The control of phosphatidylinositol 3, 4, 5-trisphosphate [PtdIns(3,4,5)P3] level depends on the activities of both PI kinase and PtdIns(3,4,5)P3 phosphatases: 5-phosphatase like SHIP1 and SHIP2, and 3-phosphatase like PTEN. The ubiquitous SH2 domain containing inositol 5-phosphatase SHIP2 contains both a series of protein interacting domains and the ability to dephosphorylate PtdIns(3,4,5)P3. Previous reports obtained in SHIP2 deficient mice have shown that SHIP2 is involved in the control of insulin sensitivity and reducing weight gain on fatty diet. Since SHIP2 is a lipid phosphatase as well as a docking protein, the initial aim that emerged in the lab was to measure the inositol lipid levels in SHIP2 +/+ and deficient cells and compare the levels of 3-phosphoinositides PtdIns(3,4,5)P3 and PtdIns(3,4)P2. At first, we developed mouse embryonic fibroblasts (MEF) as a cellular model. Amongst various stimuli tested, surprisingly, only serum showed an obvious difference in terms of PtdIns(3,4,5)P3 level. This lipid was significantly up regulated in SHIP2 -/- cells but only after short-term (i.e. 5-10 min) incubation with serum. The difference in PtdIns(3,4,5)P3 levels in heterozygous fibroblast cells was intermediate between the +/+ and -/- cells. Serum stimulated PI3K activity appeared to be comparable between +/+ and -/- cells. Moreover, PKB, but not MAP kinase activity, was also potentiated in SHIP2 deficient cells stimulated by serum. The up regulation of PKB activity in serum stimulated cells was totally reversed in the presence of the PI3K inhibitor LY-294002, in both +/+ and -/- cells. Reactive oxygen species (ROS) have emerged as physiological mediators of many cellular responses. H2O2 mimics some effects of insulin in a number of cell culture systems. It also inactivates tyrosine phosphatase activities including PTEN. In addition, in Swiss 3T3 fibroblasts, Gray et al reported that exposure of the cells to H2O2 resulted a huge increase in PtdIns(3,4)P2 level. The authors suspected that the effect was attributed to a inositol 5-phosphatase activity. We thus exposed our cells to H2O2 in order to address the question of the role of SHIP2 in response to oxidative stress. We worked on the same SHIP2 MEF model, stimulated by H2O2: at 15 min, PtdIns(3,4,5)P3 was markedly increased in SHIP2 -/- cells as compared to +/+ cells. In contrast, no significant increase in PtdIns(3,4)P2 could be detected at 15 or 120 min incubation of the cells with H2O2 (0.6 mM). PKB activity was upregulated in SHIP2 -/- cells in response to H2O2 and therefore follows the regulation of PtdIns(3,4,5)P3. As for serum, the PI3K activity appeared to be comparable between +/+ and -/- cells. The levels of PTEN and type I 4-phosphatase [an enzyme that acts on PtdIns(3,4)P2] remained unchanged between the two types of cells. SHIP2 add back experiments in SHIP2 -/- cells confirm its critical role in the control of PtdIns(3,4,5)P3 level in response to H2O2: the decrease in PtdIns(3,4,5)P3, observed in SHIP2 expressing cells, was no longer seen in cells infected with a catalytic mutant of this enzyme.

Le rôle central de VLA-4 et de CXCR4 dans le processus dimplantation médullaire des cellules souches hématopoïétiques (CSH) est bien documenté tandis que la fonction de VLA-5 est plus discutée. Plusieurs études ont rapporté que lamplification ex vivo des CSH en présence de cytokines exogènes réduisait leurs capacités de repeuplement médullaire ; le maintien dune interaction appropriée dans lenvironnement médullaire étant critique pour la conservation dune implantation efficace. Les travaux présentés contribuent à lidentification des changements fonctionnels des récepteurs dadhérence impliqués dans le processus implantatoire des CSH cultivées. En première partie, les interactions statiques et dynamiques de LTC-IC générées ex vivo vis-à-vis de ligands du stroma médullaire ont été comparées aux LTC-IC natives. Lévaluation de ladhérence des LTC-IC in vitro sur les fragments de Fn et VCAM-1 a permis didentifier une altération de létat dactivité de VLA-4 et VLA-5 après expansion. Les adhérences statiques et dynamiques médiées par VLA-4 sur VCAM-1 et Fn étaient compromises contrairement au VLA-5 dont lactivité était augmentée après expansion. Dans un second temps, leffet de lexposition cytokinique sur la contribution respective de VLA-4, VLA-5 et CXCR-4 dans limplantation et le repeuplement médullaire a été examinée chez la souris NOD/SCID et NOD/SCID b2-/-. Il a été montré que limplantation et le repeuplement par des CSH natives sont dépendants de VLA-4, lexpansion ex vivo étant associée à linactivation de VLA-4 ce qui révèle le rôle joué par VLA-5 dans la reconstitution hématopoïétique in vivo. De plus, une diminution de lactivité de CXCR-4 peut induire une perte de sélectivité médullaire lors de limplantation de CSH amplifiées.

Den här uppsatsen jämför PR-genomslaget av två lanseringskampanjer i tolv dagstidningar. Lanseringskampanjerna gäller de två mobiltelefonerna, Xperia x10 och Iphone 4. PR-genomslaget undersöks dels genom exponering av varumärken, dels genom antal publicerade artiklar. Av antalet publicerade artiklar undersöks också hur stor del av artiklarna som kan ses som textreklam. De tolv tidningarna är indelade i olika tidningstyper: morgontidningar, kvällstidningar och gratistidningar. För att undersöka PR-genomslaget och förekomsten av textreklam har jag genomfört en kvantitativ innehållsanalys av 98 artiklar. Analysen består av tabeller, textutdrag och tolkningar av dessa. Resultatet visar att morgontidningar i storstadsområden är de tidningar som sammanlagt har publicerat flest artiklar om mobiltelefonerna och skrivit mest textreklam. Många artiklar har bara en källa och den största huvudkällan är reportrar. Genomslaget för lanseringskampanjen av Iphone 4 var betydligt större än för Xperia x10. Av de 22 artiklar som kan kategoriseras som textreklam handlar alla utom en om Iphone.

The use of hydrogen is predicted to increase substantially in the future, both as chemical feedstock and also as energy carrier for transportation. The annual world production of hydrogen amounts to some 50 million tonnes and the majority is produced using fossil fuels like natural gas, coal and naphtha. High temperature nuclear reactors (HTRs) represent a novel way to produce hydrogen at large scale with high efficiency and less carbon footprint. The aim of this master thesis has been to evaluate the feasibility of HTRs for hydrogen production by analyzing both the reactor concept and its potential to be used in certain hydrogen niche markets. The work covers the production, storage, distribution and use of hydrogen as a fuel for vehicles and aviation and as chemical feedstock for the oil refining and ammonia production industry. The study indicates that HTRs may be suitable for hydrogen production under certain conditions. However, the use of hydrogen as an energy carrier necessitates a widespread hydrogen infrastructure (e.g. pipe-lines, refuelling stations and large scale storage), which is associated with major energy losses. Both mentioned industries could benefit from nuclear-based hydrogen with less infrastructural changes, but the potential market is by far smaller than if hydrogen is used as an energy carrier. A maximum of about 60 HTRs of 600 MWth worldwide has been estimated for the ammonia production industry. The Swedish refineries are likely too small to utilize the HTR but in the larger refineries HTR might be applicable.

Syftet med denna uppsats är att undersöka vad fastighetsbolag inom K3 baserar sina byggnaders avskrivningstider på och hur väl dessa stämmer med vad som rekommenderas inom forskningen på området. Företag inom K3 redovisar enligt årsredovisningslagen. Detta är intressant att titta på då det är väldigt komplext att bestämma avskrivningstider för en byggnad, än mer komplext blir det vid innehavandet av många byggnader, där den ena inte är den andre lik. För att försöka förklara de val av avskrivningstider som fastighetsbolag gör använder vi oss av institutionell teori och intressentteorin. Vi har i vår studie valt ett kvalitativt tillvägagångssätt där vi har använt oss av semistrukturerade intervjuer hos fem fastighetsbolagen inom klassificeringen K3. I studien kommer vi fram till att fastighetsbolagens val av avskrivningstider främst har påverkats av tre faktorer. Tvingande krafter, i form av lagar och direktiv från aktörer de är beroende av. Imiterande krafter, vilket ofta tar sig uttryck i hänvisning till hur andra större företag tidigare gjort. Samt normativa krafter, de normativa krafterna innebär i de flesta fall att man har diskussioner med revisorer om vad som kan anses vara en skälig avskrivningstid.Tvingande krafters påverkan leder till att de undersökta fastighetsbolagen bestämmer en avskrivningstid som faller inom ramarna för vad forskningen anser är rekommenderade avskrivningstider för olika typer av byggnader. De fastighetsbolag som påverkats av imiterande krafter samt normativa krafter har istället bestämt en avskrivningstid på ett sätt som kan ses som orimligt i förhållande till vad forskning anser vara rimligt.

Nous avons développé la synthèse d'hétérocycles indoliziniques fonctionnalisés par un cation pyridinium et étudié leur interaction avec L'ADN. L'étape-clé pour accéder aux indolizines est la cycloaddition [3+2]-dipolaire des ylures dérivés des sels quaternaires de la 4,4'-bipyridine avec des dipolarophiles. La synthèse a été effectuée par la voie classique (chauffage en solvant) et par irradiation avec des micro-ondes (“chimie verte”). Nous avons étudié les propriétés acido-basiques des sels diquaternaires et leur activité biologique sur une série de microorganismes. Par ailleurs les propriétés électriques et optiques ainsi que la photoluminescence des indolizines se sont révélées prometteuses pour des applications comme les traceurs biomédicaux. L'interaction des indolizines avec l'ADN a aussi été étudiée. Finalement, nous avons évalué les propriétés antioxydantes des indolizines, qui ont montré une activité inhibitrice de la peroxydation des huiles végétales in vitro.

This dissertation reports on the results on an exploratory investigation into the potential efficacy of VR as both a support mechanism to people living with HIV/AIDS, as well its capabilities as an emotive medium. Two hypothesis were presented viz. (1) VR will be a form of social support and (2) VR will have an emotional impact on participants. The research builds up on findings which demonstrate the therapeutic effectiveness of telling personal and collective narratives in an HIV/AIDS support group. This fact, together with the tested ability of VR as a therapeutic medium, let to the development of a virtual support group with an aim to test its therapeutic efficacy. A low cost, deployable desktop PC based system using custom software was developed. The system implemented a VR walkthrough experience of a tranquil campfire in a forest. The scene contained four interactive avatars who related narratives compiled from HIV/AIDS patients. These narratives covered the aspects of receiving an HIV+ diagnosis, intervention, and coping with living with HIV+ status. To evaluate the system, seven computer semi-literate HIV+ volunteers from townships around Cape Town used the system under the supervision of a clinical psychologist. The participants were interviewed about their experiences with their system, and the data was analyzed qualitatively using grounded theory. The group experiment showed extensive qualitative support for the potential efficacy of the VR system as both a support mechanism and an emotive medium. The comments received by the participants suggested that the VR medium would be effective as a source of social support, and could augment real counselling sessions, rather than replace them. The categories which emerged from the analysis of the interview data were emotional impact, emotional support, informational support, technology considerations, comparison with other forms of support, timing considerations and emotional presence. The categories can be grouped according to the research questions viz. + The efficacy of VR as an emotive medium (Presence, Emotional Impact, Computer Considerations) + The efficacy of the VR simulation as a source of social support (Emotional and Informational Support) Other themes not anticipated by the data included the following: Timing considerations and Comparison with other forms of counselling. The interviews suggested that both hypothesis 1 and 2 are correct viz. that the VR system provided a source of social support, and has an emotional impact on the participants.

Many complex research problems require an immense amount of computational power to solve. In order to solve such problems, the concept of the computational Grid was conceived. Although Grid technology is hailed as the next great enabling technology in Computer Science, the last being the inception of the World Wide Web, some concerns have to be addressed if this technology is going to be successful. The main difference between the Web and the Grid in terms of adoption is usability. The Web was designed with both functionality and end-users in mind, whereas the Grid has been designed solely with functionality in mind. Although large Grid installations are operational around the globe, their use is restricted to those who have an in-depth knowledge of its complex architecture and functionality. Such technology is therefore out of reach for the very scientists who need these resources because of its sheer complexity. The Grid is likely to succeed as a tool for some large-scale problem solving as there is no alternative on a similar scale. However, in order to integrate such systems into our daily lives, just as the Web has been, such systems need to be accessible to ``novice'' users. Without such accessibility, the use and growth of such systems will remain constrained. This dissertation details one possible way of making the Grid more accessible, by providing high-level access to the scheduling systems on which Grids rely. Since ``the Grid'' is a mechanism of transferring control of user submitted jobs to third-party scheduling systems, high-level access to the schedulers themselves was deemed to be a natural place to begin usability enhancing efforts. In order to design a highly usable and intuitive interface to a Grid scheduling system, a series of interviews with scientists were conducted in order to gain insight into the way in which supercomputing systems are utilised. Once this data was gathered, a paper-based prototype system was developed. This prototype was then evaluated by a group of test subjects who set out to criticise the interface and make suggestions as to where it could be improved. Based on this new data, the final prototype was developed firstly on paper and then implemented in software. The implementation makes use of lightweight Web 2.0 technologies. Designing lightweight software allows one to make use of the dynamic properties of Web technologies and thereby create more usable interfaces that are also visually appealing. Finally, the system was once again evaluated by another group of test subjects. In addition to user evaluations, performance experiments and real-world case studies were carried out on the interface. This research concluded that a dynamic Web 2.0-inspired interface appeals to a large group of users and allows for greater flexibility in the way in which data, in this case technical data, is presented. In terms of usability- the focal point of this research- it was found that it is possible to build an interface to a Grid scheduling system that can be used by users with no technical Grid knowledge. This is a significant outcome, as users were able to submit jobs to a Grid without fully comprehending the complexities involved with such actions, yet understanding the task they were required to perform. Finally, it was found that the use of a lightweight approach in terms of bandwidth usage and response time is superior to the traditional HTML-only approach. In this particular implementation of the interface, the benefits of using a lightweight approach are realised approximately halfway through a typical Grid job submission cycle.

In diabetes hyperglycemia and lack of insulin signaling are key factors in the induction of diabetic sensory neuropathy. The combination of these factors in diabetes may enhance oxidative stress and trigger distal nerve damage in the peripheral nervous system. The link between elevated reactive oxygen species (ROS) levels and nerve degeneration is not clear. We tested the hypothesis that elevation of 4-hydroxy-2-nonenal (4-HNE) induced by oxidative stress in diabetes impairs mitochondrial activity and axonal regeneration in dorsal root ganglion (DRG) neurons. Also, we investigated the association between mitochondrial dysfunction and altered mitochondrial proteome in the axons of streptozotocin–induced diabetic rats. Research design and methods. Cultured adult rat DRG sensory neurons were treated exogenously with 4-HNE, and cell survival, axonal morphology, and level of axon outgrowth assessed. Western blot and fluorescence imaging were used to determine changes in the levels of adducts of 4-HNE and abnormalities in the mitochondria. Proteomic analysis using stable isotope labeling with amino acids in cell culture (SILAC) determined expression of proteins in the mitochondria. Results. 4-HNE impaired axonal regeneration, mitochondrial activity and induced aberrant axonal structures along the axons, which mimicked axon pathology observed in nerve isolated from diabetic rats and replicated aspects of neurodegeneration observed in human diabetic neuropathy. Proteins associated with mitochondrial dysfunction, oxidative phosphorylation and biosynthesis were down regulated in diabetic samples. The axons of diabetic neurons exhibited oxidative stress and depolarized mitochondria. CNTF and resveratrol reversed abnormalities in the mitochondrial membrane potential induced by diabetes and treatment of neurons with 4-HNE. CONCLUSIONS. Elevation of 4-HNE levels in diabetes was associated with impaired mitochondrial function and might be an important link between increased ROS levels and nerve degeneration in diabetic neuropathy. Abnormal mitochondrial function correlated with a down-regulation of mitochondrial proteins, with components of the respiratory chain targeted in lumbar DRG in diabetes. The reduced activity of the respiratory chain was associated with diminished superoxide generation within the mitochondrial matrix and did not contribute to oxidative stress in axons of diabetic neurons.

Titano dioksidas, pasižymintis unikaliomis fizikinėmis bei cheminėmis savybėmis, yra gerai žinoma, plačiai naudojama bei tyrinėjama medžiaga. Tiriant TiO2 elektrines savybes, galima gauti informacijos, kokios naujos medžiagos fazės formuojasi plonasluoksnėse dangose. Elektrinė titano dioksido varža priklauso nuo bandinio stechiometriškumo, nusakančio vyraujančius defektus bei laidumo tipą. Siekiant gauti norimų savybių plonasluoksnes dangas, būtina atsižvelgti į bandinių paruošimo ir gamybos procesus. Bandinių nusodinimui naudojama vakuuminė užnešimo technika leidžia kontroliuoti procesus, lemiančius dangos savybes. Šiame darbe buvo atliekama literatūros analizė apie elektrines TiO2 savybes bei įvairių faktorių įtaką šio parametro kitimui. Taip pat atkreiptas dėmesys į plonasluoksnių struktūrų nusodinimą, naudojant fizikinį dangų nusodinimą iš garų fazės (PVD). Paviršinės TiO2 varžos tyrimas buvo atliekamas panaudojant 4 zondų metodą. / Titanium dioxide is well known, widely used and investigated material that shows unique physical and chemical properties. Investigations of TiO2 electrical conductivity gives an information about the new phases formed in thin films. Surface resistance of titanium dioxide depends on sample‘s stoichiometry and it shows predominant defects and type of conductivity being in the thin film structure. It is very important to pay an attention into processes of sample‘s preparation and formation technique in order to get thin films with desirable properties. Thin films were formed using vacuum deposition technique. There has been done a scientific literature survey in order to know the main factors that causes changes of TiO2 electrical properties in this work. An attention was paid into deposition of thin film structures using physical vapor deposition (PVD) technique as well. Measurements of TiO2 surface resistance were done using four probe method.