Rapporten ingår i ett FoU- projekt för Högskolan Dalarna, där målet är att ta fram en konstruktion utan ångspärr som ska klara dagens mått på lufttäthet och fuktkrav. Syftet med denna rapport är att utreda hur fukt påverkar en byggnad medmassivträstomme och olika isoleringsmaterial utan ångspärr. Mineralull och träfiberisolering jämförs mot varandra för att se hur dessa påverkarfuktbelastningen i en väggkonstruktion. Testobjektet är lokaliserat i Dalarna, inget fukttillskott har funnits inomhus i byggnaden. För att genomföra detta arbete har tre stycken olika metoder används. Ensimulering, verkliga uppmätta värden och en provtagning. Fuktsimuleringen genomfördes med hjälp av programmet WUFI, uppmätta värden i form av relativ fuktighet och temperatur har samlats in kontinuerligt under två års tid från väggkonstruktionen via mätsensorer. Provtagningen utfördes med ett fysiskt ingrepp på samma nivå i konstruktionen som mätsensorer var placerade. Resultat presenteras i form av diagram och tabeller där det går att avläsa konstruktionens nulägesstatus i form av relativ fuktighet, temperatur, fuktkvot och mikrobiologisk påväxt. Isoleringsmaterialen påvisar en hög relativ fuktighet under vinterhalvåret längst ut i konstruktionen mot utomhusklimatet. Utomhusklimatet har visats spela stor roll i detta. Ingen direkt mikrobiologisk påväxt har påträffats trots en hög halt av fukt. Resultaten visar att träfiberisoleringen har bättre förmåga att hantera fukt i jämförelse med mineralullen. En vidarestudie med fuktbelastning och 21 °C inomhus bör utföras. Men för att denna studie ska fungera rekommenderas en tvåstegstätad fasadlösning för att klara fuktbelastningen i väggkonstruktionen. / The report is part of a research and development project for Dalarna University,where the goal is to produce a design without a vapour barrier that will meettoday's measure of airtightness and moisture requirements. The purpose of this report is to investigate how moisture affects a building withsolid wood and various insulation materials without vapour barrier. Mineral woolinsulation and wood fiber insulation will be compared against each other to seehow they affect the moisture load in a wall. The test object is located in Dalarna,no additional moisture load affect the indoor environment. To carry out this work, three different methods are used. A moisture simulationwas performed using the program WUFI, measured values in terms of relativehumidity and temperature were collected over two years from the wall of thebuilding. A sampling was performed with a physical operation on the same levelin the wall where measurement sensors were placed. Results are presented in form of graphs and tables where you can read thecurrent state of the construction in terms of relative humidity, temperature,moisture content and microbiological fouling. Insulation materials demonstrate ahigh relative humidity at outer layers of the construction during the wintermonths. The external environment has been shown to play a major part for theresults. No direct microbiological fouling has been detected despite a highcontent of moisture. The result of wood fiber insulation demonstrates a better ability to handlemoisture. A further study with a moisture load and 21 degrees indoors should beperformed. But for this study to work it’s recommended to change the currentfacade solution to a two- step sealed facade solution to manage the moistureload in the wall.

Proteinaceous infectious particles, termed 'prions' are self-perpetuating protein isoforms that transmit neurodegenerative diseases in mammals and phenotypic traits in yeast. Each conformational variant of a prion protein is faithfully propagated to a homologous protein in the same cell environment. However, a reduction in the efficiency of prion transmission between different species is often observed and is termed "species barrier". Prion transmission to a heterologous protein may, in some cases, permanently change the structure of the prion variant, and divergent proteins may interfere with prion propagation in a species-specific manner. To identify the importance of both protein sequence and the cell environment on prion interference and cross-species transmission, we employed heterologous Sup35 proteins from three Saccharomyces sensu stricto species: Saccharomyces cerevisiae (Sc), Saccharomyces paradoxus (Sp), and Saccharomyces bayanus (Sb). We performed our experiments in two different cell environments (Sc and Sp). Our data show that Sup35 from one species can form a prion in another, and we employed a transfection procedure to perform cross-species transfer of the prion. Using a shuffle procedure, we demonstrate that the specificity of prion transmission is determined by the protein itself rather than the cell environment. Interestingly, we noted that variant-specific prion patterns can be altered irreversibly during cross-species transmission through S. bayanus module II. We further show that prion interference does not always correlate with cross-species prion transmission, and the identity of particular regions or even a specific amino acid, rather than the overall level of PrD homology is crucial for determining cross-species transmission and interference. Lastly we provide evidence to suggest that prion interference is specific to the cell environment.

Game companies are always looking for more ways to increase consumers and their revenue as well as how consumers purchase games. Several business models have been introduced that this thesis will look at, free-to-play, adding downloadable content to existing games, freemium and premium games. This thesis attempts to provide answers to what business models there are available for game developers and how that would influence the development of the single-player games to lower the point of entry for the consumers.  It will focus on narrative single-player games and will use the business models to try and answer the question. A survey was handed out that investigated the respondent’s reaction to changes for BioShock Infinite developer by Irrational Games. The models were presented and compared to how the respondents reacted to the questions. Together with how companies are releasing games now this thesis came to the conclusion that in order to lower the entry point, the games need to be split and released episodically, together with increased downloadable content that added further playability to the game.

Ischemic stroke is characterized by a disruption of blood supply to a part of the brain tissue, which leads to a focal ischemic infarct. The expression and activity of MMP-9 is increased in ischemic stroke and is considered to be one of the main factors responsible for damages to the cerebral vasculature, resulting in compromised blood-brain barrier (BBB) integrity. However, the regulatory mechanisms of MMP-9 expression and activity are not well established in ischemic stroke. Since hypoxia/ischemia and reperfusion generates reactive oxygen species (ROS), I hypothesize that ROS is one of factors involved in up-regulation of MMP-9 expression in brain cells and ROS-mediated effect may occur via MAPK signaling pathway. My study has provided the evidence that ROS is responsible for an increase in MMP-9 expression in astrocytes mediated via MAPK-AP1 signaling pathway. Preliminary studies with an in vitro model of the BBB suggest that inhibition of MMP-9 is a critical component of reducing ROS-induced BBB permeability.

The disruption of the blood-brain barrier (BBB) occurs after ischemic and hemorrhagic stroke and contributes to secondary brain damage. Matrix metalloproteinase-9 (MMP9) has been identified to be the main mediator of post-stroke BBB disruption. It is unknown whether deposition of heme/iron in the brain following stroke would affect MMP9 expression. In this study, I have demonstrated that heme/iron up-regulated MMP9 expression in rat astrocytes and that this upregulation was most likely due to reactive oxygen species (ROS) generated by heme/iron deposition on cells. ROS can activate AP-1 and NFκB signaling pathways which were responsible for increased MMP9 expression. Inhibiting AP-1 and NFκB decreased MMP9 expression. Heme/iron deposition also activated Nrf-2 and increased the expression of neuroprotective heme oxygenase-1. My study suggests that heme and iron deposition generates ROS and increases MMP9 expression through AP-1 and NFκB signaling pathways and that targeting these pathways or clearance of heme and iron may modulate MMP9 expression for reduced damage.

The cost of a road construction over its service life is a function of design, quality of construction as well as maintenance strategies and operations. An optimal life-cycle cost for a road requires evaluations of the above mentioned components. Unfortunately, road designers often neglect a very important aspect, namely, the possibility to perform future maintenance activities. Focus is mainly directed towards other aspects such as investment costs, traffic safety, aesthetic appearance, regional development and environmental effects. This doctoral thesis presents the results of a research project aimed to increase consideration of road maintenance aspects in the planning and design process. The following subgoals were established: Identify the obstacles that prevent adequate consideration of future maintenance during the road planning and design process; and Examine optimisation of life-cycle costs as an approach towards increased efficiency during the road planning and design process. The research project started with a literature review aimed at evaluating the extent to which maintenance aspects are considered during road planning and design as an improvement potential for maintenance efficiency. Efforts made by road authorities to increase efficiency, especially maintenance efficiency, were evaluated. The results indicated that all the evaluated efforts had one thing in common, namely ignorance of the interrelationship between geometrical road design and maintenance as an effective tool to increase maintenance efficiency. Focus has mainly been on improving operating practises and maintenance procedures. This fact might also explain why some efforts to increase maintenance efficiency have been less successful. An investigation was conducted to identify the problems and difficulties, which obstruct due consideration of maintainability during the road planning and design process. A method called “Change Analysis” was used to analyse data collected during interviews with experts in road design and maintenance. The study indicated a complex combination of problems which result in inadequate consideration of maintenance aspects when planning and designing roads. The identified problems were classified into six categories: insufficient consulting, insufficient knowledge, regulations and specifications without consideration of maintenance aspects, insufficient planning and design activities, inadequate organisation and demands from other authorities. Several urgent needs for changes to eliminate these problems were identified. One of the problems identified in the above mentioned study as an obstacle for due consideration of maintenance aspects during road design was the absence of a model for calculating life-cycle costs for roads. Because of this lack of knowledge, the research project focused on implementing a new approach for calculating and analysing life-cycle costs for roads with emphasis on the relationship between road design and road maintainability. Road barriers were chosen as an example. The ambition is to develop this approach to cover other road components at a later stage. A study was conducted to quantify repair rates for barriers and associated repair costs as one of the major maintenance costs for road barriers. A method called “Case Study Research Method” was used to analyse the effect of several factors on barrier repairs costs, such as barrier type, road type, posted speed and seasonal effect. The analyses were based on documented data associated with 1625 repairs conducted in four different geographical regions in Sweden during 2006. A model for calculation of average repair costs per vehicle kilometres was created. Significant differences in the barrier repair costs were found between the studied barrier types. In another study, the injuries associated with road barrier collisions and the corresponding influencing factors were analysed. The analyses in this study were based on documented data from actual barrier collisions between 2005 and 2008 in Sweden. The result was used to calculate the cost for injuries associated with barrier collisions as a part of the socio-economic cost for road barriers. The results showed significant differences in the number of injuries associated with collisions with different barrier types. To calculate and analyse life-cycle costs for road barriers a new approach was developed based on a method called “Activity-based Life-cycle Costing”. By modelling uncertainties, the presented approach gives a possibility to identify and analyse factors crucial for optimising life-cycle costs. The study showed a great potential to increase road maintenance efficiency through road design. It also showed that road components with low investment costs might not be the best choice when including maintenance and socio-economic aspects. The difficulties and problems faced during the collection of data for calculating life-cycle costs for road barriers indicated a great need for improving current data collecting and archiving procedures. The research focused on Swedish road planning and design. However, the conclusions can be applied to other Nordic countries, where weather conditions and road design practices are similar. The general methodological approaches used in this research project may be applied also to other studies. / <p>QC 20110407</p>

Little is known about potential influences of kinase pathway modulation on expression and activity of P-glycoprotein (P-gp). A protein kinase inhibitor (PKI) library was screened, to determine its effects on activity and expression of P-gp, in various cell lines. Cell lines were incubated with PKI for 24 h. Subsequent P-gp substrate accumulation studies were performed. Changes in P-gp activity and/or expression ≥ 25% compared to control were considered hits. Kinase pathways identified as P-gp activity hits were examined for their ability to modulate permeability. PKI families GSK-3, Craf1 and VEGFR2 and Tie-2, significantly modulated P-gp activity in the MDCK cell line. PKI families GSK-3, Iκκ and Jnk2/3 significantly modulated P-gp activity in the Caco-2 cell line. Few P-gp activity hits significantly modulated P-gp expression. PKIs modulate P-gp activity more than P-gp expression in a cell line dependent manner, excluding GSK-3 PKI family, which appears to be cell line independent.

Animals are confronted with potential stressors at zoos compared to in the wild, such as visitors and lack of environmental stimulation. This study included two projects conducted on the drills at Parken Zoo in Eskilstuna where I investigated: 1) the effect of visual barriers on the behaviour of the drills and if the visual barriers can moderate the visitor effect on the drills and 2) how outdoor-only access together with feeding enrichment (frozen fruit and tube feeders) affects the behaviour of the drills. 1/0- sampling method was used when observing the behaviours of the drills with 1 minute-intervals. Resting/Sleeping increased, while social agonistic behaviour and stereotypies decreased with visual barriers. A moderated visitor effect was shown in resting/sleeping and social affiliative behaviour in the drills with visual barriers. However, social agonistic behaviour and visitor interaction were still affected by visitors after the installation of the visual barriers, implying that the drills still find visitors stressful to some extent and that further alterations on the observation area viewing the indoor enclosure is recommended for the welfare of the drills. With outdoor-only access together with feeding enrichment, locomotion, foraging/eating and body-shaking increased, while resting/sleeping, social affiliative and agonistic behaviour, stereotypies, visitor interaction, scratching and self-grooming decreased. This suggests that outdoor-only access and feeding enrichment improve the behaviour of the drills and would be a valid option during summer season for the drills at Parken Zoo.

The blood brain barrier (BBB) remains a major challenge to the advancement and application of systemic anti-cancer therapeutics into the central nervous system. The structural and physiological delivery constraints of the BBB significantly limit the effectiveness of conventional chemotherapy, thereby making systemic administration a non-viable option for the vast majority of chemotherapy agents. Furthermore, the lack of specificity of conventional systemic chemotherapy when applied towards malignant brain tumors remains a major shortcoming. Hence novel therapeutic strategies that focus both on targeted and enhanced delivery across the BBB are warranted. In recent years nanoparticles (NPs) have emerged as attractive vehicles for efficient delivery of targeted anti-cancer therapeutics. In particular, gold nanoparticles (AuNPs) have gained prominence in several targeting applications involving systemic cancers. Their enhanced permeation and retention within permissive tumor microvasculature provide a selective advantage for targeting. Malignant brain tumors also exhibit transport-permissive microvasculature secondary to blood brain barrier disruption. Hence AuNPs may have potential relevance for brain tumor targeting. However, the permeation of AuNPs across the BBB has not been well characterized, and hence is a potential limitation for successful application of AuNP-based therapeutics within the central nervous system (CNS). In this dissertation, we designed and characterized AuNPs and assessed the role of polyethylene glycol (PEG) on the physical and biological properties of AuNPs. We established a size-dependent permeation profile with respect to core size as well as PEG length when AuNPs were assessed through a transport-permissive in-vitro BBB. This study was the first of its kind to systematically examine the influence of design on permeation of AuNPs through transport-permissive BBB. Given the significant delivery limitations through the non-transport permissive and intact BBB, we also assessed the role of magnetic resonance imaging (MRI) guided focused ultrasound (MRgFUS) disruption of the BBB in enhancing permeation of AuNPs across the intact BBB and tumor BBB in vivo. MRgFUS is a novel technique that can transiently increase BBB permeability thereby allowing delivery of therapeutics into the CNS. We demonstrated enhanced delivery of AuNPs with therapeutic potential into the CNS via MRgFUS. Our study was the first to establish a definitive role for MRgFUS in delivering AuNPs into the CNS. In summary, this thesis describes results from a series of research projects that have contributed to our understanding of the influence of design features on AuNP permeation through the BBB and also the potential role of MRgFUS in AuNP permeation across the BBB.

Understanding the extent of infection control measures to be taken to protect immunosuppressed and other types of patients from airborne infection agents during construction is crucial knowledge for both healthcare and construction professionals. The number of aspergillosis-related fatalities due to dust transmission during construction activity has decreased with the improvement of antifungal therapy, however the illness is particularly debilitating and the treatment is not always successful. This experimental work is the first stage in a research program to develop better dust controls for construction at existing medical facilities to reduce the incidence of dust borne fungi, such as Aspergillus spp. To better protect at-risk patients from exposure to Aspergillus spp. and other airborne fungal infections, an experiment was conducted to determine what materials can be used to create a barrier for infection control to moderate particle transmission from the construction area to the treatment area. This study investigated the relationship between construction barriers and particle transmission. A new experimental procedure and equipment simulates the transmission of disturbed dust from construction activity across a barrier. The effective of the barrier is determined from measured particle count on filter. The results show that an effective barrier manufactured from simple and readily available building supplies stops the transmission of 12-micron dust particles under a standard set of conditions. The test provides a simple and cost effective method to compare transmission rates for dust.