Made available in DSpace on 2015-04-22T22:00:55Z (GMT). No. of bitstreams: 1 Jose Elidelson Carvalho.pdf: 703131 bytes, checksum: e19421085c622156430085868340687b (MD5) Previous issue date: 2007-12-28 / SUFRAMA - Superintendência da Zona Franca de Manaus / The optimization of SMD electronics components assembly in printed circuit boards has been target of intensive research for it is one of the important point in production lines efficiency of the electronic industry. Among many techniques utilized for solving this kind of problem are the Genetics Algorithms also called Evolutionary Algorithms due it analogy with natural biologic evolution. Another kind of Evolutionary Algorithms called Memetics Algorithm has presented better results than Genetics Algorithms in many application fields. So this work proposes an investigation about using this algorithm for solving the SMD sequence placement problem. Many tests were done using Genetic and Memetics Algorithms on different placement sequence sets and the results showed a better performance of Memetic Algorithms related to Genetic Algorithms. So Memetics Algorithms has been showed to be an important tool on solving the problem of SMD placement sequence. / A otimização da seqüência de montagem de componentes SMD em placas de circuito impresso tem sido alvo de intensa pesquisa por ser um dos pontos fundamentais para a eficiência de linhas de produção de placas em indústrias de produtos eletrônicos. Entre as diversas técnicas utilizadas para resolver este tipo de problema estão os Algoritmos Genéticos chamados também de evolucionários por sua analogia com a evolução biológica natural das espécies. Outro tipo de algoritmo evolucionário chamado de Algoritmo Memético tem apresentado melhores resultados que os Algoritmos Genéticos em diversas áreas de pesquisa. Portanto este trabalho propõe uma investigação do uso deste algoritmo na resolução do problema da otimização da seqüência de montagem de componentes SMD. Foram feitos diversos testes usando Algoritmos Genéticos e Meméticos em diferentes seqüências de montagem e os resultados mostraram um melhor desempenho dos Algoritmos Meméticos em relação aos Genéticos. Portanto os Algoritmos Meméticos se mostraram uma promissora ferramenta para a otimização deste problema.

Non communiqué. / Non communiqué.

This research is to develop an auto optical inspection system for surface mount device light emitting diodes. The principal purpose is to inspect SMD LED for 2D defects which are mixed-material and resin-tearing and for3D defect which is tombstone. In terms with mixed-material inspection, using the count of gradient operator to recognize LED chip. The false alarm rate is 4.29% and misdetection rate is 7.19%. It successfully detects defects with accuracy up to 94.24%. The average computation time is 12.97 ms. In terms of resin-tearing inspection, the research uses the gray scale correlation for SMD LED image registration. The false alarm rate is 5.15% and misdetection rate is 11.34%. The accuracy is up to 91.75%. The average computation time is 10.95 ms. 3D defect continues to use 2D view finder. The advantage of this structure is simple and cost-saving. The investigation which is inspected by the 3D system, comparing with real situation, the average measurement deviation is 4.51%. The average computation time is 8.05 ms. This propose of this system is not only to inspect 2D quickly, precisely and steady, but also to inspect 3D flaws which is hard to detect, and make the wole detective system more artificially-intelligent.

This thesis presents an analysis of the signal-to-noise ratio in liquid core anti-resonant reflecting optical waveguides (ARROWs) and the application of hydrodynamic focusing to the waveguides. These concepts are presented as a method to improve the detection capabilities of the ARROW platform. The improvements are specifically targeted at achieving single molecule detection (SMD) with the devices. To analyze the SNR of the waveguides a test platform was designed and fabricated. This test platform was then used to examine relationship between the SNR and the location of the excitation region. It was determined that the excitation region should be moved closer to the solid-core. By moving the excitation region closer to the solid-core the distance the signal was required to travel in the hollow-core was reduced. This reduction led to a decrease in optical signal loss and resulted in a more than 2x increase in the SNR. Hydrodynamic focusing in the waveguides was developed as a method to increase the consistency of detection of the devices. In hydrodynamic focusing particles in the sample are forced towards the center of the waveguide with a buffer solution. With the particles focused to the center of the channel the percentage that passed through the excitation region can be increased improving the detection consistency of the device. ARROW chips designed for hydrodynamic focusing were simulated, fabricated, and preliminary testing was performed. Initial results have shown a more than 30% increase in particle focusing.

No description available.

<p>U okviru doktorske disertacije, realizovane su podešljive feritne komponente sa jezgrima koja su proizvedena od komercijalno dostupnih ESL 40011 feritnih traka čije se induktivnosti podešavaju primenom jednosmerne struje. Rad realizovanih podešljivih feritnih komponenti je verifikovan u kolu DC-DC konvertora podizača napona. U disertaciji je predložena merna metoda koja omogućava ispitivanje uticaja jednosmerne struje na karakteristike SMD induktora postavljenih u realnom okruženju. Metoda je verifikovana na komercijalno dostupnim SMD induktorima.</p> / <p>As part of this thesis variable ferite components with cores produced from comercialy available ESL 40011 ferite tapes manufactured in Low Temperature Co-fired Ceramic technology are implemented. Inductivity of the components is varied by applying DC current. Functionality of the implemented ferite components is verified in a circuit of DC-DC boost converter. This thesis proposes a measurement method which enables examining the influence of DC current on the characteristics of SMD inductors in real environment. The method is verified on comercialy available SMD inductors</p>

Objetivos: Avaliar o efeito da Estratégia de Saúde da Família (ESF) na atenção primária, com e sem apoio matricial (AM), na prevalência e gravidade de transtornos mentais (TM). Casuística e Métodos: O estudo foi dividido em duas fases. Na primeira fase (Fase 1), 20 estudantes de medicina foram capacitados em três encontros para aplicação do instrumento \"Mini - screening mental disorders (Mini-SMD)\" e para a coleta de dados sociodemográficos. Em seguida, eles receberam, após sorteio eletrônico, endereços residenciais aleatórios das três áreas do estudo - i.e., uma área com cobertura de saúde pela ESF com AM em Saúde Mental (SM), uma área com cobertura pela ESF sem AM e uma terceira área com cobertura pelo modelo de Unidade Básica de Saúde (UBS) tradicional. Na segunda fase (Fase 2), realizou-se um sorteio simples de 50% dos sujeitos da Fase 1 para confirmação diagnóstica e avaliação de gravidade de sintomas. Cinco profissionais de saúde com nível superior foram submetidas a treinamento de 20 horas para utilização dos instrumentos Mini International Neuropsychiatric Interview (MINI), MINI-TRACKING, Patient Health Questionnaire-9 (PHQ-9), General Anxiety Disorder-7 (GAD-7), Alcohol Use Disorders Identification Test (AUDIT) e Brief Psychiatric Rating Scale (BPRS). Essas profissionais de saúde, então, receberam os endereços e agendamentos dos pacientes para aplicação da entrevista MINI. Os pacientes com resultado positivo para algum diagnóstico no MINI foram, em seguida, submetidos à aplicação do(s) módulo(s) específico(s) do MINI-TRACKING e do PHQ-9 e/ou GAD-7 e/ou AUDIT e/ou BPRS. Resultados: Durante a Fase 1, 1.545 pessoas foram entrevistadas. As avaliações Mini-SMD positivas nas áreas de ESF sem AM, ESF com AM e UBS tradicional foram de 33,9%, 34,6% e 40,3%, respectivamente. O Odds ratio (OR) bruto dos resultados na comparação entre a ESF sem AM e UBS tradicional foi 0,76 (p=0,037). O OR foi ajustado para área, idade, escolaridade e nível socioeconômico (variáveis que apresentaram OR significativo), com resultado de 0,752 (p=0,042). A comparação entre o conjunto ESF com e sem AM versus UBS tradicional também mostrou tendência à menor número de TM nas áreas de ESF (OR Bruto=1,294; p=0,021; OR Ajustado=1,257; p=0,048). Na Fase 2 do estudo, 773 sujeitos foram aleatoriamente selecionados, e desses, 538 concordaram em participar. Nas áreas de ESF sem AM, ESF com AM e UBS tradicional, a avaliação MINI positiva se deu em 39,1%, 35,1% e 48,3%, respectivamente. O OR bruto dos resultados na comparação entre o conjunto ESF com e sem AM versus UBS tradicional foi 1,602 (p=0,012) e o OR ajustado para sexo, escolaridade e estado civil (variáveis com OR significativo) foi 1,523 (p=0,028). Na avaliação da influência da área de residência em função do tipo de cobertura de saúde sobre a gravidade dos TM diagnosticados, não foram observadas diferenças significativas. Conclusões: O presente estudo mostrou que o modelo específico de ESF avaliado (com e sem AM) associou-se significativamente com menor prevalência de TM quando comparado a uma área com assistência realizada por UBS tradicional. No tocante à gravidade de sintomas, não foram encontradas diferenças significativas entre as três áreas estudadas. / Objectives: To evaluate the impact of the Family Health Strategy (FHS) on primary care, with and without matrix support, on the prevalence and severity of mental disorders (MD). Casuistic and Methods: The study was divided into two phases. In the first phase (Phase 1) 20 medical students were trained in three meetings to apply the Mini - screening mental disorders (Mini - SMD) instrument and to collect sociodemographic data. Next, they received random home addresses from the three study areas - i.e., an area with health coverage by the FHS with Matrix Support (MS) in Mental Health (MH), an area covered by the FHS without MS and a third area covered by the traditional Basic Health Unit (BHU) model. In the second phase (Phase 2), a random sample of 50% of Phase 1 subjects was selected for diagnostic confirmation and symptom severity assessment. Five graduated health professionals underwent 20-hour training to apply the Mini International Neuropsychiatric Interview (MINI), MINI-TRACKING, Patient Health Questionnaire-9 (PHQ-9), General Anxiety Disorder-7 (GAD-7 ), Alcohol Use Disorders Identification Test (AUDIT) and Brief Psychiatric Rating Scale (BPRS). These health professionals then received the addresses and schedules of the patients for application of the MINI interview. Patients who had tested positive for a diagnosis in the MINI were then submitted to the application of the specific MINI-TRACKING module and PHQ-9 and/or GAD-7 and/or AUDIT and/or BPRS. Results: During Phase 1, a total of 1,545 people were interviewed. The Mini-SMD positive evaluations in the areas of FHS without MS, FHS with MS and traditional BHU were 33.9%, 34.6% and 40.3%, respectively. The crude Odds Ratio (OR) of the results in the comparison between FHS without MS and traditional BHU was 0.76 (p=0.037). The OR was adjusted for area, age, schooling and socioeconomic level (variables that presented significant OR), with a result of 0.752 (p=0.042). The comparison between the FHS set with and without MS versus traditional BHU also showed a trend towards a lower number of MD in the FHS areas (Gross OR=1.294, p=0.021, adjusted OR=1.257, p=0.048). In the Phase 2 of the study, 773 subjects were randomly selected, and of these, 538 agreed to participate. In the areas of FHS without MS, FHS with MS and traditional BHU, the MINI positive evaluation occurred in 39.1%, 35.1% e 48.3%, respectively. The crude OR of the results in the comparison between FHS with and without MS versus traditional BHU was 1.602 (p=0.012) and the adjusted OR for gender, schooling and marital status (variables with significant OR) was 1.523 (p=0.028). No significant differences were observed on the severity of symptoms in the evaluation of the influence of the area according to the type of health service delivered. Conclusions: The present study showed that the specific model of FHS evaluated (with and without MS) was significantly associated with a lower prevalence of MD when compared to an area with care performed by traditional BHU. Regarding severity of symptoms, no significant differences were found between the three areas studied.

Objetivos: Avaliar o efeito da Estratégia de Saúde da Família (ESF) na atenção primária, com e sem apoio matricial (AM), na prevalência e gravidade de transtornos mentais (TM). Casuística e Métodos: O estudo foi dividido em duas fases. Na primeira fase (Fase 1), 20 estudantes de medicina foram capacitados em três encontros para aplicação do instrumento \"Mini - screening mental disorders (Mini-SMD)\" e para a coleta de dados sociodemográficos. Em seguida, eles receberam, após sorteio eletrônico, endereços residenciais aleatórios das três áreas do estudo - i.e., uma área com cobertura de saúde pela ESF com AM em Saúde Mental (SM), uma área com cobertura pela ESF sem AM e uma terceira área com cobertura pelo modelo de Unidade Básica de Saúde (UBS) tradicional. Na segunda fase (Fase 2), realizou-se um sorteio simples de 50% dos sujeitos da Fase 1 para confirmação diagnóstica e avaliação de gravidade de sintomas. Cinco profissionais de saúde com nível superior foram submetidas a treinamento de 20 horas para utilização dos instrumentos Mini International Neuropsychiatric Interview (MINI), MINI-TRACKING, Patient Health Questionnaire-9 (PHQ-9), General Anxiety Disorder-7 (GAD-7), Alcohol Use Disorders Identification Test (AUDIT) e Brief Psychiatric Rating Scale (BPRS). Essas profissionais de saúde, então, receberam os endereços e agendamentos dos pacientes para aplicação da entrevista MINI. Os pacientes com resultado positivo para algum diagnóstico no MINI foram, em seguida, submetidos à aplicação do(s) módulo(s) específico(s) do MINI-TRACKING e do PHQ-9 e/ou GAD-7 e/ou AUDIT e/ou BPRS. Resultados: Durante a Fase 1, 1.545 pessoas foram entrevistadas. As avaliações Mini-SMD positivas nas áreas de ESF sem AM, ESF com AM e UBS tradicional foram de 33,9%, 34,6% e 40,3%, respectivamente. O Odds ratio (OR) bruto dos resultados na comparação entre a ESF sem AM e UBS tradicional foi 0,76 (p=0,037). O OR foi ajustado para área, idade, escolaridade e nível socioeconômico (variáveis que apresentaram OR significativo), com resultado de 0,752 (p=0,042). A comparação entre o conjunto ESF com e sem AM versus UBS tradicional também mostrou tendência à menor número de TM nas áreas de ESF (OR Bruto=1,294; p=0,021; OR Ajustado=1,257; p=0,048). Na Fase 2 do estudo, 773 sujeitos foram aleatoriamente selecionados, e desses, 538 concordaram em participar. Nas áreas de ESF sem AM, ESF com AM e UBS tradicional, a avaliação MINI positiva se deu em 39,1%, 35,1% e 48,3%, respectivamente. O OR bruto dos resultados na comparação entre o conjunto ESF com e sem AM versus UBS tradicional foi 1,602 (p=0,012) e o OR ajustado para sexo, escolaridade e estado civil (variáveis com OR significativo) foi 1,523 (p=0,028). Na avaliação da influência da área de residência em função do tipo de cobertura de saúde sobre a gravidade dos TM diagnosticados, não foram observadas diferenças significativas. Conclusões: O presente estudo mostrou que o modelo específico de ESF avaliado (com e sem AM) associou-se significativamente com menor prevalência de TM quando comparado a uma área com assistência realizada por UBS tradicional. No tocante à gravidade de sintomas, não foram encontradas diferenças significativas entre as três áreas estudadas. / Objectives: To evaluate the impact of the Family Health Strategy (FHS) on primary care, with and without matrix support, on the prevalence and severity of mental disorders (MD). Casuistic and Methods: The study was divided into two phases. In the first phase (Phase 1) 20 medical students were trained in three meetings to apply the Mini - screening mental disorders (Mini - SMD) instrument and to collect sociodemographic data. Next, they received random home addresses from the three study areas - i.e., an area with health coverage by the FHS with Matrix Support (MS) in Mental Health (MH), an area covered by the FHS without MS and a third area covered by the traditional Basic Health Unit (BHU) model. In the second phase (Phase 2), a random sample of 50% of Phase 1 subjects was selected for diagnostic confirmation and symptom severity assessment. Five graduated health professionals underwent 20-hour training to apply the Mini International Neuropsychiatric Interview (MINI), MINI-TRACKING, Patient Health Questionnaire-9 (PHQ-9), General Anxiety Disorder-7 (GAD-7 ), Alcohol Use Disorders Identification Test (AUDIT) and Brief Psychiatric Rating Scale (BPRS). These health professionals then received the addresses and schedules of the patients for application of the MINI interview. Patients who had tested positive for a diagnosis in the MINI were then submitted to the application of the specific MINI-TRACKING module and PHQ-9 and/or GAD-7 and/or AUDIT and/or BPRS. Results: During Phase 1, a total of 1,545 people were interviewed. The Mini-SMD positive evaluations in the areas of FHS without MS, FHS with MS and traditional BHU were 33.9%, 34.6% and 40.3%, respectively. The crude Odds Ratio (OR) of the results in the comparison between FHS without MS and traditional BHU was 0.76 (p=0.037). The OR was adjusted for area, age, schooling and socioeconomic level (variables that presented significant OR), with a result of 0.752 (p=0.042). The comparison between the FHS set with and without MS versus traditional BHU also showed a trend towards a lower number of MD in the FHS areas (Gross OR=1.294, p=0.021, adjusted OR=1.257, p=0.048). In the Phase 2 of the study, 773 subjects were randomly selected, and of these, 538 agreed to participate. In the areas of FHS without MS, FHS with MS and traditional BHU, the MINI positive evaluation occurred in 39.1%, 35.1% e 48.3%, respectively. The crude OR of the results in the comparison between FHS with and without MS versus traditional BHU was 1.602 (p=0.012) and the adjusted OR for gender, schooling and marital status (variables with significant OR) was 1.523 (p=0.028). No significant differences were observed on the severity of symptoms in the evaluation of the influence of the area according to the type of health service delivered. Conclusions: The present study showed that the specific model of FHS evaluated (with and without MS) was significantly associated with a lower prevalence of MD when compared to an area with care performed by traditional BHU. Regarding severity of symptoms, no significant differences were found between the three areas studied.

L’érythropoïèse est le processus aboutissant à la production des hématies à partir d’une cellule souche hématopoïétique. La différenciation érythroïde implique des changements morphologiques en partie liés à la perte d’expression membranaire du récepteur à activité tyrosine kinase de classe III, c-Kit. En réponse à son ligand, le SCF, c-Kit est activé puis internalisé et dégradé par la voie du protéasome, via l’ubiquitine E3-ligase c-Cbl, ou par la voie lysosomale suite à une endocytose. Dans la première partie de ce travail, nous avons pu mettre en évidence qu’en absence de SCF et en réponse à un inhibiteur de tyrosine kinase, l’imatinib, les érythroblastes cultivés ex vivo perdent l’expression membranaire de c-Kit et accélèrent leur entrée en différenciation terminale. Au vu de ces observations, nous avons cherché à comprendre les mécanismes impliqués. Sur un modèle de cellules érytholeucémiques dépendantes de l’érythropoïétine, mais exprimant de manière endogène c-Kit, nous avons montré que l’imatinib induit une internalisation du récepteur ainsi que sa dégradation par la voie lysosomale et de manière indépendant de c-Cbl. De plus, nous avons montré que cet effet est réversible et que l’imatinib ne bloque pas la réexpression de c-Kit après son internalisation en réponse au SCF. Des marquages métaboliques ont permis de montrer que l’imatinib ne modifie ni la synthèse ni la maturation de c-Kit et que le profil phospho-tyrosine des cellules traitées à l’imatinib est globalement inchangé. Enfin, nous avons montré que la fixation de l’imatinib à la poche catalytique de c-Kit est indispensable à son internalisation, et par conséquent à sa dégradation. Il apparait donc que l’imatinib lève l’auto-inhibition de c-Kit, qui semble nécessaire pour son maintien à la membrane. Dans la seconde partie de ce travail, nous nous sommes intéressés aux changements morphologiques subis par les nucléoles, lieu de la biogenèse des ribosomes, au cours de différenciation des érythroblastes. L’étude de la taille et du potentiel prolifératif des cellules, ainsi que l’analyse morphologique des nucléoles, nous a permis de confirmer que la réduction de taille des cellules est contemporaine d’un ralentissement de leur prolifération ainsi que de la réduction du volume et de la surface du composé granulaire (CG), « matrice » du nucléole. En microscopie électronique, nous montrons la persistance des CG en fin de maturation. Enfin, nous avons également étudié l’évolution des nucléoles dans un contexte pathologique de syndromes myélodysplasiques de faible risque, qui se caractérisent par une hématopoïèse inefficace. Nous observons que les cellules pathologiques immatures ont des CG plus volumineux que les cellules normales immatures, et qu’au cours de la différenciation, la morphologie des nucléoles est identique entre les cellules normales et pathologiques. En conclusion, ce travail a permis de décrire 1) le mécanisme d’internalisation d’un récepteur à activité tyrosine kinase de classe III, c-Kit par l’imatinib et 2) la morphologie du nucléole au cours de la différenciation érythroïde normale et pathologique des syndromes myélodysplasiques de faible risque. / Erythropoiesis is the process leading to the production of red blood cells from hematopoietic stem cell. The erythroid differentiation involves morphological cell changes, in part related to the loss of membrane expression of the type III receptor tyrosine kinase, c-Kit. In response to its ligand SCF, c-Kit is activated, then internalized and degraded by the proteasome pathway via the E3 ubiquitin ligase c-Cbl, or by the lysosomal pathway, after endocytosis. In the first part of this work, we demonstrated that in the absence of SCF and in response to tyrosine kinase inhibitor, imatinib, erythroblasts cultured ex vivo, lose membrane expression of c-Kit and accelerate their terminal differentiation. In view of these observations, we sought to understand the mechanisms involved. On an erythropoietin dependent cell line expressing c-Kit at the membrane, we showed that imatinib induces receptor internalization and degradation by the lysosomal pathway, independently of c -Cbl. Furthermore, we showed that this effect is reversible and that imatinib does not block the c-Kit re-expression after its internalization, in response to SCF. Metabolic labelling showed that imatinib does not alter synthesis or maturation of c -Kit and that the phospho-tyrosine profile of cells treated with imatinib is generally unchanged. Finally, we showed that the binding of imatinib to the catalytic pocket of c-Kit is essential for its internalization, and therefore its degradation. So, it appears that imatinib removes c-Kit self-inhibition, which seems necessary to its retention at the membrane. In the second part of this work, we studied the morphological changes of nucleoli, the site of ribosome biogenesis, during erythroid differentiation. We showed that the reduction of cell size takes place at the same time than reduction of cell proliferation and reduction of surface and volume of the Granular Compound (GC), the “matrix” of the nucleolus. Moreover, we showed by electronic microscopy, the persistence of GC at the end of maturation. Finally, we also studied the evolution of nucleoli in a pathological context of low risk myelodysplastic syndromes, which are characterized by ineffective hematopoiesis. We observed that immature pathological cells have larger GC than immature normal cells, but that during differentiation, the morphology of nucleoli is identical between normal and pathological cells. In conclusion, this work has allowed us to describe 1) the mechanisms of internalization of a class III receptor tyrosine kinase, c-Kit by imatinib and 2) the morphology of the nucleolus during normal and pathological low risk myelodysplastic syndromes of erythroid differentiation.

L'érythropoïèse est le processus permettant la production de globules rouges matures à partir de cellules souches hématopoïétiques. Ce programme de différenciation est en grande partie sous le contrôle du facteur de transcription GATA-1 qui active la transcription des gènes érythroïdes et de la protéine anti-apoptotique Bcl-xL. Au cours de l'apoptose, la caspase-3 clive GATA-1 induisant la diminution d'expression de Bcl-xL. Il a été montré que l'activation transitoire de la caspase-3 est indispensable pour la différenciation érythroïde terminale, mais GATA-1 n'est pas clivé. Dans ce travail, nous montrons qu'à la différence du proccessus apoptotique induit par la privation en Epo, au cours de la différenciation érythroïde, GATA-1 est protégé du clivage de la caspase-3 par la protéine chaperonne Hsp70. Au moment de l'activation de la capase-3, Hsp70 s'accumule dans le noyau des érythroblastes et protège GATA-1, permettant ainsi l'expression de Bcl-xL. Par contre, lors de la privation en Epo, Hsp70 est exportée du noyau et GATA-1 est clivé par la caspase-3 ce qui induit l'apoptose. D'autre part, la surexpression de GATA-1 induit un blocage de la maturation donc, l'expression de GATA-1 doit être finement régulée pour permettre une différenciation érythroïde normale. Nous avons montré qu'Hsp27 s'accumule dans le noyau des érythroblastes en cours de différenciation sous l'action de la phosphorylation de la MAPK p38. Hsp27 nucléaire interagit avec la forme acétylée de GATA-1 et induit son ubiquitinylation et sa dégradation par le protéasome. Ces résultats montrent un nouveau rôle d'Hsp70 et Hsp27 au cours de la différenciation érythroïde terminale en intervenant dans des mécanismes de régulation fine de l'expression de GATA-1. Nous avons déterminé les mécanismes par lesquels Hsp70 est accumulé dans le noyau des érythroblastes au cours de la différenciation érythroïde terminale. L'érythropoïèse est régulée positivement par deux facteurs indispensables à la prolifération et la survie des progéniteurs éythroïdes, le SCF pour les phases précoces jusqu'au stade d'érythroblaste basophile et l'Epo à partir des CFU-E jusqu'au stade d'érythroblastes. Avant la diminution d'expression de c-Kit, le récepteur au SCF, au stade d'érythroblastes basophiles, Hsp70 est principalement cytoplasmique. En effet, le SCF induit l'export nucléaire d'Hsp70 par la phosphorylation induite par AKT sur la sérine 400 résultant en une faible quantité d'Hsp70 nucléaire. Au stade de la diminution d'expression de c-Kit, l'export nucléaire induit par le SCF est diminué. D'autre part, l'Epo, en activant Lyn, induit la rétention nucléaire d'Hsp70. Nous décrivons donc un nouveau mécanisme du retard de la différenciation érythroïde par c-Kit puisque sa diminution est nécessaire pour que GATA-1 soit protégé du clivage de la caspase-3 par Hsp70 nucléaire. De plus, nous suggérons un nouveau mécanisme de Lyn dans la survie et la différenciation des érythroblastes sous Epo. Nous avons testé notre modèle au cours de syndromes myélodysplasiques (SMD) de bas grade, caractérisés par une anémie associée à un excès d'activation des caspases et de l'apoptose ainsi qu'un retard de différenciation des progéniteurs érythroïdes. Nous avons démontré qu'un défaut de localisation nucléaire d'Hsp70 est en partie responsable du phénotype observé puisque l'expression d'Hsp70 nucléaire restaure en partie le phénotype des progéniteurs érythroïdes de patients atteints de SMD. Ces résultats concordent avec notre modèle physiologique. De plus, il est envisageable que c-Kit pourrait être une nouvelle cible thérapeutique pour les patients atteints de SMD.