The effects of low doses of ionizing radiation on living things is a continually evolving area of research. Importantly, low dose effects were historically overlooked and not properly accounted for the assessment of risk to human health, as is the case with the contentious linear no-threshold model. These low dose effects are now known to be relevant to human health in both accidental and intentional exposures, including doses relevant to medical diagnostics and therapeutics. Furthermore, there is a relative dearth of information on low dose effects in non-human species, which necessitates further investigation and evaluation of radiosensitivity. Radiation-induced bystander effects occur in organisms due to the receipt of signals from directly irradiated cells, which act to communicate radiation damage to surrounding cells. Recent research has identified one type of bystander signal which is carried by photons of biological origin, however the effects produced in bystander cells receiving these photons has not been extensively investigated. It was suspected, based on previous research, that reactive oxygen species participate in the manifestation of this bystander effect. Three mammalian cell lines were assessed for their ability to produce bystander photons upon direct irradiation; subsequently, radiologically unexposed cells were exposed to the resulting photons and assayed for biological effects. The human cell lines used exhibited significant photon emissions and oxidative stress, clonogenic cell death, reduced cellular metabolism, and compromised mitochondrial oxidative phosphorylation following exposure to these photons. The use of a melanocyte cell line indicated that these effects are attenuated by melanin, and this is suspected to occur through photoabsorption or antioxidant mechanisms. Additionally, the same assays were conducted following cell exposure to hydrogen peroxide at low concentrations to assess responses to oxidative stress relevant to bystander responses, indicating less overall sensitivity in the examined melanocytes. These findings are significant because they contribute to our understanding of the mechanisms behind low dose biological effects, because they further challenge the linear no-threshold model and other models based on target theory, because they provide evidence for differential responses to the physical bystander signal in non-human species, and because secondary photon emissions are likely relevant to the medical radiation sciences. / Thesis / Master of Science (MSc) / Low doses of ionizing radiation interact with living things differently than high doses. Low dose effects are now known to be relevant to human health and protection of the environment. Radiation-induced bystander effects occur in cells due to the receipt of signals from irradiated cells which act to communicate radiation damage to surrounding cells. One type of bystander signal is carried by photons emitted from directly irradiated cells, however the effects produced in bystander cells receiving these photons has not been extensively investigated. This thesis investigates the cellular effects of these “biophotons”, including cell survival, oxidative stress, and metabolism.

Eagle syndrome is a rare clinical condition that is characterized by either an elongated styloid process or a calcified stylohyoid ligament. This report describes the case of a 35-year-old woman who presented with Eagle syndrome following the treatment of recurrent laryngeal carcinoma with ionizing radiation.

The ability of engineered cerium oxide nanoparticles to confer radioprotection was examined. Rat astrocytes were treated with cerium oxide nanoparticles to a final concentration of 10 nanomolar, irradiated with a single 10 Gy dose of ionizing radiation and cell death was evaluated by propidium iodine uptake at 24 and 48 hours after radiation insult. Treatment of rat astrocytes with nanoceria resulted in an approximate 3-fold decrease in radiation induced death. These results suggest that the nanoceria are conferring protection from radiation induced cell death. Further experiments with human cells were conducted. Human normal and tumor cells (MCF-7 and CRL8798) were treated with the same dosage of cerium oxide nanoparticles, irradiated and evaluated for cell survival. Treatment of normal cells (MCF-7) conferred nearly 99% protection from radiation-induced cell death while the same concentration of nanoceria showed almost no protection in tumor cells (CRL8798). TUNEL analysis results of similarly treated cells demonstrated that nanoceria reduced radiation-induced cell death by 3-fold in normal breast cells but not in MCF-7 tumor cell lines when cultured under the same conditions. We concluded that cerium oxide nanoparticles confer radioprotection in a normal human breast line (CRL 8798) but not in a human breast tumor line (MCF-7). It is hoped that the outcome of this study will guide future endeavors toward a better elucidation of the molecular pathways involved in the protection of cells with nanoceria against radiation-induced cell death, as well as the minimization of the bystander effect in radiation therapy.

The communication of information between irradiated and non-irradiated bystander cell populations and the subsequent expression of radiation-like responses in the non-irradiated population, formally referred to as the radiation-induced bystander effect, is a very well established phenomenon in the study of radiobiology. Intercellular communication of bystander signals is known to occur via the exchange of soluble factors through biological fluids and via the transfer of molecules between adjacent cells via gap-junctions. Both of these communication methods require some degree of physical contact between biological entities. However, observations made in the literature demonstrating the induction of radiation effects in optically-coupled, yet chemically-separated organisms raises the hypothesis that alternative radiation bystander communication mechanisms may exist that have not yet been explored. Following the detection of significant photon emission from human keratinocyte cells exposed to ionizing beta-radiation by Ahmad in 2013, the involvement of an electromagnetic bystander signal was proposed. While not yet established in the field of radiobiology, intercellular communication via electromagnetic signalling is widely studied in the field of biophotonics. The emission of electromagnetic radiation from biological material, called biophoton emission, and the subsequent communication of effects using those signals has been characterized both spontaneously and as a result of perturbation by various stressors. This thesis therefore aimed to investigate intercellular communication via electromagnetic signalling stimulated by low-dose ionizing radiation to identify a possible convergence between the fields of biophoton communication and radiation-induced bystander effects. The characterization of biophoton emission from human cell cultures was accomplished using a single photon counting photomultiplier tube. The results revealed that biophoton emission is exacerbated by external stimulation (beta-radiation), it possesses a dependence upon the activity of radiation delivered, the density of the irradiated cell culture, and cell viability. These results suggest that biophoton emission is governed by physical transitions between excited and ground states and may further be modulated by metabolic processes. An effect of beta-radiation-induced biophoton emission upon non-irradiated bystander cells was identified and manifested as a reduction in cell survival. The modulatory effects observed following the application of photomodulating agents to the bystander cultures support ultraviolet electromagnetic radiation as a responsible factor in the communication of bystander signals. Observation of photon emission across the entire ultraviolet, visible and infrared spectra lead to the suggestion that ultraviolet wavelengths are only a portion of the signal responsible for eliciting bystander responses and that coherent interaction of multiple wavelengths is probable in the intercellular exchange of information. The possibility of a link between biophoton bystander signalling and soluble factor mediated bystander effects was investigated next by isolating exosomes from biophoton-exposed bystander cultures. Positive bystander responses were exhibited by secondary reporter cells incubated with the exosomes isolated from the biophoton-exposed bystander cultures, thereby suggesting that biophoton signalling is a possible form of biological redundancy where it acts as an intermediary to trigger soluble factor release and further reinforce intercellular communication. Finally, the effect of beta-radiation-induced biophoton signals upon mitochondrial activity was assessed and revealed the capacity for biophotons to downregulate Complex I and ATP synthase activity. The demonstrated effect of biophotons upon mitochondria elucidates a candidate mechanism worthy of further exploration to determine how biophotons may trigger responses in bystander cells. Overall, this thesis elucidates an additional mechanism for intercellular communication between biological systems perturbed by low doses of ionizing radiation, in the form of an electromagnetic signal. This work contributes to the current perspective on biophoton bystander signalling as a potential source of biological redundancy, facilitating a means of intercellular communication when optical coupling but not chemical contact is available in a given system. / Thesis / Doctor of Philosophy (PhD)

Nickel and iron-based alloys are important structure and cladding materials for modern nuclear reactors due to their high mechanical properties and high corrosion resistance. To understand the radiative and corrosive environment influence on the mechanical strength, computer simulation works are conducted. In particular, this dissertation is focused on multiscale modeling of the effects of radiation-induced solute segregation and oxidation on grain boundary (GB) strength in nickel-based and iron-based alloys. Besides the atomistic scale density functional theory (DFT) based calculations of GB strength, continuum-scale cohesive zone model (CZM) is also used to simulate intergranular fracture at the microstructure scale. First, the effects of solute or impurity segregation at GBs on the GB strength are studied. Thermal annealing or radiation induced segregation of solute and impurity elements to GBs in metallic alloys changes GB chemistry and thus can alter the GB cohesive strength. To understand the underlying mechanisms, first principles based DFT calculations are conducted to study how the segregation of substitutional solute and impurity elements (Al, C, Cr, Cu, P, Si, Ti, Fe, which are present in Ni-based X-750 alloys) influences the cohesive strength of Σ3(111),Σ3(112),Σ5(210) and Σ5(310) GBs in Ni. It is found that C and P show strong embrittlement potencies while Cr and Ti can strengthen GBs in most cases. Other solute elements, including Si, have mixed but insignificant effects on GB strength. In terms of GB character effect, these solute and impurity elements modify the GB strength of the Σ5(210) GB most and that of the Σ3(111) least. Detailed analyses of solute-GB chemical interactions are conducted using electron localization function, charge density map, partial density of states, and Bader charge analysis. The results suggest that the bond type and charge transfer between solutes and Ni atoms at GBs may play important roles on affecting the GB strength. For non-metallic solute elements (C, P, Si), their interstitial forms are also studied but the effects are weaker than their substitutional counterparts. Nickel-base alloys are also susceptible to stress corrosion cracking (SCC), in which the fracture mainly propagates along oxidized grain boundaries (GBs). To understand how oxidation degrades GB strength, the next step is to use density functional theory (DFT) calculations to study three types of oxidized interfaces: partially oxidized GBs, fully oxidized GBs, and oxide/metal interface, using Ni as a model system. For partially oxidized GBs, both substitutional and interstitial oxygen atoms of different concentrations are inserted at three Ni GBs: Σ3(111) coherent twin, Σ3(112) incoherent twin, and Σ5(210). Simulation results show that the GB strength decreases almost linearly with the increasing oxygen coverage at all GBs. Typically, substitutional oxygen causes a stronger embrittlement effect than interstitial oxygen, except at the Σ3(111). In addition, the oxygen-induced mechanical distortion has a much smaller contribution to the embrittlement than its chemical effect, except for oxygen interstitials at the Σ3(111). For the fully oxidized GBs, three NiO GBs of the same types are studied. Although the strengths of Σ3(112) and Σ5(210) NiO GBs are much weaker than the Ni counterparts, the Σ3(111) NiO GB has a higher strength than that in Ni, indicating that Σ3(111) GB may be difficult to fracture during SCC. Finally, the strength of a Ni/NiO interface is found to be the weakest among all interfaces studied, suggesting the metal/oxide interface could be a favorable crack initiation site when the tensile stress is low. Furthermore, the effects of co-segregation of oxygen and solute/impurity elements on GB strength are studied by DFT, using the 5(210) GB in an face-centered-cubic (FCC) Fe as a model system. Four elements (Cr, Ni, P, Si) that are commonly present in stainless steels are selected. Regarding the effects of single elements on GB strength, Ni and Cr are found to the increase the GB strength, while both P and Si have embrittlement effects. When each of them is combined with oxygen at the GB, the synergetic effect can be different from the linear sum of individual contributions. The synergetic effect also depends on the spatial arrangement of solute elements and oxygen. If they are aligned on the same plane at the GB, the synergetic effect is similar to the linear sum, although P and Si show stronger embrittlement potencies when they combine with both interstitial and substitutional oxygen. When they are arranged on a trans-plane structure, only nickel combined with oxygen show larger embrittlement potencies than the linear sum in all cases. Crystal Orbital Hamilton Populations analysis of bonding and anti-bonding states is conducted to interpret how the interaction between solutes and oxygen impacts GB strength. Finally, the continuum-scale CZM method, which is based on the bilinear mixed mode traction separation law, is used to model SCC-induced intergranular fracture in polycrystalline Ni and Fe based alloys in the MOOSE framework. The previous DFT results are used to justify the input parameters for the oxidation-induced GB strength degradation. In this study, it is found that the crack path does not always propagate along the weak GBs. As expected, the fracture prefers to occur at the GB orientations perpendicular to the loading direction. In addition, triple junctions can arrest or deflect fracture propagation, which is consistent with experimental observations. Simulation results also indicate that percolated weak GBs will lead to a much lower fracture stress compared to the discontinuous ones. / Doctor of Philosophy / Iron and Nickel based alloys are important structural materials for nuclear reactors due to their good mechanical properties, corrosion resistance, and radiation resistance. Under radiation and corrosive conditions, those alloys are susceptible to radiation induced segregation (RIS) and stress corrosion cracking (SCC). This dissertation is mainly focused on understanding the influence of the two effects on grain boundary (GB) strength. Systematic atomistic scale density functional theory (DFT) simulations are applied for the nickel and iron systems. Based on the DFT results, cohesive zone model is utilized for the continuum scale fracture simulation in nickel and iron polycrystal. First, DFT calculations are conducted for studying the RIS effect on the GB strength in nickel. Al, Cr, Cu, C, Si, P, Fe, and Ti are chosen as segregated element. Σ3(111), Σ3(112), Σ5(210), Σ5(310) four types of GBs are built for GB strength calculations. It is found that substitutional C and P always embrittle the GB, while substitutional Ti and Cr can strengthen the GB in most cases. Partial density of states (PDOS) analysis indicates the formation of C-Ni and P-Ni covalent bonds is the possible reason for their embrittlement effects. Bader charge analysis shows negatively charged elements likely reduce the GB strength. Interstitial element segregation is applied for non-metal elements (C, P, and Si). The results indicate interstitial elements have weaker effects than substitution ones. On the next stage to study the SCC effect, DFT calculations are performed for nickel Σ3(111), Σ3(112), and Σ5(210) GBs with difference oxygen concentration and oxygen incorporation types. Besides partially oxidized GBs, fully oxidized GBs (NiO GBs) and metal-oxide interface are also constructed for comparison. Simulation results show that the GB strength decreases nearly monotonically as oxygen concentration goes up. Typically, substitution oxygen causes a larger embrittlement effect than interstitial oxygen except at Σ3(111). It is found that the large mechanical distortion in this coherent twin GB contributes significantly to the GB strength drop. NiO GBs can be weak (Σ3(112),Σ5(210)) or strong (Σ3(111)). NiO/Ni interface shows lowest strength compared with partially and fully oxidized GBs, indicating the importance of the metal-oxide interface in the SCC process. Furthermore, the combined effects between segregated elements and oxygen are studied in face center cubic (FCC) iron system. In this part only Σ5(210) GB is selected with substitutional Cr, Ni, P, and Si as segregated elements. The results of single element effects show Cr can strength the GB while P has an opposite effect. Other two elements show little effect. For the co-segregation effects, the trans-plane structures have larger embrittlement potencies than in-plane ones for Ni, suggesting the GB strength can also be affected by the spatial arrangement of segregated elements. Finally, cohesive zone model is applied for fracture simulations in polycrystalline nickel and iron under tensile loading condition. It is found that intergranular fracture depends on both GB strength and orientation. GBs perpendicular to the loading direction have higher chances to crack. It is also found the percolated weak GBs induce larger strength drop than the discontinuous ones.

This dissertation summarizes three research projects related to microwave radiation induced electron transport properties in the GaAs/AlGaAs two dimensional electron systems. In chronological order, the projects are: a microwave reflection and electron magneto-transport correlation study, the combined microwave power and polarization dependence on microwave radiation induced magneto-resistance oscillations study, and a comparative study about the effect of circularly polarized and linearly polarized microwaves radiation on magneto-resistance oscillations induced due to the microwave. These three research projects experimentally address many interesting issues in the non-equilibrium low dimensional electron transport under microwave irradiation and provide potential applications of utilizing microwave radiation induced magneto-resistance oscillations in two dimensional electron systems as a method to detect different qualities of microwaves or terahertz waves.

Ma thèse consiste à établir un modèle numérique 1D qui permettra d'approfondir nos connaissances dans la compréhension des mécanismes physiques régissant le transport de charges dans les matériaux diélectriques comme le Kapton ou le Téflon soumis à des irradiations hauts-flux/hautes-énergies. Ce modèle est implémenté sous l'environnement Eclipse. Ensuite, les résultats numériques seront comparés aux résultats expérimentaux pour contrôler le bon fonctionnement du code une dimension (1D). A plus ou moins long terme, cette thèse permettra de déboucher sur une bonne compréhension du transport de charges dans les polymères embarqués en environnement spatial, ce qui permettra de comprendre l'origine des décharges électriques qui se produisent sur les panneaux solaires des satellites utilisés en orbite géostationnaire. / I have to establish a 1D numerical model that enables to better understand the physical mechanisms that steer charge transport in dielectric materials such as Kapton or Teflon under high fluxes and high energy electron beams. This model is implemented in Java under the Eclipse environment. Then, numerical results will be compared to experimental results in order to verify whether the 1D model is functional or not. In the near future, this phd will allow to better understand charge transport in satellite embedded polymers. We will then be able to understand the origin of electric discharges that occur on satellite solar panels used in geostationary orbit.

Les fibres dopées erbium couvrent de nombreuses applications, particulièrement dans le domaine des télécommunications terrestres et sous marines, avec les amplificateurs optiques. Aujourd’hui, il existe un réel intérêt pour l’industrie spatiale d’utiliser ces fibres dans les satellites. Cependant, pour utiliser leur potentiel, une qualification en milieu radiatif doit être effectuée, c'est justement l'objet principal de ce travail de thèse. Grâce au partenariat industriel avec Draka-Prysmian, nous avons accès à une grande diversité de fibres en termes de compositions chimiques : ceci nous permet d’étudier leur sensibilité aux radiations, et de comprendre le rôle essentiel des dopants et des codopants dans cette sensibilité. Une étude de celle-ci en temps réel, associée à une caractérisation pré et post-irradiation des fibres optiques, rend possible l'identification fine des défauts induits sous irradiation, et la compréhension de leur mécanisme de formation, en fonction de la composition de ces fibres. Cette étude permet ainsi de proposer un modèle physique de leur dégradation, et aussi de leur guérison, complété par un modèle d'amplificateur. Il permet de prédire, en fonction de la composition des fibres, le comportement quantitatif des amplificateurs optiques associés, en termes de gain et et de bande passante, versus un dépôt de dose typique d'une mission spatiale ; il répond ainsi aux attentes des principaux acteurs du domaine. En outre, le bénéfice de ce travail ouvre des portes dans le domaine de la dosimétrie par fibre optique active, dans différents environnements radiatifs autres que le domaine spatial, tels que le milieu médical ou l'environnement nucléaire. / Erbium-doped optical fibers open up many applications, especially in the field of terrestrial and underwater telecommunications, with optical amplifiers. Nowadays, there is a real interest for the space industry to use these fibers in satellites. However, in order to use their full potential, qualification in radiative environments is to be carried out, this is the main focus of this PhD work. Thanks to the partnership with Draka-Prysmian group, we have a full access to a large diversity of specialty fibers, in terms of chemical compositions : this allows us to study their sensitivity to radiations, and to determine the important role of dopants and co-dopants in this sensitivity. A real-time study of it, associated with a qualification of pristine and irradiated optical samples, enables the detection of radiation-induced defects, and the understanding of their creation process, as a function of the fiber structure. This study provides a physical model describing the degradation and the recovery of these fibers, enhanced with an amplifier modeling. It allows the prediction of the quantitative behavior of specialty fiber-based amplifiers, in terms of gain and bandwidth, versus the chemical composition of the fibers used, for a typical space mission dose ; thus this modeling meets the needs of the spatial market key actors. Furthermore, the benefit of this work opens up another avenues for some larger opportunities, in various radiative environments, such as the medical field or the areas of nuclear facilities.

Neste trabalho realizamos uma série de medidas de correntes elétricas através de amostras de polímeros isolantes submetidos a radiação por feixe eletrônico, amostras essas inserida em um circuito em modo de corrente. A energia do feixe incidente foi sempre tal que não atravessava totalmente a amostra, depositando em seu interior excesso de carga negativa. A polaridade dessa carga foi determinada pela curva de emissão secundária. Como a energia do feixe foi sempre muito superior à energia EII (abaixo dessa energia o número de elétrons injetados pelo feixe é menor que os arrancados para fora da amostra, e acima desse valor o contrário ocorre), as amostras usadas (polifluoretileno-propileno, polietileno de alta densidade e polietileno de baixa densidade) foram carregadas negativamente. Devido à radiação parcialmente penetrante, cada amostra foi dividida em duas regiões distintas: irradiada e não-irradiada. Na região não-irradiada permanece a condutividade intrínseca do material, enquanto na irradiada a condutividade foi muito aumentada devido à geração de portadores secundários pela radiação. As curvas de corrente foram medidas durante e após a irradiação sob diferentes campos elétricos aplicados externamente. Vários modelos teóricos foram aplicados para explicar os resultados de correntes medidas. O mais simples foi o Modelo Caixa, onde a penetração dos primários era um valor fixo r, dividindo a amostra em condutividade induzida g1 de 0 a r, e condutividade intrínseca gi, de r a L, sendo g1 gi (L é a espessura da amostra). O modelo mais sofisticado levou em conta uma região &#916r em torno de r pois considera que o freamento dos elétrons não ocorre todos no mesmo ponto, mas tem uma dispersão em tomo de um ponto r. Por esse motivo a condutividade induzida é dependente da posição, e num caso mais geral depende também do tempo. Durante a irradiação da amostra inserida no circuito de medida, pode ocorrer injeção pelos eletrodos alterando, em determinadas circunstâncias, a polaridade do excesso de carga. Como resultado dos ajustes teórico-experimentais vários parâmetros elétricos dos materiais foram obtidos. / This work presents several electric current measurements in dieletric polymers under irradiation by electron beam. The samples were irradiated in a current mode circuit. The energy of the beam provided a negative charge profile charge in the bulk o the sample. The polarity of the deposited charge was determined by a secundary emission curve. Since the energy of the beam was always bigger tham EII (which defines the balance between the injected electrons and the emitted ones; below EII the sample became positively charged, while above it is negatively charged) the samples (polyethylene propylene, high density polyethylene and low density polyethylene) were always negatively charged. Each irradiated sample was divided in two regions: the irradiated region and the non-irradiated one. Due to the secondary generated carries, the condutivity of the irradiated region gi was orders of magnitude higher than the intrinsic condutivity g1. The eletric currents were measured during and after the irradiation, under different external electric fields. Several theoretical models were used to explain the experimental results. The simplest one, the box models, considers the induced condutivity gb from 0 to r, and the intrinsic condutivity gi from r to L (L being the sample thickeness). The more sophisticated model, on the other hand, considers a range value &#916r around the point r. It means that the stopping power is not abruptly but rather is distributed in a region &#916r around the point r. For this reason the induced conductivity depends on the position, and in a more general framework, also in time. During the irradiation, carriers are injected to the sample by the electrodes, and in certain conditions the excess of charge has its polarity inverted. From the theoretical-experimental fittings important electrical parametes of the materials were obtained.

Introduction Treating localized prostate cancer with combination radiotherapy consisting ofexternal beam radiotherapy (EBRT) and high-dose-rate brachytherapy (HDR-BT) has beenproven to result in better disease outcome than EBRT only. There is, however, a decreasingtrend in utilization of combination therapy, partially due to concerns for elevated toxicityrisks. Aim To determine which parameters correlate to acute and late (≤ 6 months) urinary toxicity(AUT and LUT) and acute and late rectal toxicity (ART and LRT), and thereafter createpredictive models for rectal toxicity. Methods Data on toxicity rates and 32 patient, tumor and treatment parameters were collectedfrom 359 patients treated between 2008 and 2018 with EBRT (42 Gy in 14 fractions) andHDR-BT (14.5 Gy in 1 fraction) for localized prostate cancer at Örebro University Hospital.Bivariate analyses were conducted on all parameters and the outcome variables AUT, LUT,ART and LRT grade ≥ 1, graded according to the RTOG-criteria. Parameters correlating toART and LRT in this and previous studies were included in multivariate logistic regressionanalyses for creation of predictive models. Results Most toxicities, 86%, were of grade 0 or 1, only 9% of patients had grade 2 – 3toxicity. Only 2 – 4 parameters correlated to the respective toxicities in bivariate analyses.Logistic regressions generated no significant predictors of ART or LRT. Therefore, nopredictive models were obtained. Conclusion None of the included parameters have enough discriminative abilities regardingrectal toxicity. Predictive models can most probably be obtained by including otherparameters and more patients.