Pulmonary arterial hypertension (PAH) is a lethal disease, characterized by functional or structural abnormalities involving distal pulmonary arterioles that result in increased pulmonary vascular resistance (PVR) and ultimately right heart failure. Our objective is to establish a conditional transgenic system in mice, to test the hypothesis that lung EC apoptosis at the level of distal pulmonary arterioles is necessary and sufficient to cause a PAH phenotype. In a pilot study, the Fas-Induced Apoptosis (FIA) construct was expressed under the control of endothelial-specific Tie2 promoter in transgenic mice (i.e. EFIA mice). Administration of a small molecule dimerizing agent, AP20187, resulted in lung modest dose-dependent PAH, which was associated with proliferative vascular lesions localized to distal lung arterioles in a small proportion of mice. Due to the low level of transgene expression in preliminary EFIA lines, we re-designed the transgenic vector by incorporating a more robust endothelial promoter (superTie2). The new construct was transfected into HUVEC and BAEC and analyzed by monitoring immunofluorescence (DsRed). Data from the EFIA model suggests that EC apoptosis may be sufficient to induce a PAH phenotype with the characteristic lung vascular lesions. The EFIA model will allow us to better explore the mechanism that links distal lung EC apoptosis with reactive vascular cell proliferation in the pathogenesis of this devastating disease.

In der vorliegenden Arbeit wird eine prädiktive Fahrstrategie vorgestellt, die auf Basis von Ampel-Fahrzeug-Kommunikationsdaten generiert wird. Dazu wird ein aktueller Ansatz für eine prädiktive Fahrstrategie zur Annäherung an eine Lichtsignalanlage (LSA) untersucht. Es werden verschiedene Optimierungsansätze deutlich, von denen ein großer Teil bei der Systemerweiterung berücksichtigt wird. Bei der Analyse konnte gezeigt werden, dass die bisherige Strategieempfehlung durch den Einfluss vorausfahrender Verkehrsteilnehmer eingeschränkt wird. Es ergaben sich potentielle Problemsituationen, welche sich im realen Straßenverkehr negativ auf die Funktionalität des Fahrerassistenzsystems (FAS) auswirken. Für Anfragen des Öffentlichen Personen Nachverkehrs (ÖPNV) wurde ermittelt, dass keine allgemeingültigen Aussagen über die Eignung der Assistenzfunktion gegeben werden können. Die wesentliche Neuerung zu bisheriger Strategieansätze für die Annäherung an Knotenpunkte mit LSA ist die Berücksichtigung anderer Verkehrsteilnehmer. Dazu werden die neuen Größen effektive Freigabezeit und virtuelle Position der Haltelinie eingeführt, auf Basis derer die Strategieempfehlung des FAS an die Anzahl wartender Fahrzeug angepasst wird. Zur Untersuchung des möglichen Energieeinsparpotentials durch den Einsatz eines FAS wurde ein Simulationsmodell in MATLAB/SIMULINK entwickelt. Mit dessen Hilfe konnten verschiedene Situationen dargestellt werden, an denen der Einfluss der Funkreichweite sowie die Auswirkungen der Warteschlange auf das FAS verdeutlicht werden. Ferner kann der positive Effekt auf den Kraftstoffverbrauch und die Haltezeit an der LSA bestätigt werden. Das Simulationsmodell stellt eine gute Grundlage für weiterführende Untersuchung dar und kann an unterschiedliche Situationen angepasst werden. Um den Nutzen auch praktisch zu verifizieren wird eine Reihe von Fahrversuchen durchgeführt. Dem Fahrer wird dabei die Strategie in einem Display visualisiert. Für Situationen, in denen der Fahrzeugstillstand vermeidbar ist erhält dieser eine Geschwindigkeitsempfehlung. Ist ein Stillstand nicht vermeidbar, so erfolgt unmittelbar vor der Haltelinie, die Ausgabe der Restlaufzeit der Rotphase. Bei der Versuchsauswertung wird das Einsparpotential deutlich. Durch eine entwickelte GUI wird dem Fahrer eine Strategie auf dem Display visualisiert. Innerhalb mehrerer Versuchsfahrten konnten das FAS erprobt und in der anschließenden Versuchsauswertung klar die Verbesserungen aufgezeigt werden. / In this paper a predictive driving strategy is presented, which is generated based on car to infrastructure communication data. An actual approach for a driver assistance system has been analyzed to identify room for improvements. The additional benefit of the presented work is the consideration of other road users driving ahead of the ego-vehicle in the process of finding the optimal speed for approaching the traffic-light. A MATLAB/SIMULINK model has been developed, which allows the simulation of different traffic situations to investigate the fuel consumption benefit of a vehicle equipped with the considered system. It illustrates the influence of the radio range and the length of the queue in front of the stop line. Furthermore the positive effect to the fuel consumption of the developed system could be evaluated. The simulation model is a good basis for further tests and could be easily adapted to various situations and vehicles. In addition to the simulation, a human machine interface was developed for evaluating the advanced driver assistance system in test runs. The driver assistance system was tested in several situations to show the benefit of the system. It has been tested via multiple test runs. In the following test evaluation the improvement could clearly be shown.

The Fas pathway is critical for the maintenance of normal T cell homeostasis. Humans and mice with defects in this pathway exhibit the accumulation of large numbers of peripheral lymphocytes and lupus-like autoimmunity. A major feature of these organisms is the accumulation of non-NK TCRαβ+CD4-CD8- “double negative” (DN) T cells. While regulatory T cells (Tregs) with the DN phenotype have been extensively characterized in Fas-sufficient mice and humans, limited data exist on the role of DN T cells as Tregs in Fas-deficient animals. In fact, most of the literature suggests that the DN T cells accumulating in Fas-deficiency states are pathogenic, contributing to secondary lymph node enlargement and autoimmune disease. In this body of work, data are presented that illustrate that Fas-deficient lymphoproliferative (LPR) DN T cells can act as Tregs in an interferon γ (IFNγ)- and Fas ligand (FasL)-dependent fashion toward Fas-sufficient T cells. LPR DN T cells needed to be able to secrete and respond to IFNγ in order to upregulate surface FasL, in order to ameliorate GVHD mediated by CD4+ T cells in vivo and to suppress the proliferation of and kill activated CD4+ T cells in vitro. FcRγ, a key molecule involved in innate immune responses, can substitute for CD3ζ in the T cell receptor (TCR) of mouse and human T cells in certain circumstances; in doing so, it is essential for the regulatory function of TCR transgenic DN Tregs. FcRγ-deficient LPR mice were found to have exacerbated T cell accumulation and early mortality. We show that while FcRγ expression was required for LPR DN T cells to regulate CD4+ and CD8+ T cells responding to alloantigens in vitro and in vivo, it does not control autologous lymphoproliferation in LPR mice by supporting the function of a regulatory cell, nor does it affect the rate of proliferation of LPR T cells in vivo. Instead, FcRγ-expressing LPR CD4+, CD8+ and DN T cells were found to be undergoing apoptosis at a high rate in vivo, and in contrast to their FcRγ-deficient counterparts, FcRγ+ LPR DN T cells were capable of undergoing TCR restimulation-induced cell death (RICD). The data presented in this thesis therefore show that LPR DN T cells can exhibit IFNγ-, FasL- and FcRγ-dependent regulatory function, and also illustrate a previously unknown function for FcRγ in controlling the expansion of Fas-deficient T cells. The implications of these data for autoimmune lymphoproliferative syndromes, and normal T cell homeostasis, are discussed.

Loess is a well sorted, fine grained, windblown (aeolian) sediment and deposits as a blanket over large areas, reaching from a few centimetres to several hundreds of meters in height and can drape large landscapes in form of mountains. During a more humid and warmer climate, redox conditions are changed in the loess deposits, with greater seasonal moisture creating greater soil formation (pedogenesis), i.e. palaeosol.  The Chinese Loess Plateau is dominated by the East Asian monsoon climate, and consists of an alternating Loess-palaeosol Formation, spanning back to at least the whole Quaternary period and late Pliocene (~2.8 Ma), and overlays a Red Clay Formation ranging into at least Miocene. This deposit covers therefore the onset of the latest Quaternary Ice Age. The Magnetic Susceptibility (MS) is used to investigate the magnetism of a rock which is inferred to be driven by the pedogenetic activity changes, i.e. during a stronger pedogenesis a higher amount of magnetic minerals forms. In turn the MS measurements becomes as a good indicator of the intensity and duration of the East Monsoon climate. In present study, a newly applied technique in palaeoenvironment is used to investigate the reasons for the out-of-phase response by the MS measurements. The study shows that this is due to viscous relaxation. Thus, the ultrafine superparamagnetic mineral magnetite is giving rise to the out-of-phase response and no other mechanisms. / Lössjord är ett välsorterad, finkornigt, vindblåst (eolisk) sediment som avsätts som ett täcke över stora områden, och kan variera från några centimeter till flera hundra meter i höjd och drapera stora landskap i form av berg. Under ett mer fuktigt och varmare klimat förändras de redoxa förhållandena i lössjordarna, då större säsongsfuktighet skapar en större paleosol-bildning, under en så kallad pedogenes. Den Kinesiska Lössjordsplatån domineras av det östasiatiska monsunklimatet och består av en alternerande Lössjord-paleosol Formation, som sträcker sig tillbaka till åtminstone hela kvartära perioden men även sena Pliocen (~ 2,8 Ma), och överlagrar en Rödlera Formation som sträcker sig minst tillbaka till Miocen. Dessa avlagringar täcker därför övergången till början på den kvartära istiden. Den magnetiska susceptibiliteten (MS) används för att undersöka de magnetiska egenskaperna hos avlagringarna som drivs av de pedogenetiska aktiviteterna, dvs under en starkare pedogenes bildas en högre mängd magnetiska mineraler. I sin tur blir därför MS-mätningarna en bra indikator på intensiteten och varaktigheten av östasiatiska monsunklimatet. I denna studie används en nyligen tillämpad teknik inom paleo-miljö för att undersöka orsakerna bakom ur-fas responsen som fås genom MS-mätningar på avlagringarna. Studien visar att detta beror på viskös relaxation. Således är det ultrafina superparamagnetiska mineralet magnetit som ger upphov till ur-fas responsen och inga andra mekanismer.

Magister Psychologiae - MPsych / The study made use of cross-sectional design that compared the performance of younger children (6- to 7-year-olds) with that of older children (12- to 13-year-olds) on various measures of executive function. Within this, it made use of a natural experimental design, with children exposed to alcohol as the experimental group and non-exposed children as the control group.

South Africa has the highest prevalence of Foetal Alcohol Spectrum Disorders (FASD) worldwide. Despite the high prevalence of FASD in children and the resulting need for services, appropriate identification and management of most genetic and congenital disorders are critically lacking in South Africa. As a result of the established risk for communication delay from birth, young children with FASD need early communication intervention (ECI). There appears to be a dearth in research on the communication difficulties of local young children with FASD. Determining comprehensive communication profiles of young children may serve to emphasize their need for ECI. The main aim of the study was to present the distinctive communication profiles of a group of young children with FASD. The sub-aims entailed the description of their developmental histories, family/care-giving contexts, communication functioning and identifying developmental trends across the participants. A collective case study design following a quantitative approach was selected. The study was cross-sectional and descriptive statistics was used to describe the participants’ communication skills. A purposive sampling procedure was utilized as a limited number of participants could be found with a diagnosis of FASD. Five participants diagnosed with FASD, living in the Gauteng area, between the ages of 4 to 58 months took part in the study. The empirical study comprised of two phases. Phase 1 entailed the development of the Interview Schedule, the Assessment Protocol and the conduction of a pilot study. Phase 2 comprised the data collection, analysis and interpretation of results. The results of the study indicated that all five participants presented with incomplete case histories obtained from the foster parents and general developmental delays. According to the Four-Level Early Communication Assessment Framework the greatest delays included all aspects of communication skills. A developmental trend of the combined communication profiles of the participants indicated an increase in delay with an increase in chronological age. The participants presented with complex multiple neuro-developmental needs to be viewed within a developmental systems and ecological framework. Based on the results of this study the diverse roles of the speech-language therapist working with young children with FASD and their families were identified. A framework for interdisciplinary service delivery to this population was suggested. The study succeeded in the attempt to provide a comprehensive, in-depth description of a group of the five participants’ unique communication skills. In addition the study also highlighted the shortage of services, e.g. limited early identification and services dedicated to families affected by alcohol related problems. The study is of value to the speech-language therapist in the clinical and research domain. Future research is recommended to expand and support the findings. AFRIKAANS : Suid-Afrika vertoon die hoogste prevalensie van Fetale Alkohol Spektrumafwykings (FAS) wêreldwyd. Ten spyte van die hoë prevalensie van FAS in kinders en die voortspruitende behoefte aan dienste, is toepaslike identifikasie en hantering van die meeste genetiese en kongenitale afwykings in Suid-Afrika krities ontoereikend. As ‘n resultaat van die bevestigde risiko vir kommunikasie agterstand vanaf geboorte, benodig jong kinders met FAS vroëe kommunikasie intervensie (VKI). Daar blyk ‘n gaping in die navorsing aangaande die kommunikasie probleme van plaaslike jong kinders met FAS te wees. Omvattende kommunikasie profiele van jong kinders met FAS kan die behoefte aan VKI dienste beklemtoon. Die hoofdoel van die studie was om die kommunikasie profiele van ‘n groep jong kinders met FAS voor te lê. Die sub-doelwitte het die beskrywing van hulle ontwikkelings geskiedenis, gesin/sorggewer konteks, kommunikasie funksionering en die identifisering van ontwikkelings neigings in al die deelnemers behels. ‘n Saamgestelde gevallestudie is geselekteer volgens ‘n kwantitatiewe navorsings benadering. Die studie is ‘n kruisdeursnee ontwerp en beskrywende statistieke is gebruik om die deelnemers se kommunikasie vaardighede te beskryf. ‘n Doelgerigte steekproef prosedure is gebruik omdat ‘n beperkte aantal deelnemers met ‘n diagnose van FAS gevind kon word. Die vyf deelnemers wat geselekteer was vir die steekproef was gediagnoseer met FAS, woonagtig in die Gauteng area en het binne die 0 – 5 jaar ouderdomsgroep geval. Die empiriese studie het uit twee fases bestaan. Fase 1 het die ontwikkeling van die onderhoud skedule, die assesserings protokol en die uitvoering van ‘n loodsstudie ingesluit. Fase 2 het die data insameling, analise en interpretasie van resultate behels. Die resultate van die studie het aangedui dat al die deelnemers gepresenteer het met onvolledige gevalsgeskiedenisse wat van hul pleegouers verkry is en ‘n algemene ontwikkelings agterstand. Volgens die Vier-Vlak Vroëe Kommunikasie Assesserings Raamwerk het die grootste agterstande alle aspekte van kommunikasie vaardighede behels. ‘n Ontwikkelings neiging vanuit die gekombineerde kommunikasie profiele van die deelnemers het ‘n toename in agterstand met ‘n toename in kronologiese ouderdom aangedui. Die deelnemers presenteer met veelvuldige neuro-ontwikkelings behoeftes wat binne die ontwikkelings sisteem en ekologiese raamwerk beskou moet word. Gebasseer op die resultate is die diverse rolle van die spraak-taalterapeut wat met jong kinders met FAS en hulle families werk, geïdentifiseer. ‘n Raamwerk vir interdissiplinêre dienslewering aan hierdie populasie word voorgestel. Die studie het geslaag in die poging om ‘n omvattende, in-diepte beskrywing van die deelnemers se unieke kommunikasie vaardighede te verskaf. Addisioneel het die studie ook die tekort aan dienste, naamlik beperkte vroëe identifikasie en dienste toegewy aan families geaffekteer deur alkohol verwante probleme, uitgelig. Die studie is van waarde vir die spraak-taalterapeut in die kliniese en navorsings domein. Toekomstige navorsing vir die uitbreiding en ondersteuning van die studie se bevindinge word aanbeveel. / Dissertation (MCommunication Pathology)--University of Pretoria, 2011. / Speech-Language Pathology and Audiology / Unrestricted

Pulmonary arterial hypertension (PAH) is a lethal disease, characterized by functional or structural abnormalities involving distal pulmonary arterioles that result in increased pulmonary vascular resistance (PVR) and ultimately right heart failure. Our objective is to establish a conditional transgenic system in mice, to test the hypothesis that lung EC apoptosis at the level of distal pulmonary arterioles is necessary and sufficient to cause a PAH phenotype. In a pilot study, the Fas-Induced Apoptosis (FIA) construct was expressed under the control of endothelial-specific Tie2 promoter in transgenic mice (i.e. EFIA mice). Administration of a small molecule dimerizing agent, AP20187, resulted in lung modest dose-dependent PAH, which was associated with proliferative vascular lesions localized to distal lung arterioles in a small proportion of mice. Due to the low level of transgene expression in preliminary EFIA lines, we re-designed the transgenic vector by incorporating a more robust endothelial promoter (superTie2). The new construct was transfected into HUVEC and BAEC and analyzed by monitoring immunofluorescence (DsRed). Data from the EFIA model suggests that EC apoptosis may be sufficient to induce a PAH phenotype with the characteristic lung vascular lesions. The EFIA model will allow us to better explore the mechanism that links distal lung EC apoptosis with reactive vascular cell proliferation in the pathogenesis of this devastating disease.

No description available.

Global challenges such as increasingly competitive markets, low-cost competition, shorter lead time demands, and high quality/value output are transforming the business model of the company to focus beyond the performance requirements. In order to meet these challenges, companies are highly concerned with the customer perceived value, which is to connect the product with the customer in a better way and become more proactive to fulfil the customer needs, via function-oriented business models and Product-Service Systems. In literature, the conceptual phase is distinguished as the most critical phase of the product development process. Many authors have recognized the improvement of design in the conceptual phase as the mean to deliver a successful product in the market. At the decision gate, where concepts are selected for further development, the design team needs knowledge/data about the long-term consequences of their early decision, to see how changes in design propagate to the entire lifecycle of the product. The main goal of the thesis is to describe how the design of Product-Service Systems in the conceptual phase can be improved through the use of a data-driven approach. The latter provides an opportunity to enhance decision making and to provide better support at the early development phase. The study highlights how data are managed and used in current industrial setting and indicates the room for improvement with current practices. The thesis further provides guidelines to efficiently use data into the modelling and simulation activities to increase design knowledge. As a result of this study, a data-driven approach emerged to support the early design decision.  The thesis presents initial descriptive study findings from the empirical investigations, showing a model-based approach that creates awareness about the value of a new design concept, thus acting as a key enabler to use data in design. This will create a link between the product engineering characteristic to the high-level attributes of customer satisfaction and provider’s long-term profitability. The preliminary results indicate that the application of simulation models to frontload the early design stage creates awareness about how performance can lead to value creation, helping multidisciplinary teams to perform quick trade-off and what-if analysis on design configurations. The proposed framework shows how data from various sources are used through a chain of simulations to understand the entire product lifecycle. The proposed approach holds a potential to improve the key performance indicators for Product-Service Systems development: lead time, design quality, cost and most importantly deliver a value-added product to the customer.

In this master thesis, several cooling systems for PV-systems have been looked into by doing a smaller literature review and then a cooling module for a BIPV-panel was built out from the knowledge gathered. The cooling module used a PCM material separated into 12 bags and then placed in a 3x4 shaped pattern fastened to an aluminium plate that in turn was placed on the back of a PV-panel. This was tested in first a pilot test and then tested outdoors on panels with insulation on its back to simulate BIPV-panels. Temperature data from behind the panel was gathered with and without the cooling module and then compared with each other with added ambient temperature. It was found that the PCM cooled down the panels during similar weather conditions where the outside temperature and the amount of clouds where approximately the same, and it was also found that PCM technologies needs to be more optimised in terms of its material use, the amount of material, and its arrangement for it to be used in PV-panels. An economical calculation was made and it was found that it wasn't economically viable as it takes 14 years for the PV-panel with cooling to pay for itself while it takes 13 years for the PV-panel with cooling to pay for itself. These results are then discussed in comparison to other systems and earlier work done. / I denna exjobbsrapport så har ett antal olika kylningssystem till PV-paneler setts igenom genom en mindre litteraturstudie. Därefter byggdes en kylningsmodul för en BIPV utifrån den kunskapen som samlats in. Kylningsmodulen använde sig utav ett PCM material som var uppdelat mellan 12 påsar som placerades i ett 3x4 mönster som fästs på baksidan av en aluminiumplåt som i sin tur placerades på baksidan utav PV-panelen. Denna testades först i ett pilottest och sedan utomhus på paneler som isoleras baktill för att simulera BIPV-paneler. Temperaturdata samlades in från panelens baksida, med och utan kylnings modul, som sedan jämfördes med varandra samt omgivningens temperatur. Slutsatsen är att PCM kyler panelen under liknande väderförhållanden där ute temperaturen och molnigheten var ungefär densamma, men att PCM behöver optimeras mer i form av användningen av materialet, mängden av material, och hur det sätts upp som kylning på PV-paneler. En ekonomisk kalkyl genomfördes som visar att det inte är ekonomiskt gångbart eftersom det tar 14 för PV-panelen med kylning att betala av sig själv medan det tar 13 år för PV-panelen utan kylning att göra det. Dessa resultat diskuteras sedan i jämförelse med andra system och tidigare arbeten som gjorts inom området.