本研究採用同時法與歷時法二種文獻老化研究方法，進行資訊檢索領域下系統研究及使用者研究二種主題文獻之老化研究，主要研究重點有二，一是資訊檢索領域下，系統研究及使用者研究二種不同主題文獻老化現象之差異性；二是同一主題文獻下，同時法與歷時法二種不同老化研究方法之文獻衰退情形是否一致。 同時法研究是針對現時某一特定文獻之引用參考文獻進行分析，並測得其引用年齡中數。本研究自LISA資料庫取得2006年資訊檢索領域下系統研究及使用者研究二種主題之相關文獻，作為同時法研究樣本，並利用T檢定檢測系統研究及使用者研究二種主題文獻老化現象之差異。在同時法研究結果方面，系統研究及使用者研究二種主題文獻之引用年齡中數分別為7.25歲與7.98歲，系統研究主題文獻同時法老化速度快於使用者研究主題文獻，但差異不大，T檢定結果亦顯示同時法系統研究及使用者研究二種主題文獻之老化速度無顯著差異。 歷時法研究是分析過去某特定期間所發表之文獻，其逐年被引用情形，並計算其被引用半衰期。本研究利用LISA資料庫取得1996年資訊檢索領域下系統研究及使用者研究二種主題之相關文獻，作為歷時法研究樣本，並利用WOS資料庫，取得其自1996年至2006年間逐年被引用情形。在歷時法研究結果方面，系統研究及使用者研究二種主題文獻之被引用半衰期分別為5.12歲與4.99歲，系統研究主題文獻之歷時法老化速度較使用者研究主題文獻稍慢，二者差異不大，T檢定結果亦顯示歷時法系統研究及使用者研究二種主題文獻之老化速度無顯著差異。 在同時法與歷時法二種研究方法比較部份，就文獻老化速度而言，同時法之引用參考文獻數量於高峰期後，呈現顯著文獻衰退現象；而歷時法達到被引用次數最高峰後，則未呈現明顯文獻衰退現象，可知同時法文獻老化速度較歷時法文獻老化速度快。在柯史（K-S）檢測方面，檢測結果發現，不論系統研究主題文獻或使用者研究主題文獻，同時法與歷時法之文獻老化現象皆不一致。 因此，本研究重要研究結論有二：一是資訊檢索領域下，不會因主題不同而有顯著差異；二是資訊檢索領域下，同時法所測得之文獻老化現象與歷時法所測得之文獻老化現象不一致。 / This obsolescence study uses two kinds of aging research methods - synchronous approach and diachrinous approach. Analyze two subjects of systems-centered and users-centered in the information retrieval field. The main emphasis of the research is two. First, under information retrieval field, the differences between systems-centered and user-centered in obsolescence study. Second, the difference between synchronous approach and diachrinous approach’s aging phenomenon in the same subject. Synchronous approach is targeted at the present of a particular literature references and calculated median citation age. This study acquired the information retrieval field of systems-centered and user-centered’s sample in 2006 from LISA database, and tested the difference between systems-centered and user-centered literature aging with using t-test. The result of synchronous approach, median citation age of systems-centered literature is 7.25 years and median citation age of user-centered literature is 7.98 years. So systems-centered literature aging is faster than user-centered literature. But the difference is small. T test results also revealed that difference between systems-centered and user-centered of literature aging has not significantly. Diachrinous approach was to analyze a particular during the past published literature and observed the cited times each year, and finally calculated its half-life. This study acquired the information retrieval field of systems-centered and user-centered’s sample in 1996 from LISA database, and acquired the cited times each year during 1996 to 2006 from WOS database.The result of diachrinous approach, cited half-life of system-centered literatures is 5.12 and cited half-life of user-centered literatures is 4.99 years. So user-centered literature aging was faster than system-centered literatures. But the difference was small. T test results also revealed that difference between the system-centered and user-centered of literature aging has not significantly Synchronous approach and diachrinous approach methods of comparison. By the literature on the aging speed, cited reference numbers of synchronous approach reached peak period, and the literature curve showed significant recession; cited times of diachrinous approach reached a peak, and literature curve were not significantly recession. It revealed that aging speed of synchronous approach was faster than aging speed of diachrinous approach. In the K-S test, the results showed that synchronous approach and diachrinous approach were inconsistent, whether systems-centered literatures or users-centered literatures. Therefore, the important conclusion of this study are two : First, in the information retrieval field, even different subject there will be no significant differences on literature aging phenomenon; Second, under the information retrieval field, synchronous approach and diachrinous approach which measured the aging phenomenon of literature are inconsistent.

Les premières cellules progénitrices lympho-myéloïdes (LMPP) entrent dans le thymus et commencent leur processus de différenciation au stade double négatif (DN, CD4-CD8-). Après un réarrangement fonctionnel de la chaine bêta de leur récepteur des cellules T (RCT), les cellules reçoivent des signaux de différenciation, de prolifération, de survie et de sélection et passent au stade double positif (DP, CD4+CD8+). Ensuite, la chaine alpha du RCT est réarrangée et testée via les sélections positive et négative. Si le RCT reçoit un signal ni trop fort, ni trop faible, les cellules passent au stade simple positif où elles exprimeront soit la molécule CD4 ou CD8. ERK3, une MAPK non-conventionnelle, joue un rôle important dans le développement thymique. Des études précédentes ont démontré qu’une déficience en ERK3 diminue de 50 % la cellularité thymique et de 75% le nombre de cellules simples positives CD4 (CD4SP). Nous avons posé comme hypothèses qu’il y a une augmentation de l’apoptose chez les thymocytes DP de souris Erk3-/- et que cette déficience chez les thymocytes DP affecterait la sélection positive des cellules DP, réduisant ainsi le nombre de thymocytes CD4SP. Afin de vérifier la première hypothèse, nous avons regardé les niveaux d’apoptose grâce à la cytométrie en flux et par immunohistochimie. Dans les deux cas, nous étions incapables de détecter une différence du niveau d’apoptose chez les thymocytes DP entre les souris Erk3+/+ et Erk3-/-. Ensuite, nous nous sommes posés la question suivante : La demi-vie des thymocytes DP Erk3-/- était-elle plus courte que le type sauvage? La demi-vie des thymocytes DP a été mesurée à l’aide de l’étude des réarrangements secondaires de la chaine alpha du RCT par PCR semi-quantitatif et à l’aide de cultures de thymus fœtaux. En effet, ERK3 semble important pour prolonger la demi-vie des thymocytes DP. Ensuite, nous avons utilisé des marqueurs cellulaires différentiels (CD69, CD5 et RCT) pour regarder si les thymocytes DP sont capables de passer la sélection positive. En effet, il y a moins de thymocytes DP Erk3-/- qui sont CD69fort, CD5fort et RCTfort. Finalement, nous voulons savoir si les fonctions de ERK3 passent par MK5, son seul partenaire d’interaction connu à ce jour. Après la caractérisation du thymus de la souris Mk5-/-, nous observons que seulement la réduction du nombre de thymocytes CD4SP est identique à celle des thymocytes CD4SP de la souris Erk3-/-. En conclusion, ces résultats révèlent des fonctions importantes pour la molécule ERK3 lors du processus de sélection positive, le maintient de la demi-vie des thymocytes DP et lors de la régulation de développement thymique de manière MK5-dépendante et -indépendante. / Early thymic progenitor cells (ETP) enter the thymus and begin their differentiation process at the double negative (DN) stage, having no CD4 and CD8 expression. After a functional rearrangement of the beta chain of the T-cell receptor (TCR), the cells receive differentiation, proliferation, survival, and selection signals and pass to the double positive (DP) stage and acquire the expression of CD4 and CD8 molecules. Then, the TCR alpha chain is rearranged and the fully composed TCR is tested through positive and negative selection. If the TCR receives a signal that is just right (not too strong or too weak), the cells pass to the single-positive stage by acquiring either the CD4 or CD8 molecule. ERK3, an unconventional MAPK, plays an important role in thymic development. Previous studies have shown that a deficiency in ERK3 decreases by 50% the total thymic cellularity and by 75% the number of CD4 single- positive cells (CD4SP). We hypothesized that there is an increase in apoptosis in DP thymocytes of Erk3-/- mice for and that this deficiency would affect the positive selection of DP cells, resulting in a reduced number of CD4SP. To test the first hypothesis, we looked at apoptosis levels by flow cytometry and immunohistochemistry. In both cases, we were unable to detect a difference in the level of apoptosis in DP thymocytes from Erk3+/+ and Erk3-/- mice. We then made a second assumption, that the half-life of Erk3-/- DP thymocytes for was shorter, which was measured by secondary rearrangements of the RCT alpha chain by semi-quantitative PCR and cultures of fetal thymi. Indeed, ERK3 seems important to extend the half- life of DP thymocytes. Next, we used differential cell markers (CD69, CD5, and TCR) to see if the DP thymocytes are able to pass positive selection. Indeed, there are less DP thymocytes Erk3-/- that are CD69hi, CD5hi, and TCRhi. Finally, we wanted to know whether the functions of ERK3 passes through MK5, its only interacting partner known to date. After characterization of the thymus of Mk5-/- mice, we observe that only the reduction of CD4SP thymocytes is identical to that of CD4SP thymocytes of Erk3-/-mice. In conclusion, these results reveal important functions for the molecule ERK3 for maintaining the half-life of DP thymocytes, for the process of positive selection and for regulating T-cell development in a MK5-dependent and - independent manner.

La future installation SPIRAL2 du GANIL, à Caen, permettra de produire une gamme étendue de noyaux exotiques avec des intensités très importantes. Cependant, ces faisceaux ne pourront pas être directement utilisés pour réaliser certaines études de haute précision et devront d'abord être purifiés. C'est pour réaliser ce travail que des équipes du CENBG, du MPIK (Heidelberg), du CSNSM, du LPC Caen, du GANIL et de l'IPNO développent un double-piège de Penning dans le cadre du projet PIPERADE. Ce double-piège nécessitant un travail de mise en forme préalable du faisceau (diminution de l'émittance transverse et mise en paquet), le CENBG est en charge de la réalisation d'un refroidisseur-regroupeur quadripolaire radiofréquence : le GPIB. C'est ce développement qui a constitué la majeure partie de mon travail de thèse, notamment en ce qui concerne les simulations de ce refroidisseur-regroupeur dont les résultats ont permis de trouver une méthode innovante pour la mise en paquet et de valider sa conception mécanique. Nous disposons également d'une source d'ions afin de pouvoir tester le GPIB et le double-piège et il m'a fallu la remonter, la comprendre et la caractériser pour que ces tests soient ensuite possibles. Dans un second temps j'ai aussi participer à l'analyse de l'expérience E622S menée au GANIL et qui avait pour but de déterminer précisément la demi-vie de 17F. Ce travail n'a pas permis d'améliorer la précision sur la demi-vie de 17F mais nous avons cependant quelques doutes sur les 2 précédentes mesures et sur leur détermination du taux de contamination de leurs échantillons. / The future SPIRAL2 installation of GANIL, at Caen, will produce large range of exotic nuclei with very high intensities. Nevertheless, these beams could not be used directly for some high precision studies and will have to be purified first. To achieve this work, teams of CENBG, MPIK (Heidelberg), CSNSM, LPC Caen, GANIL and IPNO develop a double Penning trap in the framework of the PIPERADE project. Because this double Penning-trap needs some shaping work (reduction of transverse emittance and bunching), the CENBG team is in charge of the realisation of a radio-frequency quadrupole cooler and buncher : the GPIB. This developpement work was the main part of my PhD work, especially for the simulations of this cooler buncher whose results lead us to find a new bunching method and allowed us to approve its mechanical design. We also have an ion source to be able to test both GPIB and Penning trap and I had to reassemble it, to understand it and to characterise it before these tests could be achieved. In a second time I also took part to the analysis of the E622S experiment which aimed to determined precisely the 17F half-life. This work did not lead to a more precise determination of this half-life but we now have some doubts concerning the 2 last measurements and their way to determine the contamination rate of their radioactive samples.

Le développement d’un médicament est non seulement complexe mais les retours sur investissment ne sont pas toujours ceux voulus ou anticipés. Plusieurs médicaments échouent encore en Phase III même avec les progrès technologiques réalisés au niveau de plusieurs aspects du développement du médicament. Ceci se traduit en un nombre décroissant de médicaments qui sont commercialisés. Il faut donc améliorer le processus traditionnel de développement des médicaments afin de faciliter la disponibilité de nouveaux produits aux patients qui en ont besoin. Le but de cette recherche était d’explorer et de proposer des changements au processus de développement du médicament en utilisant les principes de la modélisation avancée et des simulations d’essais cliniques. Dans le premier volet de cette recherche, de nouveaux algorithmes disponibles dans le logiciel ADAPT 5® ont été comparés avec d’autres algorithmes déjà disponibles afin de déterminer leurs avantages et leurs faiblesses. Les deux nouveaux algorithmes vérifiés sont l’itératif à deux étapes (ITS) et le maximum de vraisemblance avec maximisation de l’espérance (MLEM). Les résultats de nos recherche ont démontré que MLEM était supérieur à ITS. La méthode MLEM était comparable à l’algorithme d’estimation conditionnelle de premier ordre (FOCE) disponible dans le logiciel NONMEM® avec moins de problèmes de rétrécissement pour les estimés de variances. Donc, ces nouveaux algorithmes ont été utilisés pour la recherche présentée dans cette thèse. Durant le processus de développement d’un médicament, afin que les paramètres pharmacocinétiques calculés de façon noncompartimentale soient adéquats, il faut que la demi-vie terminale soit bien établie. Des études pharmacocinétiques bien conçues et bien analysées sont essentielles durant le développement des médicaments surtout pour les soumissions de produits génériques et supergénériques (une formulation dont l'ingrédient actif est le même que celui du médicament de marque, mais dont le profil de libération du médicament est différent de celui-ci) car elles sont souvent les seules études essentielles nécessaires afin de décider si un produit peut être commercialisé ou non. Donc, le deuxième volet de la recherche visait à évaluer si les paramètres calculer d’une demi-vie obtenue à partir d'une durée d'échantillonnage réputée trop courte pour un individu pouvaient avoir une incidence sur les conclusions d’une étude de bioéquivalence et s’ils devaient être soustraits d’analyses statistiques. Les résultats ont démontré que les paramètres calculer d’une demi-vie obtenue à partir d'une durée d'échantillonnage réputée trop courte influençaient de façon négative les résultats si ceux-ci étaient maintenus dans l’analyse de variance. Donc, le paramètre de surface sous la courbe à l’infini pour ces sujets devrait être enlevé de l’analyse statistique et des directives à cet effet sont nécessaires a priori. Les études finales de pharmacocinétique nécessaires dans le cadre du développement d’un médicament devraient donc suivre cette recommandation afin que les bonnes décisions soient prises sur un produit. Ces informations ont été utilisées dans le cadre des simulations d’essais cliniques qui ont été réalisées durant la recherche présentée dans cette thèse afin de s’assurer d’obtenir les conclusions les plus probables. Dans le dernier volet de cette thèse, des simulations d’essais cliniques ont amélioré le processus du développement clinique d’un médicament. Les résultats d’une étude clinique pilote pour un supergénérique en voie de développement semblaient très encourageants. Cependant, certaines questions ont été soulevées par rapport aux résultats et il fallait déterminer si le produit test et référence seraient équivalents lors des études finales entreprises à jeun et en mangeant, et ce, après une dose unique et des doses répétées. Des simulations d’essais cliniques ont été entreprises pour résoudre certaines questions soulevées par l’étude pilote et ces simulations suggéraient que la nouvelle formulation ne rencontrerait pas les critères d’équivalence lors des études finales. Ces simulations ont aussi aidé à déterminer quelles modifications à la nouvelle formulation étaient nécessaires afin d’améliorer les chances de rencontrer les critères d’équivalence. Cette recherche a apporté des solutions afin d’améliorer différents aspects du processus du développement d’un médicament. Particulièrement, les simulations d’essais cliniques ont réduit le nombre d’études nécessaires pour le développement du supergénérique, le nombre de sujets exposés inutilement au médicament, et les coûts de développement. Enfin, elles nous ont permis d’établir de nouveaux critères d’exclusion pour des analyses statistiques de bioéquivalence. La recherche présentée dans cette thèse est de suggérer des améliorations au processus du développement d’un médicament en évaluant de nouveaux algorithmes pour des analyses compartimentales, en établissant des critères d’exclusion de paramètres pharmacocinétiques (PK) pour certaines analyses et en démontrant comment les simulations d’essais cliniques sont utiles. / Drug development is complex with results often differing from those anticipated or sought after. Despite technological advances in the many fields which are a part of drug development, there are still many drugs that fail in the late stages of clinical development. Indeed, the success rate of drugs reaching commercialization is declining. Improvements to the conventional drug process are therefore required in order to facilitate development and allow new medications to be provided more rapidly to patients who require them. The aim of this Ph.D. project was to explore and propose ways to improve this inefficient drug development process with the use of advanced modeling and clinical trial simulations. For the first part of this research, new algorithms available in ADAPT 5® were tested against other available algorithms in order to determine their potential strengths and weaknesses. The two new algorithms tested were the iterative two-stage and the maximum likelihood expectation maximization (MLEM) methods. Our results demonstrated that the MLEM algorithm was consistently better than the iterative two-stage algorithm. It was also comparable with the first order conditional estimate method available in NONMEM®, with significantly fewer shrinkage issues in the estimation of the variances. Therefore, these new tools were used for the clinical trial simulations performed during the course of this Ph.D. research. In order to calculate appropriate noncompartmental pharmacokinetic parameter estimates during the drug development process, it is essential that the terminal elimination half-life be well characterized. Properly conducted and analyzed pharmacokinetic studies are essential to any drug development plan, and even more so for generic and supergeneric (a formulation similar to the reference product, containing the same active ingredient; however differing from the original reference product it its delivery process) submission where they often are the only pivotal studies that need to be done to decide if a drug product is good or not. Thus, the purpose of the second part of the research was to determine if the pharmacokinetic (PK) parameters obtained from a subject whose half-life is calculated from a sampling scheme duration that is considered too short could bias the bioequivalence conclusions of a study and if these parameters should be removed from statistical analyses. Results demonstrated that subjects with a long half-life relative to the duration of the sampling scheme negatively influenced results when these were maintained in the analysis of variance. Therefore, these subjects should be removed from the analyses and guidelines to this effect are required a priori. Pivotal pharmacokinetic studies done within the drug development process should therefore follow this recommendation to make sure that the right decision be taken on a drug product formulation. This information was utilized with the clinical trial simulations that were subsequently performed in this research in order to ensure the most accurate conclusions. Finally, clinical trial simulations were used to improve the development process of a nonsteroidal anti-inflammatory drug. A supergeneric was being developed and results from a pilot study were promising. However, some results from the pilot study required closer attention to determine if the test and reference compounds were indeed equivalent and if the test compound would meet the equivalence criteria of the different required pivotal studies. Clinical trial simulations were therefore undertaken to address the multiple questions left unanswered by the pilot study and these suggested that the test compound would probably not meet the equivalence criteria. In addition, these results helped determine what modifications to the test drug would be required to meet the equivalence criteria. This research brought forward solutions to improve different aspects of the drug development process. Notably, clinical trial simulations reduced the number of studies that would have been done for a supergeneric, decreased the number of subjects unnecessarily exposed to a drug, lowered costs and helped established new criteria for the exclusion of subjects from analyses. Research conducted during this Ph.D. provided concrete ways to improve the drug development process by evaluating some newly available tools for compartmental analyses, setting standards stipulating which estimated PK parameters should be excluded from certain PK analyses and illustrating how clinical trial simulations are useful to throughout the process.

Les premières cellules progénitrices lympho-myéloïdes (LMPP) entrent dans le thymus et commencent leur processus de différenciation au stade double négatif (DN, CD4-CD8-). Après un réarrangement fonctionnel de la chaine bêta de leur récepteur des cellules T (RCT), les cellules reçoivent des signaux de différenciation, de prolifération, de survie et de sélection et passent au stade double positif (DP, CD4+CD8+). Ensuite, la chaine alpha du RCT est réarrangée et testée via les sélections positive et négative. Si le RCT reçoit un signal ni trop fort, ni trop faible, les cellules passent au stade simple positif où elles exprimeront soit la molécule CD4 ou CD8. ERK3, une MAPK non-conventionnelle, joue un rôle important dans le développement thymique. Des études précédentes ont démontré qu’une déficience en ERK3 diminue de 50 % la cellularité thymique et de 75% le nombre de cellules simples positives CD4 (CD4SP). Nous avons posé comme hypothèses qu’il y a une augmentation de l’apoptose chez les thymocytes DP de souris Erk3-/- et que cette déficience chez les thymocytes DP affecterait la sélection positive des cellules DP, réduisant ainsi le nombre de thymocytes CD4SP. Afin de vérifier la première hypothèse, nous avons regardé les niveaux d’apoptose grâce à la cytométrie en flux et par immunohistochimie. Dans les deux cas, nous étions incapables de détecter une différence du niveau d’apoptose chez les thymocytes DP entre les souris Erk3+/+ et Erk3-/-. Ensuite, nous nous sommes posés la question suivante : La demi-vie des thymocytes DP Erk3-/- était-elle plus courte que le type sauvage? La demi-vie des thymocytes DP a été mesurée à l’aide de l’étude des réarrangements secondaires de la chaine alpha du RCT par PCR semi-quantitatif et à l’aide de cultures de thymus fœtaux. En effet, ERK3 semble important pour prolonger la demi-vie des thymocytes DP. Ensuite, nous avons utilisé des marqueurs cellulaires différentiels (CD69, CD5 et RCT) pour regarder si les thymocytes DP sont capables de passer la sélection positive. En effet, il y a moins de thymocytes DP Erk3-/- qui sont CD69fort, CD5fort et RCTfort. Finalement, nous voulons savoir si les fonctions de ERK3 passent par MK5, son seul partenaire d’interaction connu à ce jour. Après la caractérisation du thymus de la souris Mk5-/-, nous observons que seulement la réduction du nombre de thymocytes CD4SP est identique à celle des thymocytes CD4SP de la souris Erk3-/-. En conclusion, ces résultats révèlent des fonctions importantes pour la molécule ERK3 lors du processus de sélection positive, le maintient de la demi-vie des thymocytes DP et lors de la régulation de développement thymique de manière MK5-dépendante et -indépendante. / Early thymic progenitor cells (ETP) enter the thymus and begin their differentiation process at the double negative (DN) stage, having no CD4 and CD8 expression. After a functional rearrangement of the beta chain of the T-cell receptor (TCR), the cells receive differentiation, proliferation, survival, and selection signals and pass to the double positive (DP) stage and acquire the expression of CD4 and CD8 molecules. Then, the TCR alpha chain is rearranged and the fully composed TCR is tested through positive and negative selection. If the TCR receives a signal that is just right (not too strong or too weak), the cells pass to the single-positive stage by acquiring either the CD4 or CD8 molecule. ERK3, an unconventional MAPK, plays an important role in thymic development. Previous studies have shown that a deficiency in ERK3 decreases by 50% the total thymic cellularity and by 75% the number of CD4 single- positive cells (CD4SP). We hypothesized that there is an increase in apoptosis in DP thymocytes of Erk3-/- mice for and that this deficiency would affect the positive selection of DP cells, resulting in a reduced number of CD4SP. To test the first hypothesis, we looked at apoptosis levels by flow cytometry and immunohistochemistry. In both cases, we were unable to detect a difference in the level of apoptosis in DP thymocytes from Erk3+/+ and Erk3-/- mice. We then made a second assumption, that the half-life of Erk3-/- DP thymocytes for was shorter, which was measured by secondary rearrangements of the RCT alpha chain by semi-quantitative PCR and cultures of fetal thymi. Indeed, ERK3 seems important to extend the half- life of DP thymocytes. Next, we used differential cell markers (CD69, CD5, and TCR) to see if the DP thymocytes are able to pass positive selection. Indeed, there are less DP thymocytes Erk3-/- that are CD69hi, CD5hi, and TCRhi. Finally, we wanted to know whether the functions of ERK3 passes through MK5, its only interacting partner known to date. After characterization of the thymus of Mk5-/- mice, we observe that only the reduction of CD4SP thymocytes is identical to that of CD4SP thymocytes of Erk3-/-mice. In conclusion, these results reveal important functions for the molecule ERK3 for maintaining the half-life of DP thymocytes, for the process of positive selection and for regulating T-cell development in a MK5-dependent and - independent manner.

Made available in DSpace on 2016-08-12T19:18:30Z (GMT). No. of bitstreams: 1 MarcioGOS_TESE.pdf: 1110735 bytes, checksum: 819b218fddaa10cbb78767938fb399c0 (MD5) Previous issue date: 2015-02-26 / Conselho Nacional de Desenvolvimento Científico e Tecnológico / This study aimed to assess the productivity, the cost of production and fruit quality of yellow melon culture with different species of plants for green manure, built or maintained on the ground in conventional and no-till systems, respectively. The test was conducted at Agrícola Famosa, municipality of Tibau/RN, in a split-plot, distributed in a randomized block design with four replications. The main plots received two tillage systems (direct and conventional) and the subplots received twelve combinations of plants for green manure (Crotalaria; Millet; Sunnhemp + millet, more braquiaria Corn, spontaneous vegetation + compound more polyethylene film, Solo maintained without vegetation ; spontaneous vegetation; Guandu; Guandu + millet; Pork Beans, Beans pig-+ millet and soil without removing the cover (natural vegetation) + corn + Braquiaria + polyethylene film), incorporated (conventional tillage) or maintained on the soil (tillage). In each subplot, the dry weight of biomass yield was evaluated, using a framework of 0.25 m². In the first stage of the experiment, using the data obtained from melon, we determined the number of fruits per plant; average fruit weight and total and commercial productivity for export, besides the remaining dry mass of plant ground covers (straw). In the second stage, we evaluated the quality characteristics of fruits of melon (number of fruits per plant, average mass of fruits, longitudinal and transverse lengths, pulp thickness, firmness, pH, soluble solids (SS), acidity total (AT) and soluble / total acidity solid ratio (SS/TA) and total sugars) cultivated with different incorporated green manures or maintained on the ground in conventional tillage systems and direct, respectively. In the third step, we assessed the cost of production of yellow melon in each combination of plants to incorporated green manure or maintained on the ground, in conventional and no-till systems. The cost for cultural practice were estimated from the technical coefficients (inputs and operations) recorded in the experiment and extrapolated to one hectare. We considered economically viable those cultural practices which obtained a favorable benefit/cost to 1.0. It was found that the highest production of dry straw was obtained in treatments with more braquiaria followed corn millet consortium + Crotalaria and the single millet, which also showed low rate of decomposition. There was no variation between green manures incorporated on the production of melons. The no-tillage system produced higher number of fruits per plant, however smaller. The conventional tillage system presented higher yield compared to tillage. In the second trial, it was found that no-till system kept most of the qualitative characteristics of melon fruit in comparison to conventional tillage and no variation between most of the qualitative characteristics of melon fruit recommended for the green manure. With regard to production costs, treatments at the till system showed lower cost compared to conventional tillage due to the cost of polyethylene film and plowing and harrowing operations and placing the film on conventional tillage. All cultural practices in both tillage systems were considered economically viable, because they have a favorable benefit/cost of more than 1.0. However, the treatments with the production of corn for the production of green ears, intercropped with Braquiaria, stood out the best benefit / cost ratio due to the increase of revenue from the sale of green ears, in both tillage systems. The best benefit/cost ratio was observed in the treatments with conventional tillage due to the lower productivity of melon at the till / O presente trabalho teve o objetivo de avaliar a produtividade, o custo de produção e a qualidade dos frutos da cultura do melão amarelo com diferentes espécies de plantas destinadas à adubação verde, incorporadas ou mantidas sobre o solo nos sistemas de plantio convencional e direto, respectivamente. O ensaio foi conduzido na Fazenda Agrícola Famosa, município de Tibau/RN, no esquema de parcelas subdivididas, distribuídas no delineamento experimental em blocos casualizados, com quatro repetições. Nas parcelas, foram avaliados dois sistemas de plantio (direto e convencional) e nas subparcelas, doze combinações de plantas para adubação verde (Crotalária; Milheto; Crotalária + milheto; Milho mais braquiária; Vegetação espontânea + composto mais filme de polietileno; Solo mantido sem vegetação; Vegetação espontânea; Guandu; Guandu + milheto; Feijão de porco; Feijão-de-porco + milheto e Solo sem retirar a cobertura (vegetação natural) + milho + braquiária + filme de polietileno), incorporadas (plantio convencional) ou mantidas sobre o solo (plantio direto). Em cada subparcela, foi avaliado o rendimento de massa seca da parte aérea, utilizando-se um quadro de 0,25 m². Na primeira etapa do experimento, a partir dos dados obtidos com o melão, determinou-se o número de frutos por planta; peso médio de frutos e produtividade total e comercial para exportação, além da massa seca remanescente das plantas de coberturas do solo (palhada). Na segunda etapa, avaliaram-se as características qualitativas dos frutos de melão (número de frutos por planta, massa media dos frutos, comprimentos longitudinal e transversal; espessura de polpa; firmeza da polpa, pH, teor de sólidos solúveis (SS), acidez total (AT) e relação sólidos solúveis/acidez total (SS/AT) e açúcares totais) cultivado com diferentes adubos verdes incorporados ou mantidos sobre o solo nos sistemas de plantio convencional e direto, respectivamente. Na terceira etapa, avaliou-se o custo de produção do melão amarelo em cada combinação de plantas para adubação verde incorporadas ou mantidas sobre o solo, nos sistemas de plantio convencional e direto. Os custos por prática cultural foram estimados a partir dos coeficientes técnicos (insumos e operações) registrados no experimento e extrapolados para um hectare. Foram consideradas como viáveis economicamente aquelas práticas culturais que obtiveram relação benefício/custo superior a 1,0. Verificou-se que a maior produção de matéria seca de palhada foi obtida nos tratamentos com milho mais braquiária seguidos do consórcio milheto + crotalária e o milheto solteiro, que também apresentaram menor taxa de decomposição. Não houve variação entre os adubos verdes incorporados sobre a produção de melão. O sistema de plantio direto produziu maior número de frutos por planta, porém de menor tamanho. O sistema de plantio convencional apresentou maior produtividade em relação ao plantio direto. No segundo ensaio, verificou-se que o sistema de plantio direto manteve a maioria das características qualitativas dos frutos de melão em relação ao plantio convencional e não houve variação entre a maioria das características qualitativas dos frutos de melão para os adubos verdes avaliados. Com relação aos custos de produção, os tratamentos no sistema de plantio direto apresentaram menor custo em relação ao plantio convencional, em decorrência do custo do filme de polietileno e das operações de aração e gradagem e colocação do filme de polietileno no plantio convencional. Todas as práticas culturais nos dois sistemas de plantio foram consideradas viáveis economicamente, por apresentarem uma relação benefício/custo superior a 1,0, porém os tratamentos com a produção de milho, destinado à produção de espigas verdes, consorciado com braquiária, se destacaram pela melhor relação benefício/custo, em função do incremento da receita com a comercialização das espigas verdes, nos dois sistemas de plantio. A melhor relação benefício/custo foi verificada nos tratamentos com plantio convencional em razão da menor produtividade do melão no plantio direto

Submitted by Vagner Enrico Castilho Alves (vagneralves@gmail.com) on 2014-08-26T17:29:47Z No. of bitstreams: 1 MPFE_Dissertacao_Vagner Enrico Castilho Alves_VF.pdf: 1506529 bytes, checksum: 5f1fd3e54f60edb8c87d8542948d2b57 (MD5) / Approved for entry into archive by JOANA MARTORINI (joana.martorini@fgv.br) on 2014-08-26T18:38:27Z (GMT) No. of bitstreams: 1 MPFE_Dissertacao_Vagner Enrico Castilho Alves_VF.pdf: 1506529 bytes, checksum: 5f1fd3e54f60edb8c87d8542948d2b57 (MD5) / Made available in DSpace on 2014-08-26T18:40:31Z (GMT). No. of bitstreams: 1 MPFE_Dissertacao_Vagner Enrico Castilho Alves_VF.pdf: 1506529 bytes, checksum: 5f1fd3e54f60edb8c87d8542948d2b57 (MD5) Previous issue date: 2014-08-08 / Este trabalho procurar analisar a validade da Paridade do Poder de Compra entre regiões metropolitanas do Brasil através do Índice de Preços do Consumidor Amplo (IPCA). Para isso foram realizados testes de raiz unitária para modelos lineares e não lineares, sobre cinco grupos do IPCA: Índice Geral, Administrados, Bens Comercializáveis, Bens Não Comercializáveis e Alimentos no Domicílio. O banco de dados utilizado compreende o período de 1991 a 2013 e os testes foram realizados sobre 550 séries, comparando-se todos os pares possíveis de regiões. Sob o modelo linear, não foi possível validar a PPC para a maioria das séries através do teste de raiz unitária DF-GLS, o que é diferente do esperado, uma vez que a análise intranacional elimina os efeitos da taxa de câmbio e reduz a influência dos custos de transações sobre as condições de arbitragem. Já o resultado do modelo não linear, realizado através do teste de Kapetanios, confirmou a estacionariedade de 203 séries, de tal forma que podemos afirmar que a PPC é válida para praticamente todos os pares possíveis de regiões metropolitanas abrangidas pelo IPCA nos cinco grupos estudados. Além disso, é possível observar que as séries apresentam maiores desvios entre os anos de 1991 e 1994, período marcado por grande instabilidade macroeconômica no Brasil e de sucessivos planos econômicos que não funcionaram. Após o início do plano real, em 1994, a relação da variação de preços entre regiões apresenta menor volatilidade e uma convergência mais rápida. / This paper analyses the validity of Purchasing Power Parity (PPP) between metropolitan regions of Brazil through the Consumer Price Index (IPCA). For this, we conducted unit root tests for linear and nonlinear models, on five groups of the IPCA: General Index, Regulated Prices, Tradable Goods, Non Tradable Goods and Food at Home. The database covers the period of 1991-2013 and the tests were conducted on 550 series, comparing all possible pairs of regions. On the linear model, it was not possible to validate the PPP for most of the series through the DF-GLS unit root test, which was not expected since the intra-national analysis should eliminate the effects of exchange rate and reduce the influence of transaction costs on arbitrage conditions. However, the result of the linear model, done through the Kapetanios test, confirmed the stationarity of 203 series, such that is possible to validate the PPP for almost all pairs of metropolitan areas covered by the IPCA in the five studied groups. Moreover, one can observe that the series have large deviations between the years of 1991 and 1994, a period marked by great macroeconomic instability in Brazil and successive economic plans that have not worked. After the beginning of the Real Plan in 1994, the ratio of the change in prices between regions stabilizes, presenting a low volatility and a short term convergence.

Submitted by Oscar Simoes (oscar.simoes@citi.com) on 2011-09-06T20:01:02Z No. of bitstreams: 1 Dissertação Oscar Simoes FINAL.pdf: 585897 bytes, checksum: 7cd8393ba1823e9dcfc4bde821b40736 (MD5) / Approved for entry into archive by Gisele Isaura Hannickel (gisele.hannickel@fgv.br) on 2011-09-08T12:46:40Z (GMT) No. of bitstreams: 1 Dissertação Oscar Simoes FINAL.pdf: 585897 bytes, checksum: 7cd8393ba1823e9dcfc4bde821b40736 (MD5) / Approved for entry into archive by Gisele Isaura Hannickel (gisele.hannickel@fgv.br) on 2011-09-08T12:48:10Z (GMT) No. of bitstreams: 1 Dissertação Oscar Simoes FINAL.pdf: 585897 bytes, checksum: 7cd8393ba1823e9dcfc4bde821b40736 (MD5) / Made available in DSpace on 2011-09-08T12:48:49Z (GMT). No. of bitstreams: 1 Dissertação Oscar Simoes FINAL.pdf: 585897 bytes, checksum: 7cd8393ba1823e9dcfc4bde821b40736 (MD5) Previous issue date: 2011-08-12 / Este trabalho tem três objetivos básicos, tendo como base um banco de dados de taxas reais de câmbio entre Brasil e 21 parceiros comerciais no período de 1957 a 2010. O primeiro objetivo é o de verificar a validade da Paridade do Poder de Compra entre Brasil e seus parceiros comerciais através de três testes de raiz unitária (ADF, PP, KPSS). Para a maioria dos países, os testes de raiz unitária foram inconclusivos ou não rejeitaram raiz unitária quando foram utilizados dados mensais e modelos lineares. Já para dados de periodicidade anual, houve maior aceitação de estacionariedade, além de um número menor de resultados inconclusivos. O segundo objetivo é o de investigar a hipótese em Taylor (2001) de que a meia-vida é superestimada quando a amostra é formada a partir de um processo de agregação temporal pela média. Os resultados confirmam as conclusões de Taylor e superestimam a meia-vida em uma janela de 35% a 56% do que seria a meia-vida calculada a partir de dados de final de período. O terceiro objetivo do trabalho é o de verificar se a taxa real de câmbio possui uma reversão não-linear à média. Considerando dados mensais, foi verificado que na maioria dos testes rejeita-se a hipótese nula de raiz unitária contra a hipótese alternativa de globalmente estacionária, porém não-linear. / This dissertation has three main objectives and is based on real exchange rates between Brazil and 21 commercial counterparties for the period of 1957-2010. The first objective is to verify the validity of the Purchasing Power Parity through 3 different linear unit root tests (ADF, PP, and KPSS). For the majority of the cases, null hypotheses of unit roots could not be rejected or were inconclusive for monthly end-of-period data and linear models. For yearly end-ofperiod data, results were more inclined to accepting stationarity, and the number of inconclusive results was reduced. The second objective is to investigate Taylor’s (2001) conclusion that temporal aggregation overestimates the half-lives of the real exchange rates. Under the tests done, Taylor’s points are confirmed, and half-lives are overestimated by a range of 35% to 56% when aggregated temporally by its means and when compared with endof-period half-lives. The third objective is to verify if real exchange rates have non-linear mean-reversion. Considering monthly data, the majority of the tests confirm non-linearity and global stationarity against the unit root hypothesis

Made available in DSpace on 2014-10-09T12:36:04Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T13:59:49Z (GMT). No. of bitstreams: 0 / Dissertação (Mestrado) / IPEN/D / Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP

No description available.