This thesis reports the effects of ultrashort laser pulse irradiation of various materials. The morphology after irradiation was examined using several microscopy techniques. Emphasis was placed on the identification of crystallographic changes and the analysis of laser-induced periodic surface structures. Grooves were machined in silicon by translating the target under the focused laser beam. The resulting depths were measured as a function of pulse energy, translation speed, and number of consecutive passes, for 800 and 400nm wavelength irradiation. The wall morphology and a corrugation along the bottom of the grooves were characterized. Various polarization configurations relative to the translation direction were compared. Such characterizations are relevant for the practical application of femtosecond laser micromachining. Silicon and gallium phosphide exhibited periodic structures after irradiation using photon energies less than the bandgap energy, with periods as small as ~20% of the irradiation wavelength. The significantly sub-wavelength periodic structures had a shallow profile on silicon, appearing as fine lines or grids of protrusions and depressions. On gallium phosphide, the surface evolved into planar-like structures with a large aspect ratio, possessing crystalline centers coated with amorphous material. These investigations, along with additional experiments, would help identify the precise physical origins of the short-period structures. On silicon and germanium, the target crystal orientation was shown to affect the formation of certain morphological features. For multiple-pulse irradiation, the (100) and (111) surface orientations exhibited significantly different tendencies for large conical structure formation. A thin layer of defected material coated the conical structures, with some defects present within the periodic structures. The different crystalline orientations did not affect periodic structuring. Cross-sectional transmission electron microscopy of silicon after irradiation by single pulses revealed amorphous material and dislocations in the bulk for sufficiently high pulse fluences. On a sample consisting of a metal layer on thermally-grown oxide on silicon, a range of pulse fluences was found which removed the metal layer without observed thinning of the oxide layer. Within this fluence range, above a particular fluence substantial defects were formed in the underlying silicon. Although ultrashort pulse irradiation of materials is frequently considered to be 'damage-free', attention should be paid to sub-surface modifications not evident from surface imaging. For the drilling of holes in copper foils, the pulse duration did not strongly affect the final morphology for durations under several picoseconds. A photodiode below the foil during drilling recorded transmitted light, indicating the number of pulses required for penetration under a variety of conditions, and characterizing hole evolution during drilling. Periodic surface structuring on the walls of holes depended on the irradiation atmosphere, pulse duration, and laser polarization. These measurements provide insight into the physical processes of material modification, and for the selection of irradiation parameters in practical applications. / Thesis / Doctor of Philosophy (PhD)

Solving radiation shielding problems, i.e. deep penetration problems, is a challenging task from both computation time and resource aspects in field of nuclear engineering. This is mainly because of the complexity of the governing equation for neutral particle transport - Linear Boltzmann Equation (LBE). The LBE includes seven independent variables with presence of integral and differential operators. Moreover, the low successive rate of radiation shielding problem is also challenging for solving such problems. In this dissertation, the Detector Response Function (DRF) methodology is proposed and developed for real-time and accurate radiation shielding calculation. The real-time capability of solving radiation shielding problem is very important for: (1) Safety and monitoring of nuclear systems; (2) Nuclear non-proliferation; and (3) Sensitivity study and Uncertainty quantification. Traditionally, the difficulties of solving radiation problem are: (1) Very long computation time using Monte Carlo method; (2) Extremely large memory requirement for deterministic method; and (3) Re-calculations using hybrid method. Among all of them, the hybrid method, typically Monte Carlo + deterministic, is capable of solving radiation shielding problem more efficiently than either Monte Carlo or deterministic methods. However, none of the aforementioned methods are capable of performing "real-time" radiation shielding calculation. Literature survey reveals a number of investigation on improving or developing efficient methods for radiation shielding calculation. These methods can be categorized by: (1) Using variance reduction techniques to improve successive rate of Monte Carlo method; and (2) Developing numerical techniques to improve convergence rate and avoid unphysical behavior for deterministic method. These methods are considered clever and useful for the radiation transport community. However, real-time radiation shielding calculation capability is still missing although the aforementioned advanced methods are able to accelerate the calculation efficiency significantly. In addition, very few methods are "Physics-based" For example, the mean free path of neutrons are typically orders of magnitude smaller than a nuclear system, i.e. nuclear reactor. Each individual neutron will not travel too far before its history is terminated. This is called the "loosely coupled" nature of nuclear systems. In principle, a radiation shielding problem can be potentially decomposed into pieces and solved more efficient. In the DRF methodology, the DRF coefficients are pre-calculated with dependency of several parameters. These coefficients can be directly coupled with radiation source calculated from other code system, i.e. RAPID (Real-time Analysis for Particle transport and In-situ Detection) code system. With this arrangement, detector/dosimeter response can be calculated on the fly. Thus far, the DRF methodology has been incorporated into the RAPID code system, and applied on four different benchmark problems: (1) The GBC-32 Spent Nuclear Fuel (SNF) cask flooded with water with a $^3$He detector placed on the cask surface; (2) The VENUS-3 experimental Reactor Pressure Vessel (RPV) neutron fluence calculation benchmark problem; (3) RPV dosimetry using the Three-Mile Island Unit-1 (TMI-1) commercial reactor; and (4) A Dry storage SNF cask external dosimetry problem. The results show that dosimeter/detector response or dose value calculations using the DRF methodology are all within $2sigma$ relative statistical uncertainties of MCNP5 + CADIS (Consistent Adjoint Driven Importance Sampling) standard fixed-source calculation. The DRF methodology only requires order of seconds for the dosimeter/detector response or dose value calculations using 1 processor if the DRF coefficients are appropriately prepared. The DRF coefficients can be reused without re-calculations when a model configuration is changed. In contrast, the standard MCNP5 calculations typically require more than an hour using 8 processors, even using the CADIS methodology. The DRF methodology has enabled the capability of real-time radiation shielding calculation. The radiation transport community can be greatly benefited by the development of DRF methodology. Users can easily utilize the DRF methodology to perform parametric studies, sensitivity studies, and uncertainty quantifications. The DRF methodology can be applied on various radiation shielding problems, such as nuclear system monitoring and medical radiation facilities. The appropriate procedure of DRF methodology and necessary parameters on DRF coefficient dependency will be discussed in detail in this dissertation. / Doctor of Philosophy / Since the beginning of nuclear era, enormous amount of radiation applications have been proposed, developed, and applied in our daily life. The radiation is useful and beneficial when they are under control. However, there will be some "unwanted radiation" from these applications, which have to be shielded. For this, radiation shielding has become a very important task. To effectively shield the unwanted radiations, studying the thickness and design of the shields is important. Instead of directly performing experiments, computation is a more affordable and safer approach. The radiation shielding computation is typically an extremely difffficult task due to very limited "communication" between the radiation within the shield and detector outside the shield. In general, it is impractical to simulate the radiation shielding problems directly because the extremely expensive computation resources. Most of interactions of radiation are within the shield while we are only interested in how many of them penetrate through the shield. This is typically called "deep penetration" problems in the radiation transport community.

京都大学 / 新制・課程博士 / 博士(医学) / 甲第25159号 / 医博第5045号 / 新制||医||1070(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 中山 健夫, 教授 森田 智視, 教授 永井 洋士 / 学位規則第4条第1項該当 / Doctor of Agricultural Science / Kyoto University / DFAM

De nombreuses études ont montré que l'exposition de cultures cellulaires à des particules α conduit à des changements biologiques importants autant dans les cellules irradiées que dans les cellules bystander non-irradiées. L'étude des réponses biologiques non-ciblées dans des cultures cellulaires exposées à de faibles fluences d’ions lourds permet d’estimer les risques pour la santé du rayonnement spatial et de la radiothérapie. Nous avons caractérisé les mécanismes sous-jacents de l'induction d'effets stressants dans des cultures confluentes de fibroblastes normaux humains exposés à de faibles fluences d’ions fer de 1000 MeV/u (transfert d'énergie linéique (TEL) ~151 keV/µm), d’ions silicium de 600 MeV/u (TEL ~50 keV/µm) ou d’ions carbone de 290 MeV/u (TEL ~13 keV/µm). Nous avons comparé ces résultats avec ceux obtenus dans des cultures cellulaires exposées, en parallèle, à de faibles fluences de particules α de 0,92 MeV/u (TEL ~109 keV/µm). L'induction de dommages à l'ADN, les changements dans l'expression des gènes, la carbonylation des protéines et la peroxydation lipidique durant les 24 h suivant l'exposition de cultures confluentes à de faibles doses (0,2 cGy et plus) d’ions fer ou d'ions silicium ont très largement contribué à la propagation d’effets stressants des cellules irradiées aux cellules bystander non-irradiées. Pour une dose moyenne de 0,2 cGy, seules ~1 et 3 % des cellules seraient irradiées dans le noyau par un ion, respectivement, fer ou silicium. Les immunoblots ont révélés des augmentations significatives des niveaux de phospho-TP53 (sérine 15), p21Waf1 (CDKN1A), HDM2, phospho-ERK1/2, de carbonylation des protéines et de peroxydation lipidique dans les 24 h suivant l’exposition. L'ampleur de ces réponses suggère la participation de cellules non ciblées dans les effets observés. De plus, lorsque les populations cellulaires irradiées ont été ré-ensemencées dans un milieu de culture frais peu après l'irradiation, les niveaux de ces marqueurs ont aussi augmentés durant 24 h. Ensemble, ces résultats montrent un effet rapidement propagé et persistant. Des analyses in situ réalisées dans des cultures cellulaires confluentes ont montré que la formation de foyers de la protéine 53BP1, marqueur de dommages à l'ADN, touchait un nombre de cellules plus important que celui auguré par la fraction de cellules traversées dans le noyau par un ion fer ou silicium. Cet effet est exprimé dès 15 min suivant l'exposition, atteint son maximum 1 h après l’exposition puis diminue jusqu’à 24 h. Une tendance similaire s'est produite après exposition à une dose moyenne absorbée de 0,2 cGy de particules α de 3,7 MeV, mais non après 0,2 cGy d’ions carbone de 290 MeV/u.Des analyses utilisant des puits de cultures intégrant une fine épaisseur de CR-39, détecteur solide de traces nucléaires, et permettant ainsi l’identification des cellules irradiées aux ions fer ou silicium, confirment la participation de cellules bystander dans la réponse au stress. Des études mécanistiques ont, de plus, indiqué que les jonctions gap permettant la communication intercellulaire, certaines voies de la réparation de l’ADN, ainsi que le métabolisme oxydatif participent à la propagation des effets non ciblés induit par des radiations de haut TEL. Nous avons également examiné la contribution possible des particules secondaires produites le long des traces d’ions primaires dans les réponses biologiques. Les simulations réalisées avec le code de transport de particules FLUKA ont révélé que la dose due aux produits de fragmentation, autres que les électrons, est inférieure à 1 % de la dose absorbée dans les cultures cellulaires exposées à des ions lourds. De plus, la dose radiale des ions lourds secondaires est limitée à ~10-20 µm autour de l’ion primaire. Ainsi, ces derniers sont peu susceptibles de contribuer de manière significative à la réponse biologique observée dans des cellules non ciblées par des ions lourds primaires / Widespread evidence indicates that exposure of cell cultures to α particles results in significant biological changes in both the irradiated and non-irradiated bystander cells in the population. The induction of non-targeted biological responses in cell cultures exposed to low fluences of high charge (Z) and high energy (E) particles is relevant to estimates of the health risks of space radiation and to radiotherapy. Here, we investigated the mechanisms underlying the induction of stressful effects in confluent normal human fibroblast cultures exposed to low fluences of 1000 MeV/u iron ions (linear energy transfer (LET) ~151 keV/µm), 600 MeV/u silicon ions (LET ~50 keV/µm) or 290 MeV/u carbon ions (LET ~13 keV/µm). We compared the results with those obtained in cell cultures exposed, in parallel, to low fluences of 0.92 MeV/u α particles (LET ~109 keV/µm).Induction of DNA damage, changes in gene expression, protein carbonylation and lipid peroxidation during 24 h after exposure of confluent cultures to mean doses as low as 0.2 cGy of iron or silicon ions strongly supported the propagation of stressful effects from irradiated to bystander cells. At a mean dose of 0.2 cGy, only ~1 and 3 % of the cells would be targeted through the nucleus by an iron or silicon ion, respectively. Within 24 h post-irradiation, immunoblot analyses revealed significant increases in the levels of phospho-TP53 (serine 15), p21Waf1 (also known as CDKN1A), HDM2, phospho-ERK1/2, protein carbonylation and lipid peroxidation. The magnitude of the responses suggested participation of non-targeted cells in the response. Furthermore, when the irradiated cell populations were subcultured in fresh medium shortly after irradiation, greater than expected increases in the levels of these markers were also observed during 24 h. Together, the results imply a rapidly propagated and persistent bystander effect. In situ analyses in confluent cultures showed 53BP1 foci formation, a marker of DNA damage, in more cells than expected based on the fraction of cells traversed through the nucleus by an iron or silicon ion. The effect was expressed as early as 15 min after exposure, peaked at 1 h and decreased by 24 h. A similar tendency occurred after exposure to a mean absorbed dose of 0.2 cGy of 3.7 MeV α particles, but not after 0.2 cGy of 290 MeV/u carbon ions.Analyses in dishes that incorporate a CR-39 solid state nuclear track detector bottom identified the cells irradiated with iron or silicon ions and further supported the participation of bystander cells in the stress response. Mechanistic studies indicated that gap junction intercellular communication, DNA repair, and oxidative metabolism participate in the propagation of the induced effects.We also considered the possible contribution of secondary particles produced along the primary particle tracks to the biological responses. Simulations with the FLUKA multi-particle transport code revealed that fragmentation products, other than electrons, in cells cultures exposed to HZE particles comprise <1 % of the absorbed dose. Further, the radial spread of dose due to secondary heavy ion fragments is confined to approximately 10-20 µm Thus, the latter are unlikely to significantly contribute to the stressful effects in cells not targeted by primary HZE particles.

La radiothérapie guidée par résonance magnétique promet une administration de dose plus précise que les techniques conventionnelles puisqu’elle permet une visualisation en temps réel des structures internes avant et pendant le traitement. Cependant, la dosimétrie doit être réalisée en présence de champs magnétiques. Alors que le champ magnétique n’affecte pas le transport des particules neutres, il affecte le transport des particules chargées secondaires en raison de la force de Lorentz, qui modifie le champ de rayonnement et la réponse de dose du détecteur. Cette thèse vise à comprendre l’effet du champ magnétique sur la réponse de dose du détecteur, à la caractériser et à fournir des facteurs de correction de qualité prenant en compte l’impact du champ magnétique. Dans le premier article, quatre chambres d’ionisation à petite cavité ont été caractérisées via des simulations de Monte Carlo et des mesures expérimentales. Il a été constaté que le champ magnétique accentuait tous les détails géométriques. Une description précise du volume sensible effectif est cruciale dans les simulations. De plus, la géométrie modélisée doit être aussi proche que possible de la géométrie réelle, y compris les couches d’air internes. Des facteurs de correction de qualité tenant compte du champ magnétique et de son incertitude du budget d’incertitude sont présentés pour différentes configurations. Le deuxième article a évalué l’effet du champ magnétique sur les facteurs de perturbation de cinq détecteurs à petite cavité, dont trois détecteurs à petite cavité et deux détecteurs à semi-conducteurs. Les facteurs de perturbation des composants structurels, les facteurs de moyenne de densité et de volume ont été déterminés pour différentes tailles de champ et orientations. De plus, des facteurs de correction de qualité ont été calculés dans les mêmes conditions. Les résultats montrent que le champ magnétique a un impact significatif sur le facteur de perturbation de la densité dans les chambres d’ionisation. En revanche, son impact est plus prononcé dans les composants structurels des détecteurs semi-conducteurs. L’objectif du troisième article était de fournir plus d’informations sur la compréhension de la relation dose-réponse des détecteurs dans les champs magnétiques via des calculs de spectres de fluence électronique. La fluence des électrons différentiel en énergie dans la cavité du détecteur peut être fortement modifiée dans les champs magnétiques, et les perturbations de fluence sont généralement plus évidentes pour les électrons de faible énergie. Ces calculs ont montré l’interaction entre plusieurs facteurs qui rendent les effets de perturbation imprévisibles dans le faisceau de photons couplé aux champs magnétiques : 1) orientation du détecteur et du champ magnétique, 2) taille et forme de la cavité, 3) composants structurels, 4) couche d’air entre le détecteur et le milieu et leur asymétrie, et 5) l’énergie. / Magnetic resonance-guided radiation therapy promises more accurate dose delivery than conventional techniques by allowing real-time visualization of internal structures before and during treatment. However, the dosimetry must be performed in the presence of magnetic fields. While the magnetic field does not affect the transport of uncharged particles, it affects the transport of secondary charged particles due to the Lorentz force, which modifies the radiation field and the detector dose-response. This thesis aims to understand the effect of the magnetic field on detector dose-response, characterize it, and provide quality correction factors accounting for the impact of the magnetic field. In the first article, four small-cavity ionization chambers were characterized via Monte Carlo simulations and experimental measurements. It was found that the magnetic field emphasized all the geometrical details. An accurate description of the effective sensitive volume is crucial in the simulations. Also, the modelled geometry must be as close as possible to the actual geometry, including the internal air layers. Quality correction factors accounting for the magnetic field and its uncertainty budget uncertainty are presented for different configurations. The second article evaluated the magnetic field effect on perturbation factors of five small volume detectors, including three ionization chambers and two solid-state detectors. The perturbation factors from extracameral components, density and volume averaging factors were determined for different field sizes and orientation setups. Additionally, quality correction factors were calculated in the same conditions. Results show that the magnetic field significantly impacts the density perturbation factor in the ionization chambers. In contrast, its impact is more pronounced in the extracameral components in the solid-state detectors. The purpose of the third article was to provide more insight into the understanding of detector dose-response in magnetic fields via calculations of electron fluence spectra. The electron fluence differential in energy in the detector cavity can be severely modified in magnetic fields, and fluence perturbations are generally more evident for low-energy electrons. These calculations showed the interplay between multiple factors that make the perturbation effects unpredictable in photon beams coupled to magnetic fields: 1) detector and magnetic field orientation, 2) cavity size and shape, 3) extracameral components, 4) air gaps and their asymmetry, and 5) energy.

Dans le cadre de l’évaluation pré-chirurgicale de patients épileptiques, il est impératif de déterminer la spécialisation hémisphérique du langage, ainsi que de localiser les aires du langage au sein de cet hémisphère. De nouvelles méthodes d’évaluation non- invasives doivent être mises au point afin de diminuer les risques associés aux méthodes plus invasives telles que le test à l’amobarbital intracarotidien (TAI). L’objectif principal de cette thèse est donc de développer un protocole d’évaluation pré-chirurgicale alternatif et non-invasif à l’aide de la magnétoencéphalographie (MEG) pour la latéralisation et la localisation du langage, incluant la mémoire verbale qui serait éventuellement accessible à une population pédiatrique francophone épileptique. L’article 1 présente une recension de la littérature résumant les différentes études en MEG ayant pour objectif l’évaluation pré-chirurgicale du langage. Trente-sept articles en MEG ont été analysés pour déterminer quelles tâches permettaient d’obtenir les meilleurs résultats de latéralisation intrahémisphérique et de localisation du langage pour l’évaluation du langage réceptif et expressif chez des sujets neurologiquement sains et épileptiques. Parmi les tests retenus, l’épreuve de reconnaissance de mots permet d’évaluer le langage réceptif et la mémoire verbale, tandis que des épreuves de fluence verbale telles que la génération de verbes permettent d’évaluer le langage expressif de façon à obtenir de très bons résultats. L’article 2 a permis de valider un protocole auprès de sujets neurologiquement sains à l’aide des épreuves identifiées dans l’article 1. Le protocole utilisé comprend une tâche de langage réceptif et de mémoire verbale (une épreuve de reconnaissance de mots) et une tâche de langage expressif (une épreuve de fluence verbale). Suite à la validation du protocole à l’aide d’analyses par composantes principales, les épreuves ont été administrées à un groupe de patients épileptiques. Les index de latéralité et les analyses de sources i révèlent que la MEG permet de localiser et de latéraliser les fonctions langagières et pourrait donc être utilisée comme méthode d'évaluation du langage lors de l'évaluation pré- chirurgicale auprès de patients épileptiques. Toutefois, alors que l’épreuve de mémoire verbale a permis d’obtenir les meilleurs résultats auprès de l’ensemble des participants, l’épreuve de fluence verbale n’a fourni des informations supplémentaires que chez un seul patient et chez aucun participant neurologiquement sain. En résumé, les deux articles de cette thèse démontrent le potentiel clinique de la MEG pour l’évaluation pré-chirurgicale de patients souffrant d’une épilepsie réfractaire. / It is imperative to determine hemispheric dominance of language and to localize language areas in this hemisphere as part of the presurgical evaluation of epileptic patients. New non-invasive evaluation methods should be developed to reduce the risks associated with more invasive methods such as the intracarotid sodium amobarbital procedure (ISAP). The main objective of this dissertation is to develop an alternative non-invasive presurgical evaluation protocol using magnetoencephalography (MEG) to determine the lateralisation and localization of language and verbal memory that would eventually be accessible to a French-speaking paediatric population suffering from epilepsy. Article 1 is a literature review summarizing MEG studies on the presurgical evaluation of language. Thirty-seven articles were analyzed to determine which tasks allow to obtain the best results with regards to language lateralization and localization with MEG in the assessment of receptive and expressive language in neurologically healthy individuals as well as epileptic patients. We conclude that the word recognition task is well suited to assess receptive language and verbal memory, while a verbal fluency task, such as the verb generation task allows the assessment of expressive language with very good results. Article 2 allowed the validation of a language protocol with neurological healthy participants based on the tasks identified in article 1. The protocol included a task evaluating receptive language functions and verbal memory (word recognition task) and a task evaluation expressive language (verbal fluency). After having validated the tasks using principal component analysis, they were administered to a group of patients with epilepsy. Laterality findings and source analysis showed that MEG can be used to lateralize and localize language and could therefore be used in the presurgical assessment of patients with epilepsy. However, the verbal fluency task, when compared to the verbal memory task, provided additional information for only one patient and in none of the neurologically healthy participants. In summary, the two articles of this dissertation demonstrate the clinical potential of MEG for the presurgical evaluation of patients with refractory epilepsy.

Cette recherche s’intéresse au langage préfabriqué (LP) dans le discours oral spontané d’apprenants de français langue étrangère (FLE). Le LP, étudié en linguistique sous l’angle du figement et de la conventionalité, intéresse aussi les psycholinguistes. Omniprésent dans le discours des locuteurs natifs, il sous-entend que la maîtrise d’une langue ne passe pas seulement par l’application des règles grammaticales et la création des phrases mais également par la mémorisation et l’automatisation des bouts de langue préconstruits. Notre objectif est double : étudier l’évolution de la connaissance du LP chez des apprenants du FLE et, le rôle que le LP joue dans leur fluidité verbale. Dix-sept apprenants ont réalisé à six mois d’intervalle deux tâches narratives orales, et leurs productions ont été enregistrées et transcrites deux fois. Six locuteurs natifs ont été soumis aux mêmes tâches une fois. Le LP a été identifié selon des critères linguistiques et psycholinguistiques. La fluence des productions a été évaluée au moyen de quatre mesures. Elle a été mise en relation avec l’emploi effectif des séquences préfabriquées afin de vérifier en quel sens ces dernières améliorent le discours oral des apprenants. Ainsi, il existe des différences individuelles très marquées entres les sujets testés et il est difficile de tirer des conclusions d’ordre général. Cependant, les apprenants de niveau débutant progressent dans l’emploi qu’ils font du LP, en quantité et en qualité. Ils peuvent s’appuyer sur les SP pour produire un discours plus fluide. Elles améliorent le segment de parole (longueur et complexification) et servent de stratégies (compensation, structuration et planification). / This thesis focuses on formulaic language in French as a Second Language (FSL) learners’ spontaneous spoken narratives. Formulaic language is made of multi-word units which are often perceived and used as simple lexical units. ESL studies have shown that even at advanced levels the command of formulaic language can be poor. The purpose of this thesis is twofold. First we intend to examine the evolution of formulaic language among FSL learners, and then the importance of formulaic language in learners’ fluency. Seventeen learners divided into three levels were asked over a period of six months to produce two oral narratives based on a cartoon and a silent film. Their narratives were recorded and transcribed as time 1 and time 2. The formulaic language which was found in the oral productions was identified according to linguistic and psycholinguistic criteria : phonological coherence, syntactic complexity, semantic opacity, frequence and systematicity of idiosyncratic errors and deviant items. The fluency was evaluated by means of four “classical” measurements : speech rate, length of run, rate of articulation, phonation time. Our analyses show that there are individual differences among subjects and that it is difficult to draw comprehensive conclusions. Yet, the results show a steady improvement in formulaic language among beginners, both quantitatively and qualitatively. Indeed, learners can rely on formulaic sequences to gain fluency and this in different manners. Formulaic sequences improve the speech run by making it longer and more complex. They can be used as strategies of compensation and planification of speech.

Widespread evidence indicates that exposure of cell cultures to α particles results in significant biological changes in both the irradiated and non-irradiated bystander cells in the population. The induction of non-targeted biological responses in cell cultures exposed to low fluences of high charge (Z) and high energy (E) particles is relevant to estimates of the health risks of space radiation and to radiotherapy. Here, we investigated the mechanisms underlying the induction of stressful effects in confluent normal human fibroblast cultures exposed to low fluences of 1000 MeV/u iron ions (linear energy transfer (LET) ~151 keV/µm), 600 MeV/u silicon ions (LET ~50 keV/µm) or 290 MeV/u carbon ions (LET ~13 keV/µm). We compared the results with those obtained in cell cultures exposed, in parallel, to low fluences of 0.92 MeV/u α particles (LET ~109 keV/µm).Induction of DNA damage, changes in gene expression, protein carbonylation and lipid peroxidation during 24 h after exposure of confluent cultures to mean doses as low as 0.2 cGy of iron or silicon ions strongly supported the propagation of stressful effects from irradiated to bystander cells. At a mean dose of 0.2 cGy, only ~1 and 3 % of the cells would be targeted through the nucleus by an iron or silicon ion, respectively. Within 24 h post-irradiation, immunoblot analyses revealed significant increases in the levels of phospho-TP53 (serine 15), p21Waf1 (also known as CDKN1A), HDM2, phospho-ERK1/2, protein carbonylation and lipid peroxidation. The magnitude of the responses suggested participation of non-targeted cells in the response. Furthermore, when the irradiated cell populations were subcultured in fresh medium shortly after irradiation, greater than expected increases in the levels of these markers were also observed during 24 h. Together, the results imply a rapidly propagated and persistent bystander effect. In situ analyses in confluent cultures showed 53BP1 foci formation, a marker of DNA damage, in more cells than expected based on the fraction of cells traversed through the nucleus by an iron or silicon ion. The effect was expressed as early as 15 min after exposure, peaked at 1 h and decreased by 24 h. A similar tendency occurred after exposure to a mean absorbed dose of 0.2 cGy of 3.7 MeV α particles, but not after 0.2 cGy of 290 MeV/u carbon ions.Analyses in dishes that incorporate a CR-39 solid state nuclear track detector bottom identified the cells irradiated with iron or silicon ions and further supported the participation of bystander cells in the stress response. Mechanistic studies indicated that gap junction intercellular communication, DNA repair, and oxidative metabolism participate in the propagation of the induced effects.We also considered the possible contribution of secondary particles produced along the primary particle tracks to the biological responses. Simulations with the FLUKA multi-particle transport code revealed that fragmentation products, other than electrons, in cells cultures exposed to HZE particles comprise <1 % of the absorbed dose. Further, the radial spread of dose due to secondary heavy ion fragments is confined to approximately 10-20 µm Thus, the latter are unlikely to significantly contribute to the stressful effects in cells not targeted by primary HZE particles.

La décontamination microbienne est sujet majeur de préoccupation du secteur agroalimentaire. Des nouvelles technologies physiques de décontamination, dites athermiques, sont d'un emploi croissant. La Lumière Pulsée, utilisée pour décontaminer les surfaces et les liquides clairs, en fait partie. Elle utilise des flashes de lumière blanche riches en UV, et délivrés en moins d'une milliseconde. La plupart des traitements par lumière pulsée sont définis dans la littérature par des paramètres spécifiques à l'équipement utilisé. Le but de cette étude a été dans un premier temps de caractériser le traitement par lumière pulsée par les grandeurs physiques appropriées (fluence, tension aux bornes de la lampe, etc...), en reliant une dose de lumière à niveau de décontamination microbienne. L'équipement pilote de la société CLARANOR a révélé des réduction logarithmiques allant jusqu'à plus de 5 unités sur des spores de B. subtilis, et de plusieurs autres espèces de bactéries sporulées, avec des fluences inférieures à 1,5 J/cm², appliquée en un seul flash La mise au point d'une méthode d'inoculation par spray à permis d'évaluer l'efficacité décontaminante de la lumière sur différentes surfaces, y compris des hydrophobes, par pulvérisation des microorganismes en couches formées d'une seule épaisseur de cellules. L'application de la technologie sur des surfaces inertes comme le polystyrène a montré une décontamination notamment sur des spores de B. subtilis, et d'A. niger, supérieures à 4 cycles logarithmiques en utilisant des fluences inférieures à 1 J/cm². L'influence des facteurs liés au système d'éclairage a montré une importance capitale des longueurs d'onde UV, mais ne permettent pas de réduire l'efficacité à la seule action de la dose UV-C. L'efficacité de la technologie a permis de réaliser une étude concernant la décontamination de sirop de sucre dans une optique d'application industrielle. Une réduction supérieure à 3 cycles logarithmiques de spores d'A. acidoterrestris dans du sirop de saccharose a été obtenue en flux continu, sur une épaisseur de 10 mm de liquide

At the BC Cancer Agency (BCCA), Vancouver Island Centre (VIC), the clinical verification of Intensity Modulated Radiation Therapy (IMRT) treatment plans involves comparing Portal Image (PI) -based three-dimensionally reconstructed (EPIDose) dose distributions to planned doses calculated using the Pencil Beam Convolution (PBC) algorithm. Discrepancies surpassing established action levels constitute failure. Since 2007, the failure rate of IMRT verification process had been increasing, reaching as high as 18.5% in 2009. A retrospective evaluation of clinical IMRT verification failures was conducted to identify causes and possible resolutions. Thirty clinical verification failures were identified. An equipment malfunction was discovered and subsequently repaired, and several failures were resolved in the process. Statistical uncertainty in measurement outcome was small in comparison to action levels and not considered significant to the production of failures. Still, over 50% of the redelivered plans were shown to consistently fail. A subgroup of consistent verification plans were compared to ion chamber point dose measurements. Relative to ion chamber measurements, EPIDose underestimated the dose while the dose calculation algorithm (PBC, Eclipse version 8.1.18) overestimated the same point dose. Comparisons of individual fields demonstrated that none were identifiably problematic; dose discrepancies were the result of minor but accumulating dose differences. Consistent verification failures were recalculated using two advanced dose calculation engines (the Anisotropic Analytical Algorithm and Monte Carlo). In general, verification metrics improved, and all failures were resolved. Three distinct indices of fluence modulation (or complexity) were shown to correlate with verification metrics. This indicated that deficiencies in both the leaf motion calculator and the PBC (Eclipse version 8.1.18) had likely contributed to the production of failures. In conclusion, clinical verification failures were resolved retrospectively by replacing faulty equipment and using more advanced methods of planned dose calculation, supporting the efficacy and continued use of PI-based three dimensional dose reconstruction for IMRT verification.