurer la dose lorsque les niveaux sont trop faibles pour le RADFET. De plus, des capteurs à plus haute résolution permettraient de caractériser le champ de rayonnement dans un temps plus court, c'est-à-dire avec une luminosité intégrée plus faible.La première approche a été réalisée en recherchant des solutions alternatives basées sur des dispositifs COTS (Commercial Off-The-Shelf), qui réduiraient considérablement les coûts et garantiraient une disponibilité illimitée sur le marché. À cette fin, des recherches ont été menées sur un transistor NMOS discret commercial, qui s'est révélé très sensible au rayonnement.La nécessité d'améliorer la résolution de la mesure de dose a conduit à étudier le FGDOS, un dosimètre en silicium innovant à très haute sensibilité qui permet de détecter des doses extrêmement faibles.La calibration du transistor NMOS et du FGDOS a été effectuées en exposant les dosimètres à des rayons gamma. Leur réponse au rayonnement a été caractérisée en termes de linéarité, de variabilité d'un lot à l'autre et d'effet du débit de dose. L'influence de la température a été étudiée et une méthode pour compenser l'effet de la température a été développée et mise en œuvre.Le FGDOS étant un système sur puce (SoC) avec plusieurs caractéristiques qui font du dosimètre un système extrêmement flexible, la caractérisation de ses différents modes de fonctionnement (actif, passif et autonome) a été effectuée. Suite à la première caractérisation, des questions se sont posées concernant les mécanismes de dégradation de la sensibilité affectant le dosimètre. Pour étudier ce phénomène, des campagnes d’irradiations ont été effectuées avec une puce d'essai incorporant seulement le circuit sensible au rayonnement du FGDOS. L'analyse des expériences a permis de comprendre les processus responsables de la dégradation de la sensibilité, en séparant la contribution du transistor de lecture de celle du condensateur à grille flottante. Les résultats de cette étude nous ont amenés à envisager de nouvelles solutions de conception et des méthodes de compensation.L’aptitude du transistor NMOS et du FGDOS à mesurer la dose ionisante dans les champs de rayonnement mixtes produits par le complexe d’accélérateurs du CERN a été vérifiée à l’aide de test radiatifs accélérés effectués dans le centre de tests en champs mixte à haute énergie du CERN (CHARM)<br>The Total Ionizing Dose (TID) monitoring is nowadays a crucial task for a wide range of applications running in harsh radiation environments. In view of the High-Luminosity upgrade for the Large Hadron Collider, the monitoring of radiation levels along the CERN’s accelerator complex will become even more challenging. To this extent, a more detailed knowledge of the radiation field in the accelerator tunnel and its adjacent areas becomes necessary to design installation, relocation or shielding requirements of electronics sensitive to radiation. Aiming to improve the monitoring of the TID delivered by the mixed radiation field generated within the accelerator system, investigations on new suitable dosimeters have been carried out.With this research, two devices have been studied and characterized to be employed as dosimeter and possibly to complete the use of the silicon sensor currently employed at CERN for TID monitoring, i.e. the RADiation-sensitive Field Effect Transistor (RADFET): a commercial NMOS, and an ASIC (Application-Specific Integrated Circuit) named FGDOS. The devices have been selected following two opposite approaches: on the one hand, reducing the costs would allow the density of the deployed sensors to increase. As a direct consequence, a more detailed dose map would be obtained for large distributed systems like the LHC. On the other hand, the radiation monitoring can be further improved by deploying more sensitive detectors, which would allow to measure the dose where the levels are too low for the RADFET. Moreover, sensors with higher resolution would permit the characterization of the radiation field in a shorter time, which means within a lower integrated luminosity.The first approach has been accomplished by searching for alternative solutions based on COTS (Commercial Off-The-Shelf) devices, which would significantly reduce the costs and guarantee unlimited availability on the market. For this aim, investigations on a commercial discrete NMOS transistor, which was found to be very sensitive to the radiation, has been carried out.The need for improving the resolution of TID monitoring led to investigate the FGDOS, which is an innovative silicon dosimeter with a very high sensitivity that permits to detect extremely low doses.The calibration of the NMOS and the FGDOS have been performed by exposing the dosimeters to γ-ray. Their radiation response has been characterized in terms of linearity, batch-to-batch variability, and dose rate effect. The influence of the temperature has been studied and a method to compensate the temperature effect has been developed and implemented.Being the FGDOS is a System-On-Chip with several features that make the dosimeter an extremely flexible system, the characterization of its operational modes (Active, Passive and Autonomous) have been performed. Following the first characterization, some questions arose concerning the sensitivity degradation mechanisms affecting the dosimeter. To investigate this phenomenon, radiation experiments were performed with a test chip embedding only the radiation sensitive circuit of the FGDOS. The analysis of the experiments allowed the understating of the processes responsible for the sensitivity degradation, by separating the contribution of the reading transistor and the floating gate capacitor. The results of this investigation led us to considerer new design solution and compensation methods.The suitability of the NMOS and the FGDOS for TID measurement in the mixed radiation field produced by the CERN’s accelerator complex has been verified by performing accelerated radiation tests at the Cern High energy AcceleRator Mixed field facility (CHARM). The consistency of both sensors with the RADFET measurement has been demonstrated. The high sensitivity of the FGDOS leads to a significant improvement in terms of TID measurement in mixed radiation fields with respect to the RadFET, especially for low radiation intensities
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Aguirre, Fernando Rodrigues. "Estudo sobre distribuição de cargas em semicondutores sujeitos a radiação ionizante." Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/43/43134/tde-13032017-113040/.
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Os efeitos da radiação ionizante em dispositivos eletrônicos é uma preocupação crescente na tecnologia de semicondutores, especialmente devido à contínua redução dos dispositivos e ainda maior, quando são destinados para uso em ambientes agressivos com alta radiação, tais como missões espaciais, aceleradores de partículas ou reatores nucleares. Dentre os vários efeitos causados pela radiação ionizante em dispositivos eletrônicos está aquele devido à Dose Acumulada (Total Ionizing Dose - TID), o qual a acumulação de danos de radiação no dispositivo muda seu funcionamento normal. O TID causado por fótons em transístores já foi estudado no Brasil, mas o efeito de prótons num transistor bipolar, apresentado neste trabalho é um trabalho pioneiro no país. As curvas características de um transistor 2N3733 foram medidas antes, durante e após a irradiação de prótons entre 1,5 e 3,8 MeV, para quantificar as alterações das especificações elétricas do dispositivo. Nestas energias, há uma correlação direta entre a mudança na resposta elétrica e a energia do próton, exceto em algumas energias específicas, onde o pico de Bragg ocorreu perto das junções ou no meio do cristal de silício, demonstrando a importância da correta caracterização da camada de passivação em estudos de TID em dispositivos eletrônicos. A recuperação dos transistores irradiados após o recozimento a 50°C durante 8 horas também foi maior para aqueles irradiados nessas energias. Existe um limite superior de dose para o qual não foi observada alteração significativa do transistor. Este limite, da ordem de Grad, excede a maioria das aplicações em ambientes terrestres, mas está dentro do intervalo esperado para missões espaciais a Júpiter ou em grandes aceleradores de partículas.<br>The effect of ionizing radiation on electronic devices is a growing concern in semiconductor technology, especially due to the continuous reduction of the devices and even greater when they are intended for use in aggressive environments with high radiation, such as space missions, particle accelerators or nuclear reactors. Among the various effects caused by ionizing radiation on electronic devices are the effects due to Total Ionizing Dose (TID), in which the accumulation of radiation damage in the device changes its normal functioning. The TID caused by photons has already been studied in Brazil, but the effect of protons on a bipolar transistor, presented in this work is a pioneer work in the country. The characteristic curves of a 2N3733 transistor were measured before, during and after proton irradiation between 1.5 and 3.8 MeV, to quantify changes of the electrical specifications of the device. At these proton energies, there is a direct correlation between the change in the electric response to the proton energy, except at some specific energies where the Bragg peak occurred near the junctions or in the middle of the silicon crystal, demonstrating the importance of the correct characterization of the passivation layer in TID studies of electronic devices. The recovery of transistors irradiated after annealing at 50 ° C for 8 hours was also higher for those irradiated at these energies. There is an upper dose limit for which no alteration of the transistor was observed. This limit, of the order of Grad, exceeds most applications in terrestrial environments, but is within the expected range for space missions to Jupiter or large particle accelerators.
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Foo, Kerwyn Yi Min. "Methodological uncertainties in radiotherapy dose-effect analysis." Thesis, University of Sydney, 2020. https://hdl.handle.net/2123/24421.
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Cancer and normal tissues in patient populations exhibit variability in biological response to the same dose of radiation. Sources of this variability include:
• Inherent biological factors of patient, tumour or tissue
• Metrics to measure, classify or declare biological outcomes
• Volumetric (prescription of target or avoidance regions)
• Dosimetric and delivery
Dosimetric and delivery variation is easily measured and has relatively little impact on variation of outcome in modelling studies. Volumetric variation contributes greatly to uncertainty, dependent on human judgement by oncologists. However, analysis methodology is generally overlooked as a source of variation in reported dose-effect results and is the subject of investigation in this thesis.
Dosimetric and clinical data from clinical trials and prospective cohort studies have been used to illustrate the contribution of analysis methodology to variation in dose-effect relationships using evidence from prostate cancer radiation therapy. The primary data source is the Trans-Tasman Radiation Oncology Group clinical trial 03.04 “RADAR”, which investigated dose escalation in external beam radiotherapy for prostate cancer.
Systematic review of the medical physics literature shows that prostate cancer radiotherapy toxicity reporting does not fully account for fractionation, which biases and causes unreported variation in dose-effect results.
The toxicity-dose-volume-effect relationship is shown to depend on the anatomical subsite delineated and the type/grade of toxicity outcome chosen. Multivariate regression of multiple dose factors is not reliable due to multicollinearity of these factors.
Heterogeneity in method of analysis is an important and overlooked component of variability in reported results of dose effect relationships in radiotherapy studies. Harmonisation of analysis or correction for this heterogeneity will reduce uncertainties to allow better modelling of biological effects in the molecular oncology era.
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Dalloneau, Emilie. "Idendification de gènes à effet de dose impliqués dans la pathophysiologie des aneuploïdies associées au chromosome 21." Phd thesis, Université d'Orléans, 2010. http://tel.archives-ouvertes.fr/tel-00688939.
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Une variation du nombre de copies des gènes du chromosome 21 humain (HSA21) entraine des anomalies morphologiques et physiologiques d'un grand nombre d'organes chez les patients. La Trisomie 21, ou syndrome de Down et les monosomies partielles du HSA21 conduisent à des phénotypes complexes et variables. Afin d'identifier les gènes du HSA21 sensibles aux effets de dose, nous avons développé le modèle de monosomie Ms1Yah, pour la région Prmt2-Col6a1 du chromosome murin 10 (MMU10). L'analyse de ce modèle a montré que les souris Ms1Yah développent une altération des réponses inflammatoire et pulmonaire suite à une instillation de lipopolysaccharide (LPS). L'analyse, par Q-PCR, de l'expression des gènes de la région a mis en évidence deux gènes candidats : Prmt2 et S100B. Les lignées déficientes pour ces gènes ont été utilisées pour tester l'implication de Prmt2 et S100B dans la modification de la réponse inflammatoire et pulmonaire en réponse au LPS. Ces travaux ont montré d'une part que Prmt2 intervient dans la régulation de l'expression des cytokines pro-inflammatoires TNF-α et IL-6 de façon dose dépendante, via son rôle inhibiteur de la signalisation NF-κB. D'autre part, S100B ne semble pas intervenir dans la réponse inflammatoire induite par le LPS, alors que son inactivation entraîne une diminution de l'hyper réponse des voies aériennes (HRA) de façon dose dépendante. La réponse inflammatoire serait la résultante du croisement de deux voies de signalisation : LPS-TLR4-NF-κB-Prmt2 et S100B-RAGE-NFκB. Il faudrait que la voie Prmt2 soit en défaut pour observée un effet de S100B dans l'inflammation. L'injection d'un anticorps anti-S100B chez des souris B6 favorise une diminution de l'HRA induite par l'instillation de LPS. L'analyse préliminaire de l'utilisation de cet anticorps dans un modèle d'asthme montre là encore une capacité à diminuer l'HRA pour les doses les plus fortes de métacholine, ce qui laisse entrevoir le potentiel thérapeutique d'une telle molécule.
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Zerabruk, MA. "Repair of sub-lethal damage following single and split-dose irradiation using 60co-gamma and p(66)Be neutrons." Thesis, Cape Peninsula University of Technology, 2005. http://hdl.handle.net/20.500.11838/1504.
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Thesis (MTech Biomedical Technology)--Cape Peninsula University of Cape Town, 2005<br>In clinical radiotherapy, experiments are performed to determine optimal conditions of
the radiation prior to radiotherapy. These experiments focus on the relative biological
effectivness(RBE) determination and are predominantly applied in high linear energy
transfer (LET) radiations i.e. fast neutrons, as the RBE values for such radiations vary
greatly. In general, the RBE of a certain radiation relative to a given reference radiation
flCo gamma) varies widely with the energy, dose, dose rate, fractionation, type of tissue
and end-point used.
Experience with neutron therapy at iThemba LABS has shown that treatment with more
fractions and lower doses per fraction may be beneficial for some patients. To calculate
the iso-effective treatment dose needed, an appropriate alp ratio for early effects is
needed. In this study, the repair of mouse jejunum was measured for split-dose
irradiations to determine if a suitable alP ratio for neutrons could be estimated using the
known value for gamma rays and the applicable RBE.. Crypt stem cell survival was
measured 3.5 days after split-dose exposures to p(66)/Be neutrons and 6OCo gamma rays.
Dose response curves for both treatment modalities and for both acute and fractionated
exposures were constructed by counting crypts of Leiberkhiin at the base of the villi in
haematoxylin and Eosin-stained sections of mouse jejunum. Using a RBE value of 1.64
and an alP ratio of 7Gy noted for tbe fractionated photon exposures, an alP ratio of 11.5
IV
could be estimated for neutrons.
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Eiden, Céline. "Essai de faisabilité du suivi thérapeutique pharmacologique et de l'optimisation des antifongiques azolés récents : voriconazole et posaconazole." Montpellier 1, 2009. http://www.theses.fr/2009MON13508.
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Le voriconazole (VCZ) et le posaconazole (PCZ) sont des antifongiques récents à structure triazolée. Après avoir rapporté un cas d'allongement de l'espace QT avec torsade de pointes, suivi d'un arrêt cardiaque sous VCZ, nous avons effectué une étude sur l'ensemble des cas d'effets indésirables notifiés dans la Base Nationale de Pharmacovigilance et analysé les cas rapportés dans la littérature. Ces données nous ont permis de préciser les circonstances d'apparition des effets indésirables du VCZ. Nous avons ensuite mis au point et validé une méthode de dosage par chromatographie liquide haute performance avec détection ultraviolet du voriconazole et de son principal métabolite le N-oxide voriconazole. L'analyse du suivi thérapeutique et pharmacologique en conditions réelles de soins nous a ensuite permis d'établir un "profil de ratio métabolique de base" chez les patients immunodéprimés traités par VCZ dans le cadre d'une infection fongique invasive ou d'un traitement empirique. Enfin pour le PCZ, après avoir mis au point une méthode de dosage nous avons réalisé une étude pharmaco-clinique afin d'analyser les concentrations plasmatiques en PCZ à la posologie recommandée en traitement prophylactique ainsi que leurs variations dans une population de patients atteints d'hémopathies malignes. Notre travail s'intègre dans une démarche de qualité des soins visant à optimiser ces thérapeutiques chères, efficaces mais non dénuées d'effets indésirables.
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McDonald-Morken, Colleen Ann. "Hawk and Dove Stress Response Profiles in Humans." Thesis, North Dakota State University, 2011. https://hdl.handle.net/10365/29861.
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A recent evolutionary theory hypothesizes that there are two primary biobehavioral profiles of stress responding. Labeled "hawk" and "dove," each is characterized by divergent patterns of autonomic nervous system and neuroendocrine system activations in response to stress as well as distinct affective and behavioral tendencies. These profiles are prominent in a number of species, and it has been hypothesized that hawk-like and dovelike responses to stress may, in part, explain variability in stress-related health outcomes. This study is a preliminary investigation of hawk and dove biobehavioral profiles in humans. Participants included 73 Midwestern university students recruited from undergraduate-level psychology classes. Upon completion of a stressor task, participants answered questions regarding their psychological experiences during and immediately following the task and reported their emotions and health-related behaviors over the past several weeks. Physiological measures of cortisol and high frequency heart rate variability reactivity were used to identify relatively hawk-like and dove-like responders. Associations between patterns of physiological responding and emotional and behavioral
responses were tested. The results showed mixed support for the existence of hawk and dove biobehavioral profiles in humans.
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Vaccarino, Anthony Leonard. "Naloxone analgesia in BALBc mice : a dose-dependent relationship." Thesis, McGill University, 1987. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=66239.
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Platt, Gerald D. "Wind effects on a hemispherical dome." Thesis, Virginia Polytechnic Institute and State University, 1986. http://hdl.handle.net/10919/101360.
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A review of the past wind tunnel experiments involving the measurement of pressures over the surface of a hemispherical dome is made, and the flow parameters of these experiments are compared. A hemispherical dome is subjected to a flow in the open-throat wind tunnel at VPI&SU, and the resulting pressure measurements are given. An experiment utilizing the 6-ft square stability wind tunnel at VPI&SU to measure the pressures over the surface of a hemispherical dome is organized but not conducted.
ABAQUS, a nonlinear finite element program, is used to analyze a hemispherical, lamella dome subjected to a wind load. The dome is first modeled by using truss elements and then beam elements. A comparison of the two models is made.<br>M.S.
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Takam, Rungdham. "Determination of dose distribution of Ruthenium-106 Ophthalmic applicators." Title page, contents and abstract only, 2003. http://web4.library.adelaide.edu.au/theses/09SM/09smt1363.pdf.
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"August 2003" Bibliography: leaves 108-117. 1. Ruthenium-106 ophthalmic applicators -- 2. General principle of thermoluminescent dosimeter -- 3. Study of basic characteristics of CaSO4:Dy TLD -- 4. Measurements of COB and CCA type ruthenium-106 ophthalmic applicator dose distributions -- 5. Determination of the dose rate distribution using a MOSFET detector -- 6. Summary and conclusion. In this project, small CaSO4:Dy TLDs and a semiconductor MOSFET dosimeter were used for the determination of on-axis depth dose-rate distributions of 15-mm and 20-mm ruthenium-106 applicators in acrylic eye phantoms. The TLDs were also used to determine off-axis dose distributions.
21
Mazzetti, Scott A. "Akt and ERK activation in human skeletal muscle : dose-dependency of responses to increasing muscle contractions." Virtual Press, 2003. http://liblink.bsu.edu/uhtbin/catkey/1259313.
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Akt activation mediates increases in glycogen synthesis in response to insulin in humans, while extracellular signal-regulated kinase (ERK) activation increases gene transcription and protein translation in response to endurance and resistance exercise. Akt activation increases only in response to intense muscle contractions and during hypertrophy in rats. No study has examined Akt and ERK activation with increasing numbers of intense muscle contractions in humans. Therefore, the primary objectives of this investigation were to determine if Akt activation increases in response to resistance exercise in humans, and to compare the changes in Akt and ERK activation in response to increasing numbers of muscle contractions.Akt and ERK activation were compared in muscle biopsy samples from 7 men before (Pre) and after (Post) knee extension and control protocols using enzyme linkedimmunosorbent assays. Baseline information was obtained including body composition and maximal strength (1-RM). Subjects were familiarized with knee extensions performed at 70% of 1-RM and a specified repetition cadence (2sec up, 2sec down). Once/wk, subjects performed one protocol in random order: 1 repetition (rep), 10reps, 3 sets of l0reps (3x10), or 6min of sitting. Akt activation decreased 42%, while ERK activation increased 108% in response to 3x10 (p<0.05). Akt and ERK activation did not change with 1 and 10reps, and thus their responses were not dose-dependent with resistance exercise in humans. The findings from this study represent the first indication that Akt activation is reduced in response to resistance exercise in human skeletal muscle, possibly to help mediate reductions in glycogen synthesis.<br>Human Performance Laboratory
22
Ludwig, Sophie. "Comportement d'un "Perturbateur Endocrinien" et d'un "non Perturbateur Endocrinien" vis à vis de la toxicité testiculaire chez le rat." Phd thesis, Université Paris Sud - Paris XI, 2011. http://tel.archives-ouvertes.fr/tel-00658641.
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Depuis plusieurs années, des agents exogènes environnementaux appelés perturbateurs endocriniens (PE), sont soupçonnés d'interférer avec les fonctions essentielles de reproduction et de développement chez de nombreux organismes vivants. Au travers de ce travail, nous avons tenté de combler certaines lacunes afin de mieux comprendre les dangers pour l'Homme posés par ces produits. Des études ont été menées visant à caractériser la toxicité testiculaire, chez le rat adulte, induite par des composés aux mécanismes d'action toxique divers (PE et non PE), ceci dans le but d'établir in fine l'existence ou non d'un comportement propre aux PE. En évaluant les effets de l'anti-androgène flutamide, nous avons identifié des changements d'expression géniques dose-reliés pour les voies métaboliques majeures associées à la lésion du testicule (ex. métabolisme des acides gras), et démontré l'existence d'une "dose sans effet moléculaire" inférieure à la NOAEL définie sur la base des changements phénotypiques adverses. Des études ont également été conduites avec le 1,3-dinitrobenzène, composé décrit dans la littérature comme n'interférant pas avec le système endocrinien et ayant pour cibles les cellules de Sertoli. Nous avons établi qu'en plus d'induire l'apoptose des cellules germinales et d'altérer la progression du cycle cellulaire, cette substance affecte aussi la stéroïdogénèse, remettant quelque peu en question l'origine de sa toxicité. En conclusion, l'ensemble de nos résultats nous ont permis d'apporter des précisions sur le mécanisme d'action toxique des deux molécules examinées et d'identifier des doses sans effet pour chacune d'entre elles. Ils contribuent également au débat portant sur la définition des critères requis pour la détermination des propriétés de PE.
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Bannwarth, E. "Pancytopénie au méthotrexate à faible dose dans la polyarthrite rhumatoi͏̈de : à propos d'un cas et revue de la littérature." Bordeaux 2, 1992. http://www.theses.fr/1992BOR2M203.
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Egbe, Nneoyi Onen. "Measurement of dose in diagnostic radiology and the effect of dose reduction on image quality." Thesis, Available from the University of Aberdeen Library and Historic Collections Digital Resources. Online version available for University members only until March, 23, 2010, 2008. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?application=DIGITOOL-3&owner=resourcediscovery&custom_att_2=simple_viewer&pid=25469.
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Verdier, Marie-Clémence. "Les bêta-lactamines : apport de l'individualisation thérapeutique par la mesure des concentrations pour les patients hospitalisés." Rennes 1, 2012. http://www.theses.fr/2012REN1B003.
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Les bêta-lactamines sont la classe d'antibiotiques la plus diversifiée et la plus utilisée dans le monde du fait de leur très large spectre et de leur bonne tolérance. Elles ne sont pas considérées comme de bonnes candidates pour le suivi thérapeutique pharmacologique (STP) car leur index thérapeutique est supposé être large. Cependant, il y a plusieurs arguments suggérant l'utilité du STP dans certaines circonstances. Chez les patients de réanimation, les altérations physiologiques peuvent modifier de façon importante la pharmacocinétique des médicaments. Par conséquent, le risque d'un traitement inefficace, le développement de résistances, ou l'apparition d'effets indésirables est à prendre en compte. Le but de ce travail était i) de développer des méthodes de dosages simultané de plusieurs ?-lactamines dans le plasma ou autres matrices biologiques; ii) d'évaluer la variabilité interindividuelle des concentrations plasmatiques d'amoxicilline et de cloxacilline après administration de fortes doses; iii) de mesurer les concentrations plasmatiques et péritonéales du céfotaxime et de l'ertapénème chez des patients atteints de péritonite secondaire. Ces différentes études nous ont permis d'affiner les critères de justification du STP des ? -lactamines. L?utilisation raisonnée des antibiotiques sous entend une bonne justification de l?antibiothérapie, le choix de l?antibiotique le plus adapté, et également le choix de la bonne posologie. Le STP des ?-lactamines est un outil indispensable pour aider à ce choix et permettre un traitement efficace tout en limitant la survenue des effets indésirables et le développement des résistances bactériennes<br>Beta-lactam antibiotics are the largest family of antimicrobial agents, both in terms of number of compounds available and of prescription volume. These drugs are used at high doses for the treatment infections caused by susceptible bacteria, particularly in critically ill patients. They are generally not considered as good candidates for therapeutic drug monitoring (TDM), since their therapeutic index is assumed to be wide. However, there are several arguments suggesting that monitoring beta-lactam plasma levels may be useful in selected circumstances. In critically ill patients, physiological alterations may affect the pharmacokinetic parameters of antimicrobial agents and, consequently, their effectiveness and/or the risk of selecting resistant strains when underdosing. The aim of this work was i) to develop analytical methods for simultaneous determination of beta-lactams in plasma and other biological matrix; ii) to assess the interindividual variability of plasma concentrations of amoxicillin or cloxacillin in critically ill patients; iii) to determine the plasma and peritoneal concentrations of cefotaxime and ertapenem in patients requiring intensive care for secondary peritonitis. These various studies allow us to refine the criteria for the TDM of the ?-lactam antibiotics. The use of antibiotics implies a strong rationale for antibiotic therapy, choosing the most appropriate antibiotic, and also the choice of the proper dosage. The TDM of the ?-lactam antibiotics is an essential tool to ensure that the prescribed dose will achieve effective concentrations while minimizing the occurrence of adverse events and the development of bacterial resistance
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Tangboonduangjit, Puangpen. "Intensity-modulated radiation therapy dose maps the matchline effect /." Access electronically, 2006. http://www.library.uow.edu.au/adt-NWU/public/adt-NWU20060724.095712/index.html.
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Hollmark, Malin. "Absorbed dose and biological effect in light ion therapy." Doctoral thesis, Stockholm : Medical Radiation Physics, Stockholm university together with KI, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-7756.
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Davis, Kenneth Ralph 1964. "Two-dimensional simulation of the effects of total dose ionizing radiation on power-MOSFET breakdown." Thesis, The University of Arizona, 1989. http://hdl.handle.net/10150/277053.
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The effects of ionizing radiation on the breakdown-voltage degradation of power-MOSFET termination structures were examined through two-dimensional simulation. A wide variety of sensitivity to surface-charge density was found for various devices employing floating field rings and/or equipotential field plates. Termination structures that were both insensitive to surface charge and possessed a high breakdown voltage were identified. The results were compared with measurements made on selected structures. The principal ionizing radiation damaging mechanisms in MOS devices are discussed. Modifications made to an existing simulation program in order to simulate these complex field ring and field plate structures are described. Background information into how these termination structures improve the breakdown voltage and their sensitivities to positive interface charge buildup is investigated.
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Lacourt, Aude. "Mésothéliome : étiologie professionnelle à partir d’enquêtes cas-témoins françaises." Thesis, Bordeaux 2, 2010. http://www.theses.fr/2010BOR21738/document.
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Le mésothéliome pleural est considéré comme très spécifique d’une exposition à l’amiante. Cependant, certains aspects de l’étiologie de cette maladie n’ont pas encore été bien caractérisés. Les objectifs de cette étude sont : i) d’estimer la relation dose-effet entre exposition professionnelle aux fibres d’amiante et survenue de mésothéliome pleural selon différents indicateurs temporels d’exposition ; ii) d’étudier l’effet d’une exposition professionnelle aux laines minérales et aux poussières alvéolaires de silice cristalline libre sur le risque de survenue de mésothéliome pleural et iii) d’identifier les professions et secteurs d’activité à risque de survenue de mésothéliome pleural à partir de données recueillies sur une période de 20 ans. Les cas provenaient de ceux recrutés dans une précédente étude cas-témoins réalisée entre 1987 et 1993 et des cas enregistrés dans le programme national de surveillance du mésothéliome entre 1998 et 2006 (1 199 hommes). Les témoins ont été appariés en fréquence sur l’année de naissance et le sexe (2 378 hommes). L’exposition professionnelle à l’amiante, aux laines minérales et à la silice a été évaluée à partir de matrices emplois-exposition. Les relations dose-effet ont été estimées à l’aide du modèle logistique et leur forme a été obtenue grâce à l’utilisation de fonctions splines cubiques restreintes. Si la relation dose-effet à l’amiante est bien confirmée (particulièrement aux faibles doses), cette étude apporte de nouveaux résultats sur la relation temps-effet (rôle du temps écoulé depuis la dernière exposition ou effet de l’âge à la première exposition). Elle ouvre également de nouvelles perspectives sur le rôle des co-expositions (laines minérales) et permet d’identifier de nouvelles activités à risque, comme les mécaniciens automobiles<br>Asbestos exposure is recognized as the primary cause of pleural mesothelioma. However, some aspects of etiology of this disease have not been well characterized. The objective of this study was to elucidate dose-response relationships of temporal pattern of occupational asbestos exposure in males, using case-control data, to study effect of man made vitreous fibers and silica dust on the risk of pleural mesothelioma and finally, to describe occupations and industries at high risk for this cancer among men in France according a period of twenty years of observation. Cases came from a French case-control study conducted in 1987-1993 and from the French National Mesothelioma Surveillance Program in 1998-2006 (1,199 males). Population controls were frequency matched by sex and year of birth (2,378 males). Occupational asbestos exposure was evaluated with a job-exposure matrix. The dose-response relationships were estimated using logistic regression models and form of this relationship were estimated using restricted cubic spline functions. Dose-response relationship was confirmed (particularly for lowest doses). However, this study provides new results about time-effect relationships (role of time since last exposure or effect of age at first exposure). This study opens up new prospects on the role of co-exposure (mineral wool) and permit to identify new activities at risk for pleural mésothéliome as motor vehicle mechanics
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Yap, Madeline M. L. "A Study of Biochemical, Pharmacokinetic, Physiological and Psychomotor Variables and Ethanol Sensitivity after Low-dose Ethanol." Thesis, The University of Sydney, 1996. https://hdl.handle.net/2123/27473.
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The influence of ALDH2 and ADH2 genotype on the biochemical, physiological, psychomotor and subjective responses of Asian subjects to a challenge dose of ethanol were investigated.
One hundred and ten healthy male and female subjects of fill] or partial North East Asian descent (with ancestral origins in China, Japan, Korea and Vietnam), who were living in Australia at the time of testing, were genotyped for alcohol dehydrogenase (ADHz) and aldehyde dehydrogenase (ALDHz) enzymes using a combination of the polymerase chain reaction (PCR) with restriction enzyme digestion, allele specific oligonucleotide probing, or constant denaturant gel electrophoresis methods.
Volunteers were given a low oral dose (0.3 g kg^-1) of ethanol and were assessed subjectively for their degree of flush and for performance impairment using a battery of psychomotor tests (including divided attention, digit symbol coding, standing steadiness and critical flicker fusion frequency threshold). Self-report questionnaires were used to assess the subjects' perception of their intoxication and impairment. Blood ethanol concentrations (BECs) were monitored by breath analysis every fifteen minutes and blood samples were obtained from subjects before and at 15, 60 and 120 minutes afier ethanol administration. Measurements were made of the blood or plasma levels of acetaldehyde, acetate, pyruvate, lactate and ethanol. The blood pressure (systolic and diastolic), heart rate and facial temperature were also recorded at regular intervals.
The effects of the ADHz genotype, ALDH; genotype, ALDHZ/ ADHz combination genotype, the degree of flush and gender on the psychomotor performance, physiological, biochemical, pharmacokinetic and subjective responses of the subjects were explored to determine their influence on the response to ethanol.
When subjects were classified by ALDHz genotype, the BEC curve, acetaldehyde concentration, acetate concentration, facial temperature, heart rate, critical flicker fusion frequency threshold, digit symbol coding reaction time, standing steadiness and divided attention delay and excursion were all affected by whether the subject was ALDH; Homoll, Het or Hom022. The psychomotor performance of ALDHz Hom022 subjects was found to be more impaired in the divided attention delay, excursion and digit symbol coding reaction time tasks than in either Het or Homoll subjects. The standing steadiness epoch time and critical flicker fusion frequency threshold were also most affected by ethanol in the ALDHz Hom022 group.
The effect of ethanol on the pyruvate concentration, heart rate, CFFF threshold and standing steadiness also differed significantly among subjects of different ADH; genotype. The ADHz Homozygote-22 (Hom022) subjects had a higher standing steadiness epoch time and critical flicker fusion frequency threshold than either Heterozygote (Het) or Homozygote—ll (Homol 1) subjects.
The subjectively rated degree of flush was associated with differences in acetaldehyde concentration, acetate concentration, digit symbol coding reaction time, divided attention delay, facial temperature and heart rate measured. Psychomotor impairment in the divided attention delay task was greatest for the subjects who flushed with intermediate severity, although at two hours post-ethanol, the group which produced the most severe flushing was more severely affected. In the digit symbol coding reaction time, the subjects who produced the most severe flushing reactions were also most impaired.
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Chen, Jia. "Effect of dose and dose rate on benzo[a]pyrene induced mutational spectra in human cells." Thesis, Massachusetts Institute of Technology, 1994. http://hdl.handle.net/1721.1/36941.
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Hall, Susan Claire. "The C₃H 10T1/2 mouse embryo transformation assay : the role of radiation quality and dose-rate." Thesis, Open University, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.279005.
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Raines, Katherine Elizabeth. "The effects of chronic low-dose radiation on bumblebees." Thesis, University of Stirling, 2018. http://hdl.handle.net/1893/28699.
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The consequences to wildlife of living in contaminated areas with chronic low-dose rates of radiation are still relatively unknown. Laboratory studies using acute radiation have demonstrated that invertebrates are relatively radioresistant compared to other taxa. However, there is little scientific evidence to show how chronic low dose rates affect invertebrates. This is problematic for understanding the consequences to wildlife living in highly contaminated areas and also testing assumptions made for invertebrates by the International Commission on Radiological Protection (ICRP). This thesis was designed to address a number of recommendations have been suggested to improve radioecological studies and help reduce the uncertainty as to effects at low dose rates. These include environmentally relevant laboratory studies (Chapters 2 and 4), improved dosimetry and dose assessments (Chapter 3), investgating confounding factors (Chapter 4) and continuity between laboratory experiments and field work conducted in the Chernobyl Exclusion Zone (CEZ) (Chapter4). Chapter 2 presents an environmentally-relevant experiment testing how bumblebee reproduction and life history is affected by chronic low-dose rates. Unexpectedly, at dose rates equivalent to the CEZ, queen production declined and reproductive timing was altered. The estimation of dose rates to establish a dose-effect relationship for wild animals is difficult and a common criticism of radioecological studies, therefore, Chapter 3 tests whether the common approach to measuring only external ambient dose rates is suitable and whether the inclusion of life-history traits significantly alters the dose rate. The findings from this chapter reiterate the necessity to use dose-assessment tools to test different parameters to estimate dose rate in different scenarios to account for unknown variation. Chapter 4 demonstrates that in areas of elevated dose rates in the CEZ parasite burden was higher and bumblebees did not live as long. These results were reinforced by a laboratory study, which determined bumblebees exposed to increased radiation doses had high parasite burdens and were infected quicker, resulting in reduced longevity. The data in this thesis detected effects below the current dose bands used in international radioprotection and therefore advocate these dose bands be re-evaluated. However, the data do not support studies which have measured adverse effects at dose rates similar to background and suggest that confounding factors such as habitat quality and co-stressors need to be included in field and laboratory studies.
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Mughal, Safeer Kamil. "The dose and dose-rate effects of paternal irradiation on transgenerational instability in mice." Thesis, University of Leicester, 2013. http://hdl.handle.net/2381/27822.
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Of the non-targeted, delayed consequences of exposure to ionising radiation, genomic instability is a particular area of concern, especially with regard to its manifestation in the non-exposed offspring of irradiated parents. However, further analysis of these effects and their implications is mainly limited by our understanding of the underlying mechanisms and the lack of reliable data for humans. As of yet, transgenerational instability has only been consistently demonstrated in animal models using high, acute doses of ionising radiation (> 1 Sv). To investigate the effects of low-dose acute and low dose-rate (chronic) irradiation and whether or not they are capable of destabilizing the genomes of the unexposed offspring, we exposed male BALB/c mice to a range of γ-ray doses (10- 100 cGy) and dose-rates (chronic and acute), and mated them to unexposed BALB/c females 10 weeks post-irradiation. The mutation frequency at the Ms6-hm locus was established in DNA samples extracted from the sperm of directly exposed mice, as well as from the sperm and brains of their F1, using the single-molecule PCR technique. A linear dose-response was observed for direct exposure across the range of acute doses, with a doubling dose of 57 cGy. Furthermore, 100 cGy of acute γ-rays was shown to be more mutagenic than chronic exposure to the same accumulated dose. However, acute exposure to 10-25 cGy failed to manifest genomic instability in the derived offspring. This was also true of low dose-rate exposure to 100 cGy. Only acute paternal exposure to 50 and 100 cGy resulted in transgenerational instability, to a similar extent for both doses. Analogous results were found for both tissues. Taken together, this would imply the presence of a stress-like response where a threshold of acute dose determines the onset of transgenerational instability. Our results also suggest that children whose fathers are subject to most forms of human exposure to ionizing radiation would be safe from the effect.
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Adkin, Dawn Anne. "The effect of pharmaceutical exipients on small intestinal transit." Thesis, University of Nottingham, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.260596.
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Deal, Heather Elizabeth. "In vivo effects of T suppressor molecules : specificity and dose effects." Thesis, University of British Columbia, 1988. http://hdl.handle.net/2429/27870.
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The suppressor circuit and it's components have been studied extensively in this laboratory and others for the past ten years. This laboratory has produced factor-secreting hybridoma cells which are analogous to first-order T suppressor cells directed against the tumor P815 . A monoclonal antibody has been raised which recognizes a common portion of suppressor cells and factors. These tools are used in this study. It had been seen that when 20 µg A10F (factor secreted by A10, the Ts1 analogue) was injected into a mouse concurrently with P815, the suppression of the mouse's immune response was boosted. This led to increased tumor growth and accelerated death. However, when A10F was injected ten days prior to the mouse receiving P815, the opposite effect was seen. Mice had smaller tumors and longer survival times. This was not the contrasuppressive effect described by other laboratories, as the effect seen was not merely an abrogation of suppression, but rather enhancement of the immune response. The specificity and dose response of the effect was examined. This immune enhancement effect was not specific within the context of syngeneic tumor systems. It was found that the same effects were seen when P815 was replaced with L1210 or M-1, both also being H-2d tumors. In fact, L1210 was more sensitive to A10F than P815. There was some level of specificity to the enhancement effect. When A10F was replaced with Fd11F, a suppressor factor raised to ferredoxin, no effect was seen. Conversely, A10F did not produce the same effects as Fd11F in the ferredoxin system. Suppressor deletion therapy was used in both of these systems to confirm that suppressor cells were responsible for the effects seen. Dose response studies showed that the enhancement effect was dose dependent. Doses of A10F below 20 µg did not produce enhancement in the P815 system. Enhancement was seen with lower doses of A10F in the L1210 system, but the effect did decrease at the lower doses. A model is proposed for the data presented.<br>Science, Faculty of<br>Microbiology and Immunology, Department of<br>Graduate
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Beaulieu, Daniel Ryan. "A Framing Analysis: The NBA's "One-And-Done"Rule." Scholar Commons, 2012. http://scholarcommons.usf.edu/etd/4288.
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In 2006, the NBA introduced the "one-and-done" rule that restricted high school graduates to enter directly into the NBA draft following high school. In turn, a high school prospect would essentially now have the option of playing professionally elsewhere (most likely overseas), enter the NBA's Developmental League, or play NCAA basketball. The rule has proved to be quite controversial, as it has had a great effect on both NBA and NCAA basketball, as well as the players. Various media outlets have been quite vocal not only about the rule itself, but the perceived effects it has had on both collegiate and professional basketball. This study will utilize framing theory to explore the way the media has presented the issue to the public, its causal interpretation, any moral evaluations necessary, and any solutions to the problem. This study will utilize a content analysis to analyze not only the media's presentation of the rule, but also what frames have been formed pertaining to the rule's successes and failures. The study will also aim to give a greater understanding of how the basketball media form frames.
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Wong, Tony Po Yin, and tony wong@swedish org. "Improving Treatment Dose Accuracy in Radiation Therapy." RMIT University. Applied Sciences, 2007. http://adt.lib.rmit.edu.au/adt/public/adt-VIT20080104.144139.
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The thesis aims to improve treatment dose accuracy in brachytherapy using a high dose rate (HDR) Ir-192 stepping source and in external beam therapy using intensity modulated radiation therapy (IMRT). For HDR brachytherapy, this has been achieved by investigating dose errors in the near field and the transit dose of the HDR brachytherapy stepping source. For IMRT, this study investigates the volume effect of detectors in the dosimetry of small fields, and the clinical implementation and dosimetric verification of a 6MV photon beam for IMRT. For the study of dose errors in the near field of an HDR brachytherapy stepping source, the dose rate at point P at 0.25 cm in water from the transverse bisector of a straight catheter was calculated with Monte Carlo code MCNP 4.A. The Monte Carlo (MC) results were used to compare with the results calculated with the Nucletron Brachytherapy Planning System (BPS) formalism. Using the MC calculated radial dose function and anisotropy function with the BPS formalism, 1% dose calculation accuracy can be achieved even in the near field with negligible extra demand on computation time. A video method was used to analyse the entrance, exit and the inter-dwell transit speed of the HDR stepping source for different path lengths and step sizes ranging from 2.5 mm to 995 mm. The transit speeds were found to be ranging from 54 to 467 mm/s. The results also show that the manufacturer has attempted to compensate for the effects of inter-dwell transit dose by reducing the actual dwell time of the source. A well-type chamber was used to determine the transit doses. Most of the measured dose differences between stationary and stationary plus inter-dwell source movement were within 2%. The small-field dosimetry study investigates the effect of detector size in the dosimetry of small fields and steep dose gradients with a particular emphasis on IMRT measurements. Due to the finite size of the detector, local discrepancies of more than 10 % are found between calculated cross profiles of intensity modulated beams and intensity modulated profiles measured with film. A method to correct for the spatial response of finite sized detectors and to obtain the
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Figueiredo, Ricardo Tajra 1984. "Manejo da adubação potássica na cultura da batata-doce /." Botucatu, 2019. http://hdl.handle.net/11449/181414.
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Orientador: Adalton Mazetti Fernades<br>Coorientador: Pablo Forlan Vargas<br>Banca: Roberto Lyra Villas Bôas<br>Banca: Fábio Rafael Echer<br>Resumo: Para a maioria das hortaliças que produzem raízes tuberosas, o potássio (K) é o nutriente mineral exigido em maior quantidade. Entretanto, a aplicação de doses elevadas desse nutriente pode prejudicar o desenvolvimento das plantas, devido ao aumento da concentração salina ou mesmo decorrer em grandes perdas por lixiviação, especialmente em solos arenosos. Desta forma, o objetivo deste trabalho foi avaliar o crescimento e a produtividade da batata-doce submetida a doses e formas de parcelamento da adubação potássica em solos com diferentes teores iniciais de potássio (K). Foram conduzidos quatro experimentos em áreas com diferentes disponibilidades iniciais de K no solo (baixa = 0,7 mmolc dm-3; média = 1,4 e 1,5 mmolc dm-3 e alta = 3 mmolc dm-3) entre os anos de 2016 e 2018. O delineamento experimental utilizado foi o de blocos ao acaso, no esquema fatorial 3x4+1. Os tratamentos foram representados por três doses de K2O (60, 120 e 240 kg ha-1) combinadas com quatro formas de parcelamento (1 = 100% no plantio; 2 = 1/2 no plantio + 1/2 aos 40 dias após o plantio (DAP), 3 = 1/2 no plantio + 1/2 aos 90 DAP; 4 = 1/3 no plantio + 1/3 aos 40 DAP + 1/3 aos 90 DAP), além da testemunha sem K. O crescimento das plantas, em termos de biomassa produzida, aumenta em solos com baixo e médio teor inicial de K até as doses de 145 e 115 kg ha-1 de K2O, respectivamente. Em solos com alto teor inicial de K (≥ 3,0 mmolc dm-3), a adubação potássica não contribuiu para o acúmulo de matéria seca da p... (Resumo completo, clicar acesso eletrônico abaixo)<br>Abstract: Among the majority of tuberous roots vegetables, potassium (K) is the most required mineral nutrient. However, the application of high rates of this nutrient may harm the plants development, due to the increase in saline concentration or even in large losses by leaching, especially in sandy soils. Thus, the purpose of this work was to evaluate the growth and yield of sweet potato submitted to rates and forms of K split application in soils with different K concentration. Four experiments were carried out in areas with different initial K availability in the soil (low = 0.7 mmolc dm-3, medium = 1.4 and 1.5 mmolc dm-3 and high = 3 mmolc dm-3) between 2016 and 2018. The experimental design was a randomized block design in the 3x4 + 1 factorial scheme. The treatments were represented by three doses of K2O (60, 120 and 240 kg ha-1) combined with four forms of plotting (1 = 100% at planting, 2 = 1/2 at planting + 1/2 at 40 days after planting (DAP), 3 = 1/2 at planting + 1/2 at 90 DAP, 4 = 1/3 at planting + 1/3 at 40 DAP + 1/3 at 90 DAP), in addition to the control without K. In terms of biomass produced, the plant growth increases in soils with low and medium initial K concentration up to 145 and 115 kg ha-1 of K2O, respectively. In soils with a high initial concentration of K (≥ 3.0 mmolc dm-3), K fertilization did not contribute to the accumulation of dry matter of the plant, but reduces the biomass accumulation in the tuberous roots. In soil with low initial K concentration, the commercial yield increases up to 171 kg ha-1 of K2O, and in soils with a medium initial K concentration, the increase in commercial yield reaches rates between 106 and 111 kg ha-1 of K2O. However, under high initial availability of K, the commercial yield reduces with the potassium fertilization until the rate of 60 kg ha-1 of K2O. The split application of K (planting + 40 + 90DAP) was shown to be more efficient in increasing ...<br>Mestre
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Skwarchuk, Mark William. "Presence of cell-cycle dependent substructure at low dose in the radiation survival response of asynchronous V79-WNRE cells." Thesis, University of British Columbia, 1990. http://hdl.handle.net/2429/28950.
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Survival studies using cell sorting techniques together with data averaging on asynchronously dividing V79-WNRE cells reveal statistically significant evidence of substructure in the radiation survival response at low dose (2 to 3 Gy) that cannot be adequately characterized by a single linear-quadratic function, S = exp( -αD -βD²). The data suggest a two-component response that is particularly evident when plotted in the linear form of the linear-quadratic equation, -ln(S)/D = α + βD. Application of other survival models (Single Hit + Multi Target and Repair-Misrepair) does not eliminate the substructure.
The substructure may result from subpopulations of cells at different stages of the cell cycle, which differ in their radiosensitivity, giving rise to a two-component survival response. In order to explore this hypothesis, studies were carried out with populations of partially synchronized cells. The mitotic selection technique was employed alone or in combination with 12 hours exposure to 1 mM hydroxyurea or 1 μg/ml aphidicolin to obtain large numbers of synchronized cells. G1/S phase populations obtained by mitotic selection followed by hydroxyurea or aphidicolin do not show the substructure found for asynchronous cells, thus supporting the hypothesis. G1 phase populations obtained by mitotic selection alone revealed substructure which could be characterized by a single fit to the RMR or SH+MT models. Structure was also present in the response of heterogeneous S/G2 phase populations synchronized by mitotic selection followed by hydroxyurea, but may not be present in the response of S phase populations synchronized by mitotic selection alone. The data are consistent with the hypothesis that the substructure is a result of sensitive (G1, G2 or M) and resistant (S) subpopulations of cells.<br>Science, Faculty of<br>Physics and Astronomy, Department of<br>Graduate
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Blyth, Benjamin John, and benjamin blyth@flinders edu au. "Development and use of an adoptive transfer method for detecting radiation-induced bystander effects in vivo." Flinders University. School of Medicine, 2009. http://catalogue.flinders.edu.au./local/adt/public/adt-SFU20091008.150317.
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Ionising radiation can cause damage to DNA that can result in gene mutations contributing to carcinogenesis. Radiation-protection policy currently estimates cancer risks from exposures to radiation in terms of excess risk per unit dose. At very low radiation dose-rates, where not all cells are absorbing radiation energy, this formula carries the inherent assumption that risk is limited to those cells receiving direct energy depositions. Numerous studies have now called this assumption into question. Such low dose-rates are in the relevant range that the public receives from natural background and man-made sources, and, if this fundamental assumption proves unfounded, current estimations of radiation-induced cancer risk at low doses will be incorrect. Accurate predictions of stochastic cancer risks from low-dose radiation exposures are crucial to evaluating the safety of radiation-based technologies for industry, power generation and the increasing use of radiation for medical diagnostic and screening purposes.
This thesis explores phenomena known as radiation-induced bystander effects. The term bystander effects, as used here, describes biological responses to ionising radiation (hitherto observed in vitro) in cells not directly traversed by an ionising track, due to intercellular signals received from neighbouring cells that did receive energy depositions. This study aimed to determine whether radiation effects are communicated between irradiated and unirradiated cells in vivo, and if so, whether this effect alters current estimations of cancer risk following low-dose radiation exposures. In order to answer these questions, an in vivo experimental system for studying bystander effects in mice was developed. The method was based on the adoptive transfer of irradiated splenocytes into unirradiated hosts with simultaneous identification of irradiated donor cells, and biological endpoints in unirradiated bystander cells in situ using fluorescence microscopy and image analysis.
Splenocytes from donor mice were radiolabelled with 3H-thymidine or received an acute X-ray dose. The irradiated donor cells, labelled with a fluorescent probe, were then adoptively transferred into unirradiated recipient mice via the tail vein, whilst control mice received sham-irradiated donor cells. A proportion of the cells lodged in the recipient mouse spleens where they remained for a period before the tissues were cryopreserved. The locations of donor cells were identified in frozen spleen sections by the fluorescent probe, and the levels of apoptosis and proliferation were simultaneously evaluated in situ in the surrounding unirradiated bystander cells using fluorescence-based assays. Transgenic pKZ1 recipient mice were also used to quantify chromosomal inversions in bystander cells. Since three-dimensional spatial relationships were preserved, responses could be measured in the local area surrounding irradiated cells as well as further afield. Following the development of the irradiated-cell adoptive transfer protocol and validation of the sensitivity and reproducibility of the biological assays in situ, a series of experiments was performed. In the initial experiments, 500,000 radiolabelled cells (0.33 mBq.cell-1) were injected into recipient mice and the spleen tissues were isolated 22 h later. No changes in apoptosis or proliferation were detected in local bystander spleen cells or throughout the spleen, compared to mice receiving sham-radiolabelled donor cells. In subsequent experiments, the effects of a number of experimental conditions were explored including the injection of tenfold more donor cells, analysis of spleen tissues after three days lodging in vivo, radiolabelling of donor cells with 100-fold higher 3H dose-rate and irradiation of donor cells ex vivo with 0.1 or 1 Gy X-rays. In each case, no changes in apoptosis or proliferation were observed.
The in vivo method described here was designed to simulate the conditions of a bystander scenario from low dose-rate exposures relevant to public radiation protection. Contrary to the many reports of bystander effects in vitro, experiments using this sensitive method for examining the in vivo responses of unirradiated cells to neighbouring low-dose irradiated cells, have so far shown no changes in bystander cells in the spleen. This adoptive transfer method is the first in vivo method for examining the effects of known irradiated cells exposed to low radiation doses at low dose-rates, on neighbouring cells in situ that are truly unirradiated. Both the irradiated and bystander cells are normal, non-transformed primary spleen cells functioning in their natural environment. This in vivo experimental system allows the examination of tens of thousands of bystander cells and has shown a remarkable sensitivity, with statistical power to rule out changes in apoptosis <10% from the control.
The relevance of in vitro bystander findings is unclear. Many reported bystander effects are more analogous to the systemic communication of abscopal effects from highly irradiated tissues. Disagreement between experimental systems and difficulty in reproducing key results between laboratories further complicate the translation of bystander data in vitro to human risk-estimation. The radiation protection community has expressed its need for in vivo validation of the bystander phenomenon before it can be included into the appraisal of carcinogenic risk. This adoptive transfer method is now available to study a range of bystander endpoints and potential signalling mechanisms in vivo, and provides a way to translate the wealth of data previously collected in vitro into findings directly relevant to human risk-estimation.
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Baba, Kiichiro. "Experimental model for the irradiation-mediated abscopal effect and factors influencing this effect." Kyoto University, 2020. http://hdl.handle.net/2433/259722.
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Ball, Jessica Lynne. "Field and numerical investigations of lava dome hydrothermal systems and their effects on dome stability." Thesis, State University of New York at Buffalo, 2014. http://pqdtopen.proquest.com/#viewpdf?dispub=3612916.
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<p> This study investigates the potential for hydrothermal alteration and circulation in lava domes using combined analytical, remote sensing and numerical modeling approaches. This has been accomplished in three parts: <i>1) </i> A comprehensive field, geochemical and remote sensing investigation was undertaken of the hydrothermal system in the Santiaguito lava dome complex in Guatemala. The Santiaguito domes were found to contain mainly hydrous silica alteration, which is unlikely to weaken dome rock, but the summit of Santa Maria was found to contain pervasive argillic alteration (clay minerals), which do pose more of a collapse-related hazard. These results were confirmed by hot spring geochemistry which indicated that water in the domes was responsible for some rock dissolution but had a residence time too short to allow for secondary mineralization. <i>2)</i> A finite element numerical modeling approach was developed which was designed to simulate the percolation of meteoric water in two dome geometries (crater-confined and 'perched'), and the results were compared to the surface expression of hydrothermal systems on existing lava domes. In both cases, we concluded that simulated domes which lacked a high-temperature (magmatic) heat source could not develop a convecting hydrothermal system and were dominated by gravitational water flow. In these low-temperature simulations, warm springs (warmer high fluid fluxes) were produced at the base of the dome talus and cool springs were dispersed lower down the slope/substrate; fumaroles (high vapor fluxes) were confined to the dome summits. Comparison with existing dome cross sections indicates that the simulations were accurate in predicting fumarole locations and somewhat accurate at predicting spring locations, suggesting that springs may be subject to permeability contrasts created by more complicated structural features than were simulated in this study. <i>3)</i> The results of the numerical modeling were used to calculate alteration potential in the simulated domes, indicating the most likely areas where alteration processes might either reduce the strength of a dome or reduce permeability that could contribute to internal pressurization. Rock alteration potential in low-temperature lava domes was found to be controlled by material permeability and the presence or absence of a sustained heat source driving hydrothermal circulation. High RAI values were preserved longer in low-permeability domes, but were more strongly developed in domes with higher permeabilities. Potential for mineral dissolution was highest at the base of the dome core, while the potential for mineral precipitation is highest at the dome core-talus interface. If precipitated minerals are impermeable, the dome core/talus interface would be a likely location for accumulation of gases and initiation of gas-pressurization-related collapse; if alteration is depositing weak (i.e. clay) minerals in this area, the dome core/talus interface might be a candidate for collapses occurring as the result of alteration processes. </p><p> The results of this study are all geared toward answering two broad questions: <i> Where are hydrothermal alteration processes likely to occur or be focused within lava domes?</i> and <i>What effect could these processes have on dome stability?</i> In the specific case of the Santiaguito dome complex, the combination of a quickly-recharged, low-temperature hydrothermal system in the inactive domes actually indicated a low possibility of collapse related to alteration minerals. This result was reinforced by the results of the numerical modeling, which indicated that domes are unlikely to develop sustained hydrothermal convection without the presence of a significant (magmatic) heat source and—in the case of Santiaguito—are likely to produce more hydrous silica alteration minerals when they also lack a source of acidic gases. Models of alteration potential do detail, however, that both shallow and deep dome collapses are still a possibility with a low-temperature hydrothermal system, given either a) a source of acidic gases to drive the formation of clay minerals (which are most likely to be deposited at the core/talus interface of a dome, or b) enough deposition of silica minerals in pore spaces to lower permeability in dome rock and promote internal gas pressurization. The results of this study are not limited to lava domes, as the volcanic edifices on which they rest are composed of the same materials that comprise lava domes and are therefore susceptible to the same hydrothermal processes. Further simulations of both lava domes and their associated edifices, including mineral species models, could help constrain under what conditions a lava dome or volcano is likely to develop areas of weak mineral precipitates (such as clay minerals) which could provide sites for collapse, or develop an impermeable cap of silicate minerals which could trap rising vapor and contribute to the pressurization of the edifice in question (which can in turn lead to collapse).</p>
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Shintani, Takashi. "Investigation of 4D dose in volumetric modulated arc therapy-based stereotactic body radiation therapy: does fractional dose or number of arcs matter?" Kyoto University, 2020. http://hdl.handle.net/2433/253487.
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Smith, Farouk. "Total ionizing dose mitigation by means of reconfigurable FPGA computing." Thesis, Link to the online version, 2007. http://hdl.handle.net/10019/713.
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Huang, Bingsheng, and 黃炳升. "Radiation dose and cancer risk of cardiac CT scan and PET-CT scan." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2009. http://hub.hku.hk/bib/B41757993.
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Chilà, Deborah. "Dose tracking in radiation oncology using daily CBCT: effects of physical parameters on dose calculation accuracy." Master's thesis, Alma Mater Studiorum - Università di Bologna, 2020. http://amslaurea.unibo.it/20587/.
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The availability of cone beam computerized tomography (CBCT) images at the time of treatment has opened possibilities for recalculations and tracking of the delivered dose, becoming an effective tool for adaptive radiotherapy. A significant component in the accuracy of dose recalculation on CBCT images is the calibration of the Hounsfield units (HU) to density.
The aim of this thesis, developed at the Policlinic of Modena, is to assert a methodology for the characterization of the HU-to-density calibration curve, and to evaluate the impact of the calibration phantom inserts composition and phantom volume on dose calculation accuracy.
The HU-to-density calibration curves from four different phantoms were measured and compared. The HU output of a kV CBCT scan depends on the physical parameters of the phantom density inserts, with particular reference to the atomic number (Z), due to the photoelectric effect which is the main radiation-matter interaction at kV energies. The phantom radial diameter also influences the HU values on the image. The effect of scattering and beam hardening was examined as a function of phantom diameter, founding a high deviation on the HU value of the same density insert when varying the radial diameter of the phantom, especially for high densities. When we are dealing with CBCTs also the acquisition parameters influence the resulting image, that’s why we will show that a protocol-specific calibration curve is needed. The resulting calibration curves were used to compare the calculated doses against planned ones. The percent difference between recalculated and planned dose was obtained for chosen clinically important dose levels and a box plot analysis was conducted.
Results show that the best calibration curve for dose recalculation on CBCT images has been obtained when a human-tissue-equivalent inserts are used and when the radial diameter of the phantom is close to the dimensions of the real patient.
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Nedelman, Cassandra B., and L. Lee Glenn. "Effect of Tissue Plasminogen Activator Dose and Interval on Stroke Severity." Digital Commons @ East Tennessee State University, 2014. https://dc.etsu.edu/etsu-works/7480.
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Excerpt: The recent study by Sahlas et al1 in the Journal of Stroke and Cerebrovascular Diseases concluded that “the estimation of a patient's weight in the acute setting can lead to overcalculation of the tissue plasminogen activator dose, which is associated with poorer functional outcomes.” However, this conclusion is not well supported by their study1 because the most severe ischemic stroke cases were the ones that were most likely not weighed, and this severity could have led to the increased mortality that was found2 and the majority of unweighed patients were actually given an underdose that was associated with better discharge outcomes, as explained below.
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Adamus-Górka, Magdalena. "Improved dose response modeling for normal tissue damage and therapy optimization." Doctoral thesis, Stockholm University, Medical Radiation Physics (together with KI), 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-7433.
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<p>The present thesis is focused on the development and application of dose response models for radiation therapy. Radiobiological models of tissue response to radiation are an integral part of the radiotherapeutic process and a powerful tool to optimize tumor control and minimize damage to healthy tissues for use in clinical trials. Ideally, the models could work as a historical control arm of a clinical trial eliminating the need to randomize patents to suboptimal therapies. In the thesis overview part, some of the basic properties of the dose response relation are reviewed and the most common radiobiological dose-response models are compared with regard to their ability to describe experimental dose response data for rat spinal cord using the maximum likelihood method. For vascular damage the relative seriality model was clearly superior to the other models, whereas for white matter necrosis all models were quite good except possibly the inverse tumor and critical element models. The radiation sensitivity, seriality and steepness of the dose-response relation of the spinal cord is found to vary considerably along its length. The cervical region is more radiation sensitive, more parallel, expressing much steeper dose-response relation and more volume dependent probability of inducing radiation myelitis than the thoracic part. The higher number of functional subunits (FSUs) consistent with a higher amount of white matter close to the brain may be responsible for these phenomena. With strongly heterogeneous dose delivery and due to the random location of FSUs, the effective size of the FSU and the mean dose deposited in it are of key importance and the radiation sensitivity distribution of the FSU may be an even better descriptor for the response of the organ. An individual optimization of a radiation treatment has the potential to increase the therapeutic window and improve cure for a subgroup of patients.</p>
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Ström, Jakob. "The dose-dependent effects of estrogens on ischemic stroke." Doctoral thesis, Linköpings universitet, Klinisk kemi, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-77193.
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Estrogens are a group of female sex hormones that in addition to central roles in reproductive functions also have profound impact on for example brain development, blood vessels, bone tissue, metabolism and the immune system. The dominant endogenous production sites for estrogens in females are the ovaries and adipose tissue, while exogenous sources include combined contraceptive hormone treatments and menopausal hormone therapy. A few decades ago, the observation that females in comparison to men seemed to be protected against cerebral ischemia, and that this benefit was partially lost during menopause, sparked the hypothesis that estrogens protect against stroke. This was later confirmed by epidemiological studies and a large number of experimental animal studies, which motivated extensive clinical trials in which estrogens and/or progestagens were administered with the intent to prevent degenerative conditions rather than to ameliorate menopausal symptoms. However, the results were generally disappointing. The largest study, the Women’s Health Initiative (WHI), was discontinued due to the observation of an increased risk of breast cancer, cardiovascular disease and stroke. In parallel, a small number of animal studies in which estrogens were shown to increase damage from cerebral ischemia were published, one of these originating from our laboratory. This was, despite the WHI outcome, a surprising result, since the vast majority of previous animal studies had demonstrated protective effects. Therefore, in an attempt to explain the discordant results, Paper 1, and later Paper 4, of the current thesis were planned, in which four 17β-estradiol administration methods were tested. Substantial differences in serum hormone concentrations resulted from the different methods. Most importantly, the commercially available slow-release pellets used in our earlier experiments resulted in extremely high serum concentrations of 17β-estradiol. In Paper 2, 66 published studies that had investigated the effects of estrogens on stroke were meta-analyzed to pin-point the methodological reasons for the result dichotomy. Strikingly, in all six studies in which estrogens had produced damaging effects, the same type of slow-release pellets had been used, although these were used in a minority of the total number of studies. Paper 3 substantially strengthened the hypothesis that administration methods were crucial by showing that repeating the earlier experiment from our laboratory in which pellets had been used, but using a low-dose regimen instead, switched the estrogen effects from neurodamaging to neuroprotective. In Paper 5, an effort was made to challenge the assumption that the dose, and not the administration method per se, was the key factor, however this failed due to large intra-group infarct size variability. The current thesis adds evidence to the notion that differences in administration methods and their resulting serum concentrations of 17β-estradiol constitute a major factor responsible for the dichotomous results in studies investigating estrogens’ effects on cerebral ischemia. Even though results from animal studies are difficult to extrapolate to humans, this has a bearing on the menopausal hormone therapy debate, indicating that the risk of stroke could be reduced if serum concentrations of estrogens are minimized.