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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
31

嵇康 聲無哀樂論 研究 = The study of Ji-Kang's On the Grieflessness and Joylessness of Music / Study of Ji-Kang's On the Grieflessness and Joylessness of Music;"嵇康聲無哀樂論研究"

劉榕 January 2004 (has links)
University of Macau / Faculty of Social Sciences and Humanities / Department of Chinese
32

The Penitential Psalms in sixteenth-century England : bodies and texts

Wyma, Katherine Cooper January 2013 (has links)
At the center of this thesis are seven psalms, commonly known as the Penitential Psalms. The Penitential Psalms were often used in connection to corporeal expressions of the sacrament, and though sacramental practices changed, they retained this association, and even became a catalyst for literary change and experimentation. In this thesis, I will show how these psalms were connected to the sacrament of penance throughout the medieval period, and well into the religiously tumultuous sixteenth century. This thesis explores four texts that take up the Penitential Psalms, adapting, refashioning, and reappropriating them to be used in different ways. The Introduction outlines the history of the Penitential Psalms and their interconnectedness with sacramental theology and practice; it further establishes the cultural and theoretical context within which the four examined texts must be considered. These sacramental ties with the Penitential Psalms are not found only in theological writings, but they also infused lay practice and experience, as I will show in Chapter One, where I examine the staunchly Protestant Actes and Monuments by John Foxe. Additionally, I argue that Foxe's accounts of Marian martyrs point to Psalm 51 both as a text of protest and memorialization. Chapter Two then moves to Sir Thomas Wyatt's A Paraphrase of the Penitential Psalms; there I examine the presence of the male body within the work, placing the text within the setting of a visual history that illustrates David's illicit desire for Bathsheba. With this tradition in mind, I examine trajectories of ocularity within the narrative, tracing the redirection of sexual desire. Anne Lock's Meditation of a Pentient Sinner is the center of Chapter Three. Meditation, when considered in relation to the dedicatory epistle, reveals connections to the standardized penitential process, and I argue that Lock presents a modified form of repentance to her reader. The final chapter looks at The Sidney Psalter's Penitential Psalms, which reveal an incoherent view of the penitential body merging with the body of the dead war-hero, Philip. It is within this penitential affect that the penitent displays and partitions his or her own body slipping into an otherness predicated by sin.
33

Environmentální účinky radiofarmak obsahujících 223 Ra / Environmental Effects of 223-Ra Radiopharmaceuticals

Krmelová, Tereza January 2016 (has links)
Title: Environmental Effects of 223 Ra Radiopharmaceuticals Author: Tereza Krmelová Branch: Environmental chemistry Type of thesis: Diploma thesis Advisor: Doc. Ing. Stanislav Smrček, CSc Abstract: In thesis was studied the possibility of extracting the nanoparticles of titanium dioxide or hydroxyapatite with bounded 223 Ra by root system of tested plant species Avena sativa and Zea mays as a model for phytoremediation technologies. The thesis obtains data to assess the potential of residues radioactivity and nanomaterials entering the food chain. There was also verified an experiment of 223 Ra phytoextraction, in the form of nitrate, in effects on addition of EDTA, which was conducted in Bachelor thesis. This experiment was repeated because of its results, which were inconsistent with generally described phytoextraction efficiency improvements after adding the complexing agents. In this work was primary studied translocation of radioactive material from the root to shoot. Experimentally was confirmed the extraction of nanoparticles with bounded 223 Ra and translocation into shoot. In the case of Avena sativa, capturing of nanoparticles hydroxyapatite with bounded 223 Ra was 53 % of which 88 % of activity was recovered in roots and 12 % in shoots. Capturing nanoparticles of titanium dioxide with bounded 223...
34

Recherches sur le vocabulaire de la droiture et de l'innocence dans la Septante des Psaumes, Proverbes et Job / Research on the vocabulary of uprighteousness and innocence in the Septuagint of the Psalms, Proverbs and Job

Longonga Ngumbu, Stanislas 12 July 2019 (has links)
Cette thèse est consacrée à la Septante et s’inscrit dans le courant de recherche qui étudie son vocabulaire et son style. Si des études ont été menées sur différents thèmes, il n’existe pas cependant d’étude systématique sur le vocabulaire de la droiture et de l’innocence dont l’impact sur le langage religieux chrétien postérieur est pourtant remarquable. Cette thèse qui se veut une contribution à ce courant de recherche en abordant un champ lexical négligé par la recherche antérieure, limite l’enquête à trois livres sapientaux, à savoir, les livres des Psaumes, Proverbes et Job. La démarche consiste à établir l'équivalence entre la LXX et le Texte Massorétique, la LXX et la littérature grecque, la LXX et la littérature juive hellénistique en se penchant sur l'arrière-fond des termes, les similitudes et les écarts dus à l'environnement culturel, dans l’objectif de comprendre le sens et le choix des termes grecs mobilisés. / This thesis is dedicated to the Septuagint and is part of the current of research that studies its vocabulary and style. While studies have been conducted on different themes, there is no systematic study of the vocabulary of uprighteousness and innocence, which has had however an impact on later Christian religious language. This thesis which is intended as a contribution to this current of research by addressing a lexical field neglected by previous research limits the investigation to three sapiential books, namely, the books of Psalms, Proverbs and Job. The approach consists in establishing the equivalence between the LXX and the Masoretic Text, the LXX and the Greek literature, the LXX and the Hellenistic Jewish literature by examining the background of the terms, the similarities and the differences due to the cultural environment, in order to understand the meaning and the choice of the Greek terms mobilized.
35

Analys av platinaytor och platinatennytor under katalytisk etanoloxidation med röntgenfotoelektronspectroskopi / X-ray photoelectron spectroscopy analysis of platinum surfaces and a platinum-tin surface during catalytic ethanol oxidation

Löfstrand, Mats Viktor January 2023 (has links)
Fuel cells are more efficient and cleaner than combustion engines. Ethanol as a fuel has a high energy density and is safer and easier to handle than hydrogen which is normally used in fuel cells. If efficient fuel cells on alcohol were available, they could be used for engines and power sources for electronics. Platinum-tin surfaces have proven to be good catalysts for ethanol and an improvement over pure platinum. The mechanism and the structure during catalysis are not well known. An experiment was performed at the Hippie beam line at Max IV to improve the knowledge in this area. The (111) surface of Pt and Pt3Sn alloy and the (223) surface of Pt, was exposed to ethanol and oxygen. Pt and Pt3Sn both have face-centered-cubic (FCC) crystal structures. The (111) surface is the most close-packed in an FCC crystal. A (223) surface is a (111) surface cut at a low angle. So it has the appearance of a stepped (111) surface. The edges on the (223) surface should increase the activity compared to the (111) surface. The surfaces and the gas phases were measured in situ with ambient pressure x-ray photoelectron spectroscopy and a quadrupole mass spectrometer was used to analyze the gas composition. The hypothesis that increasing the number of edges as with the Pt(223) surface should increase the activity is accurate. Pt(223) was more active than Pt(111). Pt(223) and Pt3Sn(111) have similar ethanol conversion rate. Increasing the oxygen-to-ethanol ratio increased the activity both with Pt(111) and Pt(223), Pt3Sn(111) was not tested with increased oxygen-to-ethanol ratio. The gas phases were analyzed, and the existing compounds were identified. Acetaldehyde shows up in the C1s gas spectrum in all of the sequences. When ethanol decreases acetaldehyde increase. The difference between these two compounds is only two hydrogen atoms. This reaction is the start of the catalytic process and it is the same for all tested crystals. Ethylene (CH2CH2) shows up as a vague peak in the gas phase. It is only present at higher temperatures and with a low oxygen rate. Compared to the other crystals the Pt3Sn(111) sample doesn't produce CO2, at least not to a detectable degree. In the gas phases of the other crystals, the CO2 peak was visible. Pt(223) creates CO2 but to a lesser degree than Pt(111). The goal of the experiment was to investigate which Sn phases are present during ethanol oxidation. This turned out to be difficult. The Pt3Sn crystal was carbon poisoned during the first test sequence and the graphite layer was not possible to remove during the beam time. Curve fitting of the Sn3d peak resulted in two components. The components were Pt3Sn alloy and Sn with adsorbed molecules. The expected SnO2 and SnO peaks notably absent. The oxygen probably bonds with carbon instead of tin. Carbon was present on the surface due to insufficient cleaning. In the oxygen spectrum, chemically bonded oxygen seems to be present from 100 °C, as SnO2 or SnO. This peak is most likely from some other component containing oxygen. If oxygen is bonded to Sn, it should be visible in the Sn3d peak, unless it is hiding underneath one of the present peaks. According to Batzill et al. a quasimetalic state consisting of oxidized Sn alloyed with Pt has a similar binding energy as Pt3Sn alloy. So it could be that the oxygen is hiding underneath the Pt3Sn alloy component. The experiment has improved the knowledge of ethanol oxidation on platinum and platinum-tin surfaces. The knowledge gained here is a good start for further experiments and simulations.
36

Role of MicroRNAs and Their Downstream Targets in Zebrafish Thrombopoiesis

Al Qaryoute, Ayah 05 1900 (has links)
Previous studies have shown that human platelets and megakaryocytes carry microRNAs suggesting their role in platelet function and megakaryocyte development, respectively. However, there is limited information on microRNAs' role in zebrafish thrombopoiesis. Zebrafish thrombocytes could be used as a model to study their role in megakaryocyte maturation and platelet function because thrombocytes have both megakaryocyte features and platelet properties. In our laboratory, I identified 15 microRNAs in thrombocytes using single-cell RNA sequencing. Knockdown of three microRNAs, mir-7148, let-7b, and mir-223, by the piggyback method in zebrafish led to an increase in the percentage of thrombocytes. Functional thrombocyte analysis using plate tilt assay showed no modulatory effect of the three microRNAs on thrombocyte aggregation/agglutination. I then verified these findings in zebrafish larvae after the knockdown of the above microRNAs followed by an arterial laser thrombosis assay. I concluded mir-7148, let-7b, and mir-223 are repressors for thrombocyte production. Furthermore, I explored let-7b downstream genes in thrombocytes detected by RNA-seq analysis and chose 14 targets based on their role in cell differentiation (rorca, tgif1, rfx1a, deaf1, zbtb18, mafba, cebpa, spi1a, spi1b, fhl3b, ikzf1, irf5, irf8, and lbx1b) that are transcriptional regulators. The qRT-PCR analysis of expression levels the above genes following let-7b knockdown showed significant changes in the expression of 13 targets. I then studied the effect of the 14 targets on thrombocytes production and identified 5 genes (irf5, tgif1, irf8, cebpa, and rorca) that showed thrombocytosis and one gene ikzf1 that showed thrombocytopenia. Furthermore, I tested whether mir-223 regulates any of the above 13 transcription factors after mir-223 knockdown using qRT-PCR. Six of the 13 genes showed similar gene expression as observed with let-7b knockdown and 7 genes showed opposing results. Thus, our results suggested a possible regulatory network in common with both let-7b and mir-223. I also identified that tgif1, cebpa, ikzf1, irf5, irf8, and ikzf1 play a role in thrombopoiesis. Since the ikzf1 gene showed a opposite expression profiles following let-7b and mir-223 knockdowns (decreased and increased expression, respectively) and knockdown of ikzf1 resulted in thrombocytopenia I confirmed a definitive role for ikzf1 using an ikzf1 mutant obtained from the Zebrafish International Resource Center (ZIRC). The arterial laser thrombosis assay of ikzf1 mutant progeny confirmed our piggyback hybrid knockdown results. Taken together, these studies shed light on understanding the role and the regulatory effects of zebrafish microRNA on thrombopoiesis and identified novel downstream target transcription factors for let-7b and mir-223.
37

Vacina??o com pept?deo M209-223 do v?rus sincicial respirat?rio (VSR) promove uma resposta imune protetora contra infec??o e reduz a inflama??o no pulm?o / Vaccination with respiratory syncytial virus (RSV) M209-223 peptide promotes a protective immune response against infection and reduces lung inflammation

Fazolo, Tiago 20 March 2017 (has links)
Submitted by PPG Pediatria e Sa?de da Crian?a (pediatria-pg@pucrs.br) on 2018-02-16T19:08:17Z No. of bitstreams: 1 Tese Vers?o Final Tiago Fazolo 18_01_2018.pdf: 3827531 bytes, checksum: b081e8333d16cb49ba00d0df25dff485 (MD5) / Approved for entry into archive by Caroline Xavier (caroline.xavier@pucrs.br) on 2018-02-22T17:20:04Z (GMT) No. of bitstreams: 1 Tese Vers?o Final Tiago Fazolo 18_01_2018.pdf: 3827531 bytes, checksum: b081e8333d16cb49ba00d0df25dff485 (MD5) / Made available in DSpace on 2018-02-22T17:35:15Z (GMT). No. of bitstreams: 1 Tese Vers?o Final Tiago Fazolo 18_01_2018.pdf: 3827531 bytes, checksum: b081e8333d16cb49ba00d0df25dff485 (MD5) Previous issue date: 2017-03-20 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / Respiratory syncytial virus (RSV) is the most common etiologic agent in severe lower respiratory tract infections (LRTI) in children. RSV-associated LRTI is the main cause of bronchiolitis, pneumonia and exacerbation of asthma. This infection is responsible for the high rates of hospitalizations related to respiratory diseases worldwide, especially in children younger than 2 years. Currently, annual mortality rate due to RSV infections is worrying worldwide and is estimated at approximately two hundred thousand cases. The treatment strategies to RSV infections are limited. Ribavirin is an approved drug for use in RSV infections, but its use is limited due to adverse side-effects and risks posed to health professionals who handle it. Palivizumab is a monoclonal antibody which targets RSV F glycoprotein and its use is only indicated as a prophylactic measure. This treatment is already accepted in several countries for groups of high risk children (premature children, with chronic lung disease and with congenital heart disease). However, palivizumab has a high cost for public health and is not available in all countries. The development of an effective RSV vaccine to generate a long-lasting immunological memory response that prevents infection may be the best alternative because it will reduce high public health expenditures with antiviral drugs and monoclonal antibodies. The first attempt in the search for a vaccine against RSV was in the 1960s. This vaccine produced high levels of serum antibodies but could not protect against infection. Children who were vaccinated developed a more serious disease when later infected with the same virus. To date, there is no licensed vaccine for RSV, so the search for effective vaccines is an important focus of research. Natural RSV infections do not induce lasting protective memory, and multiple reinfections can occur lifetime. Nasal secretions from infected infants presented a small number of regulatory CD4 T cells (Treg) in peripheral blood, an increase in interleukin 4 (IL-4) production and T helper type 2 (Th2) response. Treg cells are important for controlling an exacerbated increase in immune responses. A reduction of the Tregs caused by the RSV infection generates an exacerbation of the pulmonary disease due to a Th2 response. The M209-223 RSV peptide was identified to increase IFN-? production by peptide-specific CD4 T cells after challenge with the virus. The treatment with this peptide also induced an increase in pulmonary Treg frequency in infected mice. Recently, it has also been shown that Tregs aid in the development of a T CD8+ effector response, which is crucial for the control of RSV viral load. Our hypothesis is that the RSV M209-223 peptide impacts in the differentiation of CD4 T cells, increasing the population of specific Treg, reducing lung inflammation and modulating the anti-RSV immune response. This peptide in animal model induces the differentiation of specific Treg. Our findings suggest that vaccination with M209-223 peptide results in the differentiation of specific CD4 T cells into conventional effectors and Treg cells. Vaccination with this peptide decreased the expansion of a Th2 response in animals infected with RSV, protecting both the infection site and systemically. We believe that this approach could be an important component in vaccination strategies against this virus. / O v?rus sincicial respirat?rio (VSR) ? o agente etiol?gico mais comum nas infec??es graves do trato respirat?rio inferior (TRI) em crian?as. As infec??es do TRI associada com o VSR s?o a principal causa de bronquiolite, pneumonia e exacerba??o da asma. As TRI causadas pelo VSR s?o respons?veis pelas altas taxas das hospitaliza??es relacionadas ?s doen?as respirat?rias em todo o mundo, principalmente em crian?as menores de dois anos. Atualmente a taxa de mortalidade anual mundial devido ?s infec??es pelo VSR ? preocupante e ? estimada em aproximadamente duzentas mil crian?as. As estrat?gias de tratamento contra o VSR utilizadas s?o limitadas. A ribavirina ? um f?rmaco aprovado no uso para infec??es pelo VSR, por?m sua utiliza??o ? limitada devido aos efeitos secund?rios adversos e aos riscos que representam para os profissionais da sa?de que o manipulam. O palivizumabe ? um anticorpo monoclonal dirigido contra a glicoprote?na F do v?rus e sua utiliza??o ? apenas como medida profil?tica. Este tratamento j? ? aceito em v?rios pa?ses nos grupos de crian?as de alto risco (crian?as prematuras, com doen?a pulmonar cr?nica e com cardiopatia cong?nita). Entretanto o palivizumabe tem um alto custo para sa?de p?blica, n?o sendo disponibilizado em todos os pa?ses. O desenvolvimento de uma vacina eficaz contra o VSR pode ser a melhor alternativa, pois ao gerar resposta de mem?ria duradoura que previne a infec??o e reduz, desta forma, os altos gastos com a sa?de p?blica, com os f?rmacos antivirais e com os anticorpos monoclonais. A primeira tentativa na busca de uma vacina contra o VSR foi na d?cada de 60. A vacina produzida estimulou n?veis moderadamente elevados de anticorpos no soro, mas n?o conseguiu proteger contra ? infec??o. As crian?as que foram vacinadas desenvolveram uma doen?a mais grave quando mais tarde infectados com o v?rus. At? o presente momento n?o existe nenhuma vacina licenciada para o VSR. Desta forma, a busca de vacinas eficazes constitui um importante foco de pesquisa em todo mundo. As infec??es naturais pelo VSR n?o induzem mem?ria protetora duradoura, ocorrendo m?ltiplas reinfec??es ao longo da vida. Em crian?as infectadas, observou-se um n?mero reduzido de c?lulas T CD4+ regulat?rias (Treg) no sangue perif?rico, um aumento na produ??o de interleucina 4 (IL-4) e uma resposta T helper do tipo 2 (Th2) nas secre??es nasais. As c?lulas Treg s?o importantes para controlar um aumento exagerado da resposta imunol?gica. Por este fato acredita-se que quando h? uma redu??o das Tregs causada pela infec??o do VSR ocorre uma exacerba??o da doen?a pulmonar devido uma resposta Th2. Foi identificado que o pept?deo M209-223 do VSR aumenta a produ??o de IFN-? nas c?lulas T CD4+ ap?s o desafio com VSR. O tratamento com este mesmo pept?deo tamb?m apresentou um aumento na frequencia de c?lulas Treg ap?s infec??o prim?ria pelo VSR. Recentemente tamb?m foi demonstrado que as Tregs auxiliam no desenvolvimento de uma resposta efetora T CD8+, que ? crucial para o controle da carga viral do VSR. Nossa hip?tese ? que o pept?deo M209-223 do VSR influencia na diferencia??o das c?lulas T CD4+, aumentando a popula??o de c?lulas T efetoras e regulat?rias espec?ficas, reduzindo a inflama??o pulmonar e modulando a resposta imune. Os nossos resultados sugerem que a vacina??o com pept?deo M209-223 resulta na diferencia??o de c?lulas T CD4+ espec?ficas em efetoras convencionais, que produzem mais IFN-? e em c?lulas Treg. A vacina??o com este pept?deo diminuiu a expans?o de uma resposta Th2 nos animais infectados com o VSR, protegendo da inflama??o exacerbada tanto no local da infec??o como sistemicamente. Acreditamos que esta abordagem pode constituir um componente importante nas estrat?gias de vacina??o contra este v?rus.
38

Citation of Psalm 68(67).19 in Ephesians 4.8 within the context of early Christian uses of the Psalms

Ehorn, Seth January 2015 (has links)
This thesis examines the citation of Ps 68(67).19 in Eph 4.8. Following an introduction that introduces the problem of the altered wording in the citation in Eph 4.8, chapter 2 comprises a History of Research that is organised around the possible sources for the author’s citation in Eph 4.8. One of several conclusions made is that the proclivity of NT scholars to attribute the source text to particular Jewish traditions has contributed to overlooking the import of Ps 68(67).19 within a normal pattern of christological reading of the Psalms in early Christianity. Following these opening chapters, the thesis is divided broadly into Part One and Part Two. The first is deconstructive in nature; the second is constructive. Part One examines textual traditions of Ps 68(67).19 within Justin Martyr, the Peshitta Psalter, and Targum Psalms. Each of these sources share the reading ‘give’ rather than ‘receive’, raising the question of the relationship between these traditions and Eph 4.8. Chapter 3 examines Justin’s Dialogue with Trypho, which contains two citations of Ps 68(67).19 that strongly resemble Ephesians. Nevertheless, as nearly all interpreters acknowledge, Justin never refers directly to ‘Paul’ or ‘Pauline’ letters in any of his writings. Is the parallel wording of Justin’s citations evidence for an early Christian tradition that was also available to Ephesians? I argue that although unmentioned by name, a reasonable case can be made that Justin is familiar with the Pauline corpus, including Eph 4.8. Chapter 4 considers the evidence of Peshitta Psalms, which agrees with the reading of Eph 4.8 in a strand of its copyist tradition. After examining scholarly construals of the Peshitta MS tradition, I consider direct evidence for the influence of Eph 4.8 upon some Peshitta MSS as intimated by Theodore of Mopsuestia. Chapter 5 examines Targum Psalms, focusing on translation techniques and the targumist’s tendency to add, alter, or modify his source in various ways. I argue that when the targumist’s techniques and tendencies are taken into consideration, the targum’s reading ‘give’ is better understood as a typical targumic insertion. The proclivity of many scholars to link Targum Psalms to Eph 4.8 is a classic example of ‘parallelomania’. Part Two turns to make a constructive case for the citation found in Eph 4.8. Chapter 6 is a close examination of the author of Ephesians’ approach to literary borrowing. I consider both his citations from the Jewish scriptures and his use of Colossians as evidence. Chapter 7 examines how early Christians read the biblical Psalms as prophecies. Following a survey of Jewish readings of the Psalms, this chapter surveys how early Christians read the Psalms in light of the death and resurrection- exaltation of Christ. Drawing insights from this, chapter 8 turns to consider the phrases ‘he ascended . . . he gave gifts’ in Eph 4.8. I argue that an ambiguity of the addressee in the text of Ps 68(67).19 allowed for the application of this text to Christ. Moreover, the ‘ascent’ language could easily be applied to the resurrection- exaltation and this association naturally led to the language of gift-giving in Eph 4.8. Chapter 9 considers how the citation of Ps 68(67).19 fits into the context of Ephesians 4, focusing on several important factors such as the language of descent in Eph 4.9–10. Part One and Part Two are followed by a short conclusion that summarises the thesis and draws out several conclusions and implications based upon this study.
39

Producing Medical Radioisotopes with CANDU Nuclear Reactors

Sutherland, Zachary January 2018 (has links)
In the field of nuclear medicine, radioisotopes are used for applications such as diagnostic imag- ing, treatment, and equipment sterilization. The most commonly used radioisotope in medicine is technetium-99m (Tc-99m). It is used in 80% of all nuclear medicine procedures. Its parent isotope is molybdenum-99 (Mo-99). NRU, which is now closed, formerly produced 40% of the worlds demand for Mo-99. The production capacity of this reactor has been supplemented by a network of cyclotrons and a modified research reactor. This study aims to provide an alternative means of production for Mo-99, as well as other radioisotopes by modifying the center pin of a standard 37-element bundle of a CANDU reactor. The neutron transport code DRAGON, and the neutron diffusion code DONJON were used to model a CANDU-9 reactor. The lowest, median, and highest power channels were chosen as candi- dates for the modified bundles. It was found that the reactor parameters were altered by a negligible amount when any one channel was used to house the modified bundles. Significant quantities of the radioisotope lutetium-177 as well as the generating isotopes of the alpha-emitting radioisotopes lead- 212/bismuth-212, and radium-223 were produced. However, only minute amounts of molybdenum-99, and the generating isotope of bismuth-213 were produced. / Thesis / Master of Applied Science (MASc)
40

Modélisation de réseaux d'interactions des microARN et analyse et validation expérimentale de leurs boucles minimales avec des facteurs de transcription

Lisi, Véronique 12 1900 (has links)
Les microARN (miARN) sont de petits ARN non-codants qui répriment la traduction de leurs gènes cibles par hybridation à leur ARN messager (ARNm). L'identification de cibles biologiquement actives de miARN est cruciale afin de mieux comprendre leurs rôles. Ce problème est cependant difficile parce que leurs sites ne sont définis que par sept nucléotides. Dans cette thèse je montre qu'il est possible de modéliser certains aspects des miARN afin d'identifier leurs cibles biologiquement actives à travers deux modélisations d'un aspect des miARN. La première modélisation s'intéresse aux aspects de la régulation des miARN par l'identification de boucles de régulation entre des miARN et des facteurs de transcription (FT). Cette modélisation a permis, notamment, d'identifier plus de 700 boucles de régulation miARN/FT, conservées entre l'humain et la souris. Les résultats de cette modélisation ont permis, en particulier, d'identifier deux boucles d'auto-régulation entre LMO2 et les miARN miR-223 et miR-363. Des expériences de transplantation de cellules souches hématopoïétiques et de progéniteurs hématopoïétiques ont ensuite permis d'assigner à ces deux miARN un rôle dans la détermination du destin cellulaire hématopoïétique. La deuxième modélisation s'intéresse directement aux interactions des miARN avec les ARNm afin de déterminer les cibles des miARN. Ces travaux ont permis la mise au point d'une méthode simple de prédiction de cibles de miARN dont les performances sont meilleures que les outils courant. Cette modélisation a aussi permis de mettre en lumière certaines conséquences insoupçonnées de l'effet des miARN, telle que la spécificité des cibles de miARN au contexte cellulaire et l'effet de saturation de certains ARNm par les miARN. Cette méthode peut également être utilisée pour identifier des ARNm dont la surexpression fait augmenter un autre ARNm par l'entremise de miARN partagés et dont les effets sur les ARNm non ciblés seraient minimaux. / microRNAs (miRNAs) are small non coding RNAs that repress the translation of their target genes by pairing to their messenger RNA (mRNA). The identification of miRNAs' biologically active targets is a difficult problem because their binding sites are defined by only seven nucleotides. In this thesis, I show that it is possible to model specific aspects of miRNAs to identify their biologically active targets through two modeling of each one aspect of miRNAs. The first modeling considers the miRNAs regulations through the identification of regulatory loops between miRNAs and transcription factors (TFs). Through this modeling, we identified over 700 miRNA/TF regulatory loops conserved between human and mouse. With the results of this modeling, we were able to identify, in particular, two regulatory loops between LMO2 and the miRNAs miR-223 and miR-363. Using hematopoietic stem cells and progenitor cells transplantation experiment we showed that miR-223 and miR-363 are involved in hematopoietic cell fate determination. The second modeling focuses directly on the interaction between miARN and messenger RNA (mRNA) to determine the miRNA targets. With this work, we developed a simple method for predicting miRNA targets that outperforms the current state of the art tool. This modeling also highlighted some unsuspected consequences of miRNA effects such as the cell context specificity and the saturation of mRNA targets by miRNA. This method can also be used to identify mRNAs whose overexpression increases the expression level of another mRNA through their shared miRNA and whose global effects on other genes are minimal.

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