Gliomas are the most common form of primary intracranial malignancy, among which astrocytomas are the most frequent. Ectodermal-cortex protein 1 (ENC 1), also known as Nuclear Restricted Protein/Brain (NRP/B), was first characterized as a protein which interacts with the cytoskeleton by binding to actin through Kelch-like domains, being related to neural fate specification during development of the nervous system. The first chapter of this thesis confirms ENC1 as a tumor suppression properties by a genomic edition approach, analyses ENC1 expression in a set of patient glioma samples and describes the correlation these data with patients survival and progression-free survival, concluding that ENC1 expression may constitute a biomarker for glioma aggressiveness. The second chapter refers to the identification and in vitro characterization of the LHTNELQ peptide, which was selected by the Phage Display method using human glioblastoma cells. This new peptide is able to be internalized by these cells and features as a new tool for the development of glioma therapeutics. The third chapter report an alternative method to generate growth curves of adherent cell cultures, which is based on the CFSE fluorescence decay over time. It is an alternative method to determine growth curves of cultured cells, with smaller variation among technical replicates than that of counting-based methods. / Gliomas são a forma mais comum de malignidades primárias intracranianas, dentre os quais os astrocitomas são os mais frequentes. A proteína Ectodermal-neural cortex 1 (ENC1), também conhecida como Nuclear Restricted Protein/Brain (NRP/B), foi primeiramente caracterizada como uma proteína que interage com o citoesqueleto por meio de ligação à actina através de domínios Kelch-like, sendo relacionada com diferenciação neuronal durante o desenvolvimento do sistema nervoso. O primeiro capítulo desta tese descreve confirmação da capacidade supressora tumoral de ENC1 por abordagem de edição genômica, analisa a expressão de ENC1 em um conjunto de amostras de pacientes com gliomas e correlaciona esses dados com tempo de sobrevida geral e sobrevida livre de progressão tumoral nos pacientes, concluindo que a expressão de ENC1 pode ser utilizada como um biomarcador da agressividade do glioma. O segundo capítulo apresenta a identificação e caracterização in vitro do peptídeo LHTNELQ, que foi selecionado pela metodologia de Phage display utilizandose de células de glioblastoma humano. Este novo peptídeo é capaz de internalizar-se nestas células e figura como uma nova ferramenta para o desenvolvimento de estratégias terapêuticas para glioblastomas. No terceiro capítulo propõe-se um método alternativo para gerar curvas de crescimento celular de cultura aderente, o qual é baseado no decaimento da fluorescência do reagente CFSE ao longo do tempo. Tratase de um método alternativo para a determinação de curvas de crescimento de culturas aderentes, com menor variação entre as réplicas técnicas do que os métodos baseados em contagem das células.

O desenvolvimento do câncer cervical depende da exposição ao HPV, fator necessário, mas não suficiente. Outras bactérias, tais como ureaplasmas, têm sido associadas como cofatores. O objetivo deste estudo foi avaliar a presença de ureaplasmas em mulheres com lesão cervical, e observar alterações em PHK causadas pela infecção por ureaplasmas. 140 swabs vaginais foram coletados. O material foi submetido a PCR para a detecção de HPV, Mollicutes, U. urealyticum, U. parvum e seus sorotipos, e outras bactérias de importância ginecológica; e qPCR para U. urealyticum e U. parvum. Também foi realizada a infecção de ureaplasmas em PHK transformados com HPV. As células foram contadas e realizou-se a dosagem das citocinas IL1-β, IL-6 e TNF-α. HPV, Mollicutes, U. parvum, sorotipos 1 e 6 de U. parvum, T. vaginalis e G. vaginalis, além de alguns fatores socioeconômicos, foram associados com lesão cervical. Verificou-se maior carga de U. parvum entre mulheres com lesão. Houve diminuição do número de células e maior liberação de IL-6 e TNF-α nos grupos infectados. Com os resultados obtidos neste estudo, foi possível verificar uma associação entre os ureaplasmas e HPV no início das lesões cervicais, contudo mais estudos precisam ser realizados para aprimorar essa hipótese. / The development of cervical cancer depends on the exposure to HPV, necessary factor, but not enough. Other bacteria, such as ureaplasmas, have been associated as cofactors. The aim of this study was to evaluate the presence of ureaplasmas in women with cervical injury, and observe changes in PHK infected by ureaplasmas. 140 vaginal swabs were collected. The material was subjected to PCR for detection of HPV, Mollicutes, Ureaplasma urealyticum, U. parvum (and serotypes) and other bacteria gynecological importance; qPCR for U. urealyticum and U. parvum was made. PHK transformed by HPV was infected by ureaplasma. Cells were counted and it was done titration of IL1-β, IL-6 and TNF-α. HPV, Mollicutes, U. parvum, serotypes 1 and 6 U. parvum, T. vaginalis and G. vaginalis, and some socioeconomic factors were associated with cervical injury. Besides this, it was detected higher load U. parvum among women with injury. There was decrease in cell number and increased release of IL-6 and TNF-α in infected groups. With the results of this study, we found an association among HPV and ureaplasmas at the beginning of cervical lesions, but more studies are needed to enhance this hypothesis.

O desenvolvimento do câncer cervical depende da exposição ao HPV, fator necessário, mas não suficiente. Outras bactérias, tais como ureaplasmas, têm sido associadas como cofatores. O objetivo deste estudo foi avaliar a presença de ureaplasmas em mulheres com lesão cervical, e observar alterações em PHK causadas pela infecção por ureaplasmas. 140 swabs vaginais foram coletados. O material foi submetido a PCR para a detecção de HPV, Mollicutes, U. urealyticum, U. parvum e seus sorotipos, e outras bactérias de importância ginecológica; e qPCR para U. urealyticum e U. parvum. Também foi realizada a infecção de ureaplasmas em PHK transformados com HPV. As células foram contadas e realizou-se a dosagem das citocinas IL1-β, IL-6 e TNF-α. HPV, Mollicutes, U. parvum, sorotipos 1 e 6 de U. parvum, T. vaginalis e G. vaginalis, além de alguns fatores socioeconômicos, foram associados com lesão cervical. Verificou-se maior carga de U. parvum entre mulheres com lesão. Houve diminuição do número de células e maior liberação de IL-6 e TNF-α nos grupos infectados. Com os resultados obtidos neste estudo, foi possível verificar uma associação entre os ureaplasmas e HPV no início das lesões cervicais, contudo mais estudos precisam ser realizados para aprimorar essa hipótese. / The development of cervical cancer depends on the exposure to HPV, necessary factor, but not enough. Other bacteria, such as ureaplasmas, have been associated as cofactors. The aim of this study was to evaluate the presence of ureaplasmas in women with cervical injury, and observe changes in PHK infected by ureaplasmas. 140 vaginal swabs were collected. The material was subjected to PCR for detection of HPV, Mollicutes, Ureaplasma urealyticum, U. parvum (and serotypes) and other bacteria gynecological importance; qPCR for U. urealyticum and U. parvum was made. PHK transformed by HPV was infected by ureaplasma. Cells were counted and it was done titration of IL1-β, IL-6 and TNF-α. HPV, Mollicutes, U. parvum, serotypes 1 and 6 U. parvum, T. vaginalis and G. vaginalis, and some socioeconomic factors were associated with cervical injury. Besides this, it was detected higher load U. parvum among women with injury. There was decrease in cell number and increased release of IL-6 and TNF-α in infected groups. With the results of this study, we found an association among HPV and ureaplasmas at the beginning of cervical lesions, but more studies are needed to enhance this hypothesis.

過去關於父母參與效果的研究發現：父母參與有助於提升子女的學習成就。由於父母參與被視為一種社會資本或文化資本的延伸，父母參與的愈多，其子女學習效果也愈好。有鑑於此，本研究主要在探討父母參與在家庭社經地位和子女學習成就之間所扮演的角色，並將研究目的細分為三個研究議題。首先，根據智力發展理論與認知能力成長曲線相關研究，第一個議題探討臺灣青少年學生學習成長軌跡的發展與變化情形為何？接著，運用 Bourdieu 的文化資本與 Coleman 的社會資本的概念說明父母參與的重要性，其它兩個議題則探討家庭社經地位對子女學習成長軌跡的影響歷程中，父母參與扮演著中介效果還是交互作用效果？ 原始資料來源取自臺灣教育長期追蹤資料庫（Taiwan Education Panel Survey）公共使用版中的第一波到第四波國中長期追蹤樣本，使用潛在成長曲線模型進行次級資料分析。研究結果發現：1.就整體學習發展型態來看，臺灣青少年學生學習成長軌跡的發展是一種非線性遞增減速的成長曲線，年級愈高，學習成長速率愈慢；2.就個別學習成長軌跡而言，學生間起始狀態與成長速率有個別差異現象，進一步透過潛在成長混合模型的分析，發現學生學習成長軌跡的發展型態並無類別上的差異；3.學生的起始能力會影響學習成長速率的變化而產生馬太效應；4.隨著時間的遞移，高起始能力組的學生，其學習成長速率高於低起始能力組的學生，兩者的學習成就間差距會逐漸擴大而產生扇形擴散效應；5.父母參與對子女學習成就表現有顯著正向的短期立即效果與長期延宕效果，但波段與波段之間的延宕效果則沒有顯著差異；6.在家庭社經地位對子女學習成長軌跡的影響歷程中，父母參與扮演著部份中介而不調節的影響效果。 最後，依據上述研究發現，就研究結果與研究方法兩方面，將提出相關研究建議以供實務參考及後續研究之用。 / The previous research has shown that parental involvement produces measurable gains in student achievement. Since parental involvement is seen as a form of social capital and cultural capital, it is possible that the more a student owns parental involvement, the bigger the effect is. Thus, this study explores what role parental involvement plays between parents’ social-economic status and their children’s academic performance. The major purpose is further categorized into three specific questions. Based on the intelligence developmental theory and growth curve analyses of cognitive ability, the first is to inquire what patterns the development and change of academic growth trajectories of Taiwanese teenager’s academic performance are. Using the concepts of Bourdieu’s cultural capital and Coleman’s social capital to explain the importance of parental involvement, the other two purposes are to explore whether the effects of parental involvement on adolescent academic growth trajectories are mediated or moderated by family socioeconomic status. Using the data from the public released core panel data of the Taiwan Education Panel Survey (TEPS) in 2001, 2003, 2005, and 2007, this study employs the method of the latent growth curve modeling to address research questions. The results are the following: (1) Academic growth trajectory of Taiwan adolescence’s achievement reveals a nonlinear de-accelerating growth curve; (2) There are significant individual differences in both the initial status and growth rate of achievement among students, but further employing different latent growth mixture models shows no individual differences in the patterns of academic growth trajectories; (3) The Matthew Effects occur in the academic growth trajectories of Taiwanese teenagers; (4) Students with lower initial status learn more slowly over time than those with higher initial status do, and the “fan-spread” effect is found; (5) There are positive short-term and longer term effects of parental involvement on the Taiwanese adolescents’ academic achievement performance, but no significant difference among patterns of longer term effects over 6 years; (6) The effects of parental involvement are partially mediated, but not moderated by family SES. Finally, the study discusses the implications of parental involvement and suggests directions for future research.

個人學習動機向來被認為是影響學習成就的重要因素，但是家庭也對學生的學習提供特定的脈絡條件。因此，在探討學生學習成就與時間發展效應之時，若能同時納入個人與家庭因素，並探討其間的交互作用，將能對於兩者的影響力進行客觀的檢驗。本研究的目的主要在探討臺灣青少年學習成就的成長軌跡變化型態，以及家庭文化資本與個人學習動機對於學習成就成長軌跡的影響機制。其中學生的文化資本是來自家庭父母所傳遞下來的先天條件，係屬於一種結構因素；而學生的學習動機則是來自個人後天的努力與學習的正向動力，係屬於一種個人因素。具體而言，本研究目的分為三個主要的研究議題，首先，根據Bourdieu（1977）的文化資本概念，以及Bandura（1977, 1986, 1997）與McInerney和McInerney（1994）的學習動機觀點，探討這兩個重要解釋變數對於各波學生學習成就的影響情形；再者，根據Sternberg（1985, 1986, 1988）的智力三元論觀點探討學生學習成就的成長變化情形；最後，探討文化資本與學習動機對於學生學習成就成長軌跡的交互作用效果。 研究資料取自臺灣教育長期追蹤資料庫（Taiwan Educational Panel Survey）的四波追蹤樣本，以潛在成長曲線模式進行次級資料分析。研究結果發現：1.臺灣青少年的學習成就成長軌跡呈現非線性的遞增漸緩的成長曲線；學生在學習成就的起始能力與成長速率存在個別差異，且學生的起始能力與成長速率具有正向的關係，顯示隨著時間的遞移，起始能力高與低的學生，其能力的差距會逐漸擴大。2.文化資本與學習動機對於學習成就成長軌跡的影響未具交互作用，顯示個人的學習動機並不能減緩或反轉文化資本對於學生學習成就的影響。3.文化資本與學習動機對於學生學習成就的主要效果，在學習的早期階段，存在正向的影響效果，但影響力會隨著時間而逐漸降低。4.文化資本係影響學生學習成就成長軌跡的重要因素，文化資本的豐富與不足會加劇學生學習成就的差距，因而造成強者恆強、弱者恆弱的「馬太效應」現象。最後，依據上述的研究發現，分別提出教育實務上、未來研究與對資料庫研究的建議，以供相關教育人員與研究者參考。 / Individual motivation has always been recognized as the key factor for influencing the students’ learning achievement. However, the family of the students is also considered as an important contextual determinant. As a result, in order to analyze the students’ learning achievement against the temporal effect of time, it is imperative that the factor of family background should be included for understanding the interaction of the factors on the learning achievement. The primary goal of this study is to inquiry the patterns the development and change of learning achievement growth trajectory of the Taiwan adolescent. Particularly, this study explores the effects of family cultural capital and learning motivation on adolescent learning achievement growth trajectory. By definition, family cultural capital which is a structural factor refers to the inherent characteristics that are passed down from the students’ parents. On the other hand, the students’ learning motivation which is a personal factor refers to the extrinsic factor that arises from later days’ hard work and positive learning efforts. In terms of research objectives, this study tries to integrate the Bourdieu’s (1977) perspective of cultural capital, and Bandura’s (1977, 1986, 1997) as well as McInerney and McInerney’s (1994) concept of learning motivation into a framework for examining the effects of the learning growth of different waves of students. Secondly, by applying the Sternberg’s (1985, 1986, 1988) triarchic theory of intelligence to examine the changes of the students’ learning growth trajectory. Finally, to analyze the interaction between the students’ cultural capital and learning motivation on their learning achievement trajectory. The data using in this study was selected from the longitudinal database Taiwan Educational Panel Survey (TEPS). A total of four waves of students’ data were downloaded and analyzed as secondary data using the latent growth curve modeling (LGCM). Major results of the study were followed: First, the learning achievement trajectory of Taiwan adolescents’ seemed to be gradually growing in a non-linear incremental curve; it also shown that at the beginning the students’ learning achievement displayed significant individual differences. Likewise results also revealed a positive relationship between the students’ initial status and growth rate of learning achievement. That is, as the passing of time, the initial status of learning achievement affected the growth of disparity among the students. Second, there were no significant interaction effect between the students’ cultural capital and learning motivation on the learning achievement growth trajectory. This means that the students’ learning motivation cannot moderate the effects of cultural capital towards the learning achievement. Third, results revealed that the main effects of the students’ cultural capital and learning motivation on the learning achievement were occurred on the early stages of learning. A significant positive effect was found in these stages, however, the positive effect gradually decreased along with the passing of time. Fourth, it was found that the minimal effect of students’ cultural capital on their learning achievement growth trajectory was determined by the abundance or deficiency of the former. The amount of cultural capital also determined the distance of the students’ gap. In other words, a phenomenon of the Mathew effect was supported; wherein the students who are in a strong stand will get stronger later on, while the weak shall get weaker. Besides the findings mentioned above, recommendations for further study and limitations of the present study were given at the end.

Contexte et objectifs. La carrière criminelle est un sujet d’intérêt criminologique depuis plus de 80 ans. Les travaux sur cette question ont permis de mieux comprendre l’évolution des personnes contrevenantes et leurs crimes au fil du temps. Bien que beaucoup d’efforts aient été déployés pour étudier les hommes, les recherches portant sur les trajectoires criminelles des femmes demeurent relativement rares, ceci étant notamment attribuable à la petite taille des échantillons. L’objectif de ce mémoire est de réaliser une étude comparative de la carrière criminelle d’hommes et de femmes de 18 à 47 ans relevant de la juridiction de la province de Québec. Méthodologie. L’échantillon est composé de 3320 délinquants sous responsabilité provinciale, soit 216 femmes (6,5 %) et 3104 hommes (93,5 %). Des statistiques descriptives seront réalisées afin de dresser un portrait de la clientèle et une approche par variable latente catégorielle sera utilisée pour modéliser les parcours criminels. Plus précisément, cette analyse permet d’estimer des sous-groupes de délinquants au sein de la population qui suivent des courbes de croissance distinctes. La proportion d’individus appartenant à chacun de ces sous-groupes peut donc être estimée. Résultats. Les analyses indiquent que les femmes ont une fréquence de délits commis plus faible que les hommes, et ce, particulièrement au début de leur carrière criminelle. En effet, la différence quant à la fréquence tend à s’atténuer avec le temps, pour disparaître vers 40 ans. Également, il apparaît que les hommes et les femmes suivent un nombre de trajectoires criminelles similaires; cependant, la prévalence chez ces dernières apparaît relativement différente. En effet, il ressort que les femmes commencent plus tardivement leur carrière criminelle que les hommes, avec une proportion plus importante pour les crimes contre les biens. Finalement, les antécédents juvéniles influent sur la chronicité et la persistance, quel que soit le genre ou le type de crime. Conclusion. Les résultats démontrent que la différence selon le sexe est un sujet d’intérêt criminologique primordial puisque les femmes présentent des risques différents quant à la fréquence et au type de crime. Qui plus est, ces dernières semblent commencer leur carrière criminelle plus tardivement que les hommes. / Context and objectives. Criminal careers has been a subject of interest among criminologists for over 80 years. This research has allowed a better understanding of the evolution of criminalised individuals over time. However, research focusing on the criminal careers of women are relatively rare, this being mainly attributed to the nature of the chosen sample. While overcoming the potential limitations found in previous studies, the objective of this research is to conduct a comparative study of criminal careers among men and women (as of 18 until 47 years old) under provincial jurisdiction. Method. The sample consists of 3,320 offenders under provincial jurisdiction. The sample includes 216 female participants (6.5%) and 3104 male participants (93.5%). Descriptive statistics will be presented in order to provide a detailed portrait of offenders from 18 to 47 years old. Then, the categorical latent variable approach will be used. This type of analysis provides an estimate of sub-groups of offenders within the population that follow the growth curves separately. Thus, the proportion of individuals belonging to each of these subgroups can be estimated. Results. Women have a lower incidence of crime than men especially at the beginning of a criminal career; however this difference disappears towards the age of 40. It appears that men and women, at a certain period of time have similarities in their criminal careers. However, the prevalence of criminality among women is quite different from men. Indeed, it appears that women begin their criminal careers later than men, with a higher proportion of crimes against property. The juvenile history of criminal offence influences the perseverance in criminal careers among men and women, regardless of the type of offence. Conclusion. The results demonstrate the relevance of the difference between men and women during their criminal career. It should be one of the top interests for criminologists since women have different risks leading to offenses, as well as frequency and type of offense. Moreover, they appear to begin their criminal careers later than men.

Tesis por compendio / [ES] Para evaluar los efectos del proceso de selección en una línea paterna de conejos, se compararon los rasgos de crecimiento y rendimiento reproductivo de la descendencia actual (generación R36) en similar ambiente con una población control rederivada de embriones de una generación anterior (R18). Para reducir/evitar el efecto del proceso de criopreservación sobre los rasgos fenotípicos se rederivaron embriones de la generación actual (R36) y obtener una 3ra población (R37V). Capítulo 1, se compara la R37V y la descendencia de la R36 nacida por inseminación artificial (R37). Hubo diferencias en rasgos de crecimiento postnatal en las 3 generaciones evaluadas, pero no en el crecimiento fetal, componentes del tamaño de la camada y rasgos reproductivos. Así, los procesos de criopreservación y transferencia de embriones causan cambios en rasgos de crecimiento de poblaciones reconstituidas que influyen en las siguientes generaciones, sin producir cambios en los reproductivos. En los siguientes capítulos, para reducir/evitar los efectos del proceso de rederivación, la deriva genética y factores ambientales sobre los rasgos fenotípicos, se usó sólo poblaciones rederivadas para comparar los rendimientos reproductivos y de crecimiento. Capítulo 2, al ser los machos usados para producir dosis seminales en centros de inseminación y granjas, se evaluó si el programa de selección modificaba los rasgos seminales, el proteoma del plasma seminal y de espermatozoides, y la fertilidad del semen al usarla en inseminación artificial. Se analizó el proteoma del plasma seminal y espermatozoides de machos maduros de c/grupo y se prepararon dosis seminales para inseminación. Sólo el porcentaje de espermatozoides anormales mostró diferencias, presentando los R21 menos espermatozoides anormales que los R39. El análisis discriminante (DA-PLS) mostró efecto de la generación para el proteoma plasmático y espermático. En plasma seminal, se reportaron 64 proteínas diferencialmente expresadas y 56 sobreexpresadas en R39 (87,5%). Del proteoma de espermatozoides 132 diferencialmente abundantes y 89 sobreexpresadas en R39 (67,4%). A pesar de las diferencias en importantes proteínas relacionadas con la capacitación, la motilidad, la inmunoprotección de espermatozoides y la fecundación, no hubo diferencias en fertilidad y prolificidad con las dosis seminales para inseminación. Capítulo 3, se analizó el efecto de la selección por ganancia media diaria de peso (GMD) post-destete después de 37 generaciones. Tras 2 generaciones post rederivación (R21 vs. R39), todos los caracteres evaluados mostraron progreso resultado de la selección, y no afecta a los parámetros estimados de la curva de crecimiento de Gompertz. Los resultados demuestran que el programa de selección mejoró la GMD sin variar el peso corporal adulto, pero tras 37 generaciones de selección, este carácter parece agotado. Capítulo 4, comparamos los parámetros reproductivos de conejas entre las poblaciones rederivadas y control. Los rasgos de desarrollo prenatal y los componentes del tamaño de camada se midieron en la 2da generación post rederivación (R20 y R38). Así la selección por GMD no tiene efectos adversos sobre los componentes del tamaño de la camada, y el área del saco fetal al día 12 de gestación, área de la placenta fetal y la longitud cráneo-rabadilla del feto al 19 de gestación fueron mayores en R38. Resultados muestran que la selección por GMD no afecta negativamente el rendimiento reproductivo. Conclusión, el estudio demuestra que los efectos de la criopreservación sobre los rasgos de crecimiento persisten dos generaciones post rederivación. Además, la línea muestra signos de agotamiento del progreso genético quizás por el bajo rendimiento reproductivo y elevada mortalidad postnatal. La selección por GMD influyó en cambios del crecimiento fetal y del proteoma del eyaculado, sin afectar al rendimiento reproductivo de hembras ni la fertilidad y prolificidad de las dosis seminales de machos. / [CA] Per avaluar els efectes del procés de selección en una línia paterna de conills, es van comparar els trets de creixement i el rendiment reproductiu de la descendència de la generació actual (R36) sota el mateix entorn amb una població control derivada dels embrions emmagatzemats d'una generació anterior (R18). Per reduir/evitar l'efecte del procés de criopreservació embrions de la generació actual (R36) es van criopreservar i transferir (rederivar) per obtenir una 3a població (R37V). Capítol 1, es compara la generació R37V i la descendència de la 36a generació nascuda per inseminació artificial (R37). Hi ha diferències en els trets de creixement postnatal a les tres generacions avaluades. Tot i que el creixement fetal, els components de la mida de la ventrada i els trets reproductius no van mostrar diferències. La rederivació provoquen canvis en els trets de creixement de les poblacions reconstituïdes que influeixen en les generacions següents, sense canvis en els trets reproductius. En els capítols següents, per reduir/evitar els efectes del procés de rederivació, la deriva genètica i els factors ambientals sobre els trets fenotípics, es van utilitzar les poblacions rederivades per comparar els rendiments reproductius i de creixement. Capítol 2, ja que els mascles s'utilitzaven per produir dosis de semen en centres d'inseminació i granges, es va estudiar si un programa de selecció per guany mitja de pes diari pot canviar els trets seminals, el proteoma del plasma i dels espermatozoides i la fertilitat del semen en la inseminació artificial. Només el percentatge d'espermatozoides anormals mostra diferències significatives, R21 presentant menys espermatozoides anormals que R39. L'anàlisi discriminant (DA-PLS) mostra efecte de la generació al proteoma del plasma i dels espermatozoides. En plasma seminal, 64 proteïnes es van expressar de manera diferent, 56 sobre-expressades en R39 (87,5%). El proteoma de l'esperma 132 proteïnes diferencialment abundants, 89 sobre-expressades en R39 (67,4%). Tot i observar diferències en proteïnes importants relacionades amb la capacitat, la motilitat o la immunoprotecció dels espermatozoides i la fecundació, La fertilitat i la prolificitat es van detectar quan es van utilitzar dosis seminals comercials per a la inseminació. Capítol 3, vam avaluar l'efecte d'una selecció a llarg termini per a l'augment de pes mitjà diari (ADG). Després de dues generacions d'ambdues poblacions rederivades (R21 vs. R39), tots els trets avaluats mostra algun progrés. Aquesta resposta no sembla afectar els paràmetres estimats de la corba de creixement de Gompertz. Resultats demostra que el programa de selecció havia millorat l'ADG sense variacions en pes corporal adult, però després de 37 generacions de selecció, aquest tret sembla esgotat. Capítol 4, compara els trets reproductius entre poblacions femenins entre ambdues poblacions (rederivades i control). El desenvolupament fetal i els components de la mida de la ventrada es mesura els trets a la segona generació després de la rederivació (R20 i R38). Resultats suggereix que la selecció per ADG no té cap efecte advers sobre els components de la mida de la ventrada i la zona del sac fetal el dia 12 de gestació i la zona de la placenta fetal i la longitud de la corona-gropa del fetus el dia 19 de gestació eren més grans a la R38. La selecció per ADG no afecta negativament els components de la mida de la ventrada, el creixement fetal i el rendiment reproductiu. Nostre estudi proporciona més proves dels efectes de la criopreservació sobre els trets de creixement que persisteixen dues generacions després de la rederivació. La línia va mostrar signes d'esgotament del progrés genètic per baix rendiment reproductiu i l'alta mortalitat postnatal. La selecció per ADG va influir en els canvis en el creixement fetal i en el proteoma ejaculat, però no va afectar el rendiment reproductiu de les femelles ni la fertilitat i la prolificitat de les dosis seminals dels mascles. / [EN] To evaluate the effects of the selection process in a paternal line of rabbits, growth traits and reproductive performance from the offspring of the current generation (R36) were compared under the same environment with a control population rederived from embryos stored of a previous generation (R18). To reduce or avoid the effect of the cryopreservation process on phenotypic traits embryos of current generation (R36) were cryopreserved and transferred to obtain a third population (R37V). In chapter 1, R37V generation and offspring of 36th generation born by artificial insemination (generation R37) were compared. Differences in postnatal growth traits were observed in the three generations assessed. Although foetal growth, litter size components and reproductive traits did not show significant differences. In conclusion, cryopreservation and embryo transfer processes cause changes in growth traits of reconstituted populations that influence the following generations, without changes in reproductive traits. In the following chapters, to reduce or avoid the effects of the rederivation process, genetic drift and environmental factors on phenotypic traits, only the rederived populations were used to compare reproductive and growth performances. In chapter 2, considering that males were used to produce semen doses at insemination centres and farms, we studied whether a programme of selection by daily gain changed the seminal traits, plasma and sperm proteome and the fertility of semen when used in artificial insemination. Seminal plasma and sperm proteome from mature males of each group were analysed and semen doses were used to inseminate females. Only the percentage of abnormal sperm showed significant differences, R21 presented fewer abnormal sperm than R39. The discriminant analysis (DA-PLS) showed an effect of the generation for plasma and sperm proteome. In seminal plasma, 64 proteins were differentially expressed, 56 were overexpressed in R39 (87.5%). Sperm proteome reported 132 differentially abundant proteins, 89 were overexpressed in R39 (67.4%). Despite differences in important proteins related to capacitation, sperm motility or immunoprotection and to the fertilization process, no differences in fertility and prolificacy were detected when commercial seminal doses were used for insemination. In chapter 3, we evaluated the effect of a long-term selection for post-weaning average daily weight gain (ADG) over 37 generations. After two generations of both rederived populations (R21 vs. R39 generations), all evaluated traits showed some progress as a result of the selection. This response does not seem to affect the estimated Gompertz growth curve parameters. Results demonstrated that the selection programme had improved ADG without variations in adult body weight but, after 37 generations of selection, this trait seems exhausted. In chapter 4, we compared female reproductive traits between both rabbit populations (rederived and control). Foetal growth and litter size traits were measured in the second generation after rederivation (R20 and R38 generations). Our study suggests that selection for growth rate has no adverse effect on litter size components and the foetal sac area at day 12 of gestation, and foetal placenta area and crown-rump length of the foetus at day 19 of gestation were higher in the R38 generation. These results show that selection for growth rate does not adversely affect on reproductive performance. In conclusion, our study provides further evidence of the effects of cryopreservation on growth traits persisting two generations after rederivation. Moreover, the paternal line showed signs of genetic progress exhaustion due to low reproductive performance and high postnatal mortality. Selection by daily weight gain influenced changes in foetal growth and ejaculate proteome, but did not affect the reproductive performance of females or the fertility of seminal doses of males. / This research was supported by AGL2017-85162-C2-1-R research project funded by Ministerio de Economía, Industria y Competitividad (MICINN, Spain). Funding for open access charge: CRUE- Universitat Politècnica de València. / Juárez Moreno, JD. (2022). Embryo cryopreservation and transfer to rederive a paternal rabbit line after 18 generations. Evaluation of growth and reproductive traits [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/185071 / TESIS / Compendio

創業初期所面對的主要問題就是資源不足的問題，要如何獲取生存與發展所需要的資源是企業的重要課題。首先，企業必須分析內部環境，找出核心資源，並將之發揮在目標事業上，為企業奠定基礎。再者，企業必須分析外部環境，透過各種組織鏈結策略，重新調整與供應商、顧客、甚至是競爭者之間的關係成為策略夥伴關係，選擇並集中核心競爭強項，形成資源互補，提供給客戶一個全面解決方案(Total solution)的服務，以滿足甚至超過顧客預期的需求，使得顧客願意持續購買，企業藉此從環境中獲取關鍵資源並得以持續發展。 本研究透過個案分析發現，組織在成為「全面解決方案提供者(TSP)」的角色過程中，因為市場力量及組織力量的融合過程的不同，我們分析出其發展軌跡可以歸類成為五大類，即「水平整合型的TSP」、「垂直整合型的TSP」、「先水平後垂直整合型的TSP」、「先垂直後水平整合型的TSP」以及「垂直及水平整合並進型的TSP」。這五大類型的發展軌跡基本上描述了組織發展的過程，讓我們更清楚的知道組織成長過程中因為環境因素以及組織因素所造就成的組織面貌。 「TSP成長曲線 (TSP Growth Curve)」的形成過程，是在個案成長過程分析及探討後發現，組織要追求持續成長，單靠本身的資源是受限的，組織必須去整合內外部的資源，包括重新建構核心資源、組織並管理外部資源網絡，透過各樣的鏈結策略使得組織獲取成長所需要的關鍵資源，透過策略再思考重新組織企業架構，建構一個學習性組織平台，鼓勵在這個平台上的每一個人去創新思考，讓組織成員得以在非傳統性架構下去思考，在非秩序中去創新，讓大家願意去共創組織的價值。 研究發現，組織獲取資源並成為TSP的四個步驟為：1.建構組織核心資源與能力2.從環境中獲取關鍵資源3.價值創新成為TSP角色使顧客滿足4.降低對環境依賴，繼續提升高一層次的成長循環。這樣良性的循環讓組織累積更多資源而逐漸壯大，擺脫了創業初期資源不足的困境，組織在壯大的同時因為建立了更多的資源而逐漸降低對於原有環境中的資源依賴，並與環境中資源提供者的關係從依賴變成互賴，此時組織已經提昇到了另一層次的成長循環。這樣的成長循環使得組織得以在不同的環境中獲取不同的資源繼續成長，讓企業一直維持企業生命週期中的成長階段，因而可能避免或延遲了衰退階段的發生。 本研究的特色是從資源依賴的角度出發，探討組織如何透過從環境中獲取成長所需的關鍵資源，並探討組織藉由成為全面解決方案提供者的角色來獲取顧客價值創新，此時組織價值亦跟隨提升。 大部分的企業皆無法規避「出生、成長、成熟、飽和、衰退」的命運，就如同生命會歷經「出生、幼年、青年、壯年、老年」的歷程一般，或許企業無法避免衰退或消失的命運，但是找出「延年益壽」方法來維持壯年期是一個可行的策略。「TSP成長曲線圖」以「TSP成長循環圖」即可以說明企業從「創業成功」到「維持成長」的策略歷程，可以作為企業經營發展的參考。 / The major problem in the early stage of entrepreneurship is the shortage of resources, so it is industries’ crucial mission to acquire the resources to sustain and develop its growth. First, industries must analyze its internal environment to identify the core sources and apply them into the target business, to lay the foundation for companies. Second, industries must conduct external analysis with organizations linkage mechanism to re-address the connection among suppliers, customers and even competitors, so that they can become the strategic partners, formulate complimentary resources, concentrate on their own core advantages in the competition. In this way, they can offer customers the service of Total Solution, to meet, even exceed customers’ expectation. Hence, this could sustain customers’ continuous purchase, and industries can keep developing its business by grabbing the crucial resources in the environment. This research discovered that, due to the different merging processes between market powers and organizations power, there are five categorized patterns when organizations become Total Solution Provides (TSP): horizontal integration TSP, vertical integration TSP, horizontal-to-vertical integration TSP, vertical-to-horizontal integration TSP and simultaneously vertical and horizontal integration TSP. These five patterns basically outline the process of organization development and bring us more diverse pictures caused by different environmental and organizational causes. After studying cases and formulating of the TSP Growth Curve, this research found out that it is limited to for organizations to pursue the growth by its own resources. Industries must integrate internal and external resources, re-construct the core resources, manage the external resource network, acquire all the necessary resources for further growth through linkage mechanism, rethink the structure of the business, establish the learning platform to encourage its member to jointly create the value for the organizations, contemplate beyond the boundary of tradition and innovate without order. There are four steps for the organizations to acquire resources and formulate the TSP Growth Curve: 1. Constructing the core resources and capability of the organizations; 2.Acquireing the core resources from the environment; 3.Becoming TSP with value innovation and satisfy the customers; 4.Lowering the dependence on the environment and upgrading the Growth circle. Organizations can grow stronger, accumulate more resources with this benign circle and leave the dilemma of insufficient resources. In this way, organizations can receive more resources than ever; it can also turn the relationship between organizations and supplier from unilateral dependence to mutual dependence and TSP Growth circle will also be upgraded while they are growing bigger. This growth circle can continuously sustain its development by collecting different resources in different environments. Hence, the stage of growth will be prolonged, and the stage of recession will be avoided of delayed. Based on the Resources dependence theory, this research has discussed how organizations obtain the crucial resources from the environment to generate growth, and also analyzed that when organizations obtain customers’ value innovation by playing TSP, organizations’ value will also raise consecutively. Most industries can not avoid the linear destiny of establishment, growth, maturity, saturation and recession as well as human’s life stage of birth, child, youth, adult and aging. Industries may not genuinely ward off the consequence of decline or disappearance, but it’s still workable to figure out a strategy to prolong the period of maturity. TSP Growth Curve and TSP Growth Circle can well explain the industries’ process from the stage of “entrepreneurship” to “the maintenance of growth”, and also offer the positive example for business operation.