(English) snRNPs are key components of the spliceosome. During their life, they are found in the cytoplasm and also in the nucleus, where carry out their function. There are five major snRNPs named according to RNA they contain U1, U2, U4, U5 and U6. Each snRNP consists from RNA, ring of seven Sm or LSm proteins and additional proteins specific for each snRNP. Their biogenesis starts in the nucleus, where they are transcribed. Then they are transported into the cytoplasm. During their cytoplasmic phase, the SMN complex forms the Sm ring around the specific sequence on snRNA and cap is trimethylated. These two modifications are the signals for reimport of snRNA into the nucleus, where they accumulate in the nuclear structures called Cajal bodies (CBs), where the final maturation steps occur. There are several quality control points during snRNP biogenesis that ensure that only fully assembled particles reach the spliceosome. The first checkpoint is in the nucleus immediately after the transcription, when the export complex is formed. The second checkpoint is in the cytoplasm and proofreads Sm ring assembly. If the Sm ring formation fails, the defective snRNPs are degraded in the cytoplasm by Xrn1 exonuclease. However, it is still unclear, how the cell distinguishes between normal and defective...

This work highlights the design process to build a MBD (Multi-Body Dynamics) model with flexible parts for a RCV (Research Concept Vehicle). Full vehicle dynamic simulations of the RCV model with flexible parts were performed for different load cases and the results were compared with that of a MBD model with rigid body components. In addition, FE modelling of the RCV body parts, selection of attachment nodes, generation and verification of Modal Neutral Files (MNFs) are discussed. RCV is a concept vehicle developed at KTH Royal Institute of technology as a research platform to implement, validate and demonstrate results of various research projects. The vehicle consists of body, suspension and tire subsystems which were designed and developed as individual projects. The body subsystem comprises of rollcage, subframe and a composite baseplate. In this project, a MBD model of the RCV was developed in ADAMS/CAR to measure the forces acting at the interface of these body components and also to consider the suspension forces acting on the individual front and rear subframe parts. Finite element (FE) models were incorporated to consider the flexibility of the body components. The RCV is a vehicle constantly evolving with addition of new components to implement and test various research results. To study the application of this method, two Models of the RCV with design modifications were developed and studied. A model of the RCV without rollcage and a model with a rigid link connecting the body components were built and the results of dynamic simulations were compared with that of the existing RCV design. When flexibility of the baseplate was considered in the models, an overall change in dynamics of the body components was observed. Further, observing the results from models with design modifications, it was evident that this method can be used to study the effect of these modifications on the dynamic behaviour of the vehicle. / Det här arbetet belyser konstruktionsprocessen för att bygga en MBD-modell (Multi-Body Dynamics) med flexibla komponenter av konceptfordonet RCV (Research Concept Vehicle). Fullständiga fordonsdynamiska simuleringar med flexibla komponenter utfördes för olika lastfall och resultaten jämfördes med en MBD-modell med stela komponenter. Dessutom diskuteras FE modellering av RCVs olika delsystem, val av kopplingsnoder, generering och verifiering av ”Modal Neutral Files” (MNFs). RCV är ett konceptfordon som utvecklats vid Kungliga Tekniska Högskolan, KTH, som en forskningsplattform för att implementera, validera och demonstrera resultaten av olika forskningsprojekt. Fordonet består av delsystemen; chassi, hjulupphängning, och däck, vilka har utvecklats tidigare i separata projekt. Chassit består i sin tur av delsystemen; ”rollcage”, ”subframe” och ”baseplate”. I detta projekt har en MBD-modell av RCV utvecklats i ADAMS/CAR för att simulera olika körfall och beräkna de krafter som verkar mellan dessa delsystem och att också studera skillnaden i belastning av främre resp. bakre ”subframe”. FE modeller importeradesäven till modellen för att studera effekten av elasticiteten hos komponenterna på fordonets beteende.RVC är ett fordon som konstant utvecklas med tillägg av nya komponenter för att implementera och testa olika forskningsresultat. För att studera tillämpningen av denna metod skapades två modeller av RCV med olika konstruktiva förändringar vilkas inverkan på fordonet studerades. En modell av RCV utan ”rollcage” och en modell med styv länk som förbinder olika delar av chassit skapades och resultaten av dynamiska simuleringar jämfördes med simuleringsresultat för den befintliga RCV-designen. När flexibiliteten hos basplattan beaktades i modellerna observerades förändringar i dynamiken hos chassit vad gäller vertikala förskjutningar och vinkelförskjutningar. Utifrån dessa simuleringar kan vi dra slutsatsen att den utvecklade metoden är användbar för att studera effekter av konstruktionsförändringar på det dynamiska beteendet hos fordonet.

The wake behind a rectangular forebody with variable inlet conditions is investigated. The perforated surface of the two-dimensional rectangular forebody, with a smooth leading edge and a blunt trailing edge, allows for boundary layer modification by means of wall suction. The test section, of which the rectangular forebody is the main part, is experimentally evaluated with a series of hot-wire and Prandtl tube measurements in the boundary layer and the wake. For a suction coefficient of Γ&gt;9, corresponding to 0.9% suction of the free stream velocity, the asymptotic suction boundary layer (ASBL) is obtained at the trailing edge of the forebody for laminar boundary layers (Rex=1.6×105−3.8×105). The key feature of the ASBL, a spatially invariant boundary thickness which can be modified independent of the Reynolds number, is used to perform a unique parametrical study. Turbulent boundary layers (Rex=4.5×105−3.0×106) subject to wall suction are also investigated. For a critical suction coefficient Γcrit, which depends on Rex, the boundary layer relaminarizes. Strong evidence is found to support the hypothesis that turbulent boundary layers will ultimately attain the ASBL as well, provided that the wall suction is strong enough. The effect of the modulated laminar and turbulent boundary layers on the wake characteristics is studied. The shape of the mean wake velocity profile, scaled with the velocity deficit U0and the wake half width ∆y1/2, is found tobe independent of x/h, for x/h&gt; 6 and Reh &gt;6.7×103. The wake width is shown to scale with the effective thickness of the body h+2δ1, where the ratio is expected to vary with the downstream location. A decrease of the displacement thickness leads to a decrease of the base pressure, with Cp,b = −0.36 in the ASBL limit. The Strouhal number based on the effective thickness becomes Sth+2δ1 ≈ 0.29 in the ASBL limit and independent of the plate thickness (h) Reynolds number, in the range Reh = 2.9×103 − 6.7×103. For the turbulent boundary Sth+2δ1 is found to be 25% lower, which shows that the wake characteristics depend on the state of the boundary layer at the trailing edge. The total drag is found to be reduced by as much as 30% for Reh = 2.7×104 when a wall normal velocity of only 3.5% of the free stream velocity is applied. Wall suction successively reduces the total drag with increasing wall suction, at least in the Reynolds number rangeReh = 8.0×103−5.5×104. / <p>QC 20140312</p>

Det är viktigt att vägarna håller så länge som möjligt. En faktor som har en påverkan i asfaltens långvarighet är bitumen. När bitumenet föråldras försämras dess egenskaper som ökar risken att skador uppstår på asfalten. Med hjälp av olika tillsatser kan bitumenets egenskaper förbättras. En av dessa egenskaper är bitumenåldring. Sammanlagt finns det tre olika skeden i bitumenåldring. Av dessa tre skeden kommer tillverknings- och användningsskedet att undersökas. I detta examensarbete kommer tre olika tillsatsers påverkan i bitumenföråldring att undersökas. Detta kommer utföras genom laborationer där olika metoder som penetration, mjukpunkt, fraass brytpunkt, DSR, Iatroscan, GPC och FTIR kommer användas. Det kommer också utföras styvhetestester på de tillverkade asfaltskropparna. Resultaten som tas fram i detta examensarbete tyder på att Rediseten har bäst värden avseende åldring utav bitumen. Men detta tros inte vara på grund av tillsatsens inverkan i bitumen utan möjligheten att sänka temperaturen vid tillverkningen av asfalten. / It is important that roads last as long as possible. One factor that has a prolonged effect on asphalt is bitumen. When bitumen ages the characteristics deteriorates which increases the risk for damages on the asphalt. With the help of different additives the characteristics of bitumen could improve. One of these characteristics is bitumen aging. There are three different stages in bitumen aging. Of these three stages will the production and user stage be examined. In this thesis will three additives effect on bitumen aging be examined. This will be performed by doing laboratory experiments where different methods will be used such as penetration, softening point, fraass breaking point, DSR, latroscan, GPC and FTIR. Stiffness tests will be made on the constructed asphalt bodies. Results in this thesis interprets that Rediset has the best values when it comes to aging of bitumen. It is not believed to be the additives effect in the bitumen but the fact that the additive gives the opportunity to lower the temperature during the production of the asphalt.

Central US bodies under the constitutions between 1781 and 1787 and their competences Abstract The subject of this thesis is the central bodies of the United States of America and their competences. In the context of this work the central bodies are the President of the United States as the head of the executive branch, bicameral Congress, consisting of the House of Representatives and the Senate, as the major body of the legislative branch and the Supreme Court as the major body of the judicial branch. The aim of this work was to analyze how these bodies function and their position within the constitutional system of the United States, both horizontally and vertically. The first part of the thesis deals with the circumstances of the establishment of the United States of America, the adoption of the Declaration of Independence and the end of the American War of Independence. The second part deals with the Articles of Confederation, the first US Constitution, and the process of their creation, the bodies that were created on their basis and their competences. The third part deals with the reasons for the creation and process of adoption of the US Constitution, the problems that accompanied its creation, the legal principles on the basis of which it was created and the content of the Bill of Rights. The...

Tremendously popular in American society, the breast cancer movement functions through a rhetoric of risk to persuade women to monitor their breasts and thus medicalize their bodies. The vast majority of breast cancer literature available is specifically aimed at women with breast cancer, while the research here examines the way the breast cancer literature actually includes women without breast cancer in its audience, expecting these women to see breast cancer as an eventual experience. The rhetoric of risk focuses on lifestyle choices, the body, genes, and the environment in order to encourage women to engage in body projects to prevent breast cancer. The attention to risk factors without reliable facts produces fear of the body. Prevention of breast cancer, really impossible, becomes synonymous with early detection, thus displacing responsibility for the disease from society to the individual. Through the rhetoric of risk, the breast cancer movement promotes the ideology of femininity by manipulating women to become complicit subjects in their subordination. Furthermore, the directives, as yet unproven, to prevent breast cancer are the same directives to attain the white heterosexist ideal of beauty. The woman is thus reinscribed into the traditional feminine role of caretaker (of her body) and femininity is not only preserved but produced despite a disease that physically threatens a woman's most visible marker of her femininity, the breast. / Master of Arts

The Pneumocystis carinii carinii DNA content in nuclei of trophic forms and cysts (spore cases) containing 2, 4, or 8 intracystic bodies, were compared using quantitative fluorescence image analysis. The nuclear DNA content was found to be lower than the theoretical limits of Feulgen cytophotometry. Several fluorescent DNA dyes provide brighter staining, but these techniques suffer from nonspecific binding to other cellular components, such as RNA. It was demonstrated that the thick glycocalyx surfaces of trophic forms and the cyst walls of P. carinii organisms, as well as the cell wall of S. cerevisiae, bound all fluorescent dyes tested to varying degrees. Hence in this study, measurements were performed on cells in which the outer surfaces of organisms were first removed with lyticase. Two stains that appeared most specific for DNA, DB181 and 4',6-diamidino-2-phenylindole (DAPI), were used for quantitations; lower deviations of fluorescence intensities were observed with DB181. Haploid wild type Saccharomyces cerevisiae and cdc-28 temperature-sensitive mutant cells, accumulated at the restrictive temperature (37°C), were used as quantitative internal standards for estimating the absolute nuclear DNA content of P. carinii. Haploid wild type and mutant nuclei stained with DAPI had the same relative fluorescence intensities. The P. carinii nuclear DNA content of trophic forms and individual intracystic bodies (spores), regardless of life cycle stage, were not different. The mean values obtained were 6.9 and 6.7 fg DNA/nucleus with DB181 and DAPI, respectively (approximately 9.26 and 8.99 Mbp nucleotides, respectively). Since these would include 2C (G-2 phase) and S-phase nuclei, a 1C population of nuclei was selected by histogram distributions of DB181-stained nuclei. Almost all nuclei analyzed in all life cycle stages fell within this population. The 1C mean of 6.55 fg DNA/nucleus (median, 6.62 fg DNA/nucleus) was estimated as representing 8.79 Mbp nucleotides, assuming only A-T binding of the dye and taking into account the G+C content of S. cerevisiae and P. carinii. A 4C (G-2-phase diploid nuclei) population was not detected in histograms of DB181- or DAPI-stained nuclei. The P. carinii nuclear DNA content values obtained in this study were similar to those independently obtained by calculating the total DNA in the organism's chromosomes resolved by electrophoretic techniques. Together, the data on total chromosome numbers and the estimated DNA content of those chromosomes, with our quantitation of nuclear DNA content of different life-cycle stages demonstrate that P. carinii carinii isolated from infected rat lungs are haploid organisms.

The extension of life span by caloric restriction has been studied across species from yeast and Caenorhabditis elegans to primates. No generally accepted theory has been proposed to explain these observations. Here, we propose that the life span extension produced by caloric restriction can be duplicated by the metabolic changes induced by ketosis. From nematodes to mice, extension of life span results from decreased signaling through the insulin/insulin-like growth factor receptor signaling (IIS) pathway. Decreased IIS diminishes phosphatidylinositol (3,4,5) triphosphate (PIP3) production, leading to reduced PI3K and AKT kinase activity and decreased forkhead box O transcription factor (FOXO) phosphorylation, allowing FOXO proteins to remain in the nucleus. In the nucleus, FOXO proteins increase the transcription of genes encoding antioxidant enzymes, including superoxide dismutase 2, catalase, glutathione peroxidase, and hundreds of other genes. An effective method for combating free radical damage occurs through the metabolism of ketone bodies, ketosis being the characteristic physiological change brought about by caloric restriction from fruit flies to primates. A dietary ketone ester also decreases circulating glucose and insulin leading to decreased IIS. The ketone body, d-β-hydroxybutyrate (d-βHB), is a natural inhibitor of class I and IIa histone deacetylases that repress transcription of the FOXO3a gene. Therefore, ketosis results in transcription of the enzymes of the antioxidant pathways. In addition, the metabolism of ketone bodies results in a more negative redox potential of the NADP antioxidant system, which is a terminal destructor of oxygen free radicals. Addition of d-βHB to cultures of C. elegans extends life span. We hypothesize that increasing the levels of ketone bodies will also extend the life span of humans and that calorie restriction extends life span at least in part through increasing the levels of ketone bodies. An exogenous ketone ester provides a new tool for mimicking the effects of caloric restriction that can be used in future research. The ability to power mitochondria in aged individuals that have limited ability to oxidize glucose metabolites due to pyruvate dehydrogenase inhibition suggests new lines of research for preventative measures and treatments for aging and aging-related disorders.

A functional central nervous system (CNS) is composed of numerous types of neurons. Neurons are derived from a limited number of multipotent neural stem cells. Previous studies have suggested three major strategies nature uses to diversify neurons: lineage identity specification that gives an individual neural stem cell distinct identity based on its position in the developing CNS; temporal identity specification that gives neurons derived from a neural stem cell distinct identities based on their birth-order within the lineage; and binary cell fate specification that gives different identities to the two sister postmitotic neurons derived from the terminal division of a common precursor. Through the combination of the three strategies, almost unlimited neuron types can be generated. To understand neuronal diversification, we have to understand the underlying molecular mechanisms of each of the three strategies. The fruit fly Drosophila melanogaster, has been an excellent model for studying neuronal diversity, mainly due to its easily traceable nervous system and an impressive collection of genetic tools. Studies in fly have provided us fundamental insights into lineage identity, temporal identity, and binary cell fate specifications. Nevertheless, previous studies mostly centered on the embryonic ventral nerve cord (VNC) because of its simpler organization. Our understanding of the generation of neuronal diversity in the fly brain is still rudimentary. In this thesis work, I focused on the mushroom body (MB) and three antennal lobe neuronal lineages, studying their neuronal diversification during postembryonic brain development. In Chapter I, I reviewed the previous studies that have built our current understanding of the neuronal diversification. In Chapter II, I showed that MB temporal identity changes are instructed by environmental cues. In Chapter III, to search for the potential factors that mediate the environmental control of the MB temporal identity changes, I silenced each of the 18 nuclear receptors (NRs) in the fly genome using RNA interference. Although I did not identify any NR important for the regulation of MB temporal identities, I found that unfulfilled is required for regulating axon guidance and for the MB neurons to acquire all major subtype-specific identities. In Chapter IV, I demonstrated that the Notch pathway and its antagonist Numb mediate binary cell fate determination in the three classical antennal lobe neuronal lineages— anterodorsal projection neuron (adPN), lateral antennal lobe (lAL), and ventral projection neuron (vPN)—in a context-dependent manner. Finally, in Chapter V, I did detailed lineage analysis for the lAL lineage, and identified four classes of local interneurons (LNs) with multiple subtypes innervating only the AL, and 44 types projection neurons (PNs) contributing to olfactory, gustatory, and auditory neural circuits. The PNs and LNs were generated simultaneously but with different tempos of temporal identity specification. I also showed that in the lAL lineage the Notch pathway not only specifies binary cell fates, but is also involved in the temporal identity specification.

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