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The economic desirability of transparency in foreign-exchange policy - Insights from Japan-
No full textCe travail étudie les couts et bénéfices liés à l'accroissement de la transparence dans les politiques d'interventions des banques centrales sur le marché des changes. Il s'articule autour de quatre articles de recherche. Chaque article repose sur des méthodes économétriques récentes et une base de données originale (politique de la banque centrale japonaise de 1991 à 2004).(DOCSESG01)--FUNDP, 200
Design, synthesis and pharmacological evaluation of carbonic anhydrase VII and IX inhibitors
No full textCarbonic anhydases (CAs) are ubiquitous enzymes present in human under 15 different isozymes. Each active one catalyzes the hydration reaction of carbon dioxide into bicarbonate anion and proton. Some isozymes contribute to basic physiological processes like among other respiration and acid-base homeostasis while other isozymes are involved in pathologies such as epilepsy (CA VII) and cancer (CA IX). Convulsions observed during epileptic seizures are partly attributed to carbonic anhydrase VII which play a role in neuronal excitation phenomenon. Carbonic anhydrase IX (CA IX) is overexpressed in most cancer tissues and is absent from their normal counterparts. It can acidify the extratumoral medium leading to metastatic behavior.
To improve our knowledge on the role of these isozymes, the design of selective CA VII and IX inhibitors is of a great interest. Otherwise, such compounds can potentially be developed as antiepileptic or anticancer agents. A molecular modeling study which combines a direct (homology modelling, docking) and an indirect (pharmacophore, virtual screening) approach of drug design was conducted to create novel and selective inhibitors. In parallel, original indanesulfonamides were designed, synthesized and their inhibitory potencies against the CAs were determined. Docking studies of some derivatives allowed to rationalize the enzymatic data. Then, we evaluated the effect of some indanesulfonamides on a model of cancer cells. The study of the anticonvulsant activity was performed on an in vivo model. Finally, during this work other series of potentially CA inhibitors were also evaluated for their CA inhibitory activities and for one of them for its anticonvulsant effect.(DOCMED02)--FUNDP, 200
Quality of Feature Diagram Languages: formal Evaluation and Comparison
No full textIn software engineering, software reuse has been a popular topic since 1968. Nowadays, Software Product Line (SPL) engineering promotes systematic reuse throughout the whole software development process. Within SPL, reusability strongly depends on variability. In this context, variability modelling and management are crucial activities that crosscuts all development stages. Different techniques are used to model variability and one of them is Feature Diagrams (FDs). FD languages are a family of popular modelling languages used to model, and reason on, variability. Since the seminal proposal of a FD language, namely FODA, many extensions have been proposed to improve it. However, the pros and cons of these languages are difficult to evaluate for two main reasons: (1) most of them are informally defined and (2) no well defined criteria were used to justify the extensions made to FODA. As a consequence, variability modelling and management techniques proposed in the literature or used by practitioners may be suboptimal.
Globally, this work underlines that the current research on FDs is fragmented and provides principles to remedy this situation. A formal approach is proposed to introduce more rigour in the motivation, definition and comparison of FD languages. Thereby, examining their qualities should be more focused and productive. A formal approach guarantees unambiguity and is a prerequisite to define formal quality criteria and to produce efficient and safe tool automation. A quality analysis is necessary to avoid the proliferation of languages and constructs that are an additional source of misinterpretations and interoperability problems. The creation or selection of a FD language should be driven and motivated by rigourous criteria. Translations from one FD language to another should be defined and carefully studied to avoid interoperability problems.
The main contributions of this work are: (1) to use a quality framework to serve as a roadmap to improve the quality of FD languages, (2) to formally evaluate and compare FD language qualities according to well-defined criteria and following a clear method, (3) to formally define and motivate a new FD language that obtains the best scoring according to the quality criteria and (4) to develop tool support for this language.(DOCSC06)--FUNDP, 200
Elaboration d'une méthode théorique pour la détermination et la prédiction des couleurs de colorants carbonylés./ Elaboration of a theoretical procedure for the evaluation and prediction of the carbonyl dyes colour
No full textPour notre travail de thèse, nous avons établi une méthodologie, basée sur la DFT et sa variante dépendante du temps, qui permet l'évaluation efficace et la prédiction rapide des couleurs de différentes familles de colorants carbonylés dans différents environnements. Ainsi, nous sommes capables de fournir des valeurs théoriques très précises pour les énergies de transition des dérivés de l'anthraquinone, de la coumarine et de l'indigo ainsi que du thioindigo. Notre stratégie prend en compte aussi bien les effets de solvatation, dans le cadre d'une modélisation en continuum, que les effets du pH, sur la position de la bande d'absorption maximale du spectre UV/VIS. / The project of the Ph. D. work consists in the elaboration of a theoretical methodology able to evaluate and predict the color of organic dyes (see the List of recent publications for more details). Our methodology takes into account the solvent effects as well as the pH impact on the color of the dyes. The theoretical tools used are the Density Functional Theory (DFT, for ground-state optimization) and the Time Dependent TDDFT for excitation spectra calculations. The solvent effects are taken into account via the PCM (Polarizable continuum Model).(DOCSC02)--FUNDP, 200
Towards Interior Proximal Point Methods for Solving Equilibrium Problems
No full textThis work is devoted to study efficient numerical methods for solving nonsmooth convex equilibrium problems in the sense of Blum and Oettli. First we consider the auxiliary problem principle which is a generalization to equilibrium problems of the classical proximal point method for solving convex minimization problems. This method is based on a fixed point property. To make the algorithm implementable we introduce the concept of -approximation and we prove that the convergence of the algorithm is preserved when in the subproblems the nonsmooth convex functions are replaced by -approximations. Then we explain how to construct -approximations using the bundle concept and we report some numerical results to show the efficiency of the algorithm. In a second part, we suggest to use a barrier function method for solving the subproblems of the previous method. We obtain an interior proximal point algorithm that we apply first for solving nonsmooth convex minimization problems and then for solving equilibrium problems. In particular, two interior extragradient algorithms are studied and compared on some test problems.(DOCSC00)--FUNDP, 200
Participative Geographical Information System (PGIS) to assist cities in addressing Food Security issues through Urban and Periurban Agriculture. The case of Bacolod City, Philippines. / laboration d'un SIG participatif au service des aménageurs urbains dans le but de sélectionner des parcelles d'agriculture urbaine, pour améliorer la sécurité alimentaire des communautés pauvres locales. Le cas de Bacolod (Philippines).
No full textDans les villes du Sud, l'un des problèmes majeurs est la croissance démographique explosive, tandis que l'agriculture est essentiellement orientée vers l'exportation. Par conséquent, lorsque les villes du Sud connaissent à la fois faible croissance économique et forte croissance démographique, le marché local ne peut répondre à la demande en besoins alimentaires. Elles sont alors nourries par le Nord, par le biais de programmes de coopération. Afin d'accroître leur autonomie, elles sont à la recherche d'alternatives telles que l'agriculture urbaine et périurbaine. Actuellement, cette dernière est présentée dans la littérature comme une contribution à la sécurité alimentaire des communautés situées dans les villes à forte croissance démographique. Parmi les différents outils de développement, techniques, sociaux, économiques, qui peuvent être intégrés dans le processus de l'agriculture urbaine, la cartographie est indispensable aux aménageurs locaux. L'intégration des perspectives des communautés aux SIG traditionnels peut conduire vers des villes plus durables en étant à l'écoute des groupes cibles avec comme objectif de mieux répondre à leurs besoins. En priorité, cette thèse contribue à répondre à la question centrale suivante: «Est-ce que l'agriculture urbaine et/où périurbaine peut mieux répondre aux besoins d'une communauté grâce à un SIG Participatif (SIGP) orienté vers l'aménagement du territoire?» Ou, en d'autres mots, «Que fait-on, ou que peut-on faire pour faciliter l'intégration des perspectives des communautés et de l'agriculture urbaine dans la planification urbaine?» La pauvreté urbaine est l'un des principaux thèmes abordés par cette recherche. La réflexion-clé initiale peut se formuler comme suit: «Est-il possible de contribuer à la sécurité alimentaire des communautés pauvres, tout en répondant aux objectifs de l'aménagement du territoire d'un gouvernement? L'agriculture urbaine peut-elle aider à répondre au défi d'une croissance urbaine rapide?». Précisément, cette recherche vise à élaborer un outil SIG Participatif permettant l'intégration des perspectives des aménageurs et des communautés, outil qui peut être utilisé facilement et mis à jour par les utilisateurs eux-mêmes. Des données provenant de l'administration locale, des enquêtes sociale et économique, de la cartographie participative, de la télédétection, ainsi que de certaines entreprises privées locales sont intégrées pour produire un Plan d'aménagement participatif qui proposera différents scénarios pour un avenir durable.
Un quartier pauvre de Bacolod City (Philippines) constitue la zone pilote. Une réplication dans la ville de Cagayan de Oro (Philippines) est en outre considérée pour tester la stabilité de la méthodologie.In Southern cities, one of the major problems is explosive urban growth due to various factors while agriculture is essentially export-oriented. Therefore, when cities of the South are in low economic growth and with an endless population growth, their local market cannot meet their food supply demand. They become fed by northern economies, namely through cooperation programs. In order to increase their autonomy they are seeking for alternatives such as urban farming. Periurban farming and urban farming' are frequently proposed in the literature as an alternative method for helping communities located in cities with a high population growth. Mapping is a useful tool for local urban planners in the creation of sustainable cities. In addition to traditional GIS process, the integration of the perspective of local communities ' may lead to more sustainable cities by listening and learning from the population with the objective of better meeting their needs. The primary aim of this study is to investigate a central question: "Can Urban Agriculture and Periurban Agriculture meet the needs of a Community through a Participative GIS (PGIS) oriented Urban Planning?", or in other words, What is being done, or what should be done to facilitate the integration of the Community perspective and the Urban Agriculture into urban planning?" Urban poverty is one of the major issues addressed in this research. The key reflection can be formulated as: "Is it possible to contribute to the food security of the poor communities while meeting the Land Planning objectives of a government? Can Urban Agriculture challenge rapid urban growth?". Precisely, this research aims to elaborate a PGIS tool, integrating cities and communities' perspectives, which can be used and easily updated by urban planners. Data from Local Government Units, social and economical surveys, community mapping, remote sensing, as well as from some local private companies are integrated to produce a Community-based Land Use Plan that will formulate various scenarios for a sustainable future. It first focuses on a case study in Bacolod City, Philippines. Replication with the aim of testing the stability of the methodology, was carried out in the city of Cagayan de Oro, Philippines.(DOCSC05 ) -- FUNDP, 200
Essays in Information Management: contributions to the Modeling and Analysis of Quality in Information Systems Engineering
No full textEfficient organization requires rigorous and systematic information management, which encompasses information processing and decision making. Within the efforts in management science and informatics invested towards advancing the knowledge on, and providing assistance to decision making, this thesis focuses on the conceptualizations and techniques intended to facilitate the identification, evaluation, and selection of decisions during the earliest stages of information systems engineering, whereby the systems of interest are deployed to partly or fully automate various organizational processes, including information processing ones. The overall motivating problem that drove to, and that unites the various contributions presented in this thesis is how to better inform decision making and guide it towards decisions that will increase the quality (as evaluated both by the engineer and the stakeholders) of the information system being engineered.
Topics in two key related areas are therefore addressed. First, boundedly rational individuals cannot take engineering decisions by accounting for all information that may be, or actually is available to them. As their information processing abilities are limited and their perception biased, it is necessary to filter the available information to a manageable level, and to bring it to a format that facilitates the rigorous reasoning invested in decision making. Second, it is necessary to provide guidance on how to use the given information in decision making.
The first part of this thesis therefore focuses on conceptualizations that facilitate the identification of relevant information and its organization for subsequent analysis, all in the aim of achieving high quality of the system being engineered. In particular, Part I discusses, shows deficiencies, and accordingly revises the conceptual foundations of requirements engineering, a field of information systems engineering that focuses on the identification and analysis of requirements communicated by the stakeholders to the engineer of the system. The novelty of the suggested revision lies primarily in (i) the separation between functional and nonfunctional (i.e., quality) requirements grounded in a foundational ontology, (ii) the introduction of stakeholders' communicated attitudes as important sources of information for the evaluation of alternative requirements engineering decisions, (iii) the reformulation of the so-called ``requirements problem' -- which precisely defines when the requirements engineering effort is successfully completed -- to account for attitudes and nonfunctional requirements, and (iv) the recognition of the importance of defeasible reasoning in the search for a solution to the requirements problem. Acknowledging the importance of defeasible reasoning leads -- in Part II -- to the study of how defeasible reasoning can be incorporated into established decision making processes involved in the identification and analysis of requirements. Novelty in Part II lies mainly in (i) the use of argumentation and justification processes in the modeling and analysis of requirements, (ii) the combined use of design rationale approaches with argumentation and justification, (iii) the recognition that the clarity of arguments is variable (due to ambiguity, vagueness, synonymy, and overgenerality of information going into premises and conclusions in arguments), (iv) the definition of a number of techniques for the detection of unclear information and its clarification, and (v) the use of ``clarity' as a criterion for the discrimination among arguments. Part III shows how the conceptualizations and techniques introduced in Parts I and II are applied within and are relevant to the engineering of information systems, including those that rely on heterogenous and distributed components, as in service-oriented and agent-oriented computing.(DOCSESG01)--FUNDP, 200
Contribution à l'étude de la biocyclisation d'oxydo-2,3 polyènes vis-à-vis de l'oxydo-2,3 squalène stérolcyclase du foie de porc
No full textRésumé Dans ce travail, nous décrivons l'étude du comportement d'oxydo-2,3 polyènes, analogue de l'oxydo-2,3 squalène, modifiés au niveau de la double liaison D18-19 vis-à-vis de l'oxydo-2,3 squalène stérolcyclase du foie de porc. Ce travail a nécessité la synthèse de ces oxydo-2,3 polyènes, leur mise en réaction avec la stérolcyclase du foie de porc, la séparation et l'identification des produits de réaction et le cas échéant, leurs purifications afin d'en déterminer leurs structures. Nous avons pu préciser les limites d'acceptation et de tolérance de la cyclase du foie de porc vis-à-vis d'oxydo-2,3 polyènes modifiés. En effet, alors que l'enzyme est inerte vis-à-vis de l'oxydo-2,3 polyène comportant deux chaînes n-propyles sur le carbone C-19 (substrat retrouvé inchangé après réaction prolongée avec l'enzyme), son homologue possédant une entité alkylidène cyclohexane est biotransformé essentiellement en un dérivé tétracyclique de type lanostérol. Ainsi, l'incorporation du carbone C-19 dans une unité cyclique à six chaînons diminue l'encombrement stérique et restaure ainsi la capacité de la cyclase à transformer ce polyène. Nous avons en outre montré pour la première fois que la biocyclisation d'un oxydo-2,3 polyène en dérivé de type lanostérol n'est pas stéréospécifique à l'inverse des précédents travaux du laboratoire. En effet, l'oxydo-2,3 polyène de stéréochimie Z, possédant sur le carbone C-19 une entité éthyle et une entité n-propyle, est transformé en deux dérivés tétracycliques 20 S et 20 R dans un rapport 79/21. Les structures de ces deux composés ont été établies par une étude spectroscopique et par comparaison de leurs caractéristiques spectroscopiques avec celles d'échantillons authentiques. Ces derniers ont été synthétisés selon une stratégie impliquant la dégradation de la chaîne latérale du lanostérol suivie de la reconstruction des chaînes alkyles adéquates.Abstract In this work, we describe the study of the behaviour of several 2,3-oxidopolyenes analogs of 2,3-oxidosqualene modified at the 18-19 double bond with the 2,3-oxidosqualene sterolcyclase of pig liver. This work has required the synthesis of these 2,3-oxidopolyenes, their reaction with the sterolcyclase of pig liver, the separation and identification of the reaction products and if necessary their purifications to establish their structures. We could specify the limits of acceptance and tolerance of the pig liver's cyclase towards the modified 2,3-oxidopolyenes. Indeed, whereas the 2,3-oxidopolyene bearing two n-propyl chains on the C-19 carbon is inert to the enzyme (unchanged substrate recovered after prolonged time in the presence of the enzyme), its counterpart having an alkylidene cyclohexane moiety is mainly biotransformed in a tetracyclic lanosterol-type derivative. Thus, the incorporation of the C-19 carbon in a cyclic six-membered unit, decreases the steric demand and restores the capacity of the cyclase to transform this polyene. Moreover, we also showed for the first time that the biocyclisation of a 2,3-oxidopolyene in lanosterol-type derivative is not stereospecific. Indeed, the 2,3-oxidopolyene with the Z stereochemistry bearing on the C-19 carbon an ethyl and a n-propyl moiety is transformed into two tetracyclic derivatives (20S, 20R) in a 79/21 ratio. Their structures were established by a spectroscopic study and by comparison of their spectroscopic characteristics with those of authentic samples. The latter were synthesized according to a strategy implying the lanosterol side-chain degradation followed by the rebuilding of the adequate alkyl chains.(DOCSC02)--FUNDP, 200
Etudes du dysfonctionnement mitochondrial dans le maintien de la biogenèse mitochondriale et de la réponse à l'apoptose induite
No full textLa mitochondrie est un organite dont les fonctions dépassent largement le rôle bioénergétique. De ce fait, il apparaît de plus en plus clairement qu'un grand nombre de pathologies sont liées à un dysfonctionnement mitochondrial. Au cours de ces dernières années l'existence d'une communication moléculaire rétrograde entre la mitochondrie non fonctionnelle et le noyau a été mise en évidence dans les cellules eucaryotes de mammifères. Les voies de signalisation moléculaire menant à l'expression différentielle de gènes nucléaires en réponse à un dysfonctionnement mitochondrial sont néanmoins encore peu connues. Dans ce domaine, l'utilisation de lignées cellulaire totalement (r0) ou partiellement (r-) déplétées en ADN mitochondrial (ADNmt) s'est révélée essentielle dans l'étude de la réponse cellulaire induite par un dysfonctionnement mitochondrial.
L'objectif de ce travail était de mieux comprendre les mécanismes moléculaires impliqués dans la réponse cellulaire à un dysfonctionnement mitochondrial 1) en recherchant comment les cellules déplétées en ADNmt maintiennent un potentiel de membrane mitochondrial en étudiant les mécanismes impliqués dans le maintien de la biogenèse mitochondriale et 3) en caractérisant la sensibilité des cellules déplétées en ADNmt à l'apoptose.
Au cours de la première partie de ce travail, nous avons mis en évidence le rôle de la protéine mtCLIC dans le maintien du Dym des cellules déplétées en ADNmt. Nous avons ainsi démontré que le gène codant cette protéine est surexprimé dans les cellules présentant un dysfonctionnement mitochondrial, et que l'activité de canal à chlore pouvait rendre compte du maintien du Dym dans ces cellules.
Dans la deuxième partie de ce travail, nous avons caractérisé et comparé les populations mitochondriales des cellules parentales et déplétées en ADNmt (143B r0, ostéosarcome humain). L'activité de certains facteurs de transcription décrits pour jouer un rôle dans le processus de biogenèse mitochondriale a été recherchée ainsi que le niveau d'expression de certaines protéines marqueurs de la biogenèse mitochondriale. Le rôle de la voie calcium-CaMKIV-CREB dans le maintien de la biogenèse mitochondriale des cellules r0 a ainsi pu être mis en évidence. Nous avons également mis en évidence une diminution de l'activité d'importation de protéines chimériques matricielles dans les mitochondries des cellules déplétées en ADNmt. Cette diminution peut s'expliquer par la réduction du Dym et de la charge en ATP dans ces cellules mais n'est pas généralisable à l'ensemble des protéines mitochondriales. En effet, l'importation du cytochrome c est augmentée et celle de la sous-unité ß de la F1-ATPase est inchangée dans des cellules 143B r0.
La dernière partie de ce travail a été consacrée à la caractérisation et à la comparaison de la réponse des cellules 143B et 143B r0 à un stimulus pro-apoptotique. Après avoir clairement établi que les cellules r0 présentent une sensibilité accrue à la staurosporine, nous avons recherché les mécanismes moléculaires pouvant expliquer cette réponse différentielle. Nous proposons que la sensibilité accrue des cellules r0 peut s'expliquer par la sous-expression constitutive des protéines anti-apoptotiques Bcl-2 et Bcl-XL. De plus, nous montrons également que les mécanismes impliqués pourraient faire intervenir la cathepsine B, libérée du lysosome par un mécanisme non encore élucidé. Nous montrons également que l'activation spécifique de l'autophagie dans les cellules 143B r0 en réponse à la staurosporine pourrait également contribuer à la plus grande sensibilité à l'apoptose des cellules présentant un dysfonctionnement mitochondrial.
Les résultats obtenus au cours de ce travail ont permis d'identifier certains mécanismes d'adaptation mis en place dans des cellules de mammifères soumises à un stress énergétique chronique, et donc de mieux comprendre les implications d'un dysfonctionnement mitochondrial, une situation associée à ou responsable de nombreuses pathologies mitochondriales.Mitochondria are involved in numerous cell processes, such as ATP production, calcium homeostasis, fatty acid metabolism, heme synthesis, urea cycle, redox cell status, autophagy and apoptosis. Impairment of its bioenergetic activity is thus obviously associated with numerous pathologies. However, while various origins and symptoms have been described for mitochondrial diseases over the past 10 years, only very few retrograde signalling pathways (that could be defined as communication between impaired mitochondria and nucleus) have been identified. In addition, little is still known about the molecular mechanisms leading to differential gene expression in response to chronic or acute mitochondrial dysfunction. In that research field, the generation of cells totally (r0) or partially (r-) depleted in mtDNA has been very useful to study the response of cells to a chronic energetic stress.
The major aim of this work was to get a better understanding of the molecular mechanisms involved in the retrograde communication between impaired mitochondria and the nucleus that participate to the maintenance of 1) the mitochondrial membrane potential (Dym), 2) the mitochondrial biogenesis and 3) the apoptotic response to staurosporine, an alkaloïd that inhibits numerous kinases.
In the first part of this work, we highlighted the role of the protein mtCLIC/CLIC4 in the maintenance of the Dym in mtDNA-depleted cells. Using a "mRNA RT-PCR differential display" approach, we first identified that the gene was over-expressed in mtDNA-depleted cells. We also show that modifications of its abundance (over expresion and silencing by siRNA) were able to modify the Dym. Finally, we evidenced that mtCLIC allows the importation of chlorine into mitochondria of r-L929 (murine fibrosarcoma cells).
In the second part of this work, we characterized and compared mitochondrial populations between 143B (osteosarcoma cell line) and 143B r0 cells. We monitored the activity status of several key transcription factors known to be involved in the control of mitochondrial biogenesis and we determined the expression level of several mitochondrial proteins used as common markers of mitochondrial biogenesis. We also clearly demonstrated the role for calcium-CaMKIV-CREB pathway in the maintenance of mitochondrial biogenesis in mtDNA-depleted cells. Indeed, we show that the over-expression of cytochrome c and the higher mitochondrial NAO (Nonyl Acridine Orange) staining (two indicators for a higher abundance of mitochondrial mass) observed in mtDNA-depleted cells could be reduced in r0 cells that over-express either a dominant negative forms of CREB or CaMKIV. Moreover, we show that the importation of matrix-targeted proteins is reduced in mtDNAdepleted cells, a feature that can be explained by the lower Dym and reduced ATP content in these cells.
As several evidence were reported to link mitochondrial dysfunction and apoptosis in vivo, the last part of this work has been dedicated to the characterization of the apoptotic response of mtDNAdepleted cells to staurosporine. Indeed, the higher or lower sensitivity of mtDNA-depleted cells to apoptotic stimuli is still a debated question in the literature. We first show that r0 143B cells are hypersensitive to staurosporine-induced apoptosis, a phenomenon that could most likely be explained by the constitutive down-regulation of anti-apoptotic proteins such as Bcl-2 an Bcl-XL in r0 cells. Moreover, we show that the mechanisms of r0 cells response to staurosporine seems to be different from those triggered in parental cells. Indeed, we show that cathepsin B might play a role in staurosporine-induced mtDNA-depleted cell apoptosis, despite the activation of many caspases. Finally, we show that autopahgy is also triggered by staurosporine in r0 143B cells, an upstream event of caspase activation as 3-methyladenine (3-MA) strongly reduces caspase activation.
In conclusion, our results bring new information in the understanding of mechanisms and cell signalling activated in mammalian cells facing a chronic energetic stress, and thus bring new insights into the cellular consequences of mitochondrial impairment, a feature found in numerous mitochondrial diseases and pathologies associated with aging.(DOCSC03)--FUNDP, 200
Implementation and assessment of bi-radionuclide seeds for permanent implant prostate brachytherapy
No full textInterstitial brachytherapy using permanent seeds is a common modality for the treatment of early stage prostate cancer. It consists of inserting hundreds of radioactive seeds (size of a grain of rice) in the prostate by means of transperineal needles. In this procedure, dose delivery to healthy surrounding organs at risk (OAR) and dose homogeneity within the prostate are of prime concern. Placement errors should therefore be minimized to avoid unacceptable area underdosage or overdosage.
At present, brachytherapy seeds can be loaded with three different radionuclides: iodine-125 (125I: 28.37 keV; 59.40 days), palladium-103 (103Pd: 20.74 keV; 16.991 days), and cesium-131 (131Cs: 30.45 keV; 9.689 days). Long or short term morbidity is the main drawback of 125I and 131Cs due to their deeper penetration in the normal tissues. However, both provide a good homogeneity of the dose distribution within the prostate. By contrast, 103Pd offers a short penetration depth that reduces the dose to OAR. Nevertheless, it could result in cold spot (underdosage) where a recurrence of the cancer could appear.
A compromise had to be found between good implant uniformity and low dose to OAR. We propose therefore to study if the combination of two radionuclides inside the same seed could be a solution. Two mixtures were considered: 103Pd0.75-125I0.25 and 103Pd0.25-131Cs0.75. The subscripts denote the fractions of internal activity of each radionuclide. The work is subdivided into three steps.
First we adapt the AAPM TG-43U1 dosimetry formalism used by the physician to make multiple-radionuclides sources compatible with Treatment Planning Systems (TPS). Then the dose distributions around the bi-radionuclide seeds are determined. Second, the prescription doses for both sources are derived using the linear quadratic model for tumor cell surviving fraction. They were computed using mono-radionuclide implants as benchmarks. Finally, treatment plans and Dose-Volume Histograms parameters have been computed on real patients virtually implanted with bi-radionuclide seeds and the results were compared with the mono-radionuclide one. These parameters can then be used to evaluate the Normal Tissue Complication Probability (NTCP) of urethra, the most exposed organ at risk in prostate brachytherapy.
First, dosimetry results show that, from a pure physical point of view (i.e. without tissue reponse), the dose distributions of both mixtures lies in between that for 103Pd and 125I/131Cs. The compromise between homogeneity and reduced dose at large distance can be reached. Second, the averaged prescription doses for the Pd-I mixture are 142+15
-16Gy and 142+6
-8Gy using 103Pd and 125I as benchmarks, respectively. The values for the Pd Cs mixture are 128+13
-13Gy and 115+6
-7Gy, using 103Pd and 131Cs, respectively, as benchmarks. Finally, urethral NTCP results fall in the 19 to 23% range. However, they are affected by large uncertainties, making the comparison difficult. At present, no conclusion could be drawn about the efficiency of bi-radionuclide brachytherapy in comparison with mono-radionuclide using the available models. Permanent seed prostate brachytherapy suffers a lot from the lack of precision on radiobiological modelling parameters. A better knowledge of their values could significantly improve the predicting models and therefore lead to better treatment outcome.(DOCSC01)--FUNDP, 200