Cancer immunotherapy aims at reversing the immunosuppressive tumor environment and enhancing anti-tumor immunity. This thesis comprises studies on murine models for prostate (TRAMP-C2) and bladder (MB49) cancer with the aim to explore if the introduction of an adenoviral vector expressing CD40 ligand (AdCD40L) can induce anti-tumor immune responses. We show in subcutaneous mouse models that AdCD40L treatment suppresses tumor growth. Bladder cancer is known to secrete immunosuppressive IL-10 which may inhibit T cell function. We show that introducing AdCD40L into mouse bladder tumors inhibits IL-10 production and reverses immunosuppression. AdCD40L-transduced mouse prostate cancer cells showed caspase activation and reduced cell viability. Vaccination with CD40L-modified prostate cancer cells induces anti-tumor responses and protects mice against rechallenge with native TRAMP-C2 cells. In order to enhance AdCD40L therapy, we explored the possibility of combining it with the histone deacetylase inhibitor FK228, also known as depsipeptide. We show that FK228 upregulates coxsackie and adenovirus receptor expression and thereby enhances adenoviral-mediated CD40L expression in both murine and human prostate cancer cells. Increasing amounts of FK228 or AdCD40L reduces prostate cancer cell viability, while the combined treatment gives at least an additive therapeutic effect. Moreover, we show that AdCD40L transduction of prostate cancer cells induces endogenous CD40 expression and sensitize them for CD40L-mediated therapy. In order to conduct prostate-specific gene therapy, prostate-specific promoters can be used to drive transgene expression. However, there are no reports on prostate-specific promoters that are transcriptionally active in mouse cells. Here we show that by using the two-step transcription activation system (TSTA), we can enhance the activity of a recombinant human promoter sequence and obtain activity in mouse prostate cancer cells as well. This finding paves the way for future studies of prostate-specific gene therapy in immunocompetent mouse models.

Estrogen stimulation of the medial amygdala (MEA) of the brain promotes male rat mating behavior. However, selective stimulation of either of the estrogen receptor subtypes found in the MEA (ERα or ERβ) does not support mating behavior. We tested the hypothesis that dual stimulation of ERα and ERβ is required to activate estrogen-dependant neural circuits in the MEA responsible for mating by local treatment of MEA with a combination of selective estrogenic agonists: propyl pyrazole triol (PPT, an ERα agonist ) and diarylpropionitrile (DPN, an ERβ agonist) administered to castrated, DHT maintained male rats. Estradiol (E2) or cholesterol (Chol) MEA implants served as positive and negative controls respectively. The animals receiving a mixture of PPT and DPN into the MEA displayed higher levels of mating behavior than the Chol treated animals but lower levels of mating behavior than the E2 treated animals.

För att skydda stater mot treaty shopping och annat missbruk av skatteavtal, har OECD utarbetat förslag till en rad åtgärder som begränsar rätten till skatteavtalets förmåner. De viktigaste åtgärderna som föreslås är en LOB-regel, en PPT-regel samt ändringar i skatteavtalets titel och preambel som anger att skatteavtalets syfte är att hindra skatteflykt. Alla länder är överens om att vidta minst någon eller några av dessa åtgärder dvs. ändringarna i skatteavtalets titel och preambel samt antingen 1) PPT-regeln och LOB-regeln eller 2) bara PPT-regeln eller 3) bara LOB-regeln. I skrivande stund arbetar Finansdepartementet för att avgöra vilka av dessa åtgärder Sverige bör implementera. Av analysen i denna uppsats framgår det att både LOB-regeln och PPT-regeln i sina nuvarande former riskerar att brista i kraven på förutsebarhet och rättssäkerhet. Med andra ord blir det svårt för skattebetalaren att förstå villkoren i dessa regler som berättigar till skatteavtalsförmåner. LOB-regeln innehåller till stor del objektiva kriterier som skulle kunna främja förutsebarheten men regelns komplexitet, omfattning och till viss del brist på riktlinjer vad gäller tolkning och tillämpning av vissa rekvisit påverkar förutsebarheten negativt. Det kan konstateras att vissa kriterier i LOB-regeln är för restriktiva och det uppstår en risk för att skattebetalaren vägras rätten till skatteavtalets förmåner även i de situationer när denne varit i god tro och inte haft för avsikt att bedriva treaty shopping eller på annat sätt missbruka skatteavtalet.Till skillnad från LOB-regeln som innehåller en uppräkning av objektiva kriterier, är PPT-regeln en generalklausul mot skatteflykt. PPT-regeln är därför allmänt utformad och har ett brett tillämpningsområde som avser att täcka alla skatteflyktssituationer som inte kunnat förutses av lagstiftaren. I likhet med många andra generalklausuler har PPT-regeln en mer subjektiv karaktär och är vag i vissa delar vilket drabbar rättssäkerheten och förutsebarheten. Slutsatsen är att, för att motverka treaty shopping, skulle det räcka med att tydligt ange i skatteavtalet ett syfte att motverka skatteflykt och skatteundandragande. PPT-regeln är också en lämplig åtgärd mot treaty shopping under förutsättning att vissa rekvisit förtydligas och mer vägledning ges om vilka situationer som regeln avser att träffa. Detta behövs i syfte att förbättra rättssäkerheten och förutsebarheten och motverka eventuellt godtycke och missbruk. I annat fall kan ett osäkert rättsläge skapa en risk för dubbelbeskattning som kan drabba internationell handel och tillväxt. Det kan däremot vara svårt att precisera de omständigheter som ska beaktas vid en prövning enligt PPT-regeln och samtidigt behålla regelns karaktär av generalklausul.

Fascial tissues form a continuous whole-body three-dimensional network penetrating all parts of the human body. They include all fibrous connective tissue that significantly contributes both to themaintaining of the integrity of the organism and the functioning of body systems and the somesthetic perception.That is because of the facia is richly populated by proprioceptiveand mechanosensitive nociceptive nerve endings. Although the stretching is a routine method used in sports and rehabilitation, its exact mechanism of influence and effects on the body are not fully understood so far. Stretching exercises affect the mechanical state of the myofascial tissues and also the quality of the nociception and proprioception by alteration of their preload. There is evidence about some differences of the mechanical properties of the tissuesboth between thesexes and hypermobile individuals. The theses assesses the effect of static stretching m. QF on the somesthetic perception by measuring pressure pain threshold (PPT) using pressure algometry and the quality of propcioception bygoniometric measurement considering the interindividual variance in quality of the connective tissues. Our research includes testing of 29 healthy subjects (14 women and 15 men) and it has proved significant impact of the intervention on the...

Pfeffermann, Krieger e Rinott (1998) apresentaram uma metodologia para modelar processos de amostragem que pode ser utilizada para avaliar se este processo de amostragem é informativo. Neste cenário, as probabilidades de seleção da amostra são aproximadas por uma função polinomial dependendo das variáveis resposta e concomitantes. Nesta abordagem, nossa principal proposta é investigar a aplicação do teste de significância FBST (Full Bayesian Significance Test), apresentado por Pereira e Stern (1999), como uma ferramenta para testar a ignorabilidade amostral, isto é, para avaliar uma relação de significância entre as probabilidades de seleção da amostra e a variável resposta. A performance desta modelagem estatística é testada com alguns experimentos computacionais. / Pfeffermann, Krieger and Rinott (1998) introduced a framework for modeling sampling processes that can be used to assess if a sampling process is informative. In this setting, sample selection probabilities are approximated by a polynomial function depending on outcome and auxiliary variables. Within this framework, our main purpose is to investigate the application of the Full Bayesian Significance Test (FBST), introduced by Pereira and Stern (1999), as a tool for testing sampling ignorability, that is, to detect a significant relation between the sample selection probabilities and the outcome variable. The performance of this statistical modelling framework is tested with some simulation experiments.

"The ablative Teflon pulsed plasma thruster (PPT) is an onboard electromagnetic propulsion enabling technology for small spacecraft missions. The integration of PPTs onboard spacecraft requires the understanding and evaluation of possible thruster/spacecraft interactions. To aid in this effort the work presented in this thesis is directed towards the development and application of Langmuir probe techniques for use in the plume of PPTs. Double and triple Langmuir probes were developed and used to measure electron temperature and density of the PPT plume. The PPT used in this thesis was a laboratory model parallel plate ablative Teflon® PPT similar in size to the Earth Observing (EO-1) PPT operating in discharge energies between 5 and 40 Joules. The triple Langmuir probe was operated in the current-mode technique that requires biasing all three electrodes and measuring the resulting probe currents. This new implementation differs from the traditional voltage-mode technique that keeps one probe floating and requires a voltage measurement that is often susceptible to noise in the fluctuating PPT plume environment. The triple Langmuir probe theory developed in this work incorporates Laframboise’s current collection model for Debye length to probe radius ratios less than 100 in order to account for sheath expansion effects on ion collection, and incorporates the thin-sheath current collection model for Debye length to probe radius ratios greater than 100. Error analysis of the non-linear system of current collection equations that describe the operation of the current-mode triple Langmuir probe is performed as well. Measurements were taken at three radial locations, 5, 10, and 15 cm from the Teflon® surface of the PPT and at angles of 20 and 40 degrees to either side of the thruster centerline as well as at the centerline. These measurements were taken on two orthogonal planes, parallel and perpendicular to the PPT electrodes. A data-processing software was developed and implements the current-mode triple Langmuir probe theory and associated error analysis. Results show the time evolution of the electron temperature and density. Characteristic to all the data is the presence of hot electrons of approximately 5 to 10 eV at the beginning of the pulse, occurring near the peak of the discharge current. The electron temperature quickly drops off from its peak values to 1-2 eV for the remainder of the pulse. Peak electron densities occur after the peak temperatures. The maximum electron density values on the centerline of the plume of a laboratory PPT 10 cm from the Teflon® surface are 6.6x10^19 +/- 1.3x10^19 m^-3 for the 5 J PPT, 7.2x10^20 +/- 1.4x10^20 m^-3 for the 20 J PPT, and 1.2x10^21 +/- 2.7x10^20 m^-3 for the 40 J PPT. Results from the double Langmuir probe taken at r=10 cm, theta perpendicular=70 degrees and 90 degrees of a laboratory PPT showed good agreement with the triple probe method."

This thesis investigates estrogens' modulation of three aspects of social cognition (aggression and agonistic behaviour, social learning, and social recognition). Sex-typical agonistic behaviour (males: overt attacks, females: more subtle dominance behaviours) was increased in gonadectomized mice by estrogen receptor alpha (ERα) agonist 1,3,5-tris(4-hydroxyphenyl)-4-propyl-1H-pyrazole (PPT), while non-overt agonistic behaviour was increased in male and female gonadally intact mice by ERβ agonist 7-Bromo-2-(4-hydroxyphenyl)-1,3-benzoxazol-5-ol (WAY-200070). Estrogens also affected the social transmission of food preferences (STFP). Acute estrogen and ERβ agonists WAY-200070 and 2,3-bis(4-hydroxyphenyl)propionitrile (DPN) prolonged the preference for the demonstrated food when administered pre-acquisition, likely by affecting motivation or the nature of the social interaction, while acute PPT blocked the STFP. All mice receiving any of the three treatments chronically showed a prolonged demonstrated food preference, suggesting a loss of ER specificity. Individual differences in social recognition may relate to increased oxytocin (OT) and vasopressin (AVP) mRNA, and ERα and ERβ gene activation, in the medial preoptic area, and decreased mRNA for ERs, OT receptor (OTR), AVP and AVP receptors 1a and 1b in the lateral amygdala. Additionally, dorsolateral septum ERs, progesterone receptor, and OTR may relate to social interest without affecting social recognition. Our and others' results suggest that estrogens, OT and AVP are all involved in social behaviours and mediate social recognition, social learning, social interactions, and aggression. ERs differently modulate the two types of social learning investigated here: ERα is critical for social recognition, but impairs social learning, while ERβ is less important in social recognition, and prolongs the demonstrated food preference in the STFP. This may be due to differences in receptor brain distributions or in downstream neurochemical systems that mediate these behaviours. The results of this thesis suggest that estrogens, through the various systems they modulate, have a key role to play in social behaviour. Further investigations of how estrogens effect change in these systems at the molecular and cellular level, as well as the critical brain areas and downstream effectors involved in these complex behaviours, are needed, and could contribute to therapeutic interventions in socially-based, sexually dimorphic disorders, like the autism spectrum disorders, and women receiving hormone replacement therapy for negative peri- or post-menopausal symptoms. / National Science and Engineering Research Council (PGS-D, CGS-M)

Pfeffermann, Krieger e Rinott (1998) apresentaram uma metodologia para modelar processos de amostragem que pode ser utilizada para avaliar se este processo de amostragem é informativo. Neste cenário, as probabilidades de seleção da amostra são aproximadas por uma função polinomial dependendo das variáveis resposta e concomitantes. Nesta abordagem, nossa principal proposta é investigar a aplicação do teste de significância FBST (Full Bayesian Significance Test), apresentado por Pereira e Stern (1999), como uma ferramenta para testar a ignorabilidade amostral, isto é, para avaliar uma relação de significância entre as probabilidades de seleção da amostra e a variável resposta. A performance desta modelagem estatística é testada com alguns experimentos computacionais. / Pfeffermann, Krieger and Rinott (1998) introduced a framework for modeling sampling processes that can be used to assess if a sampling process is informative. In this setting, sample selection probabilities are approximated by a polynomial function depending on outcome and auxiliary variables. Within this framework, our main purpose is to investigate the application of the Full Bayesian Significance Test (FBST), introduced by Pereira and Stern (1999), as a tool for testing sampling ignorability, that is, to detect a significant relation between the sample selection probabilities and the outcome variable. The performance of this statistical modelling framework is tested with some simulation experiments.

Bakgrund: Offensiv kvalitetsutveckling innebär att ständigt sträva efter att möta och helst överträffa kundförväntningar. Små till medelstora organisationer kan med hjälp av en ISO 9001-certifiering öka sin konkurrenskraft och få ökade affärsvinster, men de stöter på flera svårigheter. Fallgropar är bland annat brist på resurser, processkunskap och förståelse för kvalitetsförbättringsverktyg.  Metod: En undersökning genomfördes i tre steg. Dels undersöktes processkraven i ISO 9001 och handbok för att kartlägga brister i det praktiska stödet, dels identifierades faktorer inom litteraturen som kan ge stöd för små till medelstora företag för att uppnå processkraven i ISO 9001. Studien har genomförts som en fallstudie med en aktionsforskningsstrategi där en huvudprocess hos en fallorganisation har kartlagts för att identifiera det pågående processarbetet. Dessa sammanställda data utgjorde grunden för ett stöd för fallorganisationens framtida processarbete i ISO 9001:2015. Dataanalys innefattar metoder och verktyg bland annat tematiska analyser, tabeller och diagram.   Resultat: Bristen på praktiskt stöd i ISO 9001-standarden och dess handbok visade sig vara liten. Istället framhävs vikten av förkunskap hos organisationen och ledningens engagemang som betydande faktorer för att införa processledning, uppfylla processkrav och upprätthålla en certifiering. Fallorganisationen uppvisade få av de positiva faktorer för processledning som identifierats i litteraturen. Stödet lyfter ett systematiskt processarbete och en systemsyn som centrala punkter.    Slutsatser: Fallorganisationens brister i processledning visar sig inte kunna överbryggas genom operativa verktyg. Snarare beror de på otillräckliga kunskaper och förberedelser, vilket kräver prioritering att införskaffa förståelse för processteori och engagemang från ledningen för att framgångsrikt uppnå en ISO 9001-certifiering. / Background: The backbone of Total Quality Management is to constantly strive to meet customer needs and exceed their expectations. By obtaining an ISO 9001 certificate small to medium-sized organizations can enhance their competitive position and increase business profit, but they encounter difficulties in doing so. Pitfalls include lack of resources, process knowledge and understanding of quality improvement tools.  Method: The study was conducted in three stages. First, the process requirements in ISO 9001 and its handbook were examined to map the lack of practical support. Next, practical support factors for business process management in small to medium-sized enterprises were identified in the literature. The study employs a case study approach with an action research strategy. Therefore, a main process at a case organization was mapped to identify the current process work. This compiled data serves as the foundation for the support created for the case organization. Data analysis methods and tools include thematic analyses, tables and diagrams.  Results: The lack of practical support in the ISO 9001 standard and its handbook was relatively minor. Instead, the importance of process know-how and management commitment are highlighted as significant factors. The case organization exhibited few of the favorable factors identified in the literature. The support created emphasizes systematic process work and system view as focal points.  Conclusion: The case organization’s deficiencies in process management cannot be remedied by operative tools. Rather, they are due to insufficient knowledge and inadequate preparation for ISO 9001. Preparation should include acquiring the necessary understanding of process management theory and increased management engagement.

This paper deals with the determination of the capillary pore-size distribution (CPSD) and equilibrium moisture content (EMC) of untreated and thermally modified (TM) Norway spruce [Picea abies (L.) Karst.] by means of the pressure plate technique (PPT). Desorption experiments were conducted at very high values of relative humidity (RH) in the range between 99.2% and 100%. The thermal modification of spruce results in an alteration of the CPSD, owing to the formation of intercellular cracks in the middle lamella, as a result of cell-wall compression. The desorption curves for both untreated and TM spruce show an extremely upward bend at 99.97% RH. This step reflects an EMC of 38.1% for untreated spruce and 33.8% for TM spruce. None of the samples shrunk during the PPT measurements. Following desorption experiments at 97.4% RH, all samples shrunk. This step reflects an EMC of 27.9% for untreated spruce and 21.7% for TM spruce.