Tesi sul tema "Ionizing effects"

Reliability study and investigation of ionizing radiation effects on advanced non-volatile memories. The memories addressed in this thesis are: nanocrystal memories, Phase Change Memories (PCM), and the Oxide-Nitride-Oxide stack. In the thesis there is also a brief description of the major interaction mechanisms between ionizing particles and electronic devices.

Chinese hamster V79-171B cells grown for about 24 hours in suspension culture display increased resistance to cell killing by ionizing radiation compared with cells grown as monolayers, an observation originally termed the "contact effect". More recently, development of that resistance was shown to be accompanied by changes in the conformation of the DNA which reduce its denaturation rate in high salt/weak alkali. These changes in DNA conformation, mediated by the cellular micro-environment, appear to be responsible for the contact effect. The conditions necessary for the development of the effect are not, however, completely understood. In particular, when cells grown as monolayers on petri plates are suspended in spinner culture flasks, their growth characteristics change in three distinct ways. First, cells in suspension no longer have a solid substrate, so they remain round. Second, after several hours, they begin to aggregate to form "spheroids", so that three-dimensional intercellular cell contact develops. Third, cells in the stirred suspension cultures are not subjected to high local concentrations of metabolic by-products or surrounded by a zone depleted of nutrients, as are cells in monolayer culture. The studies described here were designed to determine how each of these factors influence changes in DNA conformation, as assayed using the alkali unwinding technique. Our results indicated that a round shape may not be an essential requirement, since cells spread out on the surface of cytodex beads in suspension culture, and sparsely-seeded cells in monolayer culture demonstrated at least a partial contact effect. Three-dimensional intercellular contact does not always seem necessary for the development of the contact effect. Cells grown in a methyl cellulose matrix developed radioresistance, even though the cells formed only small clusters of less than five cells. Similarly, suspension culture cells which were prevented from aggregating by frequent exposure to trypsin, also developed the contact effect. There was no evidence that nutrient depletion plays a role in the failure of cells grown as monolayers to develop a contact effect. However, cells grown as spheroids in the presence of monolayer cells, or in monolayer cell-conditioned medium, did not display a full contact effect. This indicates a role for monolayer cell-produced factors (possibly extracellular matrix proteins) in preventing the development of the contact effect. We conclude that changes in DNA conformation and the increase in radiation resistance, seen in V79-171b cells grown as spheroids, are not the result of intercellular contact or round shape of the cells. This radioresistance appears to be the result of an absence of monolayer cell-produced factors which could control both cell shape and DNA conformation.<br>Medicine, Faculty of<br>Pathology and Laboratory Medicine, Department of<br>Graduate

Mixed beams of ionizing radiation in our environment originate from space, the bedrock and our own houses. Radiotherapy patients treated with boron neutron capture therapy or with high energy photons are also exposed to mixed beams of gamma radiation and neutrons. Earlier investigations have reported additivity as well as synergism (a greater than additive response) when combining radiations of different linear energy transfer. However, the outcome seemed to be dependent on the experimental setup, especially the order of irradiation and the temperature at exposure. A unique facility allowing simultaneously exposure of cells to X-rays and 241Am alpha particles at 37 ºC was constructed and characterized at the Stockholm University (Paper I). To investigate the cytogenetic response to mixed beam irradiation (graded doses of alpha particles, X-rays or a mixture of both) several different cell types were utilized. AA8 Chinese Hamster Ovary cells were analyzed for clonogenic survival (Paper I), human peripheral blood lymphocytes were analyzed for micronuclei and chromosomal aberrations (Paper II and Paper III respectively) and VH10 normal human fibroblasts were scored for gamma-H2AX foci (Paper IV). For clonogenic survival, mixed beam results were additive, while a significant synergistic effect was observed for micronuclei and chromosomal aberrations. The micronuclei dose responses were linear, and a significant synergistic effect was present at all investigated doses. From the analysis of micronuclei distributions we speculated that the synergistic effect was due to an impaired repair of X-ray induced DNA damage, a conclusion that was supported by chromosomal aberration results. Gamma-H2AX foci dose responses were additive 1 h after exposure, but the kinetics indicated that the presence of low LET-induced damage engages the DNA repair machinery, leading to a delayed repair of the more complex DNA damage induced by alpha particles. These conclusions are not necessary contradictory since fast repair does not necessarily equal correct repair. Taken together, the observed synergistic effects indicate that the risks of stochastic effects from mixed beam exposure may be higher than expected from adding the individual dose components.<br><p>At the time of the doctoral defence the following papers were unpublished and had a status as follows: Paper nr 3: Manuscript; Paper nr 4: Manuscript.</p><br>DNA damage and repair in cells exposed to mixed beams of radiation

Thesis (DTech (Biomedical Technology))--Cape Technikon, 2001<br>Ionising radiation has the ability to induce, inter alia, DNA damage and is well established as a causative agent of carcinogenesis and mutagenesis. The effects of high doses of short duration have been well documented, whereas the effects of continuous exposure to low doses of ionising radiation have not, nor are they as clearly understood and current risk estimates are largely extrapolated from high-dose data of atomic bomb survivors. This study evaluated the clastogenic effects of low dose ionising radiation on a population of bats (Chiroptera) residing in an abandoned monazite mine. Bats were sampled from two areas in the mine, with external radiation levels measuring around 20 µSv/h (low dose) and 100 µSv/h (high dose). A control group of bats was collected from a cave with no detectable radiation above normal background levels. The most frequently encountered genetic event in human malignancy is the alteration of the p53 gene. Mutant p53 proteins have a longer half-life than the wild-type variant and accumulate to high levels in the nucleus of tumour cells. The study showed that not only was there a significant increase in p53 positive cells of radiation exposed bats, but also in the degree of positivity, especially in the cells lining the bronchioles of the lungs. Although experimental studies have shown that exposure to radiation may lead to the onset of fibrosis and an inflammatory response in the lung and other tissues, the magnitude of the dose exposure was not comparable to this study and histological examination of bat lung and liver tissues showed no morphological changes in radiation exposed bats when compared to the control group. It has been documented that chronic radiation exposures may give rise to a number of specific haematological defects which are collectively termed "preleukemia" or myelodysplastic syndrome. Full blood counts on bat samples showed a significant decrease in the MCV indicating microcytic erythrocytes from the radiation exposed bats. Differential counts performed on the peripheral blood of the bats showed a marked neutropenia. Neutrophils also showed marked dysplasia including psuedo-Pelger Huet cells in radiation-exposed bats. Cytochemical analysis using DAB myeIoperoxidase showed that control bats had hypogranular neutrophils andradiation-exposedbats had largely '1granularneutrophils. Bonemarrow biopsies were taken from both control and radiation-exposed bats and evaluated for ceIlularity, granulocyte: lymphocyte: erythrocyte (GLE) ratio and megakaryocyte morphology. A hypocelIular bone marrow, a decreased granulocytic haematopoeisis and dysplastic megakaryocyte morphology were observed in radiation-exposed bats. Mineralisation of bone osteoid was determined using image analysis and showed a highly significant decrease in the bone matrix from radiation-exposed bats. All haematological features observed are congruent with current literature describing secondary (radiation-induced) myelodysplastic syndrome.

Thesis (S.B.)--Massachusetts Institute of Technology, Dept. of Nuclear Science and Engineering, 2007.<br>"June 2007."<br>Includes bibliographical references (p. 37-43).<br>Lymphatic vessels play a crucial role in both the pathophysiology of tumors and in the spread cancer cells to lymph nodes. The effects of radiation on these vessels, however, are largely unknown. Here, we seek to describe the effects of ionizing radiation on normal and tumor-associated lymphatic vessels in vitro and in vivo. Clonogenic assays were employed to study the radiation dose response of lymphatic endothelial cells. Putative lymphatic endothelial cell mitogens and antiproliferative agents, including vascular endothelial growth factor-A (VEGF-A), VEGF-C and AZD2171, a tyrosine kinase inhibitor of the VEGF receptors, were tested as radiation sensitizers and protectors. Our results indicate that VEGF-A and VEGF-C are radiosensitizers while AZD2171 did not modulate the radioresponse. In vivo, normal lymphatics were studied with the experimental group receiving a single fraction of 8 Gy and the control group receiving no radiation. We observed no difference in the average lymphatic vessel diameter between these two groups over the course of 6 months. VEGF-C overexpressing tumor-associated lymphatic vessels were studied in vivo with four treatment groups: control animals (no irradiation), 8 Gy two weeks prior to implantation, 8 Gy at the time of implantation and 16 Gy given in two fractions before implantation (two weeks prior to and at the time of implantation). The average lymphatic vessel diameter and frequency of lymph node metastasis in these four groups indicates that the ability of radiation to prevent VEGF-C driven lymph node metastases is time-dependent; radiation must be delivered in close proximity to VEGF-C overexpressing tumor cell implantation to impact nodal metastases. This suggests that VEGF-C may be a functional lymphatic vessel radiosensitizer in vivo.<br>(cont.) However, reductions in lymphatic hyperplasia, as measured by lymphatic vessel diameter, did not explain the observed differential effects of radiation timing on lymph node metastasis rate.<br>by Jennifer D. Lobo.<br>S.B.

The experimental studies of this work were done using a microwave cavity spectrometer, Escherichia coli (E-coli) bacteria, and other peripheral equipment. The experiment consists of two steps. First, a general survey of frequencies from 8 GHz to 12 GHz was made. Second, a detailed experiment for specific frequencies selected from the first survey were further studied. Interesting frequency dependent results, such as unusually higher growing or killing rates of E-coli at some frequencies, were found. It is also concluded that some results are genetic, that is, the 2nd, and 3rd subcultures showed the same growing status as the 1st cultures.

Sun’s radiation, coronal mass ejections, electromagnetic storms, galactic cosmic rays, the Van Allen radiation belts, or artificial radiation environments expose microelectronics circuits to serious conditions in space as well as on Earth. Nowadays, a lot of human activities rely on satellites orbiting around the Earth such as the GPS system, video and audio communications, surveillance systems, meteorological forecasts, military applications, etc., and they must operate reliably. Civil air traffic is extremely intense around the world and of course everybody wants to land safely each time they fly. Moreover, nuclear power plants that furnish energy to most of the advanced countries on the planet must operate securely in order not to contaminate the environment around, provoking natural and social disasters. Each of these aspects is strongly dependent on electronics that manage and control every activity, permitting us to live our life peacefully. The main challenge for engineers and scientists that work in this sometimes unknown field is to manufacture and design safe electronics able to operate in those environments even for very long times. The scaling of CMOS technology toward deep-submicron feature sizes plays a fundamental role, regardless of ionizing radiation effects. In fact, as the CMOS devices shrink, featuring ultra-thin gate oxides, the reliability of MOSFETs is affected due to the increase of the operating fields that enhance the natural aging mechanisms. Hot carriers injection from the channel is one of the most important effects, especially in advanced devices because the carrier energy is directly correlated with the electric fields. This thesis in part covers this reliability aspect, both in standard open layout transistors and enclosed layout ones designed to be total-dose hard. A vast literature is available concerning hot carrier mechanisms but this work is one of the only to show the synergies with X-ray induced defects (Total Ionizing Dose, or TID). Indeed, CMOS transistors with feature size equal or below the 130-nm technological node exhibit these kinds of effects, introducing new and interesting aspects. As a result, a different approach must be followed when evaluating the suitability of devices intended for rad-applications since hot-carrier degradation for example can decrease or increase due to previous irradiation. Furthermore, the prediction of oxide lifetime is one of the main types of analysis in the field of CMOS reliability, extremely important to evaluate the quality of the dielectrics. This thesis proves that exposure to TID may affect reliability predictions due to interplay between defects, traps, and trapped charge generated by both accelerated tests. Without these aspects in mind the results can be conservative (when lucky), or can even underestimate the phenomena leading to misleading and dangerous conclusions. Total dose enhancement effects due to interconnects is also a new source of uncertainty in scaled technologies subjected to X-ray irradiation. In fact, the need to have high device density leads to an increase in the number of metal layers as well as a decrease in the inter-metal dielectric thickness, permitting secondary electrons generated by the interaction of X rays with metal tracks to reach the transistors’ active area. This aspect is studied in this thesis through the use of dedicated test structures with different metal layer layouts. The experimental results, coupled with device simulations, give radiation-IC designers some guidelines to avoid systematic criticality and better total dose results. Combined total dose and ageing related effects is not the only focus of this thesis since single events produced by charged particles have become the main source of errors in scaled technologies. Electronics mounted on spacecraft, satellites, aircraft and even at ground level are affected by single event effects, sometimes destructive, sometimes not. In particular, this thesis covers the single event gate rupture (SEGR) phenomenon induced by heavy ions, which is the most risky event during long-term missions. Various aspects have been analyzed in order to fill some gaps present in the literature, starting from the impact of device layout, the influence of the bias applied during accelerated tests and the effects of previous X-ray irradiation. The results presented here demonstrate that different sources of interplay may exist during SEGR tests. Moreover, the provided data strongly indicate use of test structures as close as possible to real scaled transistors instead of large area capacitors to have a straightforward assessment of gate rupture in modern CMOS technologies. In conclusion, this thesis wants to be the first strong contribution for combined radiation and long-term reliability studies in advanced CMOS technologies implemented in harsh radiation environments.<br>I processi termonucleari che si verificano all’interno del sole danno origine a radiazioni ionizzanti, tempeste elettromagnetiche ed emissioni di masse di plasma coronarico ionizzato che possono raggiungere l’atmosfera terrestre. Inoltre gli effetti indotti dai raggi cosmici, la presenza delle fasce di Van Allen, nonché gli ambienti radioattivi artificiali costruiti dall’uomo, espongono i circuiti microelettronici a condizioni di funzionamento estremo nello spazio e sulla terra. Al giorno d’oggi molte attività umane si basano su satelliti geostazionari che devono rimanere funzionanti ed affidabili per lungo tempo: sistemi GPS, comunicazioni audio e video, sistemi di sorveglianza, satelliti meteorologici, applicazioni per la difesa, etc. Inoltre il traffico aereo civile ad alta quota, anch’esso esposto a radiazioni, è sempre in maggiore espansione e naturalmente ogni passeggero si augura di atterrare sano e salvo ogni volta che necessiti di volare. Non da meno le centrali nucleari che forniscono il fabbisogno energetico alle nazioni più avanzate devono assolutamente operare in sicurezza evitando tremendi disastri naturali e sociali. Ognuna di queste applicazioni è tuttavia fortemente dipendente dall’elettronica che gestisce e controlla ogni attività in modo trasparente rispetto all’utente. La sfida principale per ingegneri e scienziati che lavorano in questo ambito, è quella di studiare e progettare microelettronica in grado di operare in ambienti ostili per lungo tempo e in modo affidabile. Il progresso tecnologico dei dispositivi CMOS verso dimensioni sub-micrometriche gioca un ruolo fondamentale in termini di affidabilità. Infatti, a prescindere dagli effetti delle radiazioni, la riduzione delle dimensioni dei dispositivi e l’implementazione di ossidi ultra sottili influiscono sull’affidabilità dei transistor MOS a causa dell’aumento intrinseco dei campi elettrici che accelerano i naturali processi di degradazione. Per esempio, l’iniezione di portatori caldi è una delle cause più importanti di degradazione in quanto l’energia che gli elettroni possono acquisire è correlata al campo elettrico accelerante. Questa tesi sviluppa questa problematica sia su transistor standard (Open Layout Transistor, OLT) che su transistor ad anello (Enclosed layout Transistor, ELT), questi ultimi progettati per essere immuni dagli effetti di dose totale (Total Ionizing Dose, TID). Sebbene i meccanismi e gli effetti legati ai portatori caldi siano ben documentati nella letteratura di settore, questa tesi è uno dei pochi lavori che si propone di investigare le sinergie con gli effetti indotti dai raggi X, introducendo nuovi e interessanti aspetti legati all’affidabilità. Inoltre la previsione del tempo di vita dell’ossido di gate è una delle informazioni più importanti da tenere in considerazione quando si intende pianificare una missione a lungo termine. Questa tesi dimostra che l’esposizione ai raggi X può alterare i successivi test di affidabilità a causa dell’interazione tra i difetti generati dalle radiazioni e dagli stress elettrici. Di conseguenza, un approccio nuovo va seguito quando si intende valutare l’adeguatezza dei dispositivi da implementare in applicazioni ove siano presenti radiazioni ionizzanti. Senza considerare questi aspetti le previsioni che emergono dai test sperimentali possono in alcuni casi fortunati essere conservative, in altri meno fortunati sottostimare i fenomeni portando a conclusioni fuorvianti e addirittura pericolose per il buon esito di una missione. Una nuova fonte di incertezza e di sinergia per le tecnologie CMOS avanzate esposte a raggi X riguarda il diverso assorbimento di dose totale indotto dalle interconnessioni metalliche. Infatti la necessità di integrazione sempre più spinta obbliga i progettisti ad incrementare il numero di strati di interconnessione nel back-end del dispositivo nonché la riduzione dello spessore dei dielettrici isolanti. Di conseguenza, a fronte di una esposizione ai raggi X, gli elettroni secondari generati dall’interazione con gli strati metallici possono raggiungere più facilmente l’area attiva del transistor degradandolo in modo non uniforme. In questa tesi questo effetto viene studiato grazie all’uso di strutture appositamente progettate, contribuendo cosi allo sviluppo di dispositivi il più possibile immuni da tale fenomeno. D’altro canto gli effetti indotti da particelle cariche (Single Event Effect, SEE) nelle moderne tecnologie stanno diventando la principale fonte di errore. L’elettronica implementata a bordo di navicelle spaziali, satelliti, aerei civili e militari, e perfino al livello del suolo terrestre è affetta da SEEs, a volte distruttivi, a volte no. In particolare questa tesi si focalizza sulla rottura istantanea e permanente dell’ossido di gate causata dal passaggio di uno ione pesante in presenza di alti campi elettrici (Single Event Gate Rupture, SEGR) che, a causa delle sue caratteristiche, lo pone tra gli eventi più rischiosi. In questa tesi vengono studiati diversi fattori: l’influenza del tipo di struttura di test, della polarizzazione mantenuta durante gli esperimenti e l’influenza dei raggi X. Anche in questo caso si dimostra l’esistenza di diverse forme di sinergia tra radiazioni e stress elettrico, fornendo indicazioni circa le metodologie di test e l’uso di strutture che possano fornire risultati realistici riguardo l’incidenza di questo fenomeno nei moderni transistor utilizzati per l’elettronica spaziale. In conclusione questa tesi vuole essere il primo forte contributo scientifico per lo studio degli effetti sinergici tra radiazione ionizzante e test di vita accelerati su dispositivi CMOS avanzati, da implementare in ambienti radioattivi quali lo spazio o gli esperimenti di fisica delle alte energie.

Total ionizing radiation may affect the electrical response of the electronic systems, inducing a variation of their nominal electrical characteristics and degrading their performance. The study of the radiation effects in microelectronic devices is essential in the space, avionic, and ground level applications affected by artificial and/or natural radiation environments, where the reliability is one of the most important requirements. In this thesis work, I investigate the total ionizing dose (TID) degradation mechanisms in several modern nanometer-scale technology nodes. The analysis of the TID mechanisms is focused on the evaluation of measurable effects affecting the electrical response of the devices and on the identification of the microscopical nature of the radiation-induced defects. Several transistors, based on MOSFET and FinFET structures of different manufacturers, have been tested under ionizing radiation at several temperatures, bias configurations, annealing conditions, and transistor dimensions. Technologies dedicated to high energy physics experiments have been tested at ultra-high doses, never explored thus far. Several different techniques, as DC static characterization, charge pumping and low frequency noise measurements as well as Technology Computer-Aided Design simulations, were used to identify location, density and energy levels of the radiation-induced defects. The experimental measurements presented in this work provide a unique and comprehensive set of data, pointing out the strong influence of the scaling down to the TID-induced phenomena in deeply scaled microelectronic transistors. TID mechanisms have been studied following the technological evolution of the devices at various nodes: 150 nm Si-based MOSFET, 65 nm Si-based MOSFET, 28 nm Si-based MOSFET with HfO2 gate dielectric, 16 nm InGaAs-based FinFET with HfO2/Al2O3 gate dielectrics and, at last, a new laboratory grade InGaAs MOSFET with Al2O3 gate dielectric. All results confirm the high TID tolerance of the thin gate oxide of nanoscaled technologies, due to the reduced charge trapping in the gate dielectric. However, the aggressive downsizing of devices has led to new TID-induced effects related to other thick oxides and modern production processes, e.g., shallow trench insulations oxides, spacer dielectrics, and halo implantations. In the case of compound semiconductors, I have observed how defects are associated to the properties at the interface between III-V materials and high-k dielectrics. New TID mechanisms appear, showing their dependence on irradiation/annealing bias condition, channel length, and channel width.

The classical paradigm of radiation biology is based on the notion that ionizing particle has to traverse a nucleus of a living cell in order to damage genetic material either directly or via production of short living free radicals. After DNA damage is introduced it can be either safely repaired and the cell can continue divisions unaltered; or it can result in a failure to repair and cells death; or finally, upon misrepair, the cell would be carrying genetic alteration that could result in cancer or developmental abnormality. Therefore modern risk estimations are based on the notion that nucleus is the true target of radiation effects and those are essentially stochastic with linear dependence on the dose. During the last two decades or so, a different idea was developed based on the observation that irradiated cells can communicate radiation induced stress signals to their unaffected neighbors and themselves become reprogrammed to maintained abnormal radiation-induced phenotype across multiple cellular divisions. Even more astonishingly this phenotype maybe transmitted by irradiated germ cells to unexposed progeny. Here we suggest that these non-targeted effects are maintained by epigenetic mechanisms and examine epigenetic underpinnings of bystander and transgenerational effects in vivo.<br>xi, 190 leaves ; 28 cm

The ability of ionizing radiation to enhance colon carcinogenesis and the role of diet in this process has not been documented. We hypothesized that radiation would enhance the formation of aberrant crypt foci, ACF, known precursor lesions to colon cancer, by suppressing apoptosis and upregulating proliferation in colonocytes. Diets contained a combination of fish oil or corn oil and either pectin or cellulose. We exposed 40 male Sprague-Dawley rats to 1 Gy ionizing radiation (1 GeV Fe) 10 d prior to injection with AOM. Colons were resected at the promotion stage of carcinogenesis (7 wk post initial injection) and assayed for ACF and apoptosis. Radiation treatment increased (P=0.0327) the incidence of high multiplicity ACF (foci with four or more aberrant crypts) and decreased (P=0.0340) the apoptotic index compared to non-irradiated rats. Radiation also resulted in an increase (P<0.0001) in the proliferative index compared to the nonirradiated rats. The fish oil containing diets resulted in fewer (P=0.0002) high-multiplicity ACF compared to the corn oil treatment. Dietary pectin significantly increased (P=0.0204) the apoptotic index compared to cellulose treatment. These data suggest that ionizing radiation can work synergistically with AOM and increase the formation of high-multiplicity ACF, upregulate cellular proliferation and decrease apoptosis in colonocytes. The data also suggest that diets containing fish oil and pectin may protect against colon cancer by increasing apoptosis and reducing the formation of high multiplicity ACF.

The objective of the proposed research is to analyze the effects of total ionizing dose (TID) on highly scaled CMOS and Silicon-Germanium Heterojunction Bipolar Transistors (SiGE HBTs). TID damage is caused by a build-up of charge at sensitive Si-SiO₂ interfaces and may cause device or circuit failure. TID damage is due to an accumulation of radiation particle strikes seen in extreme environments, such as space.

In this study the direct effect of ionising radiation on DNA plus additives has been studied using both ESR spectroscopy and plasmid DMA (for strand break analysis). The primary radicals were identified as the thymine radical-anion, T', and guanine radical-cation, G'*'. Under normal conditions these were formed in approximately equal yields as defined by careful computer simulations. Certain additives such as oxygen, nitroimidazoles, silver ions and the rest of the nuclear complement (i.e. RNA and histone proteins) , were added to study their effects on the relative yields of T" and G". In all cases, they were shown to capture electrons in competition with T" and have little or no effect on the yield of G"*". In the case of oxygen and nitroimidazoles the effect of reducing the yield of T" radicals was looked at using strand break analyses. Essentially this was found to protect the DNA. Since both single and double strand breaks were found at significant levels when G+ and T~ were the only detectable initial radicals, one must conclude that these radicals are responsible for strand breaks. Fran the relatively high number of double strand breaks found, we deduce that G'*' and T" centres must be close togetlier (in a range of ca. 10-50 A), and that both may give rise to strand breaks, by as yet undefined pathways. In a separate study (Chapter 4), the reaction between superoxide ions, O2"/ and dimethyl formamide has been investigated by ESR spectroscopy. Strong evidence in favour of addition of O2" at the C=0 group to give a relatively stable peroxy radical intermediate has been obtained. This has implications for the mechanism of action of O2" formed both as a result of radiation damage and by other means. Appendix I describes a study of various simple aldehyde and ketone radical-cations, using ESR spectroscopy. Interpretations of these spectra are given, together with structural implications. Appendix II is a paper on work carried out on the ESR spectra of hydroxyl radicals in aqueous glasses. This work was done in collaboration with H. Riederer and J. Hiittermann.

Tout composant envoyé dans l'espace est soumis à de nombreuses contraintes (radiations, température) qui peuvent conduire à une défaillance de l'ensemble du système. Dans un avenir proche, ces contraintes deviendront de plus en plus critiques à mesure que les agences spatiales développeront des missions visant d'autres planètes, telles que Jupiter, pour lesquelles la contrainte radiative est extrême. Dans ce travail, deux types d'effets dus aux radiations sont étudiés : les effets cumulatifs et les effets transitoires. L'un correspond à la dégradation induite par les radiations au cours du temps, tandis que l'autre correspond à un événement ponctuel qui peut se produire à tout moment lorsque le système est dans l'espace. Pour garantir le bon fonctionnement en vol, des normes de qualification des composants électroniques ont été élaborées par différentes agences spatiales. Toutes ces normes précisent que les effets cumulatifs et transitoires doivent être vérifiés à l'aide de composants intacts pour chaque essai. Par conséquent, les effets cumulatifs sont traités séparément des effets transitoires, alors qu'il y a une forte probabilité qu'ils apparaissent simultanément pendant une mission spatiale. L'étude des effets de synergie est alors le thème principal de cette thèse.Sur un amplificateur opérationnel bipolaire, la réponse de sortie du composant due à un événement transitoire est directement liée aux paramètres internes du composant, qui varient sous l’effet des radiations. A l’aide d’une comparaison entre trois amplificateurs opérationnels différents partageant la même référence, l'impact du design sur la dégradation due aux radiation est étudié.Récemment, des défaillances imprévues ont été reportées pour lesquelles le mode de défaillance semblait indiquer qu'une structure de protection contre les décharges électrostatiques (ESD) était en cause. Par conséquent, pour comprendre si ces protections peuvent causer des défaillances inattendues, la dégradation des « Gate Grounded n-MOSFET » (GGnMOS) est également étudiée<br>Any system sent to space is submitted to many constraints (radiations, temperature) which may lead to a failure of the whole system. In a close future, these constraints will become more and more critical as the space agencies are developing missions aiming at others planets such as Jupiter for which the radiative constraint is extremely harsh. In this work, two types of radiation effects are studied: the cumulative effects and the transient effects. One corresponds to the radiation-induced degradation over time, while the other corresponds to a punctual event that can happen at any time when the system is in space. To ensure a proper functioning of a system sent to space, qualifications standards for electronic components have been developed by different space agencies. All of these standards specify that the components must be tested for cumulative and transient effects, using pristine components for each test. Therefore, cumulative effects are treated separately from transient effects, while there is a significant probability that they will appear simultaneously during a space mission. The study of the synergistic effects is then the main frame of this thesis.On a bipolar operational amplifier, the output response of the component due to a transient event is directly related to the internal parameters of the component, which vary over time once in space. Through a comparison between three different operational amplifier sharing the same reference, the impact of the design over the degradation is explained.Lately, some unexpected failures were reported for which the failure mode seemed to indicate that an Electrostatic Discharge (ESD) protection structure was involved. Therefore, to understand if those protections may cause some unexpected failures, the degradation of gate grounded n-MOSFET (GGnMOS) will be investigated next

This thesis investigates the effects of ionizing radiation on frozen aqueous solutions of DNA using e.s.r. spectroscopy and a plasmid (pBR322) strand break assay. To elucidate the mechanisms subsequent to primary ionic radical formation (G˙+ and T˙¯), additives that influence the radiolytic processes were included prior to irradiation. The presence of hydrogen peroxide (Chapter Three) switched the mechanism from direct damage to a pathway in part mediated through oxygen centred radicals (˙OH, HO˙2) and resulted in a modest increase in the number of strand breaks (i.e. radiosensitization). E.s.r. observations showed the appearance of sugar radicals (strand break precursors) which were lost at temperatures well below those of base radicals. The inclusion of a variety of thiols (Chapter Four) resulted in no change to either G˙ + or T˙¯, However, on warming, the normal pattern of radical reactions was dramatically modified, the DNA radical centres being abruptly reduced in concentration. In anoxia this was concomitant with the appearance of RSSR ¯, and strand breaks were noted to decrease (i,e. radioprotection). Under oxic conditions the degree of repair was a function of the relative concentration of oxygen and thiol. E.s.r. indicated repair of DNA centred peroxyl radicals and also RSO˙2 formation. The latter may react with DNA and account for attenuation, by oxygen, of protection afforded by thiols at low concentrations. The effects of ionizing radiation on higher ordered DNA structures (nucleohistone, chromatin and cell nuclei) has been investigated (Chapter Five). Relative to DNA, all systems gave equivalent yields of G˙+, together with protein electron-loss centres (Hist)˙+. However, T˙¯ yields were enhanced, the increase being greatest for nuclei. For the protein component it was suggested that (Hist)˙+ are amide cations, readily trapped by loss of N-H protons, but that the electrons are Mobile and able to transfer to DNA. Mechanisms leading to strand breaks, involving intramolecular hydrogen atom abstraction by directly induced base radicals from neighbouring sugar residues, are proposed (Appendix B) and compared with those obtained for hydroxyl radical damage.

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Nuclear Science and Engineering, 2011.<br>Cataloged from PDF version of thesis.<br>Includes bibliographical references.<br>Biological response to ionizing radiation differs with radiation field. Particle type, energy spectrum, and dose-rate all affect biological response per unit dose. This thesis describes methods of spectral analysis, dosimetry, biological assays, and mathematical modeling for determining the relative biological response for low dose-rate fields. The spatial dimensions of optically stimulated luminescence dosimeters make them ideal for measuring dose at a specific location. However the response of these dosimeters varies with photon energy. A method is presented for measuring dose delivered by several fields with photon energies less than 60 keV using these optically-stimulated luminescence dosimeters. This method is confirmed using an ion chamber dosimeter and computer simulation. The construction of 24Am irradiators for tissue culture and animal experiments using this dosimetry method is also described. The results of tissue culture experiments performed using these irradiators are presented, and the relative biological effectiveness (RBE) is determined for two fields with approximately equal dose-rates produced by shielding 24Am foil sources with aluminum and polyethylene. Biological effects can result from single instances of energy deposition within a cell or from the combination of separate instances, but at low dose-rates biological repair mechanisms reduce the probability of effects resulting from the combination of separate instances. At a sufficiently low dose-rate the effects due to combination of separate instances are negligible. A model of low dose-rate energy deposition within a cell nucleus was developed to determine this doserate. In this model the proportion of biological effects due to single instances of energy deposition within a cell nucleus is described in terms of the DNA repair rate of the biological 'system and the dose-rate and lineal energy transfer of the radiation field. This model also describes the projection of RBE values for fields with dose-rates below this threshold.<br>by Matthew Allen Davidson.<br>S.M.

This thesis addresses two main reliability challenges of advanced UltraThin Body (UTB) Silicon On Insulator (SOI) and FinFET CMOS technologies: ElectroStatic Discharge (ESD) and (space) ionizing radiations. First, both technologies have a limited available silicon volume to dissipate the ESD current. Therefore, a detailed ESD analysis on such devices is required. Secondly, these advanced technologies will be incorporated in future Commercial-Off-The-Shelf (COTS) components that may be used in space applications, which rennires the impact of ionizing radiation on such technologies. ESD analysis has been performed on structures implemented in planar UTB SOI, SOI FinFET, and bulk FinFET technologies. Complex dependencies of the different ESD performance parameters on both device geometry and process technology are found. For UTB SOI devices, a detailed electrical investigation is carried out in order to carefully classify the observed failure mechanisms. It is found that grounded gate NMOS devices are robust enough when local clamping devices are used, and that strain improves the ESD robustness and has an impact on the device failure mechanisms. Concerning FinFET technology, non-uniform failure exists for grounded gate NMOS devices at high current levels which can be improved by increasing gate length and various ballasting techniques. On the other hand, voltage clamping capability seemed more of a concern due to the oxide breakdown voltage for long gate lengths. Narrow fin devices have improved cooling properties, especially for bulk FinFETs, but suffer from reduced area efficiency. Selective epitaxial growth, strain, and silicide blocking can improve the ESD performance of FinFET devices. From RF point of view, concerning SOI FinFET technology, the large overhead capacitance of the narrow-fin devices degrades the RF figure of merit with respect to the wide fin devices, making wide-fin devices the preferred choice. Regarding bulk FinFET technology, the landing pad of narrow-fin devices is not fully used during the current conduction; however, the full junction contributes to the parasitic capacitance. Therefore, despite the quite remarkable improvement in ESD robustness observed for narrow-fin bulk FinFET devices, narrow and wide-fin bulk FinFET diodes have similar ESD-RF performance, which is comparable to the best SOI FinFET diodes. Heavy-ions induced microdose has been investigated on MOS in planar UTB SOI and SOI FinFET technologies. The degradation of the electrical DC parameters is found to strongly depend on both device geometry and process technology. UTB SOI devices display the lack of early breakdown due to the very thin gate oxide, and varying impact on the long-term degradation kinetics depending on the adopted technological solutions. Concerning SOI FinFETs, the changes of the DC parameters after irradiation strongly depend on the Linear Energy Transfer (LET), incidence angle, strain, and channel type, depending on the balance between damage to the high-k (top and sidewall) gate oxide and to the buried oxide. In addition, heavy-ion strikes impact both on the degradation kinetics and on the time to breakdown under constant voltage stress. The soft rupture of the gate oxide is a considerable concern, not only for the increase in gate leakage, but also for the effects on the DC characteristics. Interface state generation in the side oxide/body interface, due to ions passing through the lateral gates, is another remarkable effect that can be observed only with these vertical devices. Heavy ions can induce permanent damage on FinFETs with large statistical spread. The distribution of the inverse of the gate leakage currents and of the threshold voltage shifts follows a Weibull distribution. Moreover, the reciprocal of the gate leakage current does not respect the Poisson area scaling. A new model for the gate leakage current is proposed, predicting a size of the heavy-ion damage of 30 nm and a higher defect generation takes place in the sidewall gate oxide. Dose enhancement effects due to interconnects in deep-submicron CMOS have been studied. The presence of metal-1 tracks in the proximity of the device active areas significantly modifies the response to X-rays. The impact of the secondary electron emission from metal-1 layers is strongly dependent on the relative position to the transistor lateral isolation and LDD spacers. In conclusion, ESD is not a showstopper for the introduction of UTB SOI and FinFET technologies. However, heavy-ion induced microdose is a serious concern for multiple gate technologies, while it is not a showstopper for the UTB SOI. Finally, dose enhancement in deep-submicron devices must be carefully considered when X-ray facilities are used to perform total-dose tests.<br>Questa tesi si focalizza sullo studio della robustezza alla scariche elettrostatiche (ElectroStatic Discharge ESD) e della sensibilità a radiazioni ionizzanti delle tecnologie UltraThin Body (UTB) Silicon On Insulator (SOI) e multi gate FinFET, candidate a sostituire il MOSFET convenzionale bulk a partire dal nodo tecnologico dei 22 nm. Entrambe le tecnologie presentano un ridotto volume di silicio disponibile a dissipare la corrente indotta da un evento ESD. Pertanto, la robustezza ESD di tali tecnologie deve essere analizzata in dettaglio. D'altro canto, queste tecnologie, assieme a quella convenzionale bulk, potranno essere utilizzate anche per la fabbricazione di componenti Commercial-Off-The-Shelf (COTS) per applicazioni spaziali, che richiedono un’analisi accurata degli effetti indotti da radiazioni. Robustezza ESD L’analisi delle prestazioni ESD è stata condotta su strutture (MOSFET e diodi) implementate nelle tecnologie UTB SOI, SOI FinFET e bulk FinFET. Sono state trovate complesse dipendenze dalla geometria dei dispositivi e dal processo utilizzato. Robustezza ESD della tecnologia UTB SOI Per quanto riguarda la tecnologia UTB SOI, è stata proposto un nuovo metodo di analisi basato sulle caratteristiche elettriche DC al fine di individuare quali meccanismi di guasto si verificano (ad esempio, rottura dell’ossido di gate o filamento tra i terminali di source e drain). Si è trovato che MOSFET di tipo N stressati in configurazione grounded gate (in cui l’ESD viene scaricata dal BJT parassita) mostrano una moderata robustezza a ESD (fino a 1 mA/μm) quando utilizzati come local clamp. Inoltre, si è dimostrato che lo strain, utilizzato per aumentare la mobilità dei portatori, aumenta la robustezza ESD e ha un impatto sui meccanismi di guasto. Robustezza ESD della tecnologia FinFET Per quanto riguarda la tecnologia FinFET, dispositivi NMOS in configurazione grounded gate mostrano ad alti livelli di iniezione un guasto dovuto ad una non uniforme distribuzione di corrente, che può essere migliorata aumentando la lunghezza di gate o utilizzando tecniche di ballasting (ad esempio, silicide blocking). Tuttavia, si è visto che la capacità di voltage clamping è fortemente limitata dalla rottura dell’ossido di gate per dispositivi con elevate lunghezze di gate. FinFET con fin stretto, specialmente quelli realizzati in tecnologia bulk, mostrano una migliore dissipazione del calore sviluppato durante un evento ESD, ma allo stesso tempo, a causa dello spazio esistente tra un fin e l’altro, mostrano un’efficienza di layout ridotta rispetto ai dispostivi con fin largo. Si è inoltre dimostrato che l’utilizzo della crescita epitassiale selettiva del silicio (Selective Epitaxial Growth SEG), lo strain e il silicide blocking possono aumentare la robustezza ESD nei dispositivi FinFET. Da un punto di vista RF, dispositivi SOI FinFET con fin stretti presentano una figura di merito ESD-RF degradata rispetto ai dispositivi con fin largo, a causa di una grande capacità di overhead. Pertanto, i dispositivi con fin largo sono preferibili quando utilizzati come strutture di protezione a ESD per applicazioni RF. Per quanto riguarda invece la tecnologia bulk FinFET, il landing pad dei dispositivi con fin stretto è parzialmente utilizzato durante la conduzione di corrente ESD, tuttavia, la capacità di giunzione del landing pad contribuisce alla capacità parassita totale. Pertanto, sebbene i dispositivi con fin stretto mostrino una maggiore robustezza ESD intrinseca, le prestazioni ESD-RF sono simili sia per dispositivi con fin stretto cheper quelli con fin largo e sono comparabili con le migliori prestazioni ESD-RF dei SOI FinFET. Effetti indotti da ioni pesanti Gli effetti da microdose indotti da ioni pensati sono stati studiati per MOSFET realizzati nelle tecnologie UTB SOI e SOI FinFET. La degradazione delle caratteristiche elettriche DC dipende pesantemente sia dalla geometria del dispositivo che dal processo utilizzato. Effetti da microdose in dispositivi UTB SOI Sono stati osservati interessanti cambiamenti immediatamente dopo irraggiamento e durante stress elettrici in tali dispositivi utilizzanti anche tecniche strain: mancanza di rottura del’ossido di gate anticipata a causa dello spessore molto ridotto (solo 1.5 nm SiON) e dipendenza delle cinetiche di degradazione dallo strain utilizzato. Effetti da microdose in dispositivi SOI FinFET Gli effetti permanenti indotti da ioni pesanti sulle caratteristiche elettriche di SOI FinFET con ossido di gate ad alta costante dielettrica (high-k) dipendono pesantemente dagli effetti di microdose nell’ossido sepolto, dalla rottura dell’ossido di gate, e dalla generazione di stati trappola all’interfaccia ossido di gate/silicio. Contrariamente ai risultati ottenuti in esperimenti di Single Event Gate Rupture (SEGR) di solito eseguiti su grandi condensatori anche con ossidi high-k, dispositivi multiple gate mostrano soft breakdown e una considerevole variazione delle caratteristiche elettriche. Ioni pesanti posso indurre difetti nei dispositivi FinFET con un ampio spread statistico. La distribuzione della variazione di tensione di soglia e dell’inverso della corrente di perdita dell’ossido di gate seguono la distribuzione di Weibull. Tuttavia, si è dimostrato che il reciproco della corrente di perdita non segue la cosiddetta Poisson area scaling. Un nuovo modello statistico è stato sviluppato, trovando che una maggiore generazione di difetti si verifica negli ossidi di gate verticali rispetto a quello orizzontale e che la traccia dello ione utile a creare difetti nell’ossido di gate è di circa 30 nm. Pertanto, un ulteriore scaling dei dispositivi multi gate può portare a drammatiche conseguenze per applicazioni spaziali poiché la traccia dello ione può risultare più grande del dispositivo stesso. Infine, si è valutata anche l’affidabilità di tali dispositivi mediante stress di vita accelerati ad alti campi elettrici e si è trovato una riduzione del tempo al breakdown nei dispositivi irraggiati. Dose enhancement in MOSFET planari bulk Per quanto riguarda i MOSFET planari bulk si è studiato l’impatto della presenza della prima metal di interconnessione in prossimità dell’area attiva del dispositivo. Si è dimostrato che la sensibilità a raggi X dipende fortemente dalla posizione della metal di interconnessione, specialmente se fatta in rame, rispetto all’ossido di isolamento laterale (Shallow Trench Isolation STI) e agli LDD spacers. In conclusione, la sensibilità a ESD non è un fattore di ritardo per l’introduzione nel mercato delle tecnologie UTB SOI e FinFET. Invece, per quanto riguarda la tecnologia multi gate FinFET, gli effetti da microdose indotti da ioni pesanti rappresentano un serio problema, mentre non lo è per la tecnologia UTB SOI. Infine, gli effetti indotti da dose enhancement in MOSFET convenzionali submicrometrici devono essere attentamente monitorati quando sono usate facility a raggi X per eseguire test di dose totale.

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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.

It is generally accepted that energy is required for repair of radiation-induced damage in living cells. Some of this energy is probably provided by adenosine triphosphate (ATP), which is derived from energy substrates via energy metabolism. This dissertation follows two general avenues. The first explores the effect of radiation on ATP levels after irradiation of cells. The second investigates the effect of inhibitors of certain pathways associated with energy metabolism on radiation response. It was proposed that ATP levels might be raised after irradiation in some systems and that this rise in ATP might be due to compensatory mechanisms related to repair. Experiments were conducted using B16 melanoma cells in vitro and using normal murine liver and CaNT tumours in vivo. ATP concentration was measured in extracts of these cells after irradiation using the luciferase-luciferin method. No major changes from unirradiated controls were found. Several types of substrates exist from which cells can derive energy, including glucose and glutamine which are initially metabolised via glycolysis and glutaminolysis, respectively, before their products are further metabolised in respiration. Since energy is necessary for repair of radiation damage, it has been proposed that the inhibition of energy metabolism might alter the radiation response of cells. An inhibitor of glycolysis, 2-deoxyglucose (2DG), and an inhibitor of glutaminolysis, aminooxyacetic acid (AOA), were administered to CHO cells in vitro to determine the effects of these substances on cellular radiosensitivity and repair. Repair was assessed by means of a split radiation dose experiment. The design of such an experiment required that cells be exposed to inhibitory test media for different times between two fractions of radiation. Any changes in clonogenic survival with time between tween fractions could, therefore be as a result of repair effects or as a result of changes in radiosensitivity. A method of estimating and subtracting the effects of radiosensitivity to make conclusions concerning repair is presented and discussed. Most combinations of 2DG, AOA, glucose omission and glutamine omission in culture media resulted in reductions in repair rate but the extent of repair was found to vary from one medium variation to the next. In addition, the effects of various culture media on glycolysis/PPP (glycolysis/pentose phosphate pathway) and glutaminolysis were investigated by determining the production of CO2 and lactate from radiolabelled-glucose and -glutamine substrates. It was apparent that the presence of either of the inhibitors, 2DG or AOA, could inhibit the activity of glutaminolysis and reduce oxygen consumption. 2DG was shown to inhibit glycolysis/PPP but AOA was shown to stimulate glycolysis/PPP, suggesting a regulatory link between glutaminolysis and glycolysis/PPP. The presence of either inhibitor resulted in a reduction in the rate of radiation damage repair. The medium which had the most significant effect in respect of repair inhibition and increased radiosensitivity was medium lacking both glucose and glutamine and containing both 2DG and AOA. This medium was shown to inhibit oxygen consumption and to result in a depression of both cellular glycolysis/PPP and glutaminolysis. The effect of 2DG on the rate of growth and radiation induced growth delay of three murine tumours in vivo was assessed. 2DG alone inhibited the growth of B16 tumours. However, 2DG alone produced little if any change in the rates of growth of Fib/T tumours and rhabdomyosarcomas but the combination of 2DG and AOA produced an inhibition of growth in the Fib/T tumour. 2DG appeared to enhance the effects of radiation in the Fib/T and B16 tumours but not in the rhabdomyosarcoma, although, in the Fib/T, the combination of AOA, 2DG and radiation was less effective in inhibiting tumour growth than was radiation alone. The effects of radiation and 2DG did not appear to be additive in the Fib/T tumour and the B16 tumours which may imply an influence of 2DG on repair or radiosensitivity. This work suggests that the effects of radiation can be altered by manipulation of metabolic pathways associated with the supply of energy. However, a complex interaction of pathways is probably also involved and it is the detail of this interaction which may partially determine the severity of radiation response.

Total ionizing dose (TID) radiation effects modeling and simulation on digital, analog and mixed signal systems remains a significant bottle neck in the development of radiation-hardened electronics. Unverified modeling techniques and the very high computational cost with today's commercial simulation tools are among the primary hindrances to the timely hardened IC design, particularly to the design in commercially available processes. SPICE-based methods have been used for total dose radiation degradation simulations. While SPICE is effective in predicting the circuit behavior under circumstances when the electrical parameters stay constant during operation, it's not effective predicting aging behavior with gradual change with time. Behavioral modeling language, such as VHDL-AMS is needed to effectively capture the time-dependent degradation in these parameters in response to environmental stresses, such as TID radiation.This dissertation describes a method for accurate and rapid TID effect simulation of complex mixed-signal circuits. The method uses a hierarchical structure where small sub-circuits, such as voltage comparators, references, etc. are simulated using SPICE. These SPICE simulations of small circuits for multiple radiation doses are used to tune behavioral VHDL-AMS models for the sub-circuits. The created behavioral models therefore contain the electrical circuit behavior combined with the radiation response. The entire combined system is then simulated using VHDL-AMS.In a simulation experiment that was used to validate the speed and accuracy of the new method, a commercial 8-bit sub-ranging analog to digital converter netlist containing more than 2000 MOS transistors was simulated with TID models using a contemporary SPICE-based method and the new method. The new method shortened the simulation time by three orders of magnitude, while accuracy remained within reasonable limits compared to the SPICE-based method. Moreover, the automated procedures for circuit node bias monitoring, TID model replacement and result collection that are included in the simulation code of the new method decreased the "hands-on" engineering work significantly. Results from an experiment where the new TID effect simulation method was used as a hardness assurance test procedure for integrated circuits designed to be operated in radiation-harsh environments are also included in this dissertation.

The effects of ionizing radiation on the breakdown voltage of p-channel power MOSFETs were examined through two-dimensional simulation. The response of a reverse-biased n+-p junction to positive oxide-trapped charge, Not, is examined in detail, and analytical expressions for its characteristics are derived. These results provide insight into the breakdown performance of p-channel power MOSFETs in ionizing radiation environments, whose performance was found to be very different from corresponding n-channel power MOSFETs. Insights gained through analysis of p-channel devices suggest a termination/isolation scheme, the VLD-FRR, that will enhance p-channel device reliability in radiation environments. Two introductory chapters, which also serve as literature reviews, are provided. The buildup of Not in thick oxides and breakdown voltage of the power DMOS transistor are both reviewed, with attention focused on p-channel devices in both cases. Finally, suggestions for future work are given.

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Thesis (M.A.)--Boston University PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you.<br>Previous studies have showed effects of irradiation on bone and on fracture healing. This is a histological study of the effect of a combined irradiation/fracture injury model in a strain of aged mice (SAMP6) and controls (SAMR1) and the effects of the radioprotective agent, JP4-039 (a mitochondria targeted GS-nitroxide). Hind legs in SAMR1 and SAMP6 control mice and mice pretreated with JP4-039 were exposed to a single dose of radiation (0 or 20 Gy). Twenty four hours after irradiation, unicortical osseous wounds were created in each proximal tibia. Mice were sacrificed at intervals (14, 21 days), tibias excised, radiographed, and prepared for histology (day 21 only). Tibias were examined and graded histologically for evidence of cortical bridging and intramedullary fibrosis. Irradiated SAMP6 wounds showed significantly diminished cortical bridging and significantly more intramedullary fibrosis. In contrast, JP4-039 showed a statistical trend in ameliorating intramedullary fibrosis in irradiated SAMP6 mice. In control SAMR1 mice, JP4-039 had no significant effect on cortical bridging or fibrosis with the number of replicates available. In summary, SAMP6 mice display diminished capacity to recover from the combined irradiation/fracture injury model, with subgroups pretreated with JP4-039 showing beneficial trends in mitigating irradiation induced injury.

L'objectif de la thèse est de développer une chaîne de simulation multi-échelle des effets de dose ionisante dans les technologies SOI pour évaluer les dégradations des circuits intégrés. Ce phénomène provient de la dégradation permanente des diélectriques, induisant une dérive dans le temps des caractéristiques électriques des transistors et donc des performances du circuit qu'ils constituent. Cette chaîne de simulation, qui est validée expérimentalement, est destinée à assister les concepteurs de circuits durcis aux radiations, afin de les guider vers les solutions de durcissement optimales. Tout d'abord, des simulations TCAD sont réalisées, à l'échelle composant, pour relier les dégradations des courbes courant-tension à l'origine de l'accumulation de charges et les comportements PDSOI et FDSOI influencent la réponse du dispositif. Deuxièmement, des modèles pour quantifier l'accumulation de charges dans les oxydes sont développés afin d'être utilisés dans des modèles standards. Troisièmement, une étude de cas sur une référence de tension est présentée afin de valider la pertinence de la chaîne de simulation<br>The objective of the thesis is to develop a multiscale simulation chain of the ionizing dose effects in SOI technologies to assess integrated circuit degradations. This phenomenon originates from the permanent degradation of dielectrics, inducing a drift in time of the electrical characteristics of transistors and thus of the performances of the circuit that they constitute. This simulation chain, which is validated experimentally, is intended to assist designers of radiation-hardened circuits, in order to guide them towards the optimal hardening solutions. Firstly, TCAD simulations are performed, at device scale, to relate current-voltage curves degradations to the origin of charge build-up and how PDSOI and FDSOI behaviors influence the device response. Secondly, models for quantifying the charge build-up in the oxides are developped in order to be used in standard models. Thirdly, a case study on a voltage reference is presented in order to validate the relevance of the simulation chain

Thesis (Ph. D.)--University of Missouri--Rolla, 2007.<br>Vita. The entire thesis text is included in file. Title from title screen of thesis/dissertation PDF file (viewed January 28, 2008) Includes bibliographical references (p. 117-131).

La aplicación de la radiación ionizante (RI) en ámbito médico ha llegado, sin duda, para salvar vidas. Sin embargo, hay una preocupación entre los expertos de salud pública y protección radiológica con relación al incremento de la exposición medica a RI, sobretodo en pacientes pediátricos. Esta tesis tiene como objetivo contribuir a una mejor caracterización del riesgo de radiación en pacientes oncológicos. Con ese fin, se creó un estudio de cohorte de supervivientes de cáncer infantil, como base para el análisis futuro y, anidado a esta cohorte, se implementó un estudio transversal sobre el efecto del neurodesarrollo después de haber recibido radioterapia no-craneal. Aquí se presenta un análisis descriptivo del estado de salud mental de la cohorte en forma de articulo científico. También se ha estimado la asociación entre la dosis acumulada de RI de los procedimientos de diagnóstico médico, como la exposición al radio-diagnostico y el cáncer (linfoma en adultos y tumores cerebrales en niños-adolescentes), en dos grandes estudios internacionales caso-control y dicho trabajo se unió a una estimación de dosimetría que puede ser aprovechada aún más para estudios similares. Este trabajo se presenta en forma de tres articulo científicos. En el marco de esta tesis, también, se sintetizó la evidencia actual de un efecto en el neurodesarrollo de la exposición a RI de dosis baja a moderada, en una revisión sistemática (en forma de artículo científico), concluyendo que la evidencia de este efecto es limitada e inadecuada. La estimación de los efectos de radiación médica requiere grandes esfuerzos y la colaboración entre epidemiólogos y clínicos es un aspecto clave en este tema.<br>The application of ionising radiation (IR) in the medical sector is undoubtedly lifesaving. There are, however, risks associated with IR and there is growing concern among public health and radiation protection experts, in particular for the increasing medical radiological exposure in children. The aim of this dissertation is to contribute to a better characterisation of the IR risk in patients. A hospital-based cohort study of childhood cancer survivors was developed as a basis for future analysis and, nested within the cohort, a cross-sectional study on neurodevelopmental effect after non-cranial radiotherapy was implemented. A descriptive analysis of the mental health status of the cohort is presented here in the form of a Manuscript. The association between cumulative IR from medical diagnostic procedures and cancer (adult lymphoma and childhood/adolescent brain cancer), in two large international case-control studies, were estimated and a dosimetry estimation was developed. This work has lead to three manuscripts, included in the thesis. Evidence of a neurodevelopmental effect at low-to moderate IR dose was synthesized in a systematic review (presented here in a form of a Manuscript) and was found to be limited to inadequate. The estimated effect at this low dose range requires greater effort from epidemiologists to design more informative studies, and collaboration with clinicians is key for future research in radiation epidemiology.

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Motivated by an increasing demand for functionality and reliability of systems operating in harsh, ionizing-radiation environments, the core of the present research is an investigation of the response of rare-earth-doped, aluminosilicate fibers to ionizing radiation. These rare-earth-doped fibers, consisting of fibers doped with ions of erbium (Er³⁺) and ytterbium (Yb³⁺) designed for use in amplifier systems, reveal average specific losses in response to ⁶⁰Co gamma radiation to be in the range of 0.0285 - 0.193 dB/(m•krad(Si)) at wavelengths from 1300 nm to 1400 nm. An ionizing dose rate dependence was identified in which high dose rates of approximately 40 rad(Si)/s invariably lead to higher induced losses than lower dose rates of approximately 14 rad(Si)/s, indicating the possibility of complex radiation-related phenomena underlying the observed absorption. Data clearly show that Er³⁺-doped fibers are more sensitive to ionizing-radiation in comparison to Yb³⁺-doped fibers, while Er³⁺/Yb³⁺ co-doped fibers are found to be the least sensitive to radiation of all the fibers examined. Evidence of color center formation associated with the dopant aluminum is found in results of visible spectroscopy conducted on gamma-irradiated preform samples and on fibers flown in low-Earth orbit. Near infrared spectroscopic data is consistent with absorption derived from this dopant as well, with the interpretation of band-tailing from the visible portion of the spectrum. Evidence of the formation of a defect intrinsic to the silicate host matrix, the Non-Bridging Oxygen Hole Center (NBOHC), is also found following ionizing radiation of the optical fiber preforms. Since the observed ionizing-radiation-induced absorption is concentrated in the visible portion of the spectrum, the performance of actively operated rare-earth-doped amplifiers is largely impacted by the pump wavelength, which is located at higher energies within the near-infrared portion of the spectrum and therefore closer to the visible portion of the spectrum than the lasing wavelength. Experimental results stemming from rare-earth-doped amplifiers operated under ionizing radiation substantiate the importance of the pumping wavelength, and suggest the presence of cascaded pump photon absorption processes. Based on these results, pumping at longer wavelengths is advised to reduce the effect of color center absorption on this crucial aspect of active fiber amplifier operation.