Fluorinated stationary phase in Rtx-200MS column have been characterized by determination of system constants of Abraham equation. Retention on this phase is driven by dispersive and orientation/induction forces. Significant interaction contribution of lone pair electrons or π- electrons provides unique selectivity for analytes with excess of electron density. Unusual behavior of this phase have been determined by study of separation mechanism of polar and nonpolar analytes, in comparison of their separation on polar and nonpolar phases. This behavior is due to medium polarity of the phase (system constant s), which is not so pronounced to cancel separation of nonpolar analytes due to induction forces. In some cases contribution of lone pair electrons or π-electrons can contribute to this separations. Key words fluorinated stationary phase Rtx-200MS, inverse gas chromatography, LFER method, Abraham's equation

Historically, infectious bovine keratoconjunctivitis (IBK) was believed to be under the exclusive competence of Moraxella bovis. However, the roles of other species of Genus Moraxella are also being considered in the pathogenesis of IBK, such as Moraxella ovis and particularly Moraxella bovoculi. This thesis describes phylogenetic and genotypic analysis based on the genes encoding type IV pili Q- and I-type (TfpQ/I) of M. bovis and cytotoxin of M. bovis (MbxA), M. bovoculi (MbvA) and M. ovis (MovA). The distinction between M. bovis, M. bovoculi and M. ovis was previously performed by PCR (16S-23S intergenic region) according to the protocol established in the literature. Then, there is described a molecular analysis based on the 3' region of genes tfpQ/I (including α1-C N-terminal subdomain and C-terminal domain) of 16 field strains and five vaccine strains of M. bovis from South America. All 47 sequences of tfp Q- and I-type genes analyzed resulted in 31 alleles designated 1 to 31. The phylogenetic reconstruction resulted in a distinction of 31 alleles in eleven groups (designated A through J and Epp). The analysis of the deduced amino acid sequence (aa) of the C-terminal region showed similarity levels between 67 and 100% within the groups, while the analysis of the D region (C-terminal subunit) resulted in levels of similarity between 60 and 100%. In addition, a phylogenetic analysis based on the 3' region of the cytotoxin gene was performed to investigate the genetic relationship among M. bovis (n = 17), M. bovoculi (n = 11) and M. ovis (n = 7) strains and reference strains. Phylogenetic reconstruction allowed the differentiation among species, and the older M. bovoculi strains remained in branch closer to M. bovis strains. The amino acid similarity level among the MbxA sequences stood at an average of 99.9%, while among the MbvA and MovA sequences the similarity was respectively 98.8% and 99.3%. The similarity between MbvA and MovA was 96.6%, while MbxA for MbvA and MovA was 77.6%. Thus, it is possible to conclude that the tfp gene may be inferred suitable for differentiate among M. bovis strains, while the cytotoxin-encoding gene is suitable for phylogenetic classification of M. bovis, M. bovoculi and M. ovis strains and perhaps for understanding the evolutionary relationships among three species. / Historicamente, acreditava-se que a ceratoconjuntivite infecciosa bovina (CIB) estáva sob competência exclusiva de Moraxella bovis. Contudo, outras espécies do Gênero Moraxella também vêm sendo estudadas quanto à participação na patogenia da CIB, como Moraxella ovis e principalmente Moraxella bovoculi. Esta tese descreve análises filogenéticas e de dados genotípicos com base nos genes codificadores dos pili tipo IV dos tipos Q e I (TfpQ/I) de M. bovis e da citotoxina de M. bovis (MbxA), M. bovoculi (MbvA) e M. ovis (MovA). A diferenciação entre M. bovis, M. bovoculi e M. ovis foi previamente realizada por PCR (região intergenica 16S-23S) conforme protocolo estabelecido na literatura. Após, é descrita uma análise molecular com base na região 3' dos genes tfpQ/I (compreendendo subdomínio α1-C N-terminal e o domínio C-terminal) de 16 isolados de campo e cinco cepas vacinais de M. bovis, provenientes da América do Sul. Todas as 47 sequencias do gene tfp tipo Q e tipo I analisadas resultaram em 31 alelos designados de 1 até 31. A reconstrução filogenética resultou em uma distinção dos 31 alelos em onze grupos (designados de A até J e Epp). A análise da sequencia de aminoácidos (aa) deduzidos da região C-terminal mostrou níveis de similaridade entre 67 e 100% dentro dos grupos, enquanto a análise da região D (subunidade C-terminal) resultou níveis de similaridade entre 60 e 100%. Além disso, um estudo filogenético com base na região 3' dos genes da citotoxina foi realizado para investigar a relação genética entre os isolados de M. bovis (n = 17), M. bovoculi (n = 11) e M. ovis (n = 7) e cepas de referência. A reconstrução filogenética permitiu a diferenciação entre as espécies, sendo que os isolados mais antigos de M. bovoculi permaneceram em ramo mais próximos aos isolados de M. bovis. O nível de similaridade de aminoácidos entre as sequencias de MbxA ficou em 99.9% de média, enquanto entre as sequencias de MbvA e MovA foi respectivamente de 98.8% e 99.3%. A similaridade entre MbvA e MovA foi de 96.6%, enquanto MbxA em relação a MbvA e MovA foi de 77.6%. Assim, é possível concluir que o gene tfp pode ser adequado para inferir distinção entre os isolados de M. bovis, enquanto o gene codificador da citotoxina é adequado para classificação filogenéticas dos isolados de M. bovis, M. bovoculi e M. ovis, e, talvez para a compreensão das relações evolutivas.

Zielstellung: Ziel dieser kumulativen Dissertationsarbeit war die vergleichende Untersuchung der Wirtsantwort in verschiedenen Mauslinien nach Infektion mit Streptobacillus (S.) moniliformis und Rodentibacter (R.) pneumotropicus mit Anzeigeparametern für die Klinik, die Pathologie und die Immunantwort. Es sollten neue erregerspezifische enzyme-linked immunosorbent assays (ELISA) evaluiert und durch die Bestimmung der Immunglobulin G (IgG)-Subklassen mausstammspezifische Unterschiede in der Immunantwort aufgezeigt werden. Darüber hinaus waren Sentinelsysteme zu bewerten. Material und Methoden: Es wurden BALB/c und C57BL/6-Mäuse intranasal mit S. moniliformis- oder R. pneumotropicus infiziert und mit Kontaktsentinels vergesellschaftet. Zusätzlich wurde benutzte Einstreu der Infektionskäfige auf Käfige mit nichtinfizierten CD1-Mäusen (Einstreu-Sentinels) übertragen. Die Infektionsgruppen wurden über 4 Wochen, die Sentinels mindestens 7 Wochen alle 12 Stunden klinisch untersucht und die Verläufe dokumentiert. Am Ende der Experimente bzw. bei Erreichen spezifischer Abbruchkriterien wurden die Mäuse tierschutzgerecht euthanasiert und definierte Organproben für pathohistologische und bakteriologische Untersuchungen gewonnen. Die Erreger wurden dabei massenspektrometrisch sowie mittels polymerase chain reaction (PCR) differenziert und in Proben des Respirationstraktes quantitativ erfasst. Erregerspezifische Antikörper wurden in tracheonasaler Spülflüssigkeit und im Serum in eigens etablierten ELISA‘s auf Basis von Ganzzellextrakten bestimmt. Weiterhin erfolgte die Messung des Verhältnisses der IgG-Subtypen IgG1 und IgG2 im ELISA. Ergebnisse: Der Infektionsversuch mit S. moniliformis bestätigte mit einer Mortalität von 75% die bekannte hohe Infektionsanfälligkeit der C57BL/6-Mäuse im Gegensatz zu BALB/c, die keine Krankheitsanzeichen entwickelten. Die wichtigsten pathologischen Manifestationen waren eitrig-nekrotisierende Lymphadenitiden und Pneumonien in Verbindung mit der Reisolation des Infektionsstammes. Mithilfe des etablierten ELISA‘s gelang der Nachweis erregerspezifischer IgG-Antikörper im Serum der Tiere beider Linien. Bei den Kontaktsentinels konnte, bis auf eine Ausnahme, weder kulturell, noch serologisch eine Infektion nachgewiesen werden. Gleiches gilt für alle Einstreu-Sentinels. Molekularbiologisch wurde aber Erreger-DNA in den Lungen der Sentinels festgestellt. Die Infektion mit einem R. pneumotropicus Stamm, welcher genotypisch positiv für alle drei bekannten RTX-Toxine dieses Erregers war, führte zu einer unerwartet hohen Morbidität und Mortalität in beiden Mauslinien. In frühzeitig euthanasierten Tieren beider Linien konnten katarrhalisch-eitrige bis nekrotisierende Bronchopneumonien sowie eine Dissemination des Belastungsstammes in zahlreiche innere Organe nachgewiesen werden. In überlebenden Tieren beider Linien wurde eine deutliche Kolonisation respiratorischer Schleimhäute mit dem Belastungsstamm trotz z.T. hoher mukosaler IgA-Spiegel und Serokonversion im Blut nachgewiesen. Überlebende C57BL/6 Mäuse zeigten eine signifikant niedrigere Bakterienlast in inneren Organen als BALB/c Mäuse. In allen Kontaktsentinels, aber nicht in einem einzigen Einstreu-Sentinel, konnte kulturell und indirekt serologisch eine Infektion mit R. pneumotropicus nachgewiesen werden. Die Bestimmung der IgG-Subklassen in den Seren der C57BL/6-Mäuse beider Infektionsstudien ergab eine Verschiebung des Verhältnisses IgG2/IgG1 von unter 0,8 vor zu über 1,6 nach Infektion. Dies weist auf eine T-Helferzell (Th) 1-dominierte Immunantwort hin. BALB/c-Mäuse behielten dagegen ein Verhältnis unter 0,8 auch nach der Infektion bei, sodass auf eine Th2- Antwort zu schließen war. Schlussfolgerungen: Sowohl für S. moniliformis als auch für R. pneumotropicus konnten Tiermodelle mit diversen Anzeigeparametern etabliert werden, welche für Folgestudien zur Pathogenese oder Immunprophylaxe genutzt werden können. Für beide Erreger wurden neue sensitive und spezifische ELISA-Protokolle in die Diagnostik eingeführt. Kontaktsentinels, aber nicht Einstreu-Sentinels, sind gut geeignet, um R. pneumotropicus-Infektionen nachzuweisen. Die beobachtete stammspezifische Klinik, Pathologie und Immunantwort der C57BL/6-Mäuse nach experimenteller S. moniliformis-Infektion sprach für eine pathologische Th1-Immunantwort. Im Gegensatz dazu war im R. pneumotropicus – Infektionsversuch die Th1-Immunantwort der C57BL/6-Mäuse mit einer effektiveren Reduktion des Erregers in inneren Organen assoziiert. Die unerwartet hohe Morbidität und Mortalität im R. pneumotropicus –Infektionsversuch weist auf eine besonders hohe Virulenz des eingesetzten Stammes hin, sodass in dieser Arbeit erstmalig ein septikämischer Verlauf in Wildtyp-Mäusen nach intranasaler R. pneumotropicus-Infektion nachgewiesen werden konnte.:Inhaltsverzeichnis (I) Abkürzungsverzeichnis (III) 1 Einleitung (1) 2 Literatur (3) 2.1 Streptobacillus moniliformis (3) 2.1.1 Allgemeine Charakteristika (3) 2.1.2 Differenzierung von Streptobacillus spp.(4) 2.1.3 Serologische Methoden zum indirekten Nachweis einer Streptobacillus moniliformis - Infektion (5) 2.1.4 Epidemiologie der durch Streptobacillus moniliformis hervorgerufenen Zoonose (6) 2.1.5 Klinik und Pathologie der Streptobacillus moniliformis-Infektion bei Nagetieren (8) 2.1.6 Klinik und Pathologie der Streptobacillus moniliformis-Infektion in Menschen und anderen Nebenwirten (9) 2.1.7 Pathogenese und Virulenzfaktoren (10) 2.1.8 Prävalenz in Nagern (11) 2.1.9 Sanierung Streptobacillus moniliformis infizierter Nagetierbestände und Prävention (12) 2.2 Rodentibacter (R.) pneumotropicus und heylii (Pasteurella (P.) pneumotropica Biotyp Jawetz und Heyl) (14) 2.2.1 Allgemeine Charakteristika (14) 2.2.2 Ursprüngliche Einteilung in Biotypen und Reklassifikation zu Rodentibacter spp. (14) 2.2.3 Differenzierung von Rodentibacter spp. (15) 2.2.4 Serologische Methoden zum indirekten Nachweis einer Rodentibacter- Infektion (15) 2.2.5 Übertragung (15) 2.2.6 Klinik und Pathologien der Rodentibacter-Infektion in Nagern (16) 2.2.7 Pathogenese und Virulenzfaktoren (18) 2.2.8 Prävalenz (19) 2.2.9 Sanierung Rodentibacter pneumotropicus infizierter Nagetierbestände und Prävention (20) 2.3 Mäuse als Versuchstiere (22) 2.3.1 Inzucht-Stämme (22) 2.3.1.1 Merkmale, Verwendung und Historie der BALB/c-Wildtypmäuse (22) 2.3.1.2 Merkmale, Verwendung und Historie der C57BL/6-Wildtypmäuse (23) 2.3.1.3 Unterschiede der Immunreaktionen in C57BL/6- und der BALB/c- Mäusen (23) 2.3.2 Auszucht-Stämme (24) 2.3.2.1 Merkmale, Verwendung und Historie der CD1-Wildtypmäuse (24) 2.4 Gesundheitsmonitoring in Labortierhaltungen (25) 2.4.1 Empfehlungen der Federation of Laboratory Animal Science Associations (FELASA) (25) 2.4.2 Sentinelsysteme für das Gesundheitsmonitoring in Labormausbeständen (26) 3 Publikationen (28) 3.1 Fornefett J, Krause J, Klose K, Fingas F, Hassert R, Eisenberg T, Grunwald T, Müller U, Schrödl W, Baums CG. Comparative analysis of clinics, pathologies and immune responses in BALB/c and C57BL/6J mice infected with Streptobacillus moniliformis. Microbes and Infection. 2018;20(2):101-110 (28) 3.2 Fornefett J, Krause J, Klose K, Fingas F, Hassert R, Benga L, Grunwald T, Müller U, Schrödl W, Baums CG. Comparative analysis of humoral immune responses and pathologies of BALB/c and C57BL/6 wildtype mice experimentally infected with a highly virulent Rodentibacter pneumotropicus (Pasteurella pneumotropica) strain. BMC Microbiology. 2018;18(1):45 (39) 4 Übergreifende Diskussion (51) 5 Zusammenfassung (59) 6 Summary (61) 7 Literaturverzeichnis (63) 7.1 Fachliteratur (63) 7.2 Internet (76) 7.3 Gesetzestexte (78) Anhang (79) i Ergänzende Abbildungen (79) ii Ergänzendes Material zu 3.1 “Comparative analysis of clinics, pathologies and immune responses in BALB/c and C57BL/6J mice infected with Streptobacillus moniliformis” (81) iii Ergänzendes Material zu 3.2 “Comparative analysis of humoral immune responses and pathologies of BALB/c and C57BL/6 wildtype mice experimentally infected with a highly virulent Rodentibacter pneumotropicus (Pasteurella pneumotropica) strain” (83) Liste mit weiteren Veröffentlichungen Danksagung / Objective: Aim of this cumulative doctoral thesis was the comparative analysis of the host response in different mice strains infected with Streptobacillus (S.) moniliformis and Rodentibacter (R.) pneumotropicus with readout parameters for clinics, pathology and immune response. New pathogen specific enzyme linked immunosorbent assay’s (ELISA) were evaluated. Differentiation of immunoglobulin (Ig) G subclasses was conducted to reveal differences in the immune response between the two mice strains. Furthermore, sentinel systems were assessed. Materials and methods: BALB/c and C57BL/6 mice were infected intranasally with S. moniliformis or R. pneumotropicus and housed together with contact sentinels. Soiled bedding from infection cages was transmitted to cages with uninfected CD1 mice (bedding sentinels). Infection groups were observed for 4 weeks, sentinels for at least 7 weeks and the clinical course was documented. At the end of the experiments or when predefined termination criteria were reached, animals were humanely killed. Predefined organ samples were collected for pathohistological and bacteriological screenings. Pathogens were differentiated via mass spectrometry and via polymerase chain reaction (PCR). The specific bacterial load was quantified in samples of the respiratory tract. Pathogen-specific antibodies were detected in tracheonasal lavages and sera using newly established ELISAs based on whole cell extracts. Determination of the ratios of the IgG subtypes (IgG1 to IgG2) was conducted using ELISAs. Results: The S. moniliformis experiment confirmed the known high susceptibility of C57BL/6 mice with a mortality of 75%. This was in contrast to BALB/c, which developed no signs of illness. The major pathologies were purulent-necrotizing inflammations of the lymph nodes and the lung associated with detection of the challenge strain. Specific IgG-antibodies were detected in sera of both mice strains by the newly established ELISAs. In contact and bedding sentinels the infection was not detected by culture or indirectly by serology, except for one contact sentinel. However, pathogen DNA was detectable in the lungs of these animals via PCR. The infection with the R. pneumotropicus strain, which is genotypically positive for all 3 known RTX toxins of this pathogen, leaded to an unexpected high morbidity and mortality in both mice strains. In early losses a catharal-purulent to necrotizing bronchopneumonia as well as dissemination of the challenge strain in various inner organs was recorded. Efficient colonization of the respiratory mucosa through the challenge strain was detected in survivors of both lines despite high mucosal IgA levels and seroconversion in the blood. Surviving C57BL/6 mice showed a significant lower bacterial burden in inner organs than BALB/c. All contact sentinels were culturally and serologically positive for R. pneumotropicus infection in contrast to all bedding sentinels. Differentiation of IgG subclasses in sera of C57BL/6 mice of both experiments revealed a shift of the IgG2/IgG1 ratio from 0.8 prior to infection to 1.6 post infection suggesting a T helper (Th) 1-prone immune response. BALB/c mice remained under 0.8 after infection indicating a Th2-prone immune response. Conclusions: New animal models with various readout parameters were established for both S. moniliformis and R. pneumotropicus. These models can be used in future studies on pathogenesis and immunoprophylaxis. Sensitive und specific ELISA-protocols were established for both pathogens. Contact sentinels but not bedding sentinels are appropriate for detection of R. pneumotropicus-infections. The observed distinct clinic, pathology and immune response of C57BL/6 mice experimentally infected with S. moniliformis indicated on the one hand a pathological Th1 immune response. On the other hand, the Th1 response of C57BL/6 mice to R. pneumotropicus infection was associated with a more efficient clearance of the challenge strain in internal organs. The unprecedented high morbidity and mortality in the R. pneumotropicus experiment indicates high virulence of this strain. Accordingly, this work revealed for the first time septicaemia in wildtype mice after intranasal R. pneumotropicus-infection.:Inhaltsverzeichnis (I) Abkürzungsverzeichnis (III) 1 Einleitung (1) 2 Literatur (3) 2.1 Streptobacillus moniliformis (3) 2.1.1 Allgemeine Charakteristika (3) 2.1.2 Differenzierung von Streptobacillus spp.(4) 2.1.3 Serologische Methoden zum indirekten Nachweis einer Streptobacillus moniliformis - Infektion (5) 2.1.4 Epidemiologie der durch Streptobacillus moniliformis hervorgerufenen Zoonose (6) 2.1.5 Klinik und Pathologie der Streptobacillus moniliformis-Infektion bei Nagetieren (8) 2.1.6 Klinik und Pathologie der Streptobacillus moniliformis-Infektion in Menschen und anderen Nebenwirten (9) 2.1.7 Pathogenese und Virulenzfaktoren (10) 2.1.8 Prävalenz in Nagern (11) 2.1.9 Sanierung Streptobacillus moniliformis infizierter Nagetierbestände und Prävention (12) 2.2 Rodentibacter (R.) pneumotropicus und heylii (Pasteurella (P.) pneumotropica Biotyp Jawetz und Heyl) (14) 2.2.1 Allgemeine Charakteristika (14) 2.2.2 Ursprüngliche Einteilung in Biotypen und Reklassifikation zu Rodentibacter spp. (14) 2.2.3 Differenzierung von Rodentibacter spp. (15) 2.2.4 Serologische Methoden zum indirekten Nachweis einer Rodentibacter- Infektion (15) 2.2.5 Übertragung (15) 2.2.6 Klinik und Pathologien der Rodentibacter-Infektion in Nagern (16) 2.2.7 Pathogenese und Virulenzfaktoren (18) 2.2.8 Prävalenz (19) 2.2.9 Sanierung Rodentibacter pneumotropicus infizierter Nagetierbestände und Prävention (20) 2.3 Mäuse als Versuchstiere (22) 2.3.1 Inzucht-Stämme (22) 2.3.1.1 Merkmale, Verwendung und Historie der BALB/c-Wildtypmäuse (22) 2.3.1.2 Merkmale, Verwendung und Historie der C57BL/6-Wildtypmäuse (23) 2.3.1.3 Unterschiede der Immunreaktionen in C57BL/6- und der BALB/c- Mäusen (23) 2.3.2 Auszucht-Stämme (24) 2.3.2.1 Merkmale, Verwendung und Historie der CD1-Wildtypmäuse (24) 2.4 Gesundheitsmonitoring in Labortierhaltungen (25) 2.4.1 Empfehlungen der Federation of Laboratory Animal Science Associations (FELASA) (25) 2.4.2 Sentinelsysteme für das Gesundheitsmonitoring in Labormausbeständen (26) 3 Publikationen (28) 3.1 Fornefett J, Krause J, Klose K, Fingas F, Hassert R, Eisenberg T, Grunwald T, Müller U, Schrödl W, Baums CG. Comparative analysis of clinics, pathologies and immune responses in BALB/c and C57BL/6J mice infected with Streptobacillus moniliformis. Microbes and Infection. 2018;20(2):101-110 (28) 3.2 Fornefett J, Krause J, Klose K, Fingas F, Hassert R, Benga L, Grunwald T, Müller U, Schrödl W, Baums CG. Comparative analysis of humoral immune responses and pathologies of BALB/c and C57BL/6 wildtype mice experimentally infected with a highly virulent Rodentibacter pneumotropicus (Pasteurella pneumotropica) strain. BMC Microbiology. 2018;18(1):45 (39) 4 Übergreifende Diskussion (51) 5 Zusammenfassung (59) 6 Summary (61) 7 Literaturverzeichnis (63) 7.1 Fachliteratur (63) 7.2 Internet (76) 7.3 Gesetzestexte (78) Anhang (79) i Ergänzende Abbildungen (79) ii Ergänzendes Material zu 3.1 “Comparative analysis of clinics, pathologies and immune responses in BALB/c and C57BL/6J mice infected with Streptobacillus moniliformis” (81) iii Ergänzendes Material zu 3.2 “Comparative analysis of humoral immune responses and pathologies of BALB/c and C57BL/6 wildtype mice experimentally infected with a highly virulent Rodentibacter pneumotropicus (Pasteurella pneumotropica) strain” (83) Liste mit weiteren Veröffentlichungen Danksagung

This work is focused on the RTX (Repeats in ToXin) domains structure of selected RTX toxins and its impact on secretion and protein folding. The structural analysis included RTX domains of ApxI (Actinobacillus pleuropneumoniae-RTX-toxin I) from Actinobacillus pleuropneumoniae, HlyA (Alfa-hemolysin) from Escherichia coli and LtxA (Leukotoxin A) from Aggregatibacter actinomycetemcomitans and blocs 4 a 5 RTX domain CyaA (adenylate cyclase toxin) from Bordetella pertussis. The structures of LtxA RTX domain and CyaA RTX blocs 4 and 5 were obtained and characterized. Two models of CyaA RTX domain were built based on SAXS (Small Angle X-ray Scattering) model, previously solved RTX structures and RTX structures presented here.

We present a technique for out-of-core GPU path tracing of arbitrarily large scenes that is compatible with hardware-accelerated ray-tracing. Our technique improves upon previous works by subdividing the scene spatially into streamable chunks that are loaded using a priority system that maximizes ray throughput and minimizes GPU memory usage. This allows for arbitrarily large scaling of scene complexity. Our system required under 19 minutes to render a solid color version of Disney's Moana Island scene (39.3 million instances, 261.1 million unique quads, and 82.4 billion instanced quads at a resolution of 1024x429 and 1024spp on an RTX 5000 (24GB memory total, 22GB used, 13GB geometry cache, with the remainder for temporary buffers and storage) (Wald et al.). As a scalability test, our system rendered 26 Moana Island scenes without multi-level instancing (1.02 billion instances, 2.14 trillion instanced quads, ~230GB if all resident) in under 1h:28m. Compared to state-of-the-art hardware-accelerated renders of the Moana Island scene, our system can render larger scenes on a single GPU. Our system is faster than the previous out-of-core approach and is able to render larger scenes than previous in-core approaches given the same memory constraints (Hellmuth, Zellman et al, Wald).

No description available.

This master’s thesis presents new tendency in automotive lighting – matrix LED headlamp. This thesis consists of description of matrix headlamp construction, main functions of matrix headlamp and controlling by using new integrated circuit, developed by ON Semiconductor Company. The aim of this project is concept of algorithm, which provides correct function of integrated circuit. A part of this thesis is to develop and assembly evaluation kit with this integrated circuit, which will be use to present integrated circuit for customers.

This thesis examined how and why TRPV1 function is being modulated in sensory neuropathy and explored the potential of its rescue in the urinary bladder of STZ-­‐induced diabetic rats. Diabetes induced a rapid decline in TRPV1 function and changes in neurogenically mediated electrically-­‐evoked responses together with a gradual decline in muscarinic function. Diabetic bladder was also deficient in muscarinic and TRPV1 organ bath temperature-­‐induced changes but not in those affecting spontaneous contractile activity. Exposure to a potential neuropathy causative agent, methylglyoxal was studied and its mechanism of action explored through the use of TRPA1 ligands. Methylglyoxal exposure mimicked some of the effects of diabetes on TRPV1, neurogenic electrically evoked responses and muscarinic function. Methylglyoxal effects were seen to be partly through TRPA1 receptor activation but other as yet undefined pathways were also involved. Use of TRPA1 ligands revealed an unexpected complexity of the interaction of the TRPA1 receptor with TRPV1. Finally the potential of reversing the diminished TRPV1 response was examined through the use of three known sensitising agents, bradykinin, NGF and insulin. Bradykinin was the only agent seen to reverse the TRPV1 diminished response back up to to control equivalent levels and through the use of bradykinin selective ligands, it was seen that the dual activation of BK-­‐1 and BK-­‐2 receptor was necessary to rescue the TRPV1 response. The likely mechanism of action of bradykinin was through prostaglandin production as indomethacin blocked TRPV1 rescue. In the acute stage of diabetes, TRPV1 function is downregulated and may be caused by exposure to a neuropathy-­‐causing metabolite such as methylglyoxal. The TRPV1 function still retains plasticity at this acute stage because function could be enhanced back to control levels by bradykinin receptor activation : a potential for early therapeutic intervention.

Vid GNSS-positionering i samband med fastighetsbildningsåtgärder används vanligtvis den traditionella RTK-mätningen (Real-Time Kinematic) via SWEPOS nätverks-RTK-tjänst. Denna tjänst kräver mobiltelefontäckning eller motsvarande tvåvägskommunikation, vilket kan vara problematiskt inom områden med bristfällig mobiltelefontäckning. Under dessa förhållanden kan istället PPP-mätning (Precise Point Positioning) vara användbart vid fastighetsbildningsåtgärder då dessa tjänster tar emot korrektionsdata i realtid från satelliter. PPP kräver inte någon mobiltelefontäckning, däremot krävs en kommunikationslänk, en RTX-tjänst för att erhålla korrektioner externt från en RTX-satellit. Syftet med studien är att undersöka möjligheten till att nyttja PPP i realtid vid fastighetsbildningsåtgärder som ett alternativ till traditionell GNSS-mätning med nätverks-RTK. För att PPP ska vara ett alternativ till traditionell GNSS-mätning i realtid krävs det att mätosäkerhetskraven inom fastighetsbildning uppfylls. Mätosäkerheten undersöktes genom att utgå ifrån redan kända koordinater (RIX 95-punkter). Mätningarna har genomförts på fem olika platser i Sverige, Göteborg, Vänersborg, Karlstad, Torsby och Malung-Sälen. Mätdata som erhölls från undersökningsplatserna har analyserats samt jämförts med fastighetsbildningskraven. Resultatet av studien erhölls i form av analyserad mätdata med jämförelser mot redan kända (RIX 95) punkter. Avikelsen från känd RIX 95-punkt redovisas i resultatet utifrån tidsaspekten, den systematiska avvikelsen av translativ art, förändringar i avvikelsen från söder till norr samt utifrån två beräkningsmodeller, varav en translation och en transformation. För att få den erhållna mätdatan från RTX-tjänsten att överensstämma bättre med referenspunkten (RIX 95-punkten) togs beräkningsmodellerna fram för att möjliggöra modellering av systematiska avvikelser som uppkommit och därmed uppfylla kraven inom fasighetsbildningsåtgärder. Genom att ha analyserat och granskat olika samband har det framkommit att efter ca 20 minuters mätning, börjar precisionen för mätningarna att bli stabila. Utifrån resultatet är slutsatsen att PPP inte fungerar vid fastighetsbildningsåtgärder för områden inom stomnät, däremot fungerar metoden för skogs- och jordbruksfastigheter utanför stomnät. Förutsatt att en modellering genom translation alternativt transformation som är framtagen i denna studie används för att justera koordinaterna så fungerar PPP-mätning inom samtliga fastighetsbildningsåtgärder. Detta kräver då att mätdata erhålls efter 20 minuters mätning eller mer. / GNSS positioning in conjunction with the real property is usually used the traditional RTK measuring (Real-Time Kinematic) by SWEPOS network RTK service. This service requires mobile phone coverage or equivalent two-way communication, which can be problematic in areas with poor mobile phone coverage. Under these circumstances, PPP (Point Positioning Precise) could be more useful in real property measures when such services receives the correction data in real time from the satellites. PPP does not require any cell phone coverage, however it requires a communication link, a RTX service to obtain corrections externally from a RTX satellite. The purpose of the study is to examine the possibility of using PPP in real time at the real property as an alternative to traditional GNSS measurements with network RTK. The measurement uncertainty was investigated by starting out from already known coordinates (RIX 95 points). The measurements were performed out at five different locations in Sweden, Gothenburg, Vanersborg, Karlstad, Torsby and Malung-Salen. Measurement data obtained from the observations have been analyzed and compared with real property requirements. The results of the study were obtained in the form of data analyzed by comparison of the known (RIX 95) points. The deviation is known from RIX 95 point recognized in income based on the time factor, the bias of the translative case species, changes in deviation from south to north and from two calculation models, a translation and a transformation. To correct the measured values from the RTX service for a better match to the RIX 95 points calculation models were developed to facilitate the modeling of systematic deviations incurred and meet the demands of real property. Analyzing and examining various relationships have shown that after about 20 minutes of measuring, the precision of the measurements starts to become more stable. Based on the results, the conclusion is that the PPP does not work in real property areas within the core network, however, the method works for forestry and agricultural properties outside the core network. Assuming a modelling through translational alternative transformation, developed in this study is used to adjust the coordinates, the PPP measurement is working in all real property registration measures. This requires that the measurement data is obtained after 20 minutes of measurement or more.

This presenting master’s thesis deals with a problem of digitaly controled room temperature using the software PLC. The result of this work was creating of an algorithm to control temperature on the requested leve ofl setpoint, minimizing operating costs of the building. The PLC softwares from different manufacturers were analyzed and compared with conventional PLC. The testing facility was disigned and used to control the temperature in the room and data visualization. Room temperature was regulated by PS controller or two point regulator.