There is a growing interest in alternative transport fuels. There are two underlying reasons for this interest; the desire to decrease the environmental impact of transports and the need to compensate for the declining availability of petroleum. In the light of both these factors the Diesel Dual Fuel, DDF, engine is an attractive concept. The primary fuel of the DDF engine is methane, which can be derived both from renewables and from fossil sources. Methane from organic waste; commonly referred to as biomethane, can provide a reduction in greenhouse gases unmatched by any other fuel. The DDF engine is from a combustion point of view a hybrid between the diesel and the otto engine and it shares characteristics with both. This work identifies the main challenges of DDF operation and suggests methods to overcome them. Injector tip temperature and pre-ignitions have been found to limit performance in addition to the restrictions known from literature such as knock and emissions of NOx and HC. HC emissions are especially challenging at light load where throttling is required to promote flame propagation. For this reason it is desired to increase the lean limit in the light load range in order to reduce pumping losses and increase efficiency. It is shown that the best results in this area are achieved by using early diesel injection to achieve HCCI/RCCI combustion where combustion phasing is controlled by the ratio between diesel and methane. However, even without committing to HCCI/RCCI combustion and the difficult control issues associated with it, substantial gains are accomplished by splitting the diesel injection into two and allocating most of the diesel fuel to the early injection. HCCI/RCCI and PPCI combustion can be used with great effect to reduce the emissions of unburned hydrocarbons at light load. At high load, the challenges that need to be overcome are mostly related to heat. Injector tip temperatures need to be observed since the cooling effect of diesel flow through the nozzle is largely removed. Through investigation and modeling it is shown that the cooling effect of the diesel fuel occurs as the fuel resides injector between injections and not during the actual injection event. For this reason; fuel residing close to the tip absorbs more heat and as a result the dependence of tip temperature on diesel substitution rate is highly non-linear. The problem can be reduced greatly by improved cooling around the diesel injector. Knock and preignitions are limiting the performance of the engine and the behavior of each and how they are affected by gas quality needs to be determined. Based on experiences from this project where pure methane has been used as fuel; preignitions impose a stricter limit on engine operation than knock. / QC 20120626 / Diesel Dual Fuel

<p>  </p> <p>Zebrafish (<em>Danio rerio</em>) is a well-established model to study neutrophil biology. However, a lack of standard tissue-specific knockdown or knockout technique in the zebrafish field has limited the power of this model organism when studying developmental essential genes, such as those related to mitochondrial function. We have developed a robust and flexible neutrophil-restricted knockout in zebrafish based on CRISPR/Cas9 system, with which we gained insights into the role of Rac2 in regulating the actin cytoskeleton and the subcellular location of Rac activation in zebrafish neutrophils.</p> <p>Previous study in our lab using another neutrophil-specific knockout system addressed multiple mitochondrial proteins regulate neutrophil motility in zebrafish. Interestingly, we observed <em>Mfn2</em>-deficient neutrophils trapped in the vasculature in zebrafish embryos. Here we further characterized the function of MFN2 in regulating cell migration with neutrophil-like HL-60 cells and mice embryonic fibroblasts (MEFs). We found significant changes in actin organization in both <em>MFN2</em>-deficient neutrophil-like cells and MEFs and mechanistically, disrupted mitochondria-ER interaction, increased intracellular Ca2+ levels. We also investigated the cytoskeleton proteins and observed hyperactivation of RhoA and Myosin light chain kinase, along with accumulation of phosphorylated myosin light chain at the cell boundary in <em>MFN2</em>-deficient MEFs. These altered MFN2-Ca2+-RhoA/MLCK-myosin signaling finally affects the peripheral actin bundle architecture and forms the “Peripheral Actin Myosin Belt (PAMB)” structure. The formation of PAMB hampered cell adhesive migration in <em>Mfn2</em>-null MEFs. </p> <p>Altogether, our research gained new insights into the essential role of MFN2 in cytoskeleton regulation and the underlying molecular mechanisms, which may provide a new direction to understand the relevance of this gene in immune cell dysfunction and other MFN2-associated diseases.</p>

Pour répondre aux défis environnementaux actuels, des solutions en rupture par rapport aux turbomachines existantes sont actuellement encours de développement. Elles s’appuient sur des cycles thermodynamiques plus efficients.L’objectif de ces travaux de thèse est d’étudier expérimentalement les mécanismes de transition de régime de combustion pour ce type d'applications en utilisant un surrogate de kérosène, le n-décane. Pour cela, une déflagration est initiée dans une enceinte fermée et comprime les gaz frais. La pression et la température de ces derniers augmentent jusqu’à atteindre les conditions propices à l’apparition de l’autoinflammation.3 régimes de combustion successifs sont caractérisés dans la chambre de combustion au moyen de diagnostics optiques rapides. Un premier dégagement de chaleur associé à la flamme froide pré-oxyde les gaz frais, il est suivi du dégagement de chaleur principal (Main Heat Release,MHR). Pour les températures initiales de mélange les plus élevées, une détonation est observée à la fin du processus. Deux chemins de transition différents sont mis en évidence : la transition Déflagration-Auto-inflammation (DAIT) et la transition Déflagration-Auto-inflammation-Détonation (DAIDT). La sensibilité des transitions de régime aux conditions initiales de pression, de température et de richesse a été caractérisée au moyen de plusieurs études paramétriques. Dans ce but, les conditions de température, de pression et de composition du mélange sont calculées aux instants d’apparition des différents fronts réactifs (flamme froide, MHR et détonation). Il a notamment été observé que les dégagements de chaleur successifs de l’auto-inflammation se déroulaient aux mêmes températures (740 K pour la flamme froide et 1050 K pour le MHR)quelles que soient les conditions initiales. L’étude s’est concentrée ensuite sur l’analyse d’un point de fonctionnement particulier. L’étude de ce point de fonctionnement, différents vitesses de front d’auto-inflammation ont été observées, mettant en évidence le mécanisme de SWACER lors de la transition.Un critère de transition de régime depuis l’auto-inflammation proposé de Zander et al., dans le cadre d’études numériques, a été testé dans notre configuration expérimentale. Un critère modifié a été développé en lui adjoignant la notion d’effets de compressibilité dans l’écoulement réactif. L’application de ce critère à l’ensemble des essais permet de prédire l’apparition de la détonation dans les conditions où 0 et 100 % de DAIDT sont observés. Les différents domaines de transition de régime ont également été positionnés sur le diagramme de Bradley (ξ, ϵ). Les modes de combustion prédits par le diagramme sont consistants avec ceux qui sont atteints dans la chambre.L’influence de la distribution initiale de température sur les modes de combustion atteignables dans la chambre a été étudiée. Trois topologies d’auto-inflammation ont été mises en évidence pour trois distributions de température dans la chambre. Ces topologies sont séparées en deux catégories, celles privilégiant une direction particulière lors de l’auto-inflammation séquentielle et celle présentant un comportement tridimensionnel.Les essais ayant un comportement tridimensionnel présentent une très forte propension à la DAIDT mais une propagation lente des fronts d’auto-inflammation. Dans ce cas, un autre mécanisme de transition vers la détonation est mis en évidence : l’auto-inflammation d’une poche homogène de gaz génère des ondes de choc et déclenchent des auto-inflammations successives pendant leur propagation. Le couplage choc/front réactif entraine la formation de la détonation.Différents mécanismes de transition vers la détonation ont été observés et étudiés sur une large plage de conditions de pression, température,richesse et gradient thermique. Les résultats obtenus permettront d’appuyer les études numériques réalisées sur le sujet, manquant jusque-là de données expérimentales en conditions académiques. / To meet the current environmental challenges, breakthrough solutions compared to existing turbomachines are currently under development.They rely on the use of more efficient thermodynamic cycles.The objective of this thesis is to study experimentally the mechanisms of transition of combustion regime using a kerosene surrogate, n-decane.For this purpose, a deflagration is initiated in a closed chamber and compresses the fresh gases. The pressure and the temperature of the endgas increase until reaching the conditions favorable to the appearance of the autoignition in the chamber.3 successive combustion regimes are characterized in the combustion chamber by means of fast optical diagnostics. A first heat release,associated with the cool flame phenomenon, pre-oxidizes the fresh gases, it is followed by the Main Heat Release (MHR). For the highest initial temperatures, a detonation is observed at the end of the process. Two different transition paths are highlighted: the Deflagration-Autoignition Transition (DAIT) and the Deflagration-Autoignition-Detonation Transition (DAIDT).The sensitivity of regime transitions to the initial conditions of pressure, temperature and mixture composition was characterized by means of several parametric studies. For this purpose, the conditions of temperature, pressure and composition of the mixture are calculated at the onset of the different reactive fronts (cool flame, MHR and detonation). In particular, it has been observed that the successive heat releases of theauto-ignition start at the same temperatures (740 K for the cool flame and 1050 K for the MHR) whatever the initial conditions. The study, then, focused on the analysis of a particular operating point. During the study of this operating point different self-ignition front velocities were observed, highlighting the mechanism of SWACER during the transition.A regime transition criterion proposed by Zander et al. based on numerical studies has been tested in our experimental setup. A modified criterion has been developed to take into account compressibility effects in the reactive flow. The application of this criterion to all the dataset makes possible to predict the appearance of the detonation under the conditions where 0 and 100% of DAIDT are observed. The different regime transition domains have also been positioned on the Bradley diagram (ξ, ε). The modes of combustion predicted by the diagram are consistent with those reached in the chamber.The influence of the initial temperature distribution on the combustion modes achievable in the chamber has been studied. Three topologies of autoignition have been demonstrated for three initial temperature distributions in the chamber. These topologies are separated into two categories, those favoring a particular direction during sequential self-ignition and that exhibiting a three-dimensional behavior.Three-dimensional tests show a very high propensity for DAIDT but a slow spread of autoignition fronts. In this case, another mechanism of transition to detonation is evidenced: the self-ignition of an homogeneous gas pocket generates shock waves and triggers successive autoinflammations during their propagation. The shock coupling / reactive front causes the formation of the detonation. Different transition mechanisms to detonation have been observed and studied over a wide range of pressure, temperature, equivalence ratio and thermal gradient conditions. The obtained results will be useful to support the numerical studies carried out on the subject, which lacks experimental data in academic conditions.

Cities are rapidly expanding, and global warming is intensified in urban environments due to the urban heat island effect. Therefore, urban animals may be particularly susceptible to warming associated with ongoing climate change. Thus, I used a comparative and manipulative approach to test three related hypotheses about the determinants of heat tolerance or critical thermal maximum (CTmax) in urban ants—specifically, that (1) body size, (2) hydration status, and (3) preferred micro-environments influence CTmax. I further tested a fourth hypothesis that native species are particularly physiologically vulnerable in urban environments. I manipulated water access and determined CTmax for 11 species common to cities in California's Central Valley that exhibit nearly 300-fold variation in body mass. Inter- (but not intra-) specific variation in body size influenced CTmax where larger species had higher CTmax. The sensitivity of ants’ CTmax to water availability exhibited species-specific thresholds where short-term water limitation (8 h) reduced CTmax in some species while longer-term water limitation (32 h) was required to reduce CTmax in other species. However, CTmax was not influenced by the preferred foraging temperatures of ants. Further, I did not find support for my fourth hypothesis because native species did not exhibit reduced thermal safety margins, or exhibit CTmax values that were more sensitive to water limitation relative to non-native species. In sum, understanding the links between heat tolerance and water availability will become critically important in an increasingly warm, dry, and urbanized world that may be selecting for smaller (not larger) body size.

No description available.

This licentiate thesis concerns one dimensional flow simulation of turbocharged spark ignited engines. The objective has been to contribute to the improvement of turbocharged SI engines’ performance as well as 1 D simulation capabilities. Turbocharged engines suffer from poor gas exchange due to the high exhaust pressure created by the turbine. This results in power loss as well as high levels of residual gas, which makes the engine more prone to knock. This thesis presents an alternative gas exchange concept, with the aim of removing the high exhaust pressure during the critical periods. This is done by splitting the two exhaust ports into two separate exhaust manifolds. The alternative gas exchange study was performed by measurements as well as 1-D simulations. The link between measurements and simulations is very strong, and will be discussed in this thesis. As mentioned, turbocharged engines are prone to knock. Hence, finding a method to model knock in 1-D engine simulations would improve the simulation capabilities. In this thesis a 0-D knock model, coupled to the 1-D engine model, is presented / QC 20101112

Background Hyperphosphorylation and intraneuronal aggregation of the microtubule-associated protein tau is a major pathological hallmark of Alzheimer’s disease (AD) brain. Of special interest is the effect of cerebral amyloid beta deposition, the second main hallmark of AD, on human tau pathology. Therefore, studying the influence of cerebral amyloidosis on human tau in a novel human tau knock-in (htau-KI) mouse model could help to reveal new details on their interplay. Methods We studied the effects of a novel human htau-KI under fast-progressing amyloidosis in 5xFAD mice in terms of correlation of gene expression data with human brain regions, development of Alzheimer’s-like pathology, synaptic transmission, and behavior. Results The main findings are an interaction of human beta-amyloid and human tau in crossbred 5xFADxhtau-KI observed at transcriptional level and corroborated by electrophysiology and histopathology. The comparison of gene expression data of the 5xFADxhtau-KI mouse model to 5xFAD, control mice and to human AD patients revealed conspicuous changes in pathways related to mitochondria biology, extracellular matrix, and immune function. These changes were accompanied by plaque-associated MC1-positive pathological tau that required the htau-KI background. LTP deficits were noted in 5xFAD and htau-KI mice in contrast to signs of rescue in 5xFADxhtau-KI mice. Increased frequencies of miniature EPSCs and miniature IPSCs indicated an upregulated presynaptic function in 5xFADxhtau-KI. Conclusion In summary, the multiple interactions observed between knocked-in human tau and the 5xFAD-driven progressing amyloidosis have important implications for future model development in AD.

Hepatitis E Virus (HEV), the causative agent of hepatitis E, is a zoonotic pathogen of worldwide significance. The genus Orthohepevirus A of the family Hepeviridae includes all mammalian strains of HEV and consists of 8 recognized genotypes. Genotypes 1 and 2 HEVs only infect humans and genotypes 3 and 4 infect humans and several other animal species including pigs and rabbits. An ever-expanding host range of genetically-diversified strains of HEV now include bat, fish, rat, ferret, moose, wild boar, mongoose, deer, and camel. Additionally, the ruminant species goats, sheep, and cattle have been implicated as potential reservoirs as well. My dissertation research investigates a novel animal model for HEV, examines the immune dynamics during acute infection, and evaluates the possibility of additional animal reservoirs of HEV. The first project established an immunoglobulin (Ig) heavy chain knock-out JH (-/-) gnotobiotic piglet model that mimics the course of acute HEV infection observed in humans and evaluated the pathogenesis of HEV infection in this novel animal model. The dynamics of acute HEV infection in gnotobiotic pigs were systematically determined with a genotype 3 human strain of HEV. We also investigated the potential role of immunoglobulin heavy-chain JH in HEV pathogenesis and immune dynamics during the acute stage of virus infection. This novel gnotobiotic pig model will aid in future studies into HEV pathogenicity, an aspect which has thus far been difficult to reproduce in the available animal model systems. The objective of the second project for my PhD dissertation was to determine if cattle in the United States are infected with a bovine strain of HEV. We demonstrated serological evidence of an HEV-related agent in cattle populations with a high level of IgG anti-HEV prevalence. We demonstrated that calves from a seropositive cattle herd seroconverted to IgG binding HEV during a prospective study. We also showed that the IgG anti-HEV present in cattle has an ability to neutralize genotype 3 human HEV in vitro. However, our exhaustive attempts to detect HEVrelated sequence from cattle in the United States failed, suggesting that one should be cautious in interpreting the IgG anti-HEV serological results in bovine and other species. Collectively, the work from my PhD dissertation delineated important mechanisms in HEV pathogenesis and established a novel animal model for future HEV research. / Ph. D. / Hepatitis E Virus (HEV), the causative agent of hepatitis E, is a zoonotic pathogen of worldwide significance. According to the World Health Organization, there are approximately 20 million HEV infections annually, which result in 3.3 million cases of acute hepatitis E and >44,000 HEV-related deaths. Hepatitis E is a self-limiting acute disease in general, but carries the ability to cause high mortality in pregnant women and chronic hepatitis in immunocompromised individuals. The underlying mechanisms of HEV host tropism and progression of disease to chronicity are unknown. My dissertation work investigates a novel animal model for HEV, evaluates the possibility of additional animal reservoirs of HEV, and examines the immune dynamics during acute infection. The first project established an immunoglobulin (Ig) heavy chain knock-out JH (-/-) gnotobiotic piglet model that mimics the course of acute HEV infection observed in humans. The dynamics of acute HEV infection were determined in both the knock-out and wild-type piglets with a genotype 3 strain of human HEV. We also investigated the potential role of immunoglobulin heavy-chain JH in HEV pathogenesis and virus infection. In the second project, we determined if cattle in the United States are infected with a bovine strain of HEV. We showed serological evidence of an HEV-related agent in cattle as well as calves born in a seropositive herd. Despite the detection of specific antibodies recognizing HEV in cattle, definitive evidence of virus infection could not be demonstrated. Our exhaustive attempts to detect HEV-related sequence from cattle in the United States failed, suggesting that one should be cautious in interpreting the IgG anti-HEV serological results in bovine and other species. Collectively, the work from my PhD dissertation research delineated important mechanisms in HEV pathogenesis and established a novel animal model for future HEV research.

For diesel engines, valve timing is important and is related to power efficiency and exhaust gas after-treatment. During operation, the temperature of engine components can change and thus influencing the actual valve timing. With collected data from a Scania experimental engine, a method for valve closing time detection based on knock sensors is proposed in this project using a signal processing method. For algorithm design and result evaluation purposes, two references are used in this project. One is nominal valve timing, and the other is a valve timing reference based on rocker arm force signals. The developed method is tested through 4 evaluations: (1) 30% engine load with different engine speeds (600 to 2000rpm), (2) 1200rpm engine speed with different engine loads (0 to 100%), (3) 40% load 1200rpm at different oil temperature (around 50 to 80°C), and (4) 40% load dropped to motored condition. By comparing evaluation results and previously reported data, the following conclusions can be drawn: (a) The developed method has the ability to catch the changing of valve closing time in most test cases; (b) The developed method has a maximum combined error (between detected valve closing and rocker arm unloaded time) of - 4.7CAD on the intake side and -12.6CAD on the exhaust side among all cylinders; (c) Due to interference from vibration caused by valve events of other cylinders, the developed method has worse accuracy with larger than 50% load. Further work can focus on the detection of valve opening time and the improvement of accuracy by finding better sensor positions. / För dieselmotorer är ventiltidpunkten viktig och relaterad till energieffektivitet och avgasefterbehandling. Under drift kan temperaturen på motorkomponenterna förändras och därmed påverka ventilernas faktiska timing. Med insamlade data från en Scania experimentell motor föreslås i detta projekt en metod för detektering av ventilstängningstid baserad på knackgivare med hjälp av en signalbehandlingsmetod. För algoritmdesign och resultatutvärdering används två referenser i detta projekt. Den ena är nominell ventiltidpunkt och den andra är en ventiltidsreferens baserad på vipparmskraftssignaler. Den utvecklade metoden testas genom 4 utvärderingar: (1) 30% motorbelastning med olika motorvarvtal (600 till 2000r/min), (2) 1200r/min motorvarvtal vid olika motorbelastningar (0 till 100%), (3) 40% belastning 1200r/min vid olika oljetemperatur (runt 50 till 80 °C), och (4) 40% belastning till motordrivet tillstånd. Genom att jämföra utvärderingsresultat och tidigare rapporterade data kan följande slutsatser dras: (a) Den utvecklade metoden har förmågan att fånga ändring av ventilstängningstiden i de flesta testfall; (b) Den utvecklade metoden har ett maximalt kombinerat fel (mellan detekterad ventilstängning och vipparmslasttid) på -4,7CAD på inloppssidan och -12,6CAD på avgassidan bland alla cylindrar. (c) På grund av vibrationsstörningar orsakade av ventilhändelser hos andra cylindrar har den utvecklade metoden sämre noggrannhet med större än 50% last. Det fortsatta arbetet kan fokusera på detektering av ventilernas öppningstid, förbättring av noggrannheten genom att hitta bättre givarpositioner.

No description available.