Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis-induced hospitalization in young children. A natural RSV infection fails to elicit long-lasting immunity, further increasing the need for an effective vaccine. Despite the significant healthcare burden, there is no licensed RSV vaccine currently available. While most RSV vaccine strategies focus on the induction of humoral immunity, high antibody titers do not prevent RSV infection. It remains unclear if protective immunity can be achieved through robust cellular immunity. Previous work has indicated that a relatively low frequency of virus-specific CD8 T cells is induced following an RSV infection in human infants. In addition, RSV-specific memory CD8 T cells diminish to almost undetectable frequencies in the blood of the elderly. The lack of long-lasting immunity against RSV may be explained by an absence or low frequency of memory CD8 T cells within the lung following infection. However, I determined that the majority of effector CD8 T cells reside within the lung tissue following infection with either RSV or influenza A virus (IAV), both of which replicate primarily in the airways. In addition, approximately 70% of antigen-experienced memory CD8 T cells persist in the lung tissue at day 30 following RSV infection. In contrast, the majority of CD8 T cells remain in the pulmonary vasculature following intranasal infection with either of the systemically replicating viruses lymphocytic choriomeningitis virus or vaccinia virus. Therefore, the tissue tropism of a virus will determine if CD8 T cells preferentially accumulate in the lung tissue following infection of the respiratory tract. An experimental formalin-inactivated RSV (FI-RSV) vaccine caused enhanced respiratory disease in vaccinated children following a natural RSV infection. Incomplete knowledge of the underlying immunological mechanisms that were responsible for mediating the enhanced disease has greatly hampered vaccine development. Previous studies have indicated that eosinophils, non-neutralizing antibodies, and CD4 T cells may be required to elicit FI-RSV vaccine-enhanced disease. I determined that distinct CD4 T cell subsets mediate individual disease parameters. The Th2-biased immune response, but not eosinophils specifically, was responsible for induction of airway hyperresponsiveness and mucus hypersecretion. On the other hand, the Th1-associated pro-inflammatory cytokine TNF-α was required to mediate baseline pulmonary dysfunction and weight loss. Lastly, while depletion of CD4 T cells ameliorated all disease parameters evaluated, the antibody titers remained unaltered in depleted mice. Thus, antibodies induced by FI-RSV immunization were not required for vaccine-enhanced disease. My data demonstrate that discrete disease manifestations associated with FI-RSV immunization are orchestrated by distinct subsets of CD4 T cells. The CD8 T cell response is believed to contribute to both pathogen clearance and immunopathology following an acute RSV infection. However, it is unclear if robust memory CD8 T cell responses will protect against an RSV infection. I determined that induction of a high-magnitude, epitope-specific memory CD8 T cell pool mediated increased viral clearance following RSV challenge. However, mice with robust secondary CD8 T cell responses exhibit increased airway dysfunction, weight loss, and mortality as compared to mock-immunized mice undergoing an acute RSV infection. The enhanced disease severity was unique to the context of an RSV infection as similarly immunized mice were protected from chge with a lethal dose of a recombinant IAV engineered to express an RSV-derived epitope. In addition, the increased morbidity and mortality was associated with an elevated amount of both IFN-γ and TNF-α in the serum of immunized mice. Neutralization of either IFN-γ or TNF-α led to a significant reduction in disease severity and survival of all mice. These results demonstrate that robust memory CD8 T cell responses enhance viral clearance, but also lead to severe pulmonary immunopathology following RSV infection. Overall, I establish that the majority of effector CD8 T cells are localized within the lung tissue following a respiratory infection, and determine that either memory CD4 or CD8 T cell responses elicits severe immunopathology following a RSV infection.

Competitive balance and changes in individual plant growth parameters of eight pairs of plant species exposed to enhanced UV-B irradiation were determined under field conditions simulating ozone reductions of about 0.08 atm·cm. The levels of irradiance represented ozone decreases of about 25-30 percent from approximate ambient ozone concentrations for high solar altitudes on clear days during the study. A method for calculating and statistically analyzing relative crowding coefficients was developed and used to evaluate the competitive status of the species pairs sown in a modified replacement series. The effect of UV-B irradiance was generally detrimental to plant growth, and was reflected in decreased leaf area, biomass, height and density as well as changes in competitive balance for various species. For some species inter-specific competition apparently accentuated the effect of UV-B radiation, while intensive intraspecific competition may have had the same effect for other species.

This thesis presents a light scattering-based method for biomarker detection, which could potentially be used for the quantification of multiple biomarkers specific to B-cell malignancies. This method uses fabricated gold nanoparticle probes to amplify inelastic light scattering in a process referred to as surface-enhanced Raman scattering. These gold nanoparticle probes were conjugated to antibodies for specific and targeted molecular binding. The spectrum of the amplified inelastic light scattering was detected using a spectrometer and a detector. To detect the light scattering signal from the gold nanoparticle probes, several commercial Raman spectrometer instruments were evaluated. Initial results from these evaluations are presented in this thesis. After system evaluation, a custom Raman microscope system was designed, built, and tested. This system was used for the development of a surface-enhanced Raman spectroscopy-based immunoassay. The development of this assay confirms the successful design of gold nanoparticle probes for the specific targeting and detection of immunoglobulins. The immunoassay also shows promise for the simultaneous detection of multiple biomarkers specific to B-cell malignancies.

This thesis presents results of studies using the technique of surface-enhanced Raman scattering (SERS) spectroscopy to investigate surface processes occurring on gold during electrochemical experiments in thiosulfate solutions and during leaching in ammoniacal copper(II) thiosulfate systems. The gold SERS electrode was characterised using X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), X-ray diffraction (XRD), energy dispersive X-ray analysis (EDX), linear sweep voltammetry (LSV) and cyclic voltammetry (CV). SEM investigations of the SERS activated gold surface showed the presence of electrodeposited dendrites with nanoscale features. XRD studies of the dendrites showed them to be polycrystalline with a large proportion of Au(111). Rotating disk electrode (RDE) studies of polished and SERS electrodes were undertaken in order to clarify the electrochemistry of various thiosulfate systems. The ex situ techniques of XPS and attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy were used to determine the presence of sulfur, copper and nitrogen on leached or electro-oxidised surfaces. Voltammetric methods were used to determine sulfur and copper surface coverages at various potentials in sulfide, thiosulfate and ammoniacal copper(II) thiosulfate media. The electro-oxidation of sulfide was examined as a model system in order to identify spectral features and coverage associated with various potential-dependent sulfur layers. In the hydrogen evolution region, a surface layer formed by underpotential deposition in acid and basic media was characterised by a gold-sulfur stretching band, Au-S, attributed in the literature to a monoatomic stretching mode of sulfur bonded to gold. The surface coverage in this potential region was limited to 0.35 ML, representing adsorption in a (3x3)R30 structure. Bands were found to be absent that would have indicated the adsorption of SH– species as has been reported in the literature. A facile change in the position of the Au-S band with potential, unaccompanied by Faradaic processes, was seen when the adsorbed (3x3)R30 sulfur layer was examined in a sulfide-free solution. This may indicate a change in sulfur adsorption sites with potential in the hydrogen evolution region. At potentials above the S II/S0 reversible value in sulfide solutions, the surface coverage increased and S-S bands were observed, indicating the formation of an adsorbed polysulfide species, Au-Sn. A change in the position of the Au-S band was seen to accompany the formation of the S-S bands. As coverage further increased, bands due to S-S-S bending, S-S-S, developed that were characteristic of cyclo octasulfur, S8. On removal from sulfide solution and rinsing, a characteristic SERS spectrum was observed ex situ. The spectrum showed a characteristic S-S at 460 cm-1 and Au-S at 325 cm-1 and was assigned to an adlayer of S8 adsorbed on gold in a crown configuration, Au S8. Gold was polarised in thiosulfate solutions at a potential at which gold dissolution is known to occur. In situ SERS spectra showed bands characteristic of S-S bonding and Au2S to occur after 1 hr for thiosulfate with sodium and ammonium counter-ions and for both systems in the presence of ammonia. XPS studies of polished gold held in sodium thiosulfate under these conditions showed S 2p binding energies corresponding to metal sulfide and pyritic sulfur, S22-. After 72 hrs at the mixed potential in air saturated sodium thiosulfate, SERS investigations showed a spectrum with Au-S8 characteristics. XPS studies on a polished electrode under these conditions showed a third type of S 2p binding with a binding energy between that of pyritic sulfur and S8. The sodium thiosulfate system showed an adsorbed tetrathionate-like surface species, Au-S4O6, to be present at the mixed potential and to disappear with increased potential prior to the formation of bulk S8 via an Au-S8 intermediate. In the presence of the ammonium cation at high potentials, Au-Sn bands appear in the presence of a more intense and broad Au-S characteristic of gold sulfide, Au2S. This was assigned to a mixed gold sulfide/polysulfide phase, Au2S/Sn. With addition of ammonia, the surface species Au S4O6, Au2S/Sn and, tentatively, adsorbed NH3 were observed above the mixed potential. For gold in air-saturated copper(II) ammoniacal thiosulfate media, bands due S-S at 382 cm-1 and symmetric S-O stretching, symS-O, at 1017 cm-1 developed during leaching at the mixed potential. These modes diminished and, when rinsed and examined in water, were replaced by a single band at 255 cm 1 assigned to a metal sulfide stretch. In typical leach solutions, sulfur and copper coverages showed a 2:1 atomic ratio after leaching for 16 h. Ex situ ATR and XPS studies showed that ammonia was adsorbed to a surface copper sulfide. Kinetic studies using atomic absorption spectroscopy (AAS) to measure gold in solution showed that the ammoniacal copper(II) thiosulfate leaching solution exhibited higher dissolution rates in the presence of the sodium counter ion than the ammonium. Thiourea as an additive to thiosulfate solutions was seen to disrupt S-S bonding in both Au-S8 and Au2S/Sn surface structures.

For adult English speakers studying Mandarin (Modern Standard Chinese), the acquisition of the Mandarin prosody presents major difficulties. One particularly problematic aspect of the Mandarin prosodic system, and the one singled out for research here is the acquisition of tones by second language (L2) learners of Mandarin. This thesis involves a literature review and a description of an experiment conducted for the purpose of assessing the effectiveness of a new teaching method for educating students in Mandarin prosody generally, but especially with regard to "tones." Most studies investigating the acquisition of Mandarin tones by L2 learners have treated tones as separate from other aspects of Mandarin prosody such as stress, loudness and duration. The teaching method examined in this thesis, however, takes an alternative approach. Here the acquisition of Mandarin prosody is approached as a complex dynamic that has tones as an integral part. The aims of the study are twofold: (1) to identify the principal problems encountered by most learners in order to discover the causes of recurrent error patterns and, (2) to find out how a multi-sensory approach, which in this study was called the Somatically Enhanced Approach (SEA), might influence the acquisition of Mandarin prosody in these areas. The experiment involved 22 adult Australian students studying Mandarin in the first three months of language training. The experimental component of the study consisted of an evaluation of two groups of students� oral conversations. The two groups of students were divided into a control group and an experimental group. The control group was trained in a nonmulti- sensory but communicative approach in 2001 and 2002. Their results are compared with those of a test group and with a group of students trained in the multi-sensory communicative approach (SEA) in 2003 and 2004. The test materials consisted of short dialogues that were likely to occur in everyday communication. Data was collected from each group, once during the first half of the first semester of study in each year. The findings of the experiment were that the order of difficulty of the four Mandarin tones was found to be similar for both the experimental and control groups of students. However, the order of difficulty differed from what has been reported by previous researchers. This suggests that the input and the type of task used to collect data might exert a significant influence on the learning of tones. In other words, the performance of subjects in the dialogues suggests that in the initial stages of learning, the major cause of errors was first language (L1) interference rather than the physical "difficulty" of articulating particular phonemes (or any features of Universal Grammar). Therefore, by using a multi-sensory approach (SEA) to the learning of Mandarin, it may be possible to considerablly lessen the influence of learners� L1 from the outset. Finally, a number of suggestions for improving the teaching of Mandarin prosody are made and future research directions outlined. Some salient suggestions for teaching of Mandarin prosody that arise from the research are: (1) To use movement and gesture in the early stages of learning to enhance students� perception and production of Mandarin. This approach provides students with useful memory tools for learning both in class and in self-accessed learning; (2) To teach Tone 3 not as a full Tone 3 but as a low level tone. This should not be done solely through a simple verbal explanation but through a combination of movement and gesture, provision of visual and auditory feedback and a large amount of exposure and perception training so that Tone 3 is recognised as a low level tone rather than a full Tone 3. By so doing confusion is reduced between the various realizations of Tone 3 during the initial learning stages; and (3) To caution students about the common error patterns caused by interference from their L1. This should be supplemented with opportunities for students to observe their own production of Mandarin and then experience how physically they can find ways of reducing the interference. A qualitative analysis of interview and question data obtained from this research also revealed that the extensive use of computer enhanced language learning and SEA work well together, not only efficiently conditioning students to the phonology of Mandarin, but dramatically changing students' strategies in learning and increasing their learning opportunities.

Current micro-scale electronics technology has been approaching rapidly towards its technological limit. This has shifted the focus towards nano-scale technology in recent years. More and more researchers around the globe are working in pursuit of bringing nano-scale technology into mainstream. The research carried out here is a small step towards a similar goal. The remarkable optical properties exhibited by certain nano-scale structures are in stark contrast to their bulk form and this provides the basis for this research. Two kinds of nanostructures are developed and investigated for their optical properties. One of these is nanofibers processed from a polymer known as polyaniline (PANI). The focus of this study is to investigate its optical and conductive properties under different conditions of doping environments, temperature and polymerization conditions. Optical characterization technique such as UV-Visible spectroscopy is developed to carry out the investigation. The developed nanofibers have been demonstrated to possess optical and conductive properties to be dependent on doping variables. Study of these optical properties could prove very useful in the development of electrochromic devices and gas sensors. Later in the research, UV-Visible spectroscopy has been improved into a low cost Raman spectroscopy setup which is validated by experimentation carried out on some samples. The second type of nano-structure developed and investigated, is an array of nanoparticles of noble metals such as gold and silver. Such an array is shown to exhibit a phenomenon called plasmon resonance effect when excited by light. UV-Visible spectroscopy technique is utilized to investigate this effect for metal nano-arrays. A biologically nano-structured surface (wing of an insect called cicada) is used as the substrate for the fabrication of metal array. A serious attempt has also been made to do 'Surface Enhanced Raman Spectroscopy (SERS)', making use of the metal nano-array developed. This technique improves the raman lines intensities of certain less sensitive samples such as thiophenol, which are known to give weak raman lines. This is carried out by adsorbing the sample on the metal nano-array.

Ce travail de thèse a pour objectif le traitement local des gliomes malins via l'administration de nanocapsules lipidiques (LNC) par convection enhanced delivery (CED). Deux types de complexes métalliques lipophiles aux propriétés thérapeutiques ont été encapsulés au sein des LNC. Le premier est un complexe radioactif de Rhénium-188 et le second, un agent anticancéreux dérivé du tamoxifène et du ferrocène, le ferrociphénol (Fc-diOH). Les LNC de 188Re permettent une rétention de l'émetteur β- au niveau local et une éradication complète de la tumeur est possible pour une dose de 8Gy puisque 33% des animaux sont de longs survivants. Cette dose optimisée s'est révélée être une dose efficace, intermédiaire entre des doses toxiques (10-12 Gy) ou inefficaces (3-4 Gy). Les LNC-Fc-diOH présentent des taux d'encapsulation élevés, et sont quantitativement internalisées dans les cellules 9L. De plus, l'activité du ferrociphénol est conservée après encapsulation et se révèle très efficace sur des cellules de gliome 9L (IC50=0.6μM). En revanche, l'activité est très réduite sur les astrocytes, cellules au potentiel de division quasiment nul. L'action intratumorale des LNC-Fc-diOH dans un modèle de gliome sous-cutané entraîne une réduction significative des masses et volumes tumoraux. De plus, l'association entre le ferrociphénol et les photons X est une association synergique conférant à Fc-diOH des propriétés de molécule radio-sensibilisante. La médiane de survie du groupe traité par une CED de LNC-Fc-diOH suivie d'une radiothérapie externe de 18Gy (3x6Gy) augmente de 48% par rapport au groupe contrôle avec la présence de 17% de longs survivants.

<p>Skattemyndigheter världen över arbetar med att hantera den skatteinbetalning som behövs för att finansiera och driva samhället. Fullständig skatt betalas inte in och de uteblivna skatteintäkterna utgör det så kallade skattefelet, vilket definieras som skillnaden mellan den teoretiskt korrekta skatten som borde betalats in och den faktiskt fastställda skatten. Alla skattemyndigheter arbetar med olika medel och i olika omfattning för att minska skattefelet. De utför delvis kontroller och granskningar samt informerar och uppmuntrar skattebetalarna till att göra rätt. Kontroller kan utföras dels genom olika typer av stickprov, eller genom att identifiera riskområden och primärt inrikta resurserna till dessa områden.</p><p>Globaliseringen har medfört att företag ofta både opererar och handlar i ett flertal länder. Detta bidrar till en allt mer komplicerad skattemiljö vilken har gett upphov till ett behov av en förändring. Främst påverkas de stora företagen som också står för en betydande del av skatteintäkterna. Skattemyndigheter i vissa länder har med olika metoder börjat arbeta för en ökad relation tillsammans med de stora företagen. Genom att erhålla utökad information om företagen blir det lättare att identifiera risker för fel och kontrollera dessa. Företagen tjänar på att behovet för kostsamma revisioner minskar och att de erhåller en ökad säkerhet i sin skatteposition, då avklarade ärenden inte kommer att granskas i framtiden.</p><p>Skatteverket i Sverige driver idag ett riksprojekt mot skatteplaneringsaktiva som bland annat syftar till att skapa en ökad effektivitet genom en förbättrad riskhantering. Det nya arbetssättet kan, enligt indikationer, komma att ha liknelser med en del utländska arbetssätt. I och med detta fann vi det aktuellt att utföra en komparativ fallstudie av ett urval av länder för att se hur de arbetar med riskhantering och hur det visat sig fungera.</p><p>Vår undersökning visar att dessa typer av arbetssätt överlag har fått positiv respons av både företag och skattemyndigheter i samtliga av de undersökta länderna. Det har bland annat bidragit till en ökad effektivitet i granskningsprocesser, en förbättrad relation mellan parterna samt en ökad säkerhet hos företagen gällande deras skatteposition. Dock finner vi att det har visat sig svårt att frambringa ett ändrat beteende hos företagen gällande deras skatteplanering.</p>

<p>The increasing use of data services and the importance of IP basedservices in third generation mobile communication system (3G), requires the transmission from the cell phone to the base station, i.e. uplink, to manage high speed data rates. In the air interface for 3G in Europe, WCDMA, a concept for enhancing the transmission from the cell phone to the base station, called Enhanced Uplink, is being standardized. The overall goal is to provide high speed data access for the uplink. One of the requirements is that the enhanced uplink channels must be able to coexist with already existing WCDMA releases. For example, the enhanced uplink must not impact seriously on real time services, such as speech, carried on current WCDMA channels.</p><p>The purpose of this work is to study how the quality, coverage and capacity of real time services carried on previous WCDMA releases is affected when introducing the Enhanced Uplink in a WCDMA network. The main focus of the study is thus to demonstrate the trade-off between voice and best effort performances.</p><p>Theoretical assessments and simulations show that the Enhanced Uplink has many advantages over previous WCDMA releases. For example the Enhanced Uplink yields a larger system throughput for all voice loads. The noise rise, i.e. the ratio of total received power to the background noise power is being considered as the resource. It is shown that user traffic carried on the Enhanced Uplink is able to operate under a higher noise rise level as well as to get a higher throughput per noise rise. The resource is hence more efficiently utilized.</p>

<p>Hammarby Sjöstad is a new district of southern Stockholm built with focus on reduced environmental impact by recirculation of materials and sustainability. The environmental goals aim to cut the water consumption by half and a separate storm water treatment. Thus, the wastewater will be more concentrated and will originate from the households only. The Sjöstad project includes the idea of a local treatment plant for the household wastewater. To evaluate this possibility, Sjöstadsverket, an experimental treatment plant was constructed. New wastewater treatment processes are tested and evaluated and compared to conventional methods including both aerobic and anaerobic treatment processes.</p><p>One of the aerobic treatment processes includes enhanced biological phosphorus removal (EBPR or Bio-P) as the method for the removal of phosphorus. In biological phosphorus removal the wastewater is alternately being exposed to anaerobic and aerobic conditions, which favours a certain bacteria, which can accumulate more phosphorus than is required for their growth. For this phosphorus accumulation the bacteria need volatile fatty acids (VFA) to cover their energy demand, but normally there is a shortage in VFA in the incoming wastewater.</p><p>The main purpose of this master thesis work has been to create the best possible conditions in order to produce VFA by hydrolysis and fermentation of primary sludge. In this way the organic material in the incoming wastewater can be used in biological phosphorus removal.</p><p>The sludge temperature, total solids (TS) and retention time are regarded as important parameters for a successful biological phosphorus removal and a laboratory study was set up to investigate these conditions for the wastewater at the Hammarby Sjöstad experimental plant. These laboratory-scale hydrolysis experiments showed that high temperature and high TS favours VFA-production. The results have also shown that four to five days retention time is suitable at a process temperature higher than 23°C, but also that the retention time likely should be extended at lower temperatures.</p><p>In a full-scale process experiment, primary sludge was pumped from a primary clarifier to a hydrolysis tank and then back to the primary clarifier. The hydrolysis gave rise to increased VFA-production when TS was increased. A temperature difference between the primary sludge and the hydrolysis sludge of 3°C was observed. The reason behind the difference has not been determined, but is considered important, since the temperature affects the VFA-production. Further on, analyses with gas chromatograph (GC) have shown that acetate has been the most frequently occurring VFA, although significant levels of other VFA, such as propionate, has also been detected.</p><p>Phosphorus release tests in laboratory-scale, where phosphorus was released during an anaerobic phase and taken up during an aerobic phase, proved that biological phosphorus removal occurred at the full-scale experimental train.</p><p>The full-scale hydrolysis experiment has shown that the VFA contribution by the hydrolysis tank to the biological phosphorus removal was low. The main reason is that the sludge-flow through the hydrolysis tank has been insignificant compared to the incoming wastewater flow. The problem is most likely connected to the incoming wastewater characteristics, since the low share of suspended solids (SS) entailed that not enough organic material in the primary clarifier settled.</p> / I figur 57 på sidan 76 stämmer inte trendlinjernas ekvationer i den tryckta versionen. Dessa är nu korrigerade i den elektroniska versionen, så att rätt ekvationer finns i den aktuella figuren.