Complete absence of linear immunodominant epitope regions recognized by IgG after flavivirus infection and vaccination in whole proteome analyses

The flavivirus genera comprises more than 70 viruses and has an important impact on public health in their endemic and epidemic regions all over the world. Serodiagnosis of specific flavivirus infections is difficult or even impossible, due to the high degree of antibody cross-reactivity. It is however conceivable that serodiagnosis based on one or more individual flavivirus species derived peptides allows to differentiate with high specificity between different viral infections. The primary objective of my doctoral thesis therefore was to map specific immunoglobulin G (IgG) antibody responses after natural flavivirus infections and yellow fever vaccination to identify type-specific signatures of different flaviviruses as well as to study dynamics of cross-reactivity and crossrecognition between them. Therefore, a panel of sera from flavivirus-infected study subjects as well as sera before (D0) and 28 days after (D28) YFV vaccination were tested with the RepliTope™pan-Flavivirus peptide array by the company JPT Peptide Technologies displaying 6253 peptides of various flaviviruses. In general, peptide array technique allows high-resolution, high-throughput, ultra-high-density mapping of linear antibody epitopes. Serum samples prior yellow fever vaccination (timepoint D0) served as negative controls. Data analyses were performed using R-script as well as GraphPad Prism software to further dissect the IgG immune response and to identify potential serodiagnostic peptides. The analysis was focused on detection of potential targets of IgG immune responses located in prM, E, NS1 and NS5 proteins. To summarize the data obtained by heat maps and graphs, our data has shown a high level of individual variation in antibody specificities as well as no flavivirus type-specific IgG peptide recognition signature between different flaviviruses across flavivirus-infected and YFV vaccinated study subjects. This study points out the difficulties of detecting a flavivirusspecific immune response but gives further insight into a more detailed epitope mapping and understanding of antibody responses in flavivirus infections.Die Gattung der Flaviviren umfasst über 70 Viren und hat einen wichtigen Einfluss auf das öffentliche Gesundheitswesen in endemischen sowie epidemischen Regionen weltweit. Die Serodiagnostik von speziellen Flavivirus Infektionen stellt sich aufgrund eines hohen Grades an Kreuzreaktivität der Antikörper als schwierig dar. Es ist jedoch vorstellbar, dass Serodiagnostik basierend auf einem oder mehreren individuellen Flavivirus-Peptiden die Differenzierung zwischen verschiedenen Flavivirus Infektionen mit hoher Spezifität möglich macht. Das vorrangige Ziel dieser Doktorarbeit ist die Kartierung spezifischer Immunglobulin G (IgG) Reaktionen nach natürlichen Flavivirus- Infektionen und nach Gelbfieberimpfung, um spezifische Signaturen verschiedener Flaviviren zu identifizieren sowie die Dynamik der Kreuzreaktivität und Kreuzerkennung zwischen diesen zu untersuchen. Daher wurde eine Auswahl an Seren von Flavivirus-infizierten Studienteilnehmer*innen sowie Seren von gesunden Proband*innen vor (Zeitpunkt D0) und 28 Tage nach Gelbfieber Impfung (Zeitpunkt D28) mit dem RepliTope™pan-Flavivirus Peptidarray der Firma JPT Peptide Technologies getestet, welches 6253 Peptide verschiedener Flaviviren abbildet. Im Allgemeinen ermöglicht die Peptid-Array-Technik eine hochauflösende Abbildung von linearen Antikörper-Epitopen. Serumproben vor der Gelbfieberimpfung (Zeitpunkt D0) dienten als Negativkontrollen. Die Analyse der mit den Peptidarrays gewonnenen Daten umfasste Auswertungs-methoden unter Verwendung von R-Skripten sowie der GraphPad-Prism-Software zur weiteren Aufschlüsselung der IgG-Immunantwort und zur Identifizierung serodiagnostischer Peptide. Die Analyse konzentrierte sich auf den Nachweis potenzieller, spezifischer Erkennungsstrukturen der IgG-Immunantwort, die in prM-, E, NS1- und NS5-Proteinen lokalisiert sind. Unsere Daten zeigten ein hohes Maß an individueller Variation der Antikörperspezifitäten sowie eine fehlende Flavivirus typ-spezifische IgG-Peptid-Signatur bei Flavivirus infizierten und Gelbfieber geimpften Studienteilnehmer*innen bzw. Proband*innen. Diese Studie weist auf die Schwierigkeiten des Nachweises einer Flavivirus-spezifischen Immunantwort hin, gibt jedoch Einblicke in eine detailliertere Epitop Kartierung und ein besseres Verständnis der Antikörper-Antworten bei Flavivirus-Infektionen

House Price Corrections In OECD Countries

Masteroppgave(MSc) in Master of Science in Finance - Handelshøyskolen BI, 2024We study the impact of varying monetary policies across OECD countries on international house price cycles, considering credit growth, overvaluation, and monetary policy as factors. We construct a cross-country measure of monetary policy expectations and estimate house price overvaluation via an asset pricing model. Our panel logit regression model estimates the likelihood of house price corrections. We find that our housing overvaluation model and credit growth display consistent results as predictors for house price corrections, both in the short term and in longer terms. While the expectation component only works as a predictor under certain conditions

O desenvolvimento do Estado de direito na Alemanha

A ideia do Estado de direito: Vinculação jurídica do Estado. Autonomia do indivíduo -- Etapas históricas e tipos de Estado de Direito: Idade Média. Absolutismo. O Estado constitucional da modernidade. O constitucionalismo incipiente: Estado de Direito liberal. O constitucionalismo tardio: Estado de Direito formal. A Constituição de Weimar: Estado de direito social. A lei fundamental: Estado de Direito material. Separação de poderes e primado do direito. Proteção jurídica. Certeza jurídica, segurança jurídica, proteção da confiança. Responsabilidade. ProporcionalidadeCorresponde a palestra proferida na Escola Judicial do TRF4 (Emagis), no ano de 2014, em evento co-promovido pela Escola Judicial do TRT

Retinal nerve fibre layer thickness profile in normal eyes using third-generation optical coherence tomography

Aims To establish four normal retinal nerve fibre layer (RNFL) thickness radial profiles based on third-generation optical coherence tomography (OCT) and to compare them with previously reported histologic measurements.Methods A total of 20 normal eyes were studied. A circular scan was adjusted to the size of the optic disc and three scans were performed with this radius and every 200 mu m thereafter, up to a distance of 1400 mu m. Four different radial sections (superotemporal, superonasal, inferonasal, and inferotemporal) were studied to establish RNFL thickness OCT profiles. Additionally, two radial scans orientated at 45 and 1351 crossing the optic disc centre were performed in six of 20 eyes, and RNFL thickness was measured at disc margin.Results Quadrant location and distance from disc margin interaction in RNFL thickness was statistically significant (P < 0.001). the RNFL thickness decreased (P < 0.001) as the distance from the disc margin increased for all sections. the measurements automatically generated by the OCT built-in software were thinner (P < 0.001) than histologic ones close to the disc margin.Conclusions Four normal OCT RNFL profiles were established and compared with histological data obtained from the same area. RNFL measurements assessed by OCT 3 were significantly thinner close to the optic disc margin.Hosp Olhos Araraquara, Glaucoma Sect, BR-14802530 Araraquara, SP, BrazilHosp Olhos Araraquara, Retina Diagnost & Treatment Div, BR-14802530 Araraquara, SP, BrazilUniversidade Federal de São Paulo, São Paulo, BrazilUSP, Inst Fis Sao Carlos, Sao Carlos, SP, BrazilUniv So Calif, Doheny Eye Inst, Dept Ophthalmol, Los Angeles, CA USAUniversidade Federal de São Paulo, São Paulo, BrazilWeb of Scienc

On the Convergence of Learning Algorithms in Bayesian Auction Games

Equilibrium problems in Bayesian auction games can be described as systems of differential equations. Depending on the model assumptions, these equations might be such that we do not have a rigorous mathematical solution theory. The lack of analytical or numerical techniques with guaranteed convergence for the equilibrium problem has plagued the field and limited equilibrium analysis to rather simple auction models such as single-object auctions. Recent advances in equilibrium learning led to algorithms that find equilibrium under a wide variety of model assumptions. We analyze first- and second-price auctions where simple learning algorithms converge to an equilibrium. The equilibrium problem in auctions is equivalent to solving an infinite-dimensional variational inequality (VI). Monotonicity and the Minty condition are the central sufficient conditions for learning algorithms to converge to an equilibrium in such VIs. We show that neither monotonicity nor pseudo- or quasi-monotonicity holds for the respective VIs. The second-price auction's equilibrium is a Minty-type solution, but the first-price auction is not. However, the Bayes--Nash equilibrium is the unique solution to the VI within the class of uniformly increasing bid functions, which ensures that gradient-based algorithms attain the {equilibrium} in case of convergence, as also observed in numerical experiments

Your Failure is My Opportunity - Eff ects of Elimination in Contests

In this paper, we consider a sequence of multi-prize all-pay auctions, where the contestants who exert the lowest e fforts in a round are eliminated. We analyze if and how the behavior of contestants is influenced by the possibility that strong rivals are eliminated along the way. The conditions under which behavior is not influenced are rather restrictive. For cases where these conditions are not met, we derive equilibria in a two-period model. We compare our equilibrium predictions to those of a static model and a two-stage contest where the sequential structure is not announced in the first round

Orbital Apex Syndrome in a Patient with Sphenoid Fungal Balls

Orbital apex syndrome (OAS) is a rare disease that presents with a complex of symptoms, including ophthalmoplegia, ptosis and visual loss. Due to the poor prognosis, making a prompt diagnosis and administering the appropriate treatment must be initiated without delay if OAS is suspected. We report here on a case of a patient with sphenoid fungal balls, and he presented with acute visual loss and ophthalmoplegia