In this study the importance of prohibitin1 and prohibitin2 genes for Trypanosoma brucei was examined. RNA interference showed both of them essential for parasites to survive. Knocking down of these genes resulted in altered morphology of the mitochondrion, changes in membrane potential and shut down of mitochondrial translation. No changes were observed in levels of Reactive Oxygen Species and respiration. Both prohibitines are part of big complex present in the mitochondrion.

In my senior project I work with the unseen furniture: the side table. The name, Quadro, is a combination of the italian word quattro that means four and the latin word ”quadratum” or ”quadratus.”  After conducting an analysis of different side tables, I concluded that the side table's function is primarily to elevate other artifacts. I draw connections to the creation of identity through consumption and have created a sidetble through combining furniture design and conceptual design. The project was finalized with a survey to see if identity is visible through the selection of artifacts. / I mitt projekt arbetar jag med den osedda möbeln: sidobordet. Namnet Quadro är en blandning mellan italienskans quattro som betyder fyra och latinets ”quadratum” eller ”quadratus”. Efter analys av olika sidobord kom jag fram till att sidobordets primärfunktion är att höja upp andra artefakter. Jag drar kopplingar till identitetsskapande genom konsumtion och har skapat ett sidobord genom att kombinera möbeldesign med konceptuell design. Projektet slutförs med en undersökning för att se om identitetsskapandet går att observera genom valet av artefakter.

This is a Master’s Thesis that has been carried out at the Global Outbound Logistics department at Scania. Scania manufactures trucks, buses and engines. Some trucks and buses are delivered to markets where it, due to reduced customs duties and cheaper manpower, is more profitable to do the assembly locally at so called Regional Product Centres (RPCs). Since the components are produced far away from the RPC markets the lead times become long. In addition, the customers’ buying behaviour at the RPC markets is often not comparable to the European culture were a customer can accept to wait for weeks for a unit to be delivered. The long lead time in combination with the customer behaviour implies that the RPCs need to keep a certain selection of standard models of buses and trucks in stock. It has turned out to be difficult for the pipeline managers at the RPCs to place order volumes that correspond well to what will be delivered to the business units or distributors later on. The result of this is high stock levels at the RPCs, which leads to an important amount of tied up capital. Due to what is explained above, the purpose of this study is “to create a simulation model, based upon a process mapping, that visualises future volume levels in the pipeline due to different demand and ordering scenarios”. The short term target, which is also the target of this study, is to increase the RPCs understanding for how different demand and ordering scenarios influence the future volume levels in the pipeline. The long term target is to reduce tied up capital by adjusting buffer levels and lead times, while still ensuring a certain service level. The model should contribute to more accurate decision making with respect to the previous mentioned aspects. First, a high level process mapping was made in order to select which flows that were suitable for being subject for a detailed mapping. Second, a detailed mapping was made during which several RPC-, process- and function responsible were interviewed. After the detailed mapping, common denominators between the flows were identified and all activities were clustered into a solution that could be generalised and suitable for all flows. Factors such as lead times, deviation risks and capacity limitations were taken into account during the aggregation of activities. When a common view of the different RPC flows had been created, the mathematical relationships for how the goods can move throughout the process could be established. Then, the development and validation of the simulation model, which was an iterative process, could start. A directive was to build the simulation model in Microsoft Excel. Interviews were made with experienced model creators in order to find out how to create a user-friendly and robust model. The creation of the simulation model started with the development of a structure and then the content of each part was defined. A final validation, which consisted of sensitivity analysis and user trials, was finally done in order to ensure the simulation models functioning and accuracy. To conclude, a simulation model that will serve as a helpful tool for the RPCs when they are to decide which order volumes to place has been created. By clearly visualising the simulation results, the simulation model will hopefully increase the RPCs’ comprehension for how the pipeline works with respect to different ordering and demand scenarios. On top of this, the method used, the process mapping and the mathematical relationships that have been defined are important input for a possible future development of a more permanent and robust non-Microsoft Excel solution. This solution could probably be even more precise, automatically updated and have an even higher granularity.

No description available.

No description available.

No description available.

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...

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.

Toxoplasmose ist weltweit eine der am häufigsten auftretenden parasitären Zoonosen mit einer geschätzten Infektionsrate von über 30%. Toxoplasma gondii (Phylum: Apicomplexa) besitzt ein Plastid ähnliches Organell, den Apicoplasten. In diesem befindet sich das einzig bekannte Redoxsystem, welches aus der Ferredoxin-NADP+-Reduktase und Ferredoxin (Fd) besteht. Fd als Elektonendonator liefert Elektronen an verschiedene essentielle Stoffwechselwege, wie der Isoprenoidvorstufen- und Liponsäuresynthese. Um die bei einem Elektronentransfer benötigte direkte Protein-Protein-Interaktion eingehend zu analysieren, wurde ein bakterielles Reverse Two Hybrid System verwendet, womit die Interaktion von TgFd und TgLipA gezeigt werden konnte. Da angenommen wird, dass Fd eine zentrale Rolle in verschiedenen Stoffwechselwegen übernimmt, ist für einen Fd Knockout ein komplexer biochemischer Phänotyp zu erwarten, der möglicherweise zum Absterben der Parasiten führt. Zur Untersuchung dessen wurden zwei komplementäre Wege verfolgt. Eine der Strategien basierte auf dem grundsätzlichen Nachweis, dass Fd unerlässlich für das Überleben von T. gondii ist. Mit Hilfe des DiCre Systems sollte ein definierter genetischer Fd Knockout hergestellt werden, welcher jedoch nicht zweifelsfrei generiert werden konnte. Bei der zweiten Strategie kam ein konditionales Knockdown System zur Anwendung, bei welchem die Expression des Fd Gens nach Induktion herabreguliert wird. Mit Hilfe dessen konnten weitreichende Auswirkungen der Fd Defizienz auf T. gondii gezeigt werden: die Fettsäuresynthese der im Apicoplasten synthetisierten Fettsäuren ist reduziert sowie die Motilität durch eine beeinträchtigte Isoprenoidsynthese verringert, wodurch insgesamt drastische Auswirkungen auf das Parasitenwachstum gezeigt werden konnten. Beide Stoffwechsel sind vom Elektronendonator Fd abhängig und durch die Fd Herabregulation betroffen. Die Ergebnisse unterstreichen die essentielle Rolle des Fd-Redoxsystems von T. gondii. / Toxoplasmosis is one of the most common parasitic zoonoses world-wide, around 30% of human beings are infected. Toxoplasma gondii (phylum: Apicomplexa) contains a unique intracellular organelle derived from plastids, called apicoplast. The only known redox system in the apicoplast consists of the ferredoxin NADP+-reductase and its redox partner, ferredoxin (Fd). The latter donates electrons to different essential metabolic pathways in the apicoplast like the last two enzymes of the isoprenoid precursor biosynthesis and the lipoic acid synthesis. To dissect protein protein interactions for an electron transfer a bacterial reverse two hybrid system was used. The physical interaction of both proteins TgFd and TgLipA could be shown. Fd is supposed to play an important role in diverse metabolic pathways, hence a knock-out of the Fd gene is expected to generate a complex biochemical phenotype and be lethal to the parasite. Therefore two complementary approaches were used to analyze the role of TgFd in this context. The first strategy shall verify the essentiality of TgFd for the survival of T. gondii. It is based on the DiCre system whereby a defined genetic knock out of TgFd is produced. Respectives parasites have been generated, but at the end no genetic Fd knock out could be produced. In the second approach a conditional knock-down was generated, where the expression of the TgFd gene is repressed after induction. The Fd deficiency has wide ranging effects on T. gondii: The fatty acid synthesis of the apicoplast-synthesized fatty acids is reduced as well as the motility is decreased due to an affected isoprenoid synthesis. In total this leads to a dramatic inhibition of parasite growth. Both metabolic pathways depend upon the electron carrier Fd and thus are affected by Fd deficiency. The results underline the essential role of the ferredoxin redoxsystem of T. gondii.