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No description available.

La maturation lymphocytaire B est sous le contrôle des éléments cis-régulateurs des gènes d’Ig. Les quatre activateurs transcriptionnels (hs3a, hs1,2, hs3b et hs4) de la région régulatrice en 3’ du locus IgH (3’RR) murin sont les éléments clés pour les hypermutations somatiques (SHM) et les recombinaisons isotypiques (CSR). La 3’RR stimule aussi la transcription d’Ig au stade mature du développement B. La 3’RR, en association avec un oncogène, est un dérégulateur puissant conduisant au développement de lymphomes B. Actuellement rien n’est connu sur le rôle de la 3’RR lors de réactions immunes et/ou inflammatoires normales. Durant ma thèse, nous avons étudié l’impact de la délétion de la 3’RR sur le développement d’une réaction inflammatoire en réponse au pristane chez les souris BALB/c. Ces études nous ont permis de montrer que l’absence de la 3’RR ne perturbe pas l’apparition d’une réaction inflammatoire (cinétique de l’ascite, volume, cellularité, recrutement en cellules inflammatoires et leur capacité à produire des cytokines inflammatoires et anti-inflammatoires). Ceci suggère la présence de lymphocytes B physiologiquement aptes à induire/propager/maintenir une réaction inflammatoire et immune robuste et efficiente en absence d’une 3’RR fonctionnelle. Après avoir étudié le rôle de la délétion de la 3’RR dans un contexte inflammatoire, nous avons analysé son rôle dans un contexte de lymphomagenèse. Pour cela nous avons mis l’absence de la 3’RR dans un fond génétique murin apte à développer des lymphomes B matures (souris Igλ-Myc). On observe un changement important dans le phénotype des lymphomes B en absence de la 3’RR avec un plus grand nombre de lymphomes B immatures, une baisse du nombre de lymphomes B matures CD43+ et une augmentation de lymphomes B CD5+. Le rôle de la 3’RR dans la survenue de mutations aux stades B matures durant la SHM et la CSR est suggéré pour expliquer ces résultats. En conclusion, le ciblage pharmacologique de la 3’RR pour bloquer son effet pro-oncogènique transcriptionnel sur un oncogène transloqué au locus IgH pourrait se révéler une approche prometteuse pour le traitement de certains lymphomes B matures humains. / B-cell maturation is under the control of the cis-regulatory elements of Ig genes. The four transcripional enhancers (hs3a, hs1,2, hs3b and hs4) of the mouse IgH 3’ regulatory region (3’RR) are the key elements for somatic hypermutation (SHM) and class-switch recombination (CSR). The 3'RR also stimulates Ig transcription during the mature B-cell stage. When associated with an oncogene, the 3’RR is a potent deregulator leading to B-cell lymphomas. Currently nothing is known about its role in the development of immune and inflammatory reactions. During my thesis, we have studied the impact of the 3’RR deletion on the development of inflammatory reactions in response to pristane in BALB/c mice. These studies have allowed us to show that the lack of the 3'RR does not disturb the development of an efficient inflammatory reaction in response to pristane (kinetics of appearance of ascites, volume, cellularity, recruitment of inflammatory cells and their capacity to produce inflammatory and anti-inflammatory cytokines). This suggests the presence of B-cells physiologically capable to induce/spread/maintain a robust and efficient inflammatory immune response. After studying the role of the deletion of the 3'RR in an inflammatory context we have investigated the role of the 3’RR in a lymphomagenesis. For this we brought the 3’RR deficiency in a genetic background able to develop mature B-cell lymphomas (Igλ-Myc mice). While wt mice develop mature and immature B-cell lymphomas, 3’RR-deficient mice exhibit a strong preference for immature lymphomas. Furthermore 3’RR-deficiency leads to a lowered frequency of CD43+ activated B-cell lymphomas and to an increased frequency of CD5+ B-cell lymphomas. CSR and SHM are abrogated in 3’RR-deficient mice lowering the probability of oncogenic mutations during these stages. Pharmacological targeting of 3'RR to block its transcriptional pro-oncogenic effect on translocated oncogene into IgH locus might be a promising approach for the treatment of some mature human B-cell lymphomas.

Barrier options are the most popular and traded derivatives in the financial market because of their lower prices. Many studies have been conducted to develop the methods of pricing barrier options. Barrier option prices can be calculated using the classical binomial tree method, but it is time-consuming when we have a large number of time periods. Muroi and Yamada have developed a new fast algorithm to obtain the prices of barrier options by using the spectral expansion approach. We implement and check this algorithm by doing more extensive numerical experimental studies and showing that the same prices calculated using the binomial tree method can also be obtained using the spectral binomial tree approach with a higher computational speed.

No description available.

Knocking is a type of abnormal combustion which depends on several physical factors and results in high frequency pressure oscillations inside the combustion chamber of a spark-ignited internal combustion engine (ICE). These oscillations can damage the engine and hamper its efficiency, which is why it is important for automakers to understand the knocking behavior so that it can be avoided during engine operation. Due to the catastrophic outcomes of knocking a lot of research has been done in the past on prediction of its occurrence. There can be several causes of knocking but when it occurs due to auto-ignition of fuel in the end-gas it’s called spark-knock. There are various mathematical models that predict the phenomenon of spark-knock. In this thesis, several of the previously published knock prediction models for heavy-duty natural-gas engine are studied and analyzed. The main objective of this project is to assess the accuracy of different types of knock prediction models.Amongst all the types of knock prediction models emphasize has been given to empirical correlation models, particularly to the ones which are based on chemical kinetics pertaining to the combustion process of methane. These are the models that claim to predict ignition delay time based on concentration of air and fuel in the unburned zone of the cylinder. The models are assessed based on the knocking behavior they represent across the engine operation range. Results pertaining to the knock prediction models are evaluated in a 1D engine simulation model using AVL BOOST. The BOOST performance prediction model is calibrated against experimentally measured engine test-cell data and the same data is used to assess the knock prediction models.The knock prediction model whose results correlate with experimental observations is analyzed further while other models are discarded. Using the validated model, variation in knock occurrence is evaluated with change in the combustion phasing. Two of the parameter that are used to define the combustion phasing are spark-advance and combustion duration. It was found that when the brake mean effective pressure is kept constant the knock prediction parameter increases linearly with increase in spark advance and decreases linearly with increase in combustion duration. The variation of knock prediction parameter with spark advance showed increasing gradient with increase in engine torque. / Knack i en förbränningsmotor är en typ av onormal förbränning. Det är ett komplicerat fenomen som beror på flera fysiska faktorer och resulterar i högfrekventa tryckoscillationer inuti förbränningskammaren. Dessa oscillationer kan skada motorn och fenomenet hämmar motorns effektivitet. Knack kan uppstå på två sätt i en Otto-motor och detta examensarbete kommer att handla om självantändning. Självantändning, i detta fall, är när ändgasen börjar brinna utan att ha blivit påverkad av flamfronten eller gnistan från tändstiftet. Det finns flera olika matematiska modeller som i olika grader kan prediktera knackfenomenet. I detta examensarbete studeras några av de tidigare publicerade prediktionsmodellerna för knack i Otto-förbränning och modelleras för analys. Huvudsyftet med detta projekt är således att bedöma noggrannheten hos olika typer av knackmodeller. Extra fokus har lagts på empiriska korrelationsmodeller, särskilt till de som är baserade på kemisk kinetik avseende förbränningsprocessen av metan. Dessa modeller förutsäger den tid det tar för ändgasen att självantända, baserat på dess koncentration av luft och bränsle. Knackmodellerna bedöms sedan utifrån det beteende som de förutsäger över motorns driftområde och dess överensstämmelse med kända motorkalibreringsstrategier. Resultatet av knackpredikteringen för de olika knackmodellerna utvärderas och valideras i en motorsimuleringsmodell i mjukvaran AVL BOOST. BOOST-modellen kalibreras mot experimentellt uppmätta motortestdata. Baserat på resultaten från de valda knockmodellerna så blev den modell som bäst korrelerar med kända motorkalibreringsstrategier analyserad djupare. Den utvalda modellen var en ECM modell och den utvärderas ytterligare med avseende på variation i predikterad knack-parameter. Detta görs genom att modifiera två förbränningsparametrar: tändvinkel och förbränningsduration. Det visade sig att modellerna predikterade en linjär ökning då tändningen tidigareläggs och ett linjärt minskande vid längre förbränningsduration, vilket är i enlighet med motortestdata. Vidare visade det sig att variationer i tändvinkel resulterade i en högre gradient i knackpredikteringen vid högre motorbelastningar och korresponderande minskning vid lägre belastning.

Knack i en förbränningsmotor är en typ av onormal förbränning. Det är ett komplicerat fenomen som beror på flera fysiska faktorer och resulterar i högfrekventa tryckoscillationer inuti förbränningskammaren. Dessa oscillationer kan skada motorn och fenomenet hämmar motorns effektivitet. Knack kan uppstå på två sätt i en Otto-motor och detta examensarbete kommer att handla om självantändning. Självantändning, i detta fall, är när ändgasen börjar brinna utan att ha blivit påverkad av flamfronten eller gnistan från tändstiftet. Det finns flera olika matematiska modeller som i olika grader kan prediktera knackfenomenet. I detta examensarbete studeras några av de tidigare publicerade prediktionsmodellerna för knack i Otto-förbränning och modelleras för analys. Huvudsyftet med detta projekt är således att bedöma noggrannheten hos olika typer av knackmodeller. Extra fokus har lagts på empiriska korrelationsmodeller, särskilt till de som är baserade på kemisk kinetik avseende förbränningsprocessen av metan. Dessa modeller förutsäger den tid det tar för ändgasen att självantända, baserat på dess koncentration av luft och bränsle. Knackmodellerna bedöms sedan utifrån det beteende som de förutsäger över motorns driftområde och dess överensstämmelse med kända motorkalibreringsstrategier. Resultatet av knackpredikteringen för de olika knackmodellerna utvärderas och valideras i en motorsimuleringsmodell i mjukvaran AVL BOOST. BOOST-modellen kalibreras mot experimentellt uppmätta motortestdata. Baserat på resultaten från de valda knockmodellerna så blev den modell som bäst korrelerar med kända motorkalibreringsstrategier analyserad djupare. Den utvalda modellen var en ECM modell och den utvärderas ytterligare med avseende på variation i predikterad knack-parameter. Detta görs genom att modifiera två förbränningsparametrar: tändvinkel och förbränningsduration. Det visade sig att modellerna predikterade en linjär ökning då tändningen tidigareläggs och ett linjärt minskande vid längre förbränningsduration, vilket är i enlighet med motortestdata. Vidare visade det sig att variationer i tändvinkel resulterade i en högre gradient i knackpredikteringen vid högre motorbelastningar och korresponderande minskning vid lägre belastning. / Knocking is a type of abnormal combustion which depends on several physical factors and results in high frequency pressure oscillations inside the combustion chamber of a spark-ignited internal combustion engine (ICE). These oscillations can damage the engine and hamper its efficiency, which is why it is important for automakers to understand the knocking behavior so that it can be avoided during engine operation. Due to the catastrophic outcomes of knocking a lot of research has been done in the past on prediction of its occurrence. There can be several causes of knocking but when it occurs due to auto-ignition of fuel in the end-gas it’s called spark-knock. There are various mathematical models that predict the phenomenon of spark-knock. In this thesis, several of the previously published knock prediction models for heavy-duty natural-gas engine are studied and analyzed. The main objective of this project is to assess the accuracy of different types of knock prediction models. Amongst all the types of knock prediction models emphasize has been given to empirical correlation models, particularly to the ones which are based on chemical kinetics pertaining to the combustion process of methane. These are the models that claim to predict ignition delay time based on concentration of air and fuel in the unburned zone of the cylinder. The models are assessed based on the knocking behavior they represent across the engine operation range. Results pertaining to the knock prediction models are evaluated in a 1D engine simulation model using AVL BOOST. The BOOST performance prediction model is calibrated against experimentally measured engine test-cell data and the same data is used to assess the knock prediction models. The knock prediction model whose results correlate with experimental observations is analyzed further while other models are discarded. Using the validated model, variation in knock occurrence is evaluated with change in the combustion phasing. Two of the parameter that are used to define the combustion phasing are spark-advance and combustion duration. It was found that when the brake mean effective pressure is kept constant the knock prediction parameter increases linearly with increase in spark advance and decreases linearly with increase in combustion duration. The variation of knock prediction parameter with spark advance showed increasing gradient with increase in engine torque.

Au cours d'une étude sur le contrôle transcriptionnel du gène de l'alpha-foetoprotéine, le laboratoire s'était intéressé aux facteurs de transcription de la famille SP/KLF et S. Scohy avait découvert une séquence définissant un nouveau membre: SP6. Afin de déterminer la structure du gène chez la souris, nous avons isolé un fragment génomique contenant la totalité du gène et nous l'avons séquencé. Une analyse informatique de cette séquence, l'isolement d'ESTs ainsi qu'une expérience d'extension d'amorce, nous ont permis d'affirmer que le gène Sp6 murin possède deux exons, générant une protéine de 376 acides aminés à partir d'un ATG repéré au début de l'exon 2. En même temps, des travaux réalisés sur un gène nommé epiprofin ont été publiés (Nakamura et al. 2004). Ce gène s'est avéré correspondre au gène Sp6 car il code pour la même protéine. Les exons 2 sont en effet identiques, seuls les exons 1 diffèrent. Nos études sur l'expression du gène Sp6 ont indiqué qu'elle est ubiquiste mais que c'est durant le développement embryonnaire, et surtout pendant les stades les plus tardifs de celui-ci, qu'il est le plus exprimé. Cette expression se localise surtout au niveau des dents, de l'épithélium olfactif, du cerveau, des bourgeons de membres et des follicules pileux de l'embryon. A l'état adulte, l'expression de Sp6 se réduit fortement dans tous les tissus; seuls les poumons présentent un taux d'expression relativement important. Ce travail a également permis de mettre en évidence l'existence d'un transcrit non-codant issu d'une transcription antisens du locus Sp6 et dont le premier exon inclu la totalité de l'exon 2 du gène Sp6. Nous l'avons appelé Sp6os et avons montré que son expression est absente dans de nombreux tissus et est très faible dans les tissus où on détecte le transcrit. Une comparaison de l'expression des transcrits Sp6 et Sp6os nous a permis d'imaginer un rôle pour Sp6 dans le développement et une possible modulation de son activité, par Sp6os, dans certains tissus. Afin de préciser la fonction du locus Sp6, nous l'avons invalidé chez la souris. Les mutants Sp6-/- se sont avérés viables mais présentent des anomalies dans tous les tissus où Sp6 est le plus fortement exprimé. En effet, ils n'ont ni pelage, ni vibrisse et montrent des anomalies des dents, des membres et des poumons. Nous avons également noté une dérégulation importante de l'apoptose (et parfois aussi de la prolifération cellulaire) chez ces souris Sp6-/-.

2 Abstract Eukaryotic initiation factor 3 (eIF3) is a critical player involved in many steps of translation initiation, which ultimately result in the formation of the elongation competent 80S ribosome. With its 13 subunits (eIF3a - eIF3m) it is the largest and the most complex translation initiation factor composed of three mutually interconnected modules (i - iii), however, the role of individual subunits involved in its structural integrity and proper function is not fully explored. The eIF3e subunit was shown to be a part of the human eIF3 structural core and to help in the mRNA recruitment to the 43S pre-initiation complex by forming a molecular bridge between the 40S ribosomal subunit and the mRNA cap-binding complex. In this study, we employed siRNA-directed downregulation of eIF3e in HeLa cells and analysed its impact on the overall eIF3 integrity and function in vivo. The eIF3e knock-down (eIF3eK.D. ) led to the severe reduction of protein amounts of other three subunits (eIF3d, k and l), which together with the subunit eIF3c and e form module ii of the eIF3 complex. Remaining module i (composed of a, b, g and i) and iii (containing f, h and m) stayed partially bound perhaps thanks to a bridging effect of eIF3c, and showed reduced binding efficiency towards the 40S subunit compared to control...

Este trabalho apresenta um estudo para a qualificação do sensor de detonação como elemento de realimentação para o sistema de controle eletrônico de motores de combustão interna. A metodologia proposta consiste no uso do sensor de detonação, previamente instalado pelo fabricante do motor com a finalidade de eliminar o indesejável efeito da combustão espontânea, para amostrar as vibrações mecânicas produzidas pelo motor em funcionamento. Tal vibração, resultado de massas em movimento e da oscilação natural do sistema excitado pela combustão, produz uma figura espectral na faixa de freqüências do som audível. O método proposto contempla ainda as variações espectrais das vibrações de um mesmo motor operando com diferentes misturas combustíveis. / This dissertation analyses the suitability of using the knock sensor as a feedback element for the electronic control of internal combustion engines. The proposed approach consists of using the knock sensor, originally installed by the engine maker in order to eliminate the spontaneous combustion effect, to sample the mechanical vibration produced by the engine. This vibration, which results from the moving parts and the natural oscillation of the system in combustion, produces an output in the range of audible sound. This research contemplates using the spectral variation of that sound to estimate information about an engine operating with different fuel blends.