@incollection{Kreutzer2023, author = {Kreutzer, Ansgar}, title = {„Die im Dunkeln sieht man doch." Christliche Offenbarung als Wahrnehmungsschulung f{\"u}r sozialen Ausschluss}, series = {UnSichtbar. Interdisziplin{\"a}re Stimmen zu Vulnerabilit{\"a}t, Vulneranz und Menschenrechten}, booktitle = {UnSichtbar. Interdisziplin{\"a}re Stimmen zu Vulnerabilit{\"a}t, Vulneranz und Menschenrechten}, editor = {Keul, Hildegund}, publisher = {W{\"u}rzburg University Press}, address = {W{\"u}rzburg}, doi = {10.25972/WUP-978-3-95826-203-4-257}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-325377}, publisher = {W{\"u}rzburg University Press}, pages = {257-275}, year = {2023}, abstract = {No abstract available.}, language = {de} } @incollection{Czapski2023, author = {Czapski, Jutta}, title = {Verwundbares Antlitz. Die Menschenrechte im Denken von Emmanuel Levinas}, series = {UnSichtbar. Interdisziplin{\"a}re Stimmen zu Vulnerabilit{\"a}t, Vulneranz und Menschenrechten}, booktitle = {UnSichtbar. Interdisziplin{\"a}re Stimmen zu Vulnerabilit{\"a}t, Vulneranz und Menschenrechten}, editor = {Keul, Hildegund}, publisher = {W{\"u}rzburg University Press}, address = {W{\"u}rzburg}, doi = {10.25972/WUP-978-3-95826-203-4-237}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-325365}, publisher = {W{\"u}rzburg University Press}, pages = {237-255}, year = {2023}, abstract = {No abstract available.}, language = {de} } @incollection{Keul2023, author = {Keul, Hildegund}, title = {Zwischenruf: Toxische Theologien - toxische Therapien. Der uns{\"a}gliche Fall des Tony Anatrella}, series = {UnSichtbar. Interdisziplin{\"a}re Stimmen zu Vulnerabilit{\"a}t, Vulneranz und Menschenrechten}, booktitle = {UnSichtbar. Interdisziplin{\"a}re Stimmen zu Vulnerabilit{\"a}t, Vulneranz und Menschenrechten}, editor = {Keul, Hildegund}, publisher = {W{\"u}rzburg University Press}, address = {W{\"u}rzburg}, doi = {10.25972/WUP-978-3-95826-203-4-197}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-325345}, publisher = {W{\"u}rzburg University Press}, pages = {197-204}, year = {2023}, abstract = {No abstract available.}, language = {de} } @incollection{Keul2023, author = {Keul, Hildegund}, title = {Sexuelle Gewalt und Machtmissbrauch in „Neuen Geistlichen Gemeinschaften" - {\"u}ber die gef{\"a}hrlichen Seiten dessen, was Menschen heilig ist}, series = {UnSichtbar. Interdisziplin{\"a}re Stimmen zu Vulnerabilit{\"a}t, Vulneranz und Menschenrechten}, booktitle = {UnSichtbar. Interdisziplin{\"a}re Stimmen zu Vulnerabilit{\"a}t, Vulneranz und Menschenrechten}, editor = {Keul, Hildegund}, publisher = {W{\"u}rzburg University Press}, address = {W{\"u}rzburg}, doi = {10.25972/WUP-978-3-95826-203-4-131}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-325320}, publisher = {W{\"u}rzburg University Press}, pages = {131-168}, year = {2023}, abstract = {No abstract available.}, language = {de} } @incollection{BauerAmin2023, author = {Bauer-Amin, Sabine}, title = {Emergente Vulnerabilit{\"a}t von Gefl{\"u}chteten im Aufnahmeland: Homo Saber}, series = {UnSichtbar. Interdisziplin{\"a}re Stimmen zu Vulnerabilit{\"a}t, Vulneranz und Menschenrechten}, booktitle = {UnSichtbar. Interdisziplin{\"a}re Stimmen zu Vulnerabilit{\"a}t, Vulneranz und Menschenrechten}, editor = {Keul, Hildegund}, publisher = {W{\"u}rzburg University Press}, address = {W{\"u}rzburg}, doi = {10.25972/WUP-978-3-95826-203-4-23}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-325280}, publisher = {Universit{\"a}t W{\"u}rzburg}, pages = {23-55}, year = {2023}, abstract = {No abstract available.}, language = {de} } @incollection{Leimgruber2023, author = {Leimgruber, Ute}, title = {Welche Erinnerung z{\"a}hlt? Die UnSichtbarkeit geschlechtsspezifischer Gewalt im Raum der Kirche}, series = {UnSichtbar. Interdisziplin{\"a}re Stimmen zu Vulnerabilit{\"a}t, Vulneranz und Menschenrechten}, booktitle = {UnSichtbar. Interdisziplin{\"a}re Stimmen zu Vulnerabilit{\"a}t, Vulneranz und Menschenrechten}, editor = {Keul, Hildegund}, publisher = {W{\"u}rzburg University Press}, address = {W{\"u}rzburg}, doi = {10.25972/WUP-978-3-95826-203-4-103}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-325311}, publisher = {W{\"u}rzburg University Press}, pages = {103-130}, year = {2023}, abstract = {No abstract available.}, language = {de} } @incollection{Heek2023, author = {Heek, Andreas}, title = {„M{\"a}nnlich und weiblich schuf Gott sie" (Gen 1,27)? Trans- und Intergeschlechtlichkeit als Herausforderung f{\"u}r Theologie und kirchliche Lehre}, series = {UnSichtbar. Interdisziplin{\"a}re Stimmen zu Vulnerabilit{\"a}t, Vulneranz und Menschenrechten}, booktitle = {UnSichtbar. Interdisziplin{\"a}re Stimmen zu Vulnerabilit{\"a}t, Vulneranz und Menschenrechten}, editor = {Keul, Hildegund}, publisher = {W{\"u}rzburg University Press}, address = {W{\"u}rzburg}, doi = {10.25972/WUP-978-3-95826-203-4-169}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-325335}, publisher = {W{\"u}rzburg University Press}, pages = {169-196}, year = {2023}, abstract = {No abstract available.}, language = {de} } @incollection{Lessenich2023, author = {Lessenich, Stephan}, title = {Leben machen und sterben lassen: Die Politik mit der Vulnerabilit{\"a}t}, series = {UnSichtbar. Interdisziplin{\"a}re Stimmen zu Vulnerabilit{\"a}t, Vulneranz und Menschenrechten}, booktitle = {UnSichtbar. Interdisziplin{\"a}re Stimmen zu Vulnerabilit{\"a}t, Vulneranz und Menschenrechten}, editor = {Keul, Hildegund}, publisher = {W{\"u}rzburg University Press}, address = {W{\"u}rzburg}, doi = {10.25972/WUP-978-3-95826-203-4-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-325271}, publisher = {Universit{\"a}t W{\"u}rzburg}, pages = {1-21}, year = {2023}, abstract = {No abstract available.}, language = {de} } @incollection{Hoefner2023, author = {H{\"o}fner, Steven}, title = {Das Westjordanland - Wo Vulnerabilit{\"a}ten ein politisches Vakuum erzeugen und damit gef{\"a}hrlich werden}, series = {UnSichtbar. Interdisziplin{\"a}re Stimmen zu Vulnerabilit{\"a}t, Vulneranz und Menschenrechten}, booktitle = {UnSichtbar. Interdisziplin{\"a}re Stimmen zu Vulnerabilit{\"a}t, Vulneranz und Menschenrechten}, editor = {Keul, Hildegund}, publisher = {W{\"u}rzburg University Press}, address = {W{\"u}rzburg}, doi = {10.25972/WUP-978-3-95826-203-4-79}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-325303}, publisher = {W{\"u}rzburg University Press}, pages = {79-99}, year = {2023}, abstract = {No abstract available.}, language = {de} } @incollection{Kirchschlaeger2023, author = {Kirchschl{\"a}ger, Peter G.}, title = {Verletzbarkeit und Menschenrechte}, series = {UnSichtbar. Interdisziplin{\"a}re Stimmen zu Vulnerabilit{\"a}t, Vulneranz und Menschenrechten}, booktitle = {UnSichtbar. Interdisziplin{\"a}re Stimmen zu Vulnerabilit{\"a}t, Vulneranz und Menschenrechten}, editor = {Keul, Hildegund}, publisher = {W{\"u}rzburg University Press}, address = {W{\"u}rzburg}, doi = {10.25972/WUP-978-3-95826-203-4-209}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-325359}, publisher = {W{\"u}rzburg University Press}, pages = {209-236}, year = {2023}, abstract = {No abstract available.}, language = {de} } @incollection{Pistrol2023, author = {Pistrol, Florian}, title = {Der K{\"o}rper zwischen Abh{\"a}ngigkeit und Widerstand. Mit Judith Butler unterwegs zu einer Politik der Vulnerabilit{\"a}t}, series = {UnSichtbar. Interdisziplin{\"a}re Stimmen zu Vulnerabilit{\"a}t, Vulneranz und Menschenrechten}, booktitle = {UnSichtbar. Interdisziplin{\"a}re Stimmen zu Vulnerabilit{\"a}t, Vulneranz und Menschenrechten}, editor = {Keul, Hildegund}, publisher = {W{\"u}rzburg University Press}, address = {W{\"u}rzburg}, doi = {10.25972/WUP-978-3-95826-203-4-57}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-325292}, publisher = {W{\"u}rzburg University Press}, pages = {57-78}, year = {2023}, abstract = {No abstract available.}, language = {de} } @phdthesis{Kraff2023, author = {Kraff, Nicolas Johannes}, title = {Analyse raumzeitlicher Ver{\"a}nderungen und ontologische Kategorisierung morphologischer Armutserscheinungen - Eine globale Betrachtung mithilfe von Satellitenbildern und manueller Bildinterpretation}, doi = {10.25972/OPUS-32026}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-320264}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {Die st{\"a}dtische Umwelt ist in steter Ver{\"a}nderung, vor allem durch den Bau, aber auch durch die Zerst{\"o}rung von st{\"a}dtischen Elementen. Die formelle Entwicklung ist ein Prozess mit langen Planungszeitr{\"a}umen und die bebaute Landschaft wirkt daher statisch. Dagegen unterliegen informelle oder spontane Siedlungen aufgrund ihrer stets unvollendeten st{\"a}dtischen Form einer hohen Dynamik - so wird in der Literatur berichtet. Allerdings sind Dynamik und die morphologischen Merkmale der physischen Transformation in solchen Siedlungen, die st{\"a}dtische Armut morphologisch repr{\"a}sentieren, auf globaler Ebene bisher kaum mit einer konsistenten Datengrundlage empirisch untersucht worden. Hier setzt die vorliegende Arbeit an. Unter der Annahme, dass die erforschte zeitliche Dynamik in Europa geringer ausf{\"a}llt, stellt sich die generelle Frage nach einer katalogisierten Erfassung physischer Wohnformen von Armut speziell in Europa. Denn Wohnformen der Armut werden oft ausschließlich mit dem ‚Globalen S{\"u}den' assoziiert, insbesondere durch die Darstellung von Slums. Tats{\"a}chlich ist Europa sogar die Wiege der Begriffe ‚Slum' und ‚Ghetto', die vor Jahrhunderten zur Beschreibung von Missst{\"a}nden und Unterdr{\"u}ckung auftauchten. Bis heute weist dieser facettenreiche Kontinent eine enorme Vielfalt an physischen Wohnformen der Armut auf, die ihre Wurzeln in unterschiedlichen Politiken, Kulturen, Geschichten und Lebensstilen haben. Um {\"u}ber diese genannten Aspekte Aufschluss zu erlangen, bedarf es u.a. der Bildanalyse durch Satellitenbilder. Diese Arbeit wird daher mittels Fernerkundung bzw. Erdbeobachtung (EO) sowie zus{\"a}tzlicher Literaturrecherchen und einer empirischen Erhebung erstellt. Um Unsicherheiten konzeptionell und in der Erfassung offenzulegen, ist die Methode der manuellen Bildinterpretation von Armutsgebieten kritisch zu hinterfragen. Das {\"u}bergeordnete Ziel dieser Arbeit ist eine bessere Wissensbasis {\"u}ber Armut zu schaffen, um Maßnahmen zur Reduzierung von Armut entwickeln zu k{\"o}nnen. Die Arbeit dient dabei als eine Antwort auf die Nachhaltigkeitsziele der Vereinten Nationen. Es wird Grundlagenforschung betrieben, indem Wissensl{\"u}cken in der Erdbeobachtung zu physisch-baulichen bzw. morphologischen Erscheinungen von Armut auf Geb{\"a}ude-Ebene explorativ analysiert werden. Die Arbeit wird in drei Forschungsthemen bzw. Studienteile untergliedert: Ziel des ersten Studienteils ist die globale raumzeitliche Erfassung von Dynamiken durch Ankn{\"u}pfung an bisherige Kategorisierungen von Armutsgebieten. Die bisherige Wissensl{\"u}cke soll gef{\"u}llt werden, indem {\"u}ber einen Zeitraum von etwa sieben Jahren in 16 dokumentierten Manifestationen st{\"a}dtischer Armut anhand von Erdbeobachtungsdaten eine zeitliche Analyse der bebauten Umwelt durchgef{\"u}hrt wird. Neben einer global verteilten Gebietsauswahl wird die visuelle Bildinterpretation (MVII) unter Verwendung von hochaufl{\"o}senden optischen Satellitendaten genutzt. Dies geschieht in Kombination mit in-situ- und Google Street View-Bildern zur Ableitung von 3D-Stadtmodellen. Es werden physische Raumstrukturen anhand von sechs r{\"a}umlichen morphologischen Variablen gemessen: Anzahl, Gr{\"o}ße, H{\"o}he, Ausrichtung und Dichte der Geb{\"a}ude sowie Heterogenit{\"a}t der Bebauung. Diese ‚temporale Analyse' zeigt zun{\"a}chst sowohl inter- als auch intra-urbane Unterschiede. Es lassen sich unterschiedliche, aber generell hohe morphologische Dynamiken zwischen den Untersuchungsgebieten finden. Dies dr{\"u}ckt sich in vielf{\"a}ltiger Weise aus: von abgerissenen und rekonstruierten Gebieten bis hin zu solchen, wo Ver{\"a}nderungen innerhalb der gegebenen Strukturen auftreten. Geographisch gesehen resultiert in der Stichprobe eine fortgeschrittene Dynamik, insbesondere in Gebieten des Globalen S{\"u}dens. Gleichzeitig l{\"a}sst sich eine hohe r{\"a}umliche Variabilit{\"a}t der morphologischen Transformationen innerhalb der untersuchten Gebiete beobachten. Trotz dieser teilweise hohen morphologischen Dynamik sind die r{\"a}umlichen Muster von Geb{\"a}udefluchten, Straßen und Freifl{\"a}chen {\"u}berwiegend konstant. Diese ersten Ergebnisse deuten auf einen geringen Wandel in Europa hin, weshalb diese europ{\"a}ischen Armutsgebiete im folgenden Studienteil von Grund auf erhoben und kategorisiert werden. Ziel des zweiten Studienteils ist die Erschaffung einer neuen Kategorisierung, speziell f{\"u}r das in der Wissenschaft unterrepr{\"a}sentierte Europa. Die verschiedenen Formen nicht indizierter Wohnungsmorphologien werden erforscht und kategorisiert, um das bisherige globale wissenschaftliche ontologische Portfolio f{\"u}r Europa zu erweitern. Hinsichtlich dieses zweiten Studienteils bietet eine Literaturrecherche mit mehr als 1.000 gesichteten Artikeln die weitere Grundlage f{\"u}r den folgenden Fokus auf Europa. Auf der Recherche basierend werden mittels der manuellen visuellen Bildinterpretation (engl.: MVII) erneut Satellitendaten zur Erfassung der physischen Morphologien von Wohnformen genutzt. Weiterhin kommen selbst definierte geographische Indikatoren zu Lage, Struktur und formellem Status zum Einsatz. Dar{\"u}ber hinaus werden gesellschaftliche Hintergr{\"u}nde, die durch Begriffe wie ‚Ghetto', ‚Wohnwagenpark', ‚ethnische Enklave' oder ‚Fl{\"u}chtlingslager' beschrieben werden, recherchiert und implementiert. Sie sollen als Erkl{\"a}rungsansatz f{\"u}r Armutsviertel in Europa dienen. Die Stichprobe der europ{\"a}ischen, insgesamt aber unbekannten Grundgesamtheit verdeutlicht eine große Vielfalt an physischen Formen: Es wird f{\"u}r Europa eine neue Kategorisierung von sechs Hauptklassen entwickelt, die von ‚einfachsten Wohnst{\"a}tten' (z. B. Zelten) {\"u}ber ‚behelfsm{\"a}ßige Unterk{\"u}nfte ' (z. B. Baracken, Container) bis hin zu ‚mehrst{\"o}ckigen Bauten' - als allgemeine Taxonomie der Wohnungsnot in Europa - reicht. Die Untersuchung zeigt verschiedene Wohnformen wie z. B. unterirdische oder mobile Typen, verfallene Wohnungen oder große Wohnsiedlungen, die die Armut im Europa des 21. Jahrhunderts widerspiegeln. {\"U}ber die Wohnungsmorphologie hinaus werden diese Klassen durch die Struktur und ihren rechtlichen Status beschrieben - entweder als geplante oder als organisch-gewachsene bzw. weiterhin als formelle, informelle oder hybride (halblegale) Formen. Geographisch lassen sich diese {\"a}rmlichen Wohnformen sowohl in st{\"a}dtischen als auch in l{\"a}ndlichen Gebieten finden, mit einer Konzentration in S{\"u}deuropa. Der Hintergrund bei der Mehrheit der Morphologien betrifft Fl{\"u}chtlinge, ethnische Minderheiten und sozio{\"o}konomisch benachteiligte Menschen - die ‚Unterprivilegierten'. Ziel des dritten Studienteils ist eine kritische Analyse der Methode. Zur Erfassung all dieser Siedlungen werden heutzutage Satellitenbilder aufgrund der Fortschritte bei den Bildklassifizierungsmethoden meist automatisch ausgewertet. Dennoch spielt die MVII noch immer eine wichtige Rolle, z.B. um Trainingsdaten f{\"u}r Machine-Learning-Algorithmen zu generieren oder f{\"u}r Validierungszwecke. In bestimmten st{\"a}dtischen Umgebungen jedoch, z.B. solchen mit h{\"o}chster Dichte und struktureller Komplexit{\"a}t, fordern spektrale und textur-basierte Verflechtungen von {\"u}berlappenden Dachstrukturen den menschlichen Interpreten immer noch heraus, wenn es darum geht einzelne Geb{\"a}udestrukturen zu erfassen. Die kognitive Wahrnehmung und die Erfahrung aus der realen Welt sind nach wie vor unumg{\"a}nglich. Vor diesem Hintergrund zielt die Arbeit methodisch darauf ab, Unsicherheiten speziell bei der Kartierung zu quantifizieren und zu interpretieren. Kartiert werden Dachfl{\"a}chen als ‚Fußabdr{\"u}cke' solcher Gebiete. Der Fokus liegt dabei auf der {\"U}bereinstimmung zwischen mehreren Bildinterpreten und welche Aspekte der Wahrnehmung und Elemente der Bildinterpretation die Kartierung beeinflussen. Um letztlich die Methode der MVII als drittes Ziel selbstkritisch zu reflektieren, werden Experimente als sogenannte ‚Unsicherheitsanalyse' geschaffen. Dabei digitalisieren zehn Testpersonen bzw. Probanden/Interpreten sechs komplexe Gebiete. Hierdurch werden quantitative Informationen {\"u}ber r{\"a}umliche Variablen von Geb{\"a}uden erzielt, um systematisch die Konsistenz und Kongruenz der Ergebnisse zu {\"u}berpr{\"u}fen. Ein zus{\"a}tzlicher Fragebogen liefert subjektive qualitative Informationen {\"u}ber weitere Schwierigkeiten. Da die Grundlage der hierf{\"u}r bisher genutzten Kategorisierungen auf der subjektiven Bildinterpretation durch den Menschen beruht, m{\"u}ssen etwaige Unsicherheiten und damit Fehleranf{\"a}lligkeiten offengelegt werden. Die Experimente zu dieser Unsicherheitsanalyse erfolgen quantifiziert und qualifiziert. Es lassen sich generell große Unterschiede zwischen den Kartierungsergebnissen der Probanden, aber eine hohe Konsistenz der Ergebnisse bei ein und demselben Probanden feststellen. Steigende Abweichungen korrelieren mit einer steigenden baustrukturellen (morphologischen) Komplexit{\"a}t. Ein hoher Grad an Individualit{\"a}t bei den Probanden {\"a}ußert sich in Aspekten wie z.B. Zeitaufwand beim Kartieren, in-situ Vorkenntnissen oder Vorkenntnissen beim Umgang mit Geographischen Informationssystemen (GIS). Nennenswert ist hierbei, dass die jeweilige Datenquelle das Kartierungsverfahren meist beeinflusst. Mit dieser Studie soll also auch an der Stelle der angewandten Methodik eine weitere Wissensl{\"u}cke gef{\"u}llt werden. Die bisherige Forschung komplexer urbaner Areale unter Nutzung der manuellen Bildinterpretation implementiert oftmals keine Unsicherheitsanalyse oder Quantifizierung von Kartierungsfehlern. Fernerkundungsstudien sollten k{\"u}nftig zur Validierung nicht nur zweifelsfrei auf MVII zur{\"u}ckgreifen k{\"o}nnen, sondern vielmehr sind Daten und Methoden notwendig, um Unsicherheiten auszuschließen. Zusammenfassend tr{\"a}gt diese Arbeit zur bisher wenig erforschten morphologischen Dynamik von Armutsgebieten bei. Es werden inter- wie auch intra-urbane Unterschiede auf globaler Ebene pr{\"a}sentiert. Dabei sind allgemein hohe morphologische Transformationen zwischen den selektierten Gebieten festzustellen. Die Ergebnisse deuten auf einen grundlegenden Kenntnismangel in Europa hin, weshalb an dieser Stelle angekn{\"u}pft wird. Eine {\"u}ber Europa verteilte Stichprobe erlaubt eine neue morphologische Kategorisierung der großen Vielfalt an gefundenen physischen Formen. Die Menge an Gebieten erschließt sich in einer unbekannten Grundgesamtheit. Zur Datenaufbereitung bisheriger Analysen m{\"u}ssen Satellitenbilder manuell interpretiert werden. Das Verfahren birgt Unsicherheiten. Als kritische Selbstreflexion zeigt eine Reihe von Experimenten signifikante Unterschiede zwischen den Ergebnissen der Probanden auf, verdeutlicht jedoch bei ein und derselben Person Best{\"a}ndigkeit.}, subject = {Slum}, language = {de} } @book{OPUS4-32281, title = {UnSichtbar : Interdisziplin{\"a}re Stimmen zu Vulnerabilit{\"a}t, Vulneranz und Menschenrechten}, editor = {Keul, Hildegund}, publisher = {W{\"u}rzburg University Press}, address = {W{\"u}rzburg}, isbn = {978-3-95826-202-7}, doi = {10.25972/WUP-978-3-95826-203-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-322810}, publisher = {W{\"u}rzburg University Press}, pages = {II, 278}, year = {2023}, abstract = {Wo etwas Verborgenes, das vom {\"o}ffentlichen Diskurs ausgeschlossen wurde, pl{\"o}tzlich sichtbar wird, ereignen sich Offenbarungen. Wenn es dabei um Menschenrechte geht, so entsteht ein prek{\"a}rer Augenblick, der große Chancen und zugleich un{\"u}bersehbare Risiken birgt. Verworfenes Leben kann sich Bahn brechen; oder es wird durch schmerzliche Vulneranz erneut verfemt und zerst{\"o}rt. In Verwundungen, die an der Schwelle des UnSichtbaren geschehen, tritt die Vulnerabilit{\"a}t der Menschenrechte hervor. Das vorliegende Buch erscheint 2023 und damit 75 Jahre nach der "Allgemeinen Erkl{\"a}rung der Menschenrechte" der Vereinten Nationen. Menschenrechte sind eine gegen viele Widerst{\"a}nde und mit großen Opfern durchgesetzte Errungenschaft der Menschheit. Heute werden sie erneut zu einem verletzten und verletzbaren Gut. Daher analysiert das Buch die ambivalente Macht der Vulnerabilit{\"a}t an signifi kanten Diskursorten der Gegenwart; es legt die Vulneranz der katholischen Kirche bez{\"u}glich Missbrauch, Vertuschung und Gendertrouble frei; und es fragt nach der offenbarenden Kraft an jener Schwelle, wo die Menschenrechte in Gefahr sind. Mit Beitr{\"a}gen von Prof. Dr. Stephan Lessenich, Dr. Sabine Bauer-Amin, Florian Pistrol, Steven H{\"o}fner, Prof. Dr. Ute Leimgruber, Prof. Dr. Hildegund Keul, Dr. Andreas Heek, Prof. Dr. Peter G. Kirchschl{\"a}ger, Dr. Jutta Czapski, Prof. Dr. Ansgar Kreutzer.}, language = {de} } @phdthesis{Preitschopf2023, author = {Preitschopf, Tobias}, title = {Disentangling the Formation of PAHs in Extreme Environments by IR/UV Double Resonance Spectroscopy}, doi = {10.25972/OPUS-32279}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-322791}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {Polycyclic Aromatic Hydrocarbons (PAHs) are considered as key building blocks in the formation of carbonaceous particles such as soot. In our immediate surroundings, they are mainly generated in incomplete combustion processes and are further considered as carriers of the Unidentified Infrared Bands which are detected in a wide variety of astrophysical envelopes in the interstellar medium. Currently, astrochemical as well as combustion related models favour small resonance stabilized radicals (RSR) as major contributors to PAHs in sequential reactions. Therefore, we generated two RSR under well-defined conditions to investigate their contribution to PAH formation in a pyrolysis microreactor. The various reaction products were identified by IR/UV ion dip spectroscopy which combines the mass-selectivity of UV light with the structural sensitivity of IR radiation. Finally, we investigated the intermolecular interactions in azaphenanthrene dimers in combination with high-level theoretical calculations and found a preferential formation of pi-stacked van der Waals cluster in a molecular jet expansion.}, subject = {Infrarotspektroskopie}, language = {en} } @phdthesis{Nemec2023, author = {Nemec, Katarina}, title = {Modulation of parathyroid hormone 1 receptor (PTH1R) signaling by receptor activity-modifying proteins (RAMPs)}, doi = {10.25972/OPUS-28858}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-288588}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {The receptor activity-modifying proteins (RAMPs) are ubiquitously expressed membrane proteins that interact with several G protein-coupled receptors (GPCRs), the largest and pharmacologically most important family of cell surface receptors. RAMPs can regulate GPCR function in terms of ligand-binding, G-protein coupling, downstream signaling, trafficking, and recycling. The integrity of their interactions translates to many physiological functions or pathological conditions. Regardless of numerous reports on its essential importance for cell biology and pivotal role in (patho-)physiology, the molecular mechanism of how RAMPs modulate GPCR activation remained largely elusive. This work presents new insights that add to the common understanding of the allosteric regulation of receptor activation and will help interpret how accessory proteins - RAMPs - modulate activation dynamics and how this affects the fundamental aspects of cellular signaling. Using a prototypical class B GPCR, the parathyroid hormone 1 receptor (PTH1R) in the form of advanced genetically encoded optical biosensors, I examined RAMP's impact on the PTH1R activation and signaling in intact cells. A panel of single-cell FRET and confocal microscopy experiments as well canonical and non-canonical functional assays were performed to get a holistic picture of the signaling initiation and transduction of that clinically and therapeutically relevant GPCR. Finally, structural modeling was performed to add molecular mechanistic details to that novel art of modulation. I describe here that RAMP2 acts as a specific allosteric modulator of PTH1R, shifting PTH1R to a unique pre-activated state that permits faster activation in a ligand-specific manner. Moreover, RAMP2 modulates PTH1R downstream signaling in an agonist-dependent manner, most notably increasing the PTH-mediated Gi3 signaling sensitivity and kinetics of cAMP accumulation. Additionally, RAMP2 increases PTH- and PTHrP-triggered β-arrestin2 recruitment to PTH1R and modulates cytosolic ERK1/2 phosphorylation. Structural homology modeling shows that structural motifs governing GPCR-RAMP interaction originate in allosteric hotspots and rationalize functional modulation. Moreover, to interpret the broader role of RAMP's modulation in GPCRs pharmacology, different fluorescent tools to investigate RAMP's spatial organization were developed, and novel conformational biosensors for class B GPCRs were engineered. Lastly, a high throughput assay is proposed and prototyped to expand the repertoire of RAMPs or other membrane protein interactors. These data uncover the critical role of RAMPs in GPCR activation and signaling and set up a novel platform for studying GPCR modulation. Furthermore, these insights may provide a new venue for precise modulation of GPCR function and advanced drug design.}, subject = {G-Protein gekoppelter Rezeptor}, language = {en} } @phdthesis{Sivarajan2023, author = {Sivarajan, Rinu}, title = {Engineered Human Airway Mucosa for Modelling Respiratory Infections: Characterisation and Applications}, doi = {10.25972/OPUS-32241}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-322414}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {Respiratory infections are a significant health concern worldwide, and the airway epithelium plays a crucial role in regulating airway function and modulating inflammatory processes. However, most studies on respiratory infections have used cell lines or animal models, which may not accurately reflect native physiological conditions, especially regarding human pathogens. We generated human nasal mucosa (hNM) and tracheobronchial mucosa (hTM) models to address this issue using primary human airway epithelial cells and fibroblasts. We characterised these human airway tissue models (hAM) using high speed video microscopy, single cell RNA sequencing, immunofluorescence staining, and ultrastructural analyses that revealed their complexity and cellular heterogeneity. We demonstrated that Bordetella pertussis virulence factor adenylate cyclase toxin (CyaA) elevated the intracellular production of cyclic adenosine monophosphate (cAMP) and secretion of interleukin (IL) 6, IL 8, and human beta defensin 2 (HBD2). In addition, we compared the responses of the tissue models from two different anatomical sites (the upper and lower respiratory mucosa) and are the first to report such differential susceptibility towards CyaA using 3D primary airway cell derivedmodels. The effect of toxin treatment on the epithelial barrier integrity of the tissue models was assessed by measuring the flux of fluorescein isothiocyanate (FITC)-conjugated dextran across the models. Though we observed a cell type specific response with respect to intracellular cAMP production and IL 6, IL 8, and HBD2 secretion in the models treated with CyaA on the apical side, the epithelial membrane barrier integrity was not compromised. In addition to toxin studies, using these characterised models, we established viral infection studies for Influenza A (IAV), Respiratory Syncytial Virus subtype B (RSV), and severe acute respiratory syndrome coronavirus 2. We visualised the morphological consequences of the viral infection using ultrastructural analysis and immunofluorescence. We verified the effective infection in hAM by measuring the viral RNA using RTqPCR and detected elevated cytokine levels in response to infection using biochemical assays. In contrast to cell lines, studies on viral infection using hAM demonstrated that infected areas were localized to specific regions. This led to the formation of infection hotspots, which were more likely to occur when models derived from different donors were infected separately with all three viruses. IAV infected tissue models replicate the clinical findings of H1N1 infection, such as mucus hypersecretion, cytokine release, and infection-associated epithelial cell damage.Finally, we paved the steps towards understanding the impact of IAV infection on disease models. We generated hTM from biopsies obtained from chronic obstructive pulmonary disease (COPD) patients. As a model to study the impact of COPD on respiratory infections, considering the increase in COPD cases in the past decade and the continued predicted increase in the future. We established the IAV infection protocol to capture the early infection signatures in non-COPD and COPD conditions using scRNA-seq. We investigated the infection kinetics of IAV (H1N1-clinical isolate) in hTM and found that viruses were actively released approximately 24 hours post infection. The scRNA-seq data from the hTM derived from non-COPD and COPD patients, revealed lower levels of SCGB1A1 (club cell marker) gene expression in the COPD-control group compared to the non-COPD control group, consistent with previous clinical studies. Furthermore, we observed that IAV infection elevated SCGB1A1 gene expression especially in secretory cells of both the COPD and non COPD groups. This may imply the role of club cells as early responders during IAV infection providing epithelial repair, regeneration, and resistance to spread of infection. This is the first study to address the molecular diversity in COPD and non-COPD disease models infected with IAV investigating the early response (6 h) of specific cell types in the human lower airways towards infection using scRNA-seq. These findings highlight the potential interplay between COPD, IAV infection, and altered vulnerability to other viral infections and respiratory illnesses making the hAM applicable for addressing more specific research questions and validating potential targets, such as SCGB1A1 targeted therapy for chronic lung diseases. Our findings demonstrate the potential of the hNM and hTM for investigating respiratory infections, innate immune responses, and trained immunity in non-immune cells. Our experiments show that hAM may represent a more accurate representation of the native physiological condition and improve our understanding of the disease mechanisms. Furthermore, these models promote non-animal research as they replicate clinical findings. We can further increase their complexity by incorporating dynamic flow systems and immune cells catered to the research question.}, subject = {Atemwege}, language = {en} } @article{OkudaLenzSeitzetal.2023, author = {Okuda, Takumi and Lenz, Ann-Kathrin and Seitz, Florian and Vogel, J{\"o}rg and H{\"o}bartner, Claudia}, title = {A SAM analogue-utilizing ribozyme for site-specific RNA alkylation in living cells}, series = {Nature Chemistry}, journal = {Nature Chemistry}, doi = {10.1038/s41557-023-01320-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-328762}, year = {2023}, abstract = {Post-transcriptional RNA modification methods are in high demand for site-specific RNA labelling and analysis of RNA functions. In vitro-selected ribozymes are attractive tools for RNA research and have the potential to overcome some of the limitations of chemoenzymatic approaches with repurposed methyltransferases. Here we report an alkyltransferase ribozyme that uses a synthetic, stabilized S-adenosylmethionine (SAM) analogue and catalyses the transfer of a propargyl group to a specific adenosine in the target RNA. Almost quantitative conversion was achieved within 1 h under a wide range of reaction conditions in vitro, including physiological magnesium ion concentrations. A genetically encoded version of the SAM analogue-utilizing ribozyme (SAMURI) was expressed in HEK293T cells, and intracellular propargylation of the target adenosine was confirmed by specific fluorescent labelling. SAMURI is a general tool for the site-specific installation of the smallest tag for azide-alkyne click chemistry, which can be further functionalized with fluorophores, affinity tags or other functional probes.}, language = {en} } @phdthesis{Jia2023, author = {Jia, Xiaoxi}, title = {Augmented Lagrangian Methods invoking (Proximal) Gradient-type Methods for (Composite) Structured Optimization Problems}, doi = {10.25972/OPUS-32374}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-323745}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {This thesis, first, is devoted to the theoretical and numerical investigation of an augmented Lagrangian method for the solution of optimization problems with geometric constraints, subsequently, as well as constrained structured optimization problems featuring a composite objective function and set-membership constraints. It is then concerned to convergence and rate-of-convergence analysis of proximal gradient methods for the composite optimization problems in the presence of the Kurdyka--{\L}ojasiewicz property without global Lipschitz assumption.}, subject = {Optimierung}, language = {en} } @phdthesis{Krenzer2023, author = {Krenzer, Adrian}, title = {Machine learning to support physicians in endoscopic examinations with a focus on automatic polyp detection in images and videos}, doi = {10.25972/OPUS-31911}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-319119}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {Deep learning enables enormous progress in many computer vision-related tasks. Artificial Intel- ligence (AI) steadily yields new state-of-the-art results in the field of detection and classification. Thereby AI performance equals or exceeds human performance. Those achievements impacted many domains, including medical applications. One particular field of medical applications is gastroenterology. In gastroenterology, machine learning algorithms are used to assist examiners during interventions. One of the most critical concerns for gastroenterologists is the development of Colorectal Cancer (CRC), which is one of the leading causes of cancer-related deaths worldwide. Detecting polyps in screening colonoscopies is the essential procedure to prevent CRC. Thereby, the gastroenterologist uses an endoscope to screen the whole colon to find polyps during a colonoscopy. Polyps are mucosal growths that can vary in severity. This thesis supports gastroenterologists in their examinations with automated detection and clas- sification systems for polyps. The main contribution is a real-time polyp detection system. This system is ready to be installed in any gastroenterology practice worldwide using open-source soft- ware. The system achieves state-of-the-art detection results and is currently evaluated in a clinical trial in four different centers in Germany. The thesis presents two additional key contributions: One is a polyp detection system with ex- tended vision tested in an animal trial. Polyps often hide behind folds or in uninvestigated areas. Therefore, the polyp detection system with extended vision uses an endoscope assisted by two additional cameras to see behind those folds. If a polyp is detected, the endoscopist receives a vi- sual signal. While the detection system handles the additional two camera inputs, the endoscopist focuses on the main camera as usual. The second one are two polyp classification models, one for the classification based on shape (Paris) and the other on surface and texture (NBI International Colorectal Endoscopic (NICE) classification). Both classifications help the endoscopist with the treatment of and the decisions about the detected polyp. The key algorithms of the thesis achieve state-of-the-art performance. Outstandingly, the polyp detection system tested on a highly demanding video data set shows an F1 score of 90.25 \% while working in real-time. The results exceed all real-time systems in the literature. Furthermore, the first preliminary results of the clinical trial of the polyp detection system suggest a high Adenoma Detection Rate (ADR). In the preliminary study, all polyps were detected by the polyp detection system, and the system achieved a high usability score of 96.3 (max 100). The Paris classification model achieved an F1 score of 89.35 \% which is state-of-the-art. The NICE classification model achieved an F1 score of 81.13 \%. Furthermore, a large data set for polyp detection and classification was created during this thesis. Therefore a fast and robust annotation system called Fast Colonoscopy Annotation Tool (FastCAT) was developed. The system simplifies the annotation process for gastroenterologists. Thereby the i gastroenterologists only annotate key parts of the endoscopic video. Afterward, those video parts are pre-labeled by a polyp detection AI to speed up the process. After the AI has pre-labeled the frames, non-experts correct and finish the annotation. This annotation process is fast and ensures high quality. FastCAT reduces the overall workload of the gastroenterologist on average by a factor of 20 compared to an open-source state-of-art annotation tool.}, subject = {Deep Learning}, language = {en} } @article{BruennertSeupelGoyaletal.2023, author = {Br{\"u}nnert, Daniela and Seupel, Raina and Goyal, Pankaj and Bach, Matthias and Schraud, Heike and Kirner, Stefanie and K{\"o}ster, Eva and Feineis, Doris and Bargou, Ralf C. and Schlosser, Andreas and Bringmann, Gerhard and Chatterjee, Manik}, title = {Ancistrocladinium A induces apoptosis in proteasome inhibitor-resistant multiple myeloma cells: a promising therapeutic agent candidate}, series = {Pharmaceuticals}, volume = {16}, journal = {Pharmaceuticals}, number = {8}, issn = {1424-8247}, doi = {10.3390/ph16081181}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-362887}, year = {2023}, abstract = {The N,C-coupled naphthylisoquinoline alkaloid ancistrocladinium A belongs to a novel class of natural products with potent antiprotozoal activity. Its effects on tumor cells, however, have not yet been explored. We demonstrate the antitumor activity of ancistrocladinium A in multiple myeloma (MM), a yet incurable blood cancer that represents a model disease for adaptation to proteotoxic stress. Viability assays showed a potent apoptosis-inducing effect of ancistrocladinium A in MM cell lines, including those with proteasome inhibitor (PI) resistance, and in primary MM cells, but not in non-malignant blood cells. Concomitant treatment with the PI carfilzomib or the histone deacetylase inhibitor panobinostat strongly enhanced the ancistrocladinium A-induced apoptosis. Mass spectrometry with biotinylated ancistrocladinium A revealed significant enrichment of RNA-splicing-associated proteins. Affected RNA-splicing-associated pathways included genes involved in proteotoxic stress response, such as PSMB5-associated genes and the heat shock proteins HSP90 and HSP70. Furthermore, we found strong induction of ATF4 and the ATM/H2AX pathway, both of which are critically involved in the integrated cellular response following proteotoxic and oxidative stress. Taken together, our data indicate that ancistrocladinium A targets cellular stress regulation in MM and improves the therapeutic response to PIs or overcomes PI resistance, and thus may represent a promising potential therapeutic agent.}, language = {en} } @article{BucheltBloetheKuenzeretal.2023, author = {Buchelt, Sebastian and Bl{\"o}the, Jan Henrik and Kuenzer, Claudia and Schmitt, Andreas and Ullmann, Tobias and Philipp, Marius and Kneisel, Christof}, title = {Deciphering small-scale seasonal surface dynamics of rock glaciers in the Central European Alps using DInSAR time series}, series = {Remote Sensing}, volume = {15}, journal = {Remote Sensing}, number = {12}, issn = {2072-4292}, doi = {10.3390/rs15122982}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-362939}, year = {2023}, abstract = {The Essential Climate Variable (ECV) Permafrost is currently undergoing strong changes due to rising ground and air temperatures. Surface movement, forming characteristic landforms such as rock glaciers, is one key indicator for mountain permafrost. Monitoring this movement can indicate ongoing changes in permafrost; therefore, rock glacier velocity (RGV) has recently been added as an ECV product. Despite the increased understanding of rock glacier dynamics in recent years, most observations are either limited in terms of the spatial coverage or temporal resolution. According to recent studies, Sentinel-1 (C-band) Differential SAR Interferometry (DInSAR) has potential for monitoring RGVs at high spatial and temporal resolutions. However, the suitability of DInSAR for the detection of heterogeneous small-scale spatial patterns of rock glacier velocities was never at the center of these studies. We address this shortcoming by generating and analyzing Sentinel-1 DInSAR time series over five years to detect small-scale displacement patterns of five high alpine permafrost environments located in the Central European Alps on a weekly basis at a range of a few millimeters. Our approach is based on a semi-automated procedure using open-source programs (SNAP, pyrate) and provides East-West displacement and elevation change with a ground sampling distance of 5 m. Comparison with annual movement derived from orthophotos and unpiloted aerial vehicle (UAV) data shows that DInSAR covers about one third of the total movement, which represents the proportion of the year suited for DInSAR, and shows good spatial agreement (Pearson R: 0.42-0.74, RMSE: 4.7-11.6 cm/a) except for areas with phase unwrapping errors. Moreover, the DInSAR time series unveils spatio-temporal variations and distinct seasonal movement dynamics related to different drivers and processes as well as internal structures. Combining our approach with in situ observations could help to achieve a more holistic understanding of rock glacier dynamics and to assess the future evolution of permafrost under changing climatic conditions.}, language = {en} } @article{WinterSchulzSchmitteretal.2023, author = {Winter, Anna and Schulz, Stefan M. and Schmitter, Marc and M{\"u}ller-Richter, Urs and K{\"u}bler, Alexander and Kasper, Sylvia and Hartmann, Stefan}, title = {Comprehensive geriatric assessment and quality of life aspects in patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC)}, series = {Journal of Clinical Medicine}, volume = {12}, journal = {Journal of Clinical Medicine}, number = {17}, issn = {2077-0383}, doi = {10.3390/jcm12175738}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-363096}, year = {2023}, abstract = {To define frailty in older cancer patients, the aim of this study was to assess the geriatric status and quality of life (QoL) aspects in patients suffering from recurrent/metastatic head and neck squamous cell carcinoma (r/m HNSCC) under palliative treatment. A comprehensive geriatric assessment (CGA) was performed on 21 r/m HNSCC patients at two defined assessments, and the QoL aspects and the impact of descriptive data were evaluated. The Kolmogorov-Smirnov test, Spearman's rho correlation, and two-way mixed ANOVA were used for statistical analysis. All patients were found to be "frail". Pain, fatigue, and the burden of illness were the highest-rated symptoms. Oral function and orofacial appearance were highly impaired. A significant impact of descriptive data on the CGA and QoL results was found (all p ≤ 0.05). Thus, the CGA results revealed high frailty, severe comorbidities, and high impairments in QoL aspects. The CGA and QoL results were negatively affected by the primary HNSCC treatment approach, the need for prosthetic treatment, and worse oral functional capacity. Therefore, frailty in r/m HNSCC patients seems to be multidimensional. The evaluation of the CGA and QoL aspects in r/m HNSCC patients can be recommended to detect special needs, organize aftercare, and improve the support for frail and vulnerable cancer patients to create a multidisciplinary treatment approach.}, language = {en} } @article{HellerReiterLeichtetal.2023, author = {Heller, Bianca and Reiter, Florian P. and Leicht, Hans Benno and Fiessler, Cornelia and Bergheim, Ina and Heuschmann, Peter U. and Geier, Andreas and Rau, Monika}, title = {Salt-intake-related behavior varies between sexes and is strongly associated with daily salt consumption in obese patients at high risk for MASLD}, series = {Nutrients}, volume = {15}, journal = {Nutrients}, number = {18}, issn = {2072-6643}, doi = {10.3390/nu15183942}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-363107}, year = {2023}, abstract = {Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) imposes a significant burden on Westernized regions. The Western diet, high in salt intake, significantly contributes to disease development. However, there are a lack of data on salt literacy and salt intake among MASLD patients in Germany. Our study aims to analyze daily salt intake and salt-intake-related behavior in MASLD patients. Methods: 234 MASLD patients were prospectively included. Daily salt intake and salt-intake-related behavior were assessed via a food frequency questionnaire (FFQ—DEGS) and a salt questionnaire (SINU). Statistical analyses were performed using SPSS. Results: Mean daily salt intake was higher in men than in women (7.3 ± 5 g/d vs. 5.3 ± 4 g/d; p \< 0.001). There was significant agreement between increased daily salt intake (6 g/d) and the behavioral salt index (SI) (p \< 0.001). Men exhibited higher SI scores compared to women, indicating lower awareness of salt in everyday life. Multivariate analysis identified specific salt-intake-related behaviors impacting daily salt consumption. Conclusions: Our study reveals a strong link between daily salt intake and salt-intake-related behavior, highlighting sex-specific differences in an MASLD cohort. To enhance patient care in high-cardiovascular-risk populations, specific behavioral approaches may be considered, including salt awareness, to improve adherence to lifestyle changes, particularly in male patients.}, language = {en} } @article{HartmannKnierimMaureretal.2023, author = {Hartmann, Nico and Knierim, Maria and Maurer, Wiebke and Dybkova, Nataliya and Hasenfuß, Gerd and Sossalla, Samuel and Streckfuss-B{\"o}meke, Katrin}, title = {Molecular and functional relevance of Na\(_V\)1.8-induced atrial arrhythmogenic triggers in a human SCN10A knock-out stem cell model}, series = {International Journal of Molecular Sciences}, volume = {24}, journal = {International Journal of Molecular Sciences}, number = {12}, issn = {1422-0067}, doi = {10.3390/ijms241210189}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-362708}, year = {2023}, abstract = {In heart failure and atrial fibrillation, a persistent Na\(^+\) current (I\(_{NaL}\)) exerts detrimental effects on cellular electrophysiology and can induce arrhythmias. We have recently shown that Na\(_V\)1.8 contributes to arrhythmogenesis by inducing a I\(_{NaL}\). Genome-wide association studies indicate that mutations in the SCN10A gene (Na\(_V\)1.8) are associated with increased risk for arrhythmias, Brugada syndrome, and sudden cardiac death. However, the mediation of these Na\(_V\)1.8-related effects, whether through cardiac ganglia or cardiomyocytes, is still a subject of controversial discussion. We used CRISPR/Cas9 technology to generate homozygous atrial SCN10A-KO-iPSC-CMs. Ruptured-patch whole-cell patch-clamp was used to measure the I\(_{NaL}\) and action potential duration. Ca\(^{2+}\) measurements (Fluo 4-AM) were performed to analyze proarrhythmogenic diastolic SR Ca\(^{2+}\) leak. The I\(_{NaL}\) was significantly reduced in atrial SCN10A KO CMs as well as after specific pharmacological inhibition of Na\(_V\)1.8. No effects on atrial APD\(_{90}\) were detected in any groups. Both SCN10A KO and specific blockers of Na\(_V\)1.8 led to decreased Ca\(^{2+}\) spark frequency and a significant reduction of arrhythmogenic Ca\(^{2+}\) waves. Our experiments demonstrate that Na\(_V\)1.8 contributes to I\(_{NaL}\) formation in human atrial CMs and that Na\(_V\)1.8 inhibition modulates proarrhythmogenic triggers in human atrial CMs and therefore Na\(_V\)1.8 could be a new target for antiarrhythmic strategies.}, language = {en} } @article{EwaldFuchsBoegeleinetal.2023, author = {Ewald, Andrea and Fuchs, Andreas and Boegelein, Lasse and Grunz, Jan-Peter and Kneist, Karl and Gbureck, Uwe and Hoelscher-Doht, Stefanie}, title = {Degradation and bone-contact biocompatibility of two drillable magnesium phosphate bone cements in an in vivo rabbit bone defect model}, series = {Materials}, volume = {16}, journal = {Materials}, number = {13}, issn = {1996-1944}, doi = {10.3390/ma16134650}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-362824}, year = {2023}, abstract = {The use of bone-cement-enforced osteosynthesis is a growing topic in trauma surgery. In this context, drillability is a desirable feature for cements that can improve fracture stability, which most of the available cement systems lack. Therefore, in this study, we evaluated a resorbable and drillable magnesium-phosphate (MgP)-based cement paste considering degradation behavior and biocompatibility in vivo. Two different magnesium-phosphate-based cement (MPC) pastes with different amounts of phytic acid (IP 6) as setting retarder (MPC 22.5 and MPC 25) were implanted in an orthotopic defect model of the lateral femoral condyle of New Zealand white rabbits for 6 weeks. After explantation, their resorption behavior and material characteristics were evaluated by means of X-ray diffraction (XRD), porosimetry measurement, histological staining, peripheral quantitative computed tomography (pQCT), cone-beam computed tomography (CBCT) and biomechanical load-to-failure tests. Both cement pastes displayed comparable results in mechanical strength and resorption kinetics. Bone-contact biocompatibility was excellent without any signs of inflammation. Initial resorption and bone remodeling could be observed. MPC pastes with IP 6 as setting retardant have the potential to be a valuable alternative in distinct fracture patterns. Drillability, promising resorption potential and high mechanical strength confirm their suitability for use in clinical routine.}, language = {en} } @article{HeinzWildEidmannetal.2023, author = {Heinz, Tizian and Wild, Moritz and Eidmann, Annette and Weißenberger, Manuel and Rak, Dominik and Nedopil, Alexander Johannes and Rudert, Maximilian and Stratos, Ioannis}, title = {Impact of COVID-19 on fracture incidence in germany: a comparative age and gender analysis of pre- and post-outbreak periods}, series = {Healthcare}, volume = {11}, journal = {Healthcare}, number = {15}, issn = {2227-9032}, doi = {10.3390/healthcare11152139}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-362686}, year = {2023}, abstract = {In March 2020, Germany imposed a nationwide lockdown to curb the spread of COVID-19, prompting questions about the impact on the incidence of common fractures. This study examined 15 fracture types in pre-outbreak (2010-2019) and post-outbreak (2020-2021) periods, using data categorized by age (18-64 years, 65 years) and sex (male, female). Linear regression assessed annual growth rates, and mean fracture numbers were compared across periods for significant differences. Results indicated a positive correlation between fracture incidence rates and time for various types, such as cervical, thoracic, lumbar, and pelvic spine fractures, rib fractures, femoral neck, pertrochanteric femur, femoral shaft, and ankle fractures. Frequencies of proximal humerus, distal radius, femoral neck, pertrochanteric femur, femoral shaft, and ankle fractures in 2020 and 2021 were within predicted ranges from previous years. However, rib fractures and spinal fractures (cervical, thoracic, lumbar, and pelvic spine) occurred less frequently during this time. Notably, this study found a consistent decline in most fracture types for individuals aged 18-64 after the pandemic's onset, while the fracture incidence of hip fractures, often referred to as fragility fractures, for those over 65 remained unchanged. Fibula fractures showed the most considerable decrease in both age groups. In conclusion, the COVID-19 pandemic substantially impacted fracture incidence, with lower rates among individuals under 65 and unchanged fragility fractures in the elderly population.}, language = {en} } @article{EidmannHeinzOberfeldetal.2023, author = {Eidmann, Annette and Heinz, Tizian and Oberfeld, Jan and Weißenberger, Manuel and Rudert, Maximilian and Stratos, Ioannis}, title = {Epidemiology and trends in cartilage surgery of the foot and ankle in Germany: an analysis of national healthcare billing and reporting data from 2006 to 2020}, series = {Medicina}, volume = {59}, journal = {Medicina}, number = {7}, issn = {1648-9144}, doi = {10.3390/medicina59071256}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-362835}, year = {2023}, abstract = {Background and objectives: Cartilage surgery constitutes a standard intervention in foot and ankle procedures. Currently, there is a lack of epidemiological data on its frequency, age distribution, and surgical options for cartilage surgery. This study aimed to investigate the current landscape of cartilage surgery in Germany and identify the most common procedures from an epidemiological standpoint. Materials and methods: Medical billing and reporting data from the Federal Statistical Office of Germany, encompassing the period 2006-2020, was examined, including all foot and ankle cartilage surgical procedures (summarized under OPS codes 5-812 and 5-801). The dataset incorporated information on the affected joint, patient age and sex, and surgery type. Each surgical procedure was categorized as "debridement", "regeneration" or "refixation". Linear and nonlinear regression analyses were employed, with a statistical significance threshold of 0.05. Results: From the total of 136,501 procedures conducted during the study period, the most frequently performed interventions were microfracture (58,252) and chondroplasty (56,135), and thus, debridement procedures were in the leading position. The use of acellular membranes was the most used regenerative technique (n = 11,414). At the ankle joint, interventions were mostly arthroscopic and in men, while foot cartilage surgeries were preferably performed via open surgery and mostly in women. Age distribution analysis revealed two primary peaks: the first in the 20-25-year-old group (ankle and foot) and the second in the 45-50-year-old group (ankle) and 55-60-year-old group (foot). Refixation and regenerative procedures were more frequent among younger individuals, while debriding procedures were more frequent among older individuals. Regenerative procedures, particularly in the ankle, significantly increased over time. Conclusions: Cartilage surgery of the foot and ankle was common, with two primary age groups predominantly affected. Notably, recent years have witnessed a considerable rise in cartilage regenerative procedures.}, language = {en} } @article{BuchmannBaumannMengetal.2023, author = {Buchmann, J. and Baumann, N. and Meng, K. and Semrau, J. and Kuhl, J. and Pfeifer, K. and Vogel, H. and Faller, H.}, title = {Volitional Action Control and Depression in Chronic Pain: Does Action versus State Orientation Moderate the Relations of Pain-Related Cognitions to Depression?}, series = {Current Psychology}, volume = {42}, journal = {Current Psychology}, issn = {1046-1310}, doi = {10.1007/s12144-021-01914-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-308508}, pages = {7591-7608}, year = {2023}, abstract = {In this study, we examined the conditional indirect and direct relations of pain-related cognitions to depression. Subjective helplessness was included as presumably mediating the relations of catastrophizing and thought suppression to depression due to motivational deficits. In addition, moderating effects of dispositional action versus state orientation were analyzed, whereby state orientation indicates volitional deficits in coping with distress. The study was based on self-report data from 536 patients with chronic non-specific low back pain at the beginning of inpatient rehabilitation. Moderated mediation analyses were performed. The indirect catastrophizing- and thought suppression-depression relations were (partially) mediated by subjective helplessness; and moderated by failure-related action versus state orientation. Moreover, action versus state orientation moderated the direct relation of thought suppression to depression. Results suggest that catastrophizing, thought suppression, and subjective helplessness do not lead to depression unless associated with self-regulatory inability (i.e., state orientation). In contrast, action-oriented patients more effectively self-regulate pain-related emotions, disengage from rumination, and distract from pain and thus better avoid the debilitating effects of negative pain-related cognitions on depression. Future research and treatment may more strongly focus on the role of motivational and volitional deficits underlying learned helplessness and depression in chronic pain.}, language = {en} } @article{StichtWeinreich2023, author = {Sticht, Oliver and Weinreich, Melina}, title = {Obdach, Speisung und Heilung. Zur Geschichte des Seelhauses an der Juliuspromenade in W{\"u}rzburg}, series = {W{\"u}rzburger Di{\"o}zesangeschichtsbl{\"a}tter}, volume = {86}, journal = {W{\"u}rzburger Di{\"o}zesangeschichtsbl{\"a}tter}, issn = {0342-3093}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-361319}, pages = {359-375}, year = {2023}, abstract = {Das 1379 gestiftete Seelhaus befindet sich seit 1587 an der heutigen Juliuspromenade in W{\"u}rzburg. Urspr{\"u}nglich zur Beherbergung bed{\"u}rftiger Reisender eingerichtet, entwickelte es sich seit dem 17. Jahrhundert zum Alterssitz f{\"u}r M{\"a}gde und Hausangestellte, bevor es im 19. Jahrhundert ganz aufgel{\"o}st wurde. Durch den Kauf der Hausnummern 9-11 durch die Oberzeller Schwestern 1927 erlebte sein karitativer Auftrag bis zur Zerst{\"o}rung am 16. M{\"a}rz 1945 eine Wiederbelebung.}, subject = {Seelhaus W{\"u}rzburg}, language = {de} } @phdthesis{Engelmann2023, author = {Engelmann, Daria Marie}, title = {Regulation of Mammalian Phosphoglycolate Phosphatase}, doi = {10.25972/OPUS-19957}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-199577}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {Mammalian phoshoglycolate phosphatase (PGP, also known as AUM) belongs to the ubiquitous HAD superfamily of phosphatases. As several other members of HAD phosphatases, the Mg2+-dependent dephosphorylation is conducted via a nucleophilic attack from a conserved aspartate residue in the catalytic cleft. The protein structure of PGP could not yet be solved entirely. Only a hybrid consisting of the PGP cap and the PDXP core (pyridoxal phosphatase, closest enzyme paralog) was crystallizable so far. PGP is able to efficiently dephosphorylate 2-phosphoglycolate, 2-phospho-L-lactate, 4-phospho-D-erythronate, and glycerol-3-phosphate in vitro which makes them likely physiological substrates. The first three substrates can be derived from metabolic side reactions (during glycolysis) and inhibit key enzymes in glycolysis and pentose phosphate pathway, the latter is situated at the intersection between glycolysis and lipogenesis. 2-phosphoglycolate can also be released in the context of repair of oxidative DNA damage. The activity of purified PGP can be reversibly inhibited by oxidation - physiologically likely in association with epidermal growth factor (EGF) signal transduction. In fact, an association between persistently lacking PGP activity (via downregulation) and the presence of hyperphosphorylated proteins after EGF stimulation has been identified. Reversible oxidation and transient inactivation of PGP may be particularly important for short-term and feedback regulatory mechanisms (as part of the EGF signaling). Furthermore, cellular proliferation in PGP downregulated cells is constantly reduced. Whole-body PGP inactivation in mice is embryonically lethal. Despite the many well-known features and functions, the knowledge about PGP is still incomplete. In the present work the influence of reactive oxygen species (ROS) on PGP activity in cells und a possible connection between oxidative stress and the proliferation deficit of PGP downregulated cells was investigated. For the experiments, a spermatogonial cell line was used (due to the high PGP expression in testis). PGP activity can be reversibly inhibited in cellular lysates by H2O2 (as a ROS representative). Reversible oxidation could thus indeed be physiologically important. More oxidative DNA damage (by bleomycin) showed no PGP-dependent effects here. EGF stimulation (as an inducer of transient and well-controlled ROS production), low concentrations of menadione (as an oxidant) and N-acetylcysteine (as an antioxidant) were able to approximate the proliferation rate in PGP downregulated cells to that of control cells. The redox regulation of PGP could thus have an influence on cellular proliferation as a feedback mechanism - a mechanism that could not take place in PGP downregulated cells. However, the connections are probably even more complex and cannot be elucidated by a sole examination of the proliferation rate. The present results can thus only be regarded as preliminary experiments. For a better understanding of the features and functions of PGP, this work then focused on specific regulation of enzyme activity by pharmacologically applicable small molecules. Four potent inhibitors had previously been identified in a screening campaign. In this work, three of these four inhibiting compounds could be further characterized in experiments with highly purified, recombinant murine and human PGP. Compounds \#2 and \#9 showed competitive inhibition properties with a markedly rising KM value with little or no change in vmax. The results were consistent for all tested protein variants: the murine and the human PGP as well as a PGP/PDXP hybrid protein. Compound \#1 was the most potent and interesting PGP-inhibitory molecule: less change in KM and a constant decrease in vmax as well as a lower impact on the PGP/PDXP hybrid hint at a mixed mode of inhibition as a combination of competitive and non-competitive inhibition. The characterization of the potential inhibitors can serve as a basis for further structural analysis and studies on the complex physiological role of PGP.}, subject = {Phosphoglykolatphosphatase}, language = {en} } @phdthesis{Behnke2023, author = {Behnke, Jennifer Kim}, title = {Charakterisierung der Krankheitsprogression im genetischen hm\(^2\)α-SYN-39 Mausmodell des Morbus Parkinson}, doi = {10.25972/OPUS-30204}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-302040}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {In dieser Arbeit wurde die Krankheitsprogression im Parkinson-Mausmodell hm2α-SYN-39 mit zunehmendem Alter charakterisiert. Die M{\"a}use wurden in 4 Altersgruppen (2-3, 7-8, 11-12, 16-17 Monate) mit motorischen Verhaltenstests auf einen Parkinson-Ph{\"a}notyp untersucht. Zudem erfolgten Untersuchungen des dopaminergen Systems zur Detektion von neurochemischen Ver{\"a}nderungen und einer Neurodegeneration im nigrostriatalen Trakt. Weiterhin wurden neuroinflammatorische Prozesse des adaptiven und angeborenen IS in der SN und im Striatum mittels immunhistochemischer F{\"a}rbungen beurteilt. Ein Parkinson-Ph{\"a}notyp in diesem Mausmodell zeigte sich nur leicht ausgepr{\"a}gt, sodass der Rotarod- und Zylinder-Test lediglich den Hinweis auf eine nicht-signifikante Einschr{\"a}nkung der Motorik erbrachte. Dennoch ergab die stereologische Quantifizierung TH- und Nissl-positiver Zellen in der SNpc der hm2α-SYN-39 M{\"a}use eine altersabh{\"a}ngige, signifikant-progrediente Reduktion der dopaminergen Neurone mit zunehmendem Alter. Eine signifikant niedrigere TH-positive Zellzahl dieser tg M{\"a}use zeigte sich ab einem Alter von 16-17 Monaten verglichen zu gleichaltrigen wt Tieren. Dagegen war die Neurodegeneration im Striatum etwas weniger ausgepr{\"a}gt. Die tg M{\"a}use pr{\"a}sentierten im Alter von 16-17 Monaten eine nicht-signifikante Erniedrigung der dopaminergen Terminalen verglichen zu gleichaltrigen wt Tieren. Ein DA-Mangel im Striatum der tg M{\"a}use konnte mittels HPLC best{\"a}tigt werden. Bis zum Alter von 16-17 Monaten wurde eine signifikante Reduktion der DA-Level von 23,2 \% verglichen zu gleichaltrigen wt M{\"a}usen gezeigt. Außerdem erniedrigt waren die striatalen Level von NA und 5-HAT bei tg M{\"a}usen, passend zu den bisherigen Ergebnissen bei Parkinson-Patienten. Immunhistochemische Untersuchungen einer Neuroinflammation im nigrostriatalen Trakt ergaben eine tendenziell erh{\"o}hte Infiltration von CD4- und CD8-positiven T-Zellen bei hm2α-SYN-39 M{\"a}usen mit zunehmendem Alter, wobei die Infiltration CD8-positiver Zellen ausgepr{\"a}gter war als bei CD4-positiven Zellen. Eine noch deutlichere neuroinflammatorische Reaktion zeigte das angeborene IS. Hierbei ergab die immunhistologische Quantifizierung CD11b-positiver mikroglialer Zellen einen hochsignifikanten Anstieg im nigrostriatalen Trakt bei hm2α-SYN-39 M{\"a}usen schon im jungen Alter. Zusammenfassend pr{\"a}sentierte dieses Parkinson-Mausmodell eine langsam-progrediente Parkinson-Pathologie mit begleitender Neuroinflammation im nigrostriatalen Trakt w{\"a}hrend des Alterns, wobei die Immunantwort der mikroglialen Zellen zu einem fr{\"u}heren Zeitpunkt einsetzte als die T-Zellinfiltration und Neurodegeneration. Dieses Mausmodell bietet zahlreiche M{\"o}glichkeiten zur zuk{\"u}nftigen Erforschung der Pathophysiologie beim MP. Generell weist diese Arbeit auf eine bedeutende Rolle neuroinflammatorischer Prozesse in der Krankheitsprogression der Parkinsonerkrankung hin und soll dazu ermutigen Neuroinflammation durchaus intensiver in tg Tiermodellen zu untersuchen.}, subject = {Parkinson-Krankheit}, language = {de} } @phdthesis{Jovic2023, author = {Jovic, Sebastian}, title = {Die Healing Response Technik - langfristige Ergebnisse nach Anmeißelung des vorderen Kreuzbandes bei Partialrupturen}, doi = {10.25972/OPUS-29904}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-299040}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {Minimalinvasive Behandlungsmethoden von Partialrupturen des VKBs wurden seit den 1990 er Jahren diskutiert. Erstmalige Ergebnisse ver{\"o}ffentlichte Richard Steadman 2006 und stellte diese Methode als Alternative zur Kreuzbandersatzplastik vor (Steadman, 2006). Ziel dieser Arbeit war es zu untersuchen, ob die Healing Response Technik eine suffiziente, langfristige Therapieoption bei Partialrupturen des VKBs ist. Bei der Healing Response Technik wird arthroskopisch das verletzte VKB auf seine Stabilit{\"a}t untersucht und die Ruptur anschließend klassifiziert. Bei einer Partialruptur wird der proximale Ansatz des VKBs angemeißelt. Dadurch kommt es zu reaktiven Einblutungen, Einsprossen von mesenchymalen Stammzellen und Wachstumsfaktoren. Erfolgt eine suffiziente Vernarbung kann eine Stabilisierung des VKBs erzielt werden. Das Patientenkollektiv wurde in einem Zeitraum von 2005-2010 im Sporthopaedicum in Straubing mittels Healing Response Technik operativ versorgt. Einschlusskriterien waren ein stattgehabtes Trauma, eine kernspintomografisch beschriebene Ruptur oder Partialruptur des VKB, ein positiver Lachman-Test mit unsicherem oder vorhandenem Anschlag, ein maximal einfach positiver Pivot Shift Test, sowie eine subjektive Instabilit{\"a}t. Es wurden 163 Patienten eingeschlossen. Das initiale Nachuntersuchungsintervall betrug 4,5 Jahre. Die Langzeitergebnisse wurden mittels Mixed-Mode-Befragung mit einem Follow up von 11,4 Jahren erfasst. Insgesamt konnten so 138 Patienten nachuntersucht werden. Die Differenz der Roliometer Messung konnte von pr{\"a}operativ 10 ± 2 mm auf postoperativ 7 ± 2 mm signifikant verbessert werden. Der postoperative Lyshom Score betrug 90 ±12 Punkte. Der Tegner Activity Score lag bei 5 ± 2. Im Langzeitfollow-up betrug die Revisionsrate 13\% mit einem Revisionszeitpunkt von 51 ± 30 Monaten. 8\% der befragten Patienten erlitten eine Reruptur. 93\% der Patienten beurteilten ihr Kniegelenk subjektiv als stabil. Somit stellt die Healing Response Technik unter Ber{\"u}cksichtigung der Einschlusskriterien und der intraoperativen Befunderhebung eine suffiziente Therapieoption f{\"u}r Partialrupturen des VKBs dar.}, subject = {Kreuzband}, language = {de} } @phdthesis{Steininger2023, author = {Steininger, Michael}, title = {Deep Learning for Geospatial Environmental Regression}, doi = {10.25972/OPUS-31312}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-313121}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {Environmental issues have emerged especially since humans burned fossil fuels, which led to air pollution and climate change that harm the environment. These issues' substantial consequences evoked strong efforts towards assessing the state of our environment. Various environmental machine learning (ML) tasks aid these efforts. These tasks concern environmental data but are common ML tasks otherwise, i.e., datasets are split (training, validatition, test), hyperparameters are optimized on validation data, and test set metrics measure a model's generalizability. This work focuses on the following environmental ML tasks: Regarding air pollution, land use regression (LUR) estimates air pollutant concentrations at locations where no measurements are available based on measured locations and each location's land use (e.g., industry, streets). For LUR, this work uses data from London (modeled) and Zurich (measured). Concerning climate change, a common ML task is model output statistics (MOS), where a climate model's output for a study area is altered to better fit Earth observations and provide more accurate climate data. This work uses the regional climate model (RCM) REMO and Earth observations from the E-OBS dataset for MOS. Another task regarding climate is grain size distribution interpolation where soil properties at locations without measurements are estimated based on the few measured locations. This can provide climate models with soil information, that is important for hydrology. For this task, data from Lower Franconia is used. Such environmental ML tasks commonly have a number of properties: (i) geospatiality, i.e., their data refers to locations relative to the Earth's surface. (ii) The environmental variables to estimate or predict are usually continuous. (iii) Data can be imbalanced due to relatively rare extreme events (e.g., extreme precipitation). (iv) Multiple related potential target variables can be available per location, since measurement devices often contain different sensors. (v) Labels are spatially often only sparsely available since conducting measurements at all locations of interest is usually infeasible. These properties present challenges but also opportunities when designing ML methods for such tasks. In the past, environmental ML tasks have been tackled with conventional ML methods, such as linear regression or random forests (RFs). However, the field of ML has made tremendous leaps beyond these classic models through deep learning (DL). In DL, models use multiple layers of neurons, producing increasingly higher-level feature representations with growing layer depth. DL has made previously infeasible ML tasks feasible, improved the performance for many tasks in comparison to existing ML models significantly, and eliminated the need for manual feature engineering in some domains due to its ability to learn features from raw data. To harness these advantages for environmental domains it is promising to develop novel DL methods for environmental ML tasks. This thesis presents methods for dealing with special challenges and exploiting opportunities inherent to environmental ML tasks in conjunction with DL. To this end, the proposed methods explore the following techniques: (i) Convolutions as in convolutional neural networks (CNNs) to exploit reoccurring spatial patterns in geospatial data. (ii) Posing the problems as regression tasks to estimate the continuous variables. (iii) Density-based weighting to improve estimation performance for rare and extreme events. (iv) Multi-task learning to make use of multiple related target variables. (v) Semi-supervised learning to cope with label sparsity. Using these techniques, this thesis considers four research questions: (i) Can air pollution be estimated without manual feature engineering? This is answered positively by the introduction of the CNN-based LUR model MapLUR as well as the off-the-shelf LUR solution OpenLUR. (ii) Can colocated pollution data improve spatial air pollution models? Multi-task learning for LUR is developed for this, showing potential for improvements with colocated data. (iii) Can DL models improve the quality of climate model outputs? The proposed DL climate MOS architecture ConvMOS demonstrates this. Additionally, semi-supervised training of multilayer perceptrons (MLPs) for grain size distribution interpolation is presented, which can provide improved input data. (iv) Can DL models be taught to better estimate climate extremes? To this end, density-based weighting for imbalanced regression (DenseLoss) is proposed and applied to the DL architecture ConvMOS, improving climate extremes estimation. These methods show how especially DL techniques can be developed for environmental ML tasks with their special characteristics in mind. This allows for better models than previously possible with conventional ML, leading to more accurate assessment and better understanding of the state of our environment.}, subject = {Deep learning}, language = {en} } @phdthesis{Eismann2023, author = {Eismann, Simon}, title = {Performance Engineering of Serverless Applications and Platforms}, doi = {10.25972/OPUS-30313}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-303134}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {Serverless computing is an emerging cloud computing paradigm that offers a highlevel application programming model with utilization-based billing. It enables the deployment of cloud applications without managing the underlying resources or worrying about other operational aspects. Function-as-a-Service (FaaS) platforms implement serverless computing by allowing developers to execute code on-demand in response to events with continuous scaling while having to pay only for the time used with sub-second metering. Cloud providers have further introduced many fully managed services for databases, messaging buses, and storage that also implement a serverless computing model. Applications composed of these fully managed services and FaaS functions are quickly gaining popularity in both industry and in academia. However, due to this rapid adoption, much information surrounding serverless computing is inconsistent and often outdated as the serverless paradigm evolves. This makes the performance engineering of serverless applications and platforms challenging, as there are many open questions, such as: What types of applications is serverless computing well suited for, and what are its limitations? How should serverless applications be designed, configured, and implemented? Which design decisions impact the performance properties of serverless platforms and how can they be optimized? These and many other open questions can be traced back to an inconsistent understanding of serverless applications and platforms, which could present a major roadblock in the adoption of serverless computing. In this thesis, we address the lack of performance knowledge surrounding serverless applications and platforms from multiple angles: we conduct empirical studies to further the understanding of serverless applications and platforms, we introduce automated optimization methods that simplify the operation of serverless applications, and we enable the analysis of design tradeoffs of serverless platforms by extending white-box performance modeling.}, subject = {Leistungsbewertung}, language = {en} } @phdthesis{Wagner2023, author = {Wagner, Jan Cetric}, title = {Maximalnetzplan zur reaktiven Steuerung von Produktionsabl{\"a}ufen}, isbn = {978-3-945459-43-0}, doi = {10.25972/OPUS-30545}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-305452}, school = {Universit{\"a}t W{\"u}rzburg}, pages = {182}, year = {2023}, abstract = {In produzierenden Unternehmen werden verschiedene Vorgehensweisen zur Planung, {\"U}berwachung und Steuerung von Produktionsabl{\"a}ufen eingesetzt. Einer dieser Methoden wird als Vorgangsknotennetzplantechnik bezeichnet. Die einzelnen Produktionsschritte werden als Knoten definiert und durch Pfeile miteinander verbunden. Die Pfeile stellen die Beziehungen der jeweiligen Vorg{\"a}nge zueinander und damit den Produktionsablauf dar. Diese Technik erlaubt den Anwendern einen umfassenden {\"U}berblick {\"u}ber die einzelnen Prozessrelationen. Zus{\"a}tzlich k{\"o}nnen mit ihr Vorgangszeiten und Produktfertigstellungszeiten ermittelt werden, wodurch eine ausf{\"u}hrliche Planung der Produktion erm{\"o}glicht wird. Ein Nachteil dieser Technik begr{\"u}ndet sich in der alleinigen Darstellung einer ausf{\"u}hrbaren Prozessabfolge. Im Falle eines St{\"o}rungseintritts mit der Folge eines nicht durchf{\"u}hrbaren Vorgangs muss von dem origin{\"a}ren Prozess abgewichen werden. Aufgrund dessen wird eine Neuplanung erforderlich. Es werden Alternativen f{\"u}r den gest{\"o}rten Vorgang ben{\"o}tigt, um eine Fortf{\"u}hrung des Prozesses ungeachtet der St{\"o}rung zu erreichen. Innerhalb dieser Arbeit wird daher eine Erweiterung der Vorgangsknotennetzplantechnik beschrieben, die es erlaubt, erg{\"a}nzend zu dem geplanten Soll-Prozess Alternativvorg{\"a}nge f{\"u}r einzelne Vorg{\"a}nge darzulegen. Diese Methode wird als Maximalnetzplan bezeichnet. Die Alternativen werden im Falle eines St{\"o}rungseintritts automatisch evaluiert und dem Anwender in priorisierter Reihenfolge pr{\"a}sentiert. Durch die Verwendung des Maximalnetzplans kann eine aufwendige Neuplanung vermieden werden. Als Anwendungsbeispiel dient ein Montageprozess, mithilfe dessen die Verwendbarkeit der Methode dargelegt wird. Weiterf{\"u}hrend zeigt eine zeitliche Analyse zufallsbedingter Maximalnetzpl{\"a}ne eine Begr{\"u}ndung zur Durchf{\"u}hrung von Alternativen und damit den Nutzen des Maximalnetzplans auf. Zus{\"a}tzlich sei angemerkt, dass innerhalb dieser Arbeit verwendete Begrifflichkeiten wie Anwender, Werker oder Mitarbeiter in maskuliner Schreibweise niedergeschrieben werden. Dieses ist ausschließlich der Einfachheit geschuldet und nicht dem Zweck der Diskriminierung anderer Geschlechter dienlich. Die verwendete Schreibweise soll alle Geschlechter ansprechen, ob m{\"a}nnlich, weiblich oder divers.}, subject = {Produktionsplanung}, language = {de} } @phdthesis{Tcakaev2023, author = {Tcakaev, Abdul-Vakhab}, title = {Soft X-ray Spectroscopic Study of Electronic and Magnetic Properties of Magnetic Topological Insulators}, doi = {10.25972/OPUS-30378}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-303786}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {After the discovery of three-dimensional topological insulators (TIs), such as tetradymite chalcogenides Bi\$_2\$Se\$_3\$, Bi\$_2\$Te\$_3\$ and Sb\$_2\$Te\$_3\$ - a new class of quantum materials characterized by their unique surface electronic properties - the solid state community got focused on topological states that are driven by strong electronic correlations and magnetism. An important material class is the magnetic TI (MTI) exhibiting the quantum anomalous Hall (QAH) effect, i.e. a dissipationless quantized edge-state transport in the absence of external magnetic field, originating from the interplay between ferromagnetism and a topologically non-trivial band structure. The unprecedented opportunities offered by these new exotic materials open a new avenue for the development of low-dissipation electronics, spintronics, and quantum computation. However, the major concern with QAH effect is its extremely low onset temperature, limiting its practical application. To resolve this problem, a comprehensive understanding of the microscopic origin of the underlying ferromagnetism is necessary. V- and Cr-doped (Bi,Sb)\$_2\$Te\$_3\$ are the two prototypical systems that have been widely studied as realizations of the QAH state. Finding microscopic differences between the strongly correlated V and Cr impurities would help finding a relevant model of ferromagnetic coupling and eventually provide better control of the QAH effect in these systems. Therefore, this thesis first focuses on the V- and Cr-doped (Bi,Sb)\$_2\$Te\$_3\$ systems, to better understand these differences. Exploiting the unique capabilities of x-ray absorption spectroscopy and magnetic circular dichroism (XAS/XMCD), combined with advanced modeling based on multiplet ligand-field theory (MLFT), we provide a detailed microscopic insight into the local electronic and magnetic properties of these systems and determine microscopic parameters crucial for the comparison with theoretical models, which include the \$d\$-shell filling, spin and orbital magnetic moments. We find a strongly covalent ground state, dominated by the superposition of one and two Te-ligand-hole configurations, with a negligible contribution from a purely ionic 3+ configuration. Our findings indicate the importance of the Te \$5p\$ states for the ferromagnetism in (Bi, Sb)\$_2\$Te\$_3\$ and favor magnetic coupling mechanisms involving \$pd\$-exchange. Using state-of-the-art density functional theory (DFT) calculations in combination with XMCD and resonant photoelectron spectroscopy (resPES), we reveal the important role of the \$3d\$ impurity states in mediating magnetic exchange coupling. Our calculations illustrate that the kind and strength of the exchange coupling varies with the impurity \$3d\$-shell occupation. We find a weakening of ferromagnetic properties upon the increase of doping concentration, as well as with the substitution of Bi at the Sb site. Finally, we qualitatively describe the origin of the induced magnetic moments at the Te and Sb sites in the host lattice and discuss their role in mediating a robust ferromagnetism based on a \$pd\$-exchange interaction scenario. Our findings reveal important clues to designing higher \$T_{\text{C}}\$ MTIs. Rare-earth ions typically exhibit larger magnetic moments than transition-metal ions and thus promise the opening of a wider exchange gap in the Dirac surface states of TIs, which is favorable for the realization of the high-temperature QAH effect. Therefore, we have further focused on Eu-doped Bi\$_2\$Te\$_3\$ and scrutinized whether the conditions for formation of a substantial gap in this system are present by combining spectroscopic and bulk characterization methods with theoretical calculations. For all studied Eu doping concentrations, our atomic multiplet analysis of the \$M_{4,5}\$ x-ray absorption and magnetic circular dichroism spectra reveals a Eu\$^{2+}\$ valence, unlike most other rare earth elements, and confirms a large magnetic moment. At temperatures below 10 K, bulk magnetometry indicates the onset of antiferromagnetic ordering. This is in good agreement with DFT results, which predict AFM interactions between the Eu impurities due to the direct overlap of the impurity wave functions. Our results support the notion of antiferromagnetism coexisting with topological surface states in rare-earth doped Bi\$_2\$Te\$_3\$ and corroborate the potential of such doping to result in an antiferromagnetic TI with exotic quantum properties. The doping with impurities introduces disorder detrimental for the QAH effect, which may be avoided in stoichiometric, well-ordered magnetic compounds. In the last part of the thesis we have investigated the recently discovered intrinsic magnetic TI (IMTI) MnBi\$_6\$Te\$_{10}\$, where we have uncovered robust ferromagnetism with \$T_{\text{C}} \approx 12\$ K and connected its origin to the Mn/Bi intermixing. Our measurements reveal a magnetically intact surface with a large moment, and with FM properties similar to the bulk, which makes MnBi\$_6\$Te\$_{10}\$ a promising candidate for the QAH effect at elevated temperatures. Moreover, using an advanced ab initio MLFT approach we have determined the ground-state properties of Mn and revealed a predominant contribution of the \$d^5\$ configuration to the ground state, resulting in a \$d\$-shell electron occupation \$n_d = 5.31\$ and a large magnetic moment, in excellent agreement with our DFT calculations and the bulk magnetometry data. Our results together with first principle calculations based on the DFT-GGA\$+U\$, performed by our collaborators, suggest that carefully engineered intermixing plays a crucial role in achieving a robust long-range FM order and therefore could be the key for achieving enhanced QAH effect properties. We expect our findings to aid better understanding of MTIs, which is essential to help increasing the temperature of the QAH effect, thus facilitating the realization of low-power electronics in the future.}, subject = {Topologischer Isolator}, language = {en} } @phdthesis{Huber2023, author = {Huber, Stephan}, title = {Proxemo: Documenting Observed Emotions in HCI}, doi = {10.25972/OPUS-30573}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-305730}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {For formative evaluations of user experience (UX) a variety of methods have been developed over the years. However, most techniques require the users to interact with the study as a secondary task. This active involvement in the evaluation is not inclusive of all users and potentially biases the experience currently being studied. Yet there is a lack of methods for situations in which the user has no spare cognitive resources. This condition occurs when 1) users' cognitive abilities are impaired (e.g., people with dementia) or 2) users are confronted with very demanding tasks (e.g., air traffic controllers). In this work we focus on emotions as a key component of UX and propose the new structured observation method Proxemo for formative UX evaluations. Proxemo allows qualified observers to document users' emotions by proxy in real time and then directly link them to triggers. Technically this is achieved by synchronising the timestamps of emotions documented by observers with a video recording of the interaction. In order to facilitate the documentation of observed emotions in highly diverse contexts we conceptualise and implement two separate versions of a documentation aid named Proxemo App. For formative UX evaluations of technology-supported reminiscence sessions with people with dementia, we create a smartwatch app to discreetly document emotions from the categories anger, general alertness, pleasure, wistfulness and pride. For formative UX evaluations of prototypical user interfaces with air traffic controllers we create a smartphone app to efficiently document emotions from the categories anger, boredom, surprise, stress and pride. Descriptive case studies in both application domains indicate the feasibility and utility of the method Proxemo and the appropriateness of the respectively adapted design of the Proxemo App. The third part of this work is a series of meta-evaluation studies to determine quality criteria of Proxemo. We evaluate Proxemo regarding its reliability, validity, thoroughness and effectiveness, and compare Proxemo's efficiency and the observers' experience to documentation with pen and paper. Proxemo is reliable, as well as more efficient, thorough and effective than handwritten notes and provides a better UX to observers. Proxemo compares well with existing methods where benchmarks are available. With Proxemo we contribute a validated structured observation method that has shown to meet requirements formative UX evaluations in the extreme contexts of users with cognitive impairments or high task demands. Proxemo is agnostic regarding researchers' theoretical approaches and unites reductionist and holistic perspectives within one method. Future work should explore the applicability of Proxemo for further domains and extend the list of audited quality criteria to include, for instance, downstream utility. With respect to basic research we strive to better understand the sources leading observers to empathic judgments and propose reminisce and older adults as model environment for investigating mixed emotions.}, subject = {Gef{\"u}hl}, language = {en} } @article{ThieleRichterHilger2023, author = {Thiele, Jonas A. and Richter, Aylin and Hilger, Kirsten}, title = {Multimodal brain signal complexity predicts human intelligence}, series = {eNeuro}, volume = {10}, journal = {eNeuro}, number = {2}, doi = {10.1523/ENEURO.0345-22.2022}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312949}, year = {2023}, abstract = {Spontaneous brain activity builds the foundation for human cognitive processing during external demands. Neuroimaging studies based on functional magnetic resonance imaging (fMRI) identified specific characteristics of spontaneous (intrinsic) brain dynamics to be associated with individual differences in general cognitive ability, i.e., intelligence. However, fMRI research is inherently limited by low temporal resolution, thus, preventing conclusions about neural fluctuations within the range of milliseconds. Here, we used resting-state electroencephalographical (EEG) recordings from 144 healthy adults to test whether individual differences in intelligence (Raven's Advanced Progressive Matrices scores) can be predicted from the complexity of temporally highly resolved intrinsic brain signals. We compared different operationalizations of brain signal complexity (multiscale entropy, Shannon entropy, Fuzzy entropy, and specific characteristics of microstates) regarding their relation to intelligence. The results indicate that associations between brain signal complexity measures and intelligence are of small effect sizes (r ∼ 0.20) and vary across different spatial and temporal scales. Specifically, higher intelligence scores were associated with lower complexity in local aspects of neural processing, and less activity in task-negative brain regions belonging to the default-mode network. Finally, we combined multiple measures of brain signal complexity to show that individual intelligence scores can be significantly predicted with a multimodal model within the sample (10-fold cross-validation) as well as in an independent sample (external replication, N = 57). In sum, our results highlight the temporal and spatial dependency of associations between intelligence and intrinsic brain dynamics, proposing multimodal approaches as promising means for future neuroscientific research on complex human traits.}, language = {en} } @phdthesis{Mitschke2023, author = {Mitschke, Vanessa}, title = {Facing Enemies. Modulation of Revenge Interactions based on Opponent State Indicators of Suffering}, doi = {10.25972/OPUS-29938}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-299389}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {Research on revenge often treats vengeful acts as singular one-way experiences, an approach which fails to account for the social nature and functions of revenge. This dissertation aims to integrate emotional punishment reactions into dynamic revenge sequences to investigate the affective and cognitive consequences of revenge within a social interaction. Exacting revenge can evoke intense affective consequences, from feelings of guilt to the genuine enjoyment of the suffering of others. In Chapter 2, affective responses towards suffering opponents and the regulation of aggression based on the appraisal of distinct suffering indicators were investigated. Results indicate that the observation of opponent pain evokes positive affect (measured via facial muscle contractions during the observation), which is followed by a downregulation of subsequent punishment. Both, positive affective reactions and the downregulation of punishment, were only observed following pain and not sadness expressions. Empathic distress, indexed by negative affective reactions, was only present following the observation of pain in non-provoking opponents. Showcasing the modulation of empathy related processes due to provocation and competition. In Chapter 3, a significant escalation of punishment, when being confronted with Schadenfreude, was observed. Results are interpreted as supporting the assumption that opponent monitoring processes inform subsequent action selection. The observation of opponent smiles led to imitation behavior (facial mimicry), which was partially attenuated due to previous provocation. The different functions of smile mimicry in the context of the aggressive competitive setting are discussed as containing simulation aspects (to aid in opponent understanding) and as a potential mirroring of dominance gestures, to avoid submission. In an additional series of studies, which are presented in Chapter 4, changes in memory of opponent faces following vengeful encounters were measured. Based on provocation, and punishment outcomes (pain \& anger), face memory was distorted, resulting in more positive representations of opponents that expressed pain. These results are discussed as evidence of the impact of outcome appraisals in the formation of opponent representations and are theorized to aid empathy avoidance in future interactions. The comparison of desired and observed opponent states, is theorized to result in appraisals of the punishment outcomes, which evoke affective states, inform the action selection of subsequent punishments, and are integrated into the representation of the opponent in memory. Overall, the results indicate that suffering cues that are congruent with the chosen punishment action are appraised as positive, evoking an increase in positive affect. The emergence of positive affect during the observation of successful aggressive actions supports recent theories about the chronification of aggressive behavior based on reinforcement learning. To allow positive affect to emerge, affective empathic responses, such as distress, are theorized to be suppressed to facilitate the goal attainment process. The suffering of the opponent constitutes the proximate goal during revenge taking, which highlights the importance of a theoretical differentiation of proximate and ultimate goals in revenge to allow for a deeper understanding of the underlying motives of complex revenge behavior.}, subject = {Aggression}, language = {en} } @article{NollGrossShoyamaetal.2023, author = {Noll, Niklas and Groß, Tobias and Shoyama, Kazutaka and Beuerle, Florian and W{\"u}rthner, Frank}, title = {Folding-Induced Promotion of Proton-Coupled Electron Transfers via Proximal Base for Light-Driven Water Oxidation}, series = {Angewandte Chemie International Edition}, volume = {62}, journal = {Angewandte Chemie International Edition}, number = {7}, doi = {10.1002/anie.202217745}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312020}, year = {2023}, abstract = {Proton-coupled electron-transfer (PCET) processes play a key role in biocatalytic energy conversion and storage, for example, photosynthesis or nitrogen fixation. Here, we report a series of bipyridine-containing di- to tetranuclear Ru(bda) macrocycles 2 C-4 C (bda: 2,2′-bipyridine-6,6′-dicarboxylate) to promote O-O bond formation. In photocatalytic water oxidation under neutral conditions, all complexes 2 C-4 C prevail in a folded conformation that support the water nucleophilic attack (WNA) pathway with remarkable turnover frequencies of up to 15.5 s\(^{-1}\) per Ru unit respectively. Single-crystal X-ray analysis revealed an increased tendency for intramolecular π-π stacking and preorganization of the proximal bases close to the active centers for the larger macrocycles. H/D kinetic isotope effect studies and electrochemical data demonstrate the key role of the proximal bipyridines as proton acceptors in lowering the activation barrier for the crucial nucleophilic attack of H\(_{2}\)O in the WNA mechanism.}, language = {en} } @article{PreitschopfSturmStroganovaetal.2023, author = {Preitschopf, Tobias and Sturm, Floriane and Stroganova, Iuliia and Lemmens, Alexander K. and Rijs, Anouk M. and Fischer, Ingo}, title = {IR/UV Double Resonance Study of the 2-Phenylallyl Radical and its Pyrolysis Products}, series = {Chemistry - A European Journal}, volume = {29}, journal = {Chemistry - A European Journal}, number = {13}, doi = {10.1002/chem.202202943}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312338}, year = {2023}, abstract = {Isolated 2-phenylallyl radicals (2-PA), generated by pyrolysis from a nitrite precursor, have been investigated by IR/UV ion dip spectroscopy using free electron laser radiation. 2-PA is a resonance-stabilized radical that is considered to be involved in the formation of polycyclic aromatic hydrocarbons (PAH) in combustion, but also in interstellar space. The radical is identified based on its gas-phase IR spectrum. Furthermore, a number of bimolecular reaction products are identified, showing that the self-reaction as well as reactions with unimolecular decomposition products of 2-PA form several PAH efficiently. Possible mechanisms are discussed and the chemistry of 2-PA is compared with the one of the related 2-methylallyl and phenylpropargyl radicals.}, language = {en} } @phdthesis{Diebold2023, author = {Diebold, Mathias}, title = {Virtuelles Screening und Entwicklung selektiver Liganden des Aurora-A - MYCN Komplexes und computergest{\"u}tzte Methoden zur Analyse und Design von PROTACs}, doi = {10.25972/OPUS-31759}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-317594}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {Die Interaktion des onkogenen Transkriptionsfaktors MYCN mit der Ser/Thr Kinase Aurora-A verhindert dessen Abbau {\"u}ber das Ubiquitin Proteasomsystem indem die Rekrutierung des SCF FbxW7 Komplexes verhindert wird. Die Kinase nimmt mit der Bindung an MYCN eine aktive Konformation ein und erh{\"a}lt somit die F{\"a}higkeit zur Kinaseaktivit{\"a}t ohne die sonst notwendige Phosphorylierung von Thr288 oder die Anwesenheit eines Aktivators wie TPX2. Da hohe MYCN Konzentrationen Tumore wie Neuroblastome antreiben, ist die St{\"o}rung der Komplexbildung mit Aurora-A eine valide Strategie zur Entwicklung von Chemotherapeutika. Einige Inhibitoren von Aurora-A wie Alisertib (MLN8237) sind in der Lage, eine Konformations{\"a}nderung in der Kinase zu verursachen, die mit der Bindung von MYCN inkompatibel ist und auf diese Weise den Abbau des Transkriptionsfaktors induziert. Da Aurora-A wichtige Funktionen in der Mitose {\"u}bernimmt, k{\"o}nnte eine direkte Adressierung des Komplexes anstelle einer systemischen Inhibition der Kinase vielversprechender sein. Ziel des Projektes war die Identifizierung von Molek{\"u}len, die selektiv an das Interface des Aurora-A - MYCN Komplexes binden und weiter optimiert werden k{\"o}nnen, um einen gezielten Abbau des Transkriptionsfaktors {\"u}ber einen PROTAC Ansatz zu erm{\"o}glichen. Virtuelle Screenings und molekulardynamische Simulationen wurden durchgef{\"u}hrt, um kommerziell erh{\"a}ltliche Verbindungen zu identifizieren, welche mit einer Bindetasche des Komplexes interagieren, die nur zustande kommt, wenn beide Proteine miteinander interagieren. Aus einem ersten Set von zehn potentiellen Liganden wurde f{\"u}r vier eine selektive Interaktion mit dem Protein - Protein Komplex gegen{\"u}ber Aurora-A oder MYCN alleine in STD-NMR Experimenten best{\"a}tigt. Zwei der Hits besaßen ein identisches Grundger{\"u}st und wurden als Ausganspunkt f{\"u}r die Optimierung zu potenteren Liganden genutzt. Das Ger{\"u}st wurde fragmentweise vergr{\"o}ßert und in Richtung besserer in-silico Ergebnisse und Funktionalisierung zur Anbringung von E3-Ligase-Liganden optimiert. Neun dieser Liganden der zweiten Generation wurden synthetisiert. Um quantitative Bindungsdaten zu erhalten, wurde ein kovalent verkn{\"u}pftes Aurora-A - MYCN Konstrukt entworfen. Die strukturelle und funktionale Integrit{\"a}t wurde in STD-NMR und BLI Experimenten mit bekannten Aurora-A Inhibitoren best{\"a}tigt, sowie in NMR-basierten ATPase Assays. Zus{\"a}tzlich konnte die Kristallstruktur des Konstrukts gel{\"o}st und damit die Validit{\"a}t des Designs best{\"a}tigt werden. Quantitative Messungen der synthetisierten Molek{\"u}le identifizierten HD19S als Hit mit einer zehnfach h{\"o}heren Affinit{\"a}t f{\"u}r das Aurora-A - MYCN Konstrukt im Vergleich zu der Kinase allein. Zus{\"a}tzlich wurden in-silico Untersuchungen zu PROTACs der Aurora-A Kinase durchgef{\"u}hrt. Interaktionen zwischen Aurora-A, der E3-Ligase Cereblon und den Liganden wurden modelliert und f{\"u}r die Erkl{\"a}rung unterschiedlicher Aktivit{\"a}ten der eingesetzten PROTACs verwendet. Zudem zeigte das aktivste PROTAC eine hohe Selektivit{\"a}t f{\"u}r Aurora-A gegen{\"u}ber Aurora-B, obwohl die verwendete Erkennungseinheit (Alisertib) an beide Aurora-Proteine bindet. Dieser Umstand konnte durch energetische Analysen von molekulardynamischen Simulationen der tern{\"a}ren Komplexe erkl{\"a}rt werden. Optimierungsm{\"o}glichkeiten f{\"u}r eine effizientere Degradation von Aurora-A durch die PROTACs wurden basierend auf modifizierten Erkennungseinheiten und verbesserten Linkern untersucht.}, subject = {Arzneimitteldesign}, language = {de} } @misc{LangePohlmannRother2023, author = {Lange, Sarah D{\´e}sir{\´e}e and Pohlmann-Rother, Sanna}, title = {Skalenhandbuch zur BLUME I-FB Fragebogenstudie zu den {\"U}berzeugungen von Grundschullehrkr{\"a}ften zum Umgang mit Mehrsprachigkeit}, doi = {10.25972/OPUS-30611}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-306110}, year = {2023}, abstract = {Ziel der Studie ist es, berufsbezogene {\"U}berzeugungen von Grundschullehrkr{\"a}ften zum Umgang mit Mehrsprachigkeit im unterrichtlichen Kontext anhand einer online-Fragebogenstudie zu erfassen. Das Thema Mehrsprachigkeit ist von hoher und wachsender p{\"a}dagogischer und gesellschaftlicher Relevanz, da Lehrkr{\"a}fte t{\"a}glich sprachlicher Heterogenit{\"a}t begegnen. Im Unterricht stehen sie vor der Aufgabe, innerhalb eines einsprachig gepr{\"a}gten institutionellen Rahmens eine Sprachbildung f{\"u}r alle Kinder zu erm{\"o}glichen und dabei dem grundschulp{\"a}dagogischen Anspruch nachzukommen, die sprachlichen Ausgangslagen der Sch{\"u}lerinnen und Sch{\"u}ler wertsch{\"a}tzend und reflexiv einzubeziehen. Angesichts dieser Herausforderungen wird mit dem Vorhaben auf die folgenden Forschungsdesiderata reagiert: Der Umgang mit Mehrsprachigkeit - insbesondere in Bezug auf berufst{\"a}tige Grundschullehrkr{\"a}fte und deren {\"U}berzeugungen - wurde bisher nicht umfassend untersucht. Methodisch leistet die Studie einen Beitrag zu einer differenzierten und umf{\"a}nglicheren quantitativen Operationalisierung berufsbezogener {\"U}berzeugungen von Lehrkr{\"a}ften.}, subject = {Mehrsprachigkeit}, language = {de} } @phdthesis{Dippell2023, author = {Dippell, Marvin}, title = {Constraint Reduction in Algebra, Geometry and Deformation Theory}, doi = {10.25972/OPUS-30167}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-301670}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {To study coisotropic reduction in the context of deformation quantization we introduce constraint manifolds and constraint algebras as the basic objects encoding the additional information needed to define a reduction. General properties of various categories of constraint objects and their compatiblity with reduction are examined. A constraint Serre-Swan theorem, identifying constraint vector bundles with certain finitely generated projective constraint modules, as well as a constraint symbol calculus are proved. After developing the general deformation theory of constraint algebras, including constraint Hochschild cohomology and constraint differential graded Lie algebras, the second constraint Hochschild cohomology for the constraint algebra of functions on a constraint flat space is computed.}, subject = {Differentialgeometrie}, language = {en} } @phdthesis{Wendlinger2023, author = {Wendlinger, Simone Alice}, title = {Function of Peripheral Blood Eosinophils in Melanoma}, publisher = {Cancers (Basel)}, doi = {10.25972/OPUS-30119}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-301194}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {Despite accounting for only a small proportion of all skin cancers, malignant melanoma displays a serious health risk with increasing incidence and high mortality rate. Fortunately, advances in the treatment of malignant melanoma now prolong survival and enhance response and treatment efficacy. Established biomarkers help evaluate disease progression and facilitate choosing appropriate and individual treatment options. However, the need for easily accessible and reliable biomarkers is rising to predict patient-specific clinical outcome. Eosinophil infiltration into the tumor and high peripheral eosinophil counts prior and during treatment have been associated with better response in patients for various cancer entities, including melanoma. An analysis of a heterogeneous study cohort reported high serum ECP levels in non-responders. Hence, eosinophil frequency and serum ECP as a soluble eosinophil-secreted mediator were suggested as prognostic biomarkers in melanoma. We examined whether melanoma patients treated with first-line targeted therapy could also benefit from the effects of eosinophils. In total, 243 blood and serum samples from patients with advanced melanoma were prospectively and retrospectively collected before and after drug initiation. To link eosinophil function to improved clinical outcome, soluble serum markers and peripheral blood counts were used for correlative studies using a homogeneous study cohort. In addition, functional and phenotypical characterizations provided insights into the expression profile and activity of freshly isolated eosinophils, including comparisons between patients and healthy donors. Our data showed a significant correlation between high pre-treatment blood eosinophil counts and improved response to targeted therapy and by trend to combinatorial immunotherapy in patients with metastatic melanoma. In accordance with previous studies our results links eosinophil blood counts to better response in melanoma patients. High pre-treatment ECP serum concentration correlated with response to immunotherapy but not to targeted therapy. Eosinophils from healthy donors and patients showed functional and phenotypical similarities. Functional assays revealed a strong cytotoxic potential of blood eosinophils towards melanoma cells in vitro, inducing apoptosis and necrosis. In addition, in vitro cytotoxicity was an active process of peripheral eosinophils and melanoma cells with bidirectional features and required close cell-cell interaction. The extent of cytotoxicity was dose-dependent and showed susceptibility to changes in physical factors like adherence. Importantly, we provide evidence of an additive tumoricidal function of eosinophils and combinatorial targeted therapy in vitro. In summary, we give valuable insights into the complex and treatment-dependent role of eosinophils in melanoma. As a result, our data support the suggestion of eosinophils and their secreted mediators as potential prognostic biomarkers. It will take additional studies to examine the molecular mechanisms that underlie our findings.}, subject = {Melanom}, language = {en} } @phdthesis{Ramge2023, author = {Ramge, Vanessa Magali}, title = {Untersuchung der Genotoxizit{\"a}t von Pyrrolizidinalkaloiden \(in\) \(vitro\) am Beispiel von Riddelliin und Lasiocarpin}, doi = {10.25972/OPUS-31979}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-319793}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {PA sind nat{\"u}rliche Pflanzeninhaltsstoffe, die wegen ihres genotoxischen Potentials bekannt sind. Nach Applikation mikromolarer Konzentrationen k{\"o}nnen bei in vitro Untersuchungen von Leberzellen chromosomale Sch{\"a}den detektiert werden. PA stehen im Verdacht nach Aufnahme bei Menschen hepatotoxische und kanzerogene Wirkungen nach sich zu ziehen. In dieser Studie wurden Lasiocarpin und Riddelliin an der humanen Leberkarzinomzelllinie Huh6 auf Genotoxizit{\"a}t getestet. Die ausgew{\"a}hlten Methoden waren der MK-Test, der alkalische und der FPG Comet Assay und die γ-H2AX-F{\"a}rbung. In den Vorversuchen mit BaP und CPA wurde gezeigt, dass die Zellen durch Prodrugs genotoxisch gesch{\"a}digt werden. Zusammenfassend kann gesagt werden, dass Riddelliin und Lasiocarpin im MK-Test eine dosisabh{\"a}ngige, genotoxische Wirkung auf die Huh6 Zellen haben. Der Einfluss von Lasiocarpin war im MK-Test im Vergleich zum Einfluss von Riddelliin bei geringerer Konzentration detektierbar. Nach einer simultanen Behandlung der Huh6 Zellen mit verschiedenen PA kann konkludiert werden, dass keine signifikante Erh{\"o}hung an DNA-Sch{\"a}den im Vergleich zu Behandlungen mit den Einzelsubstanzen festgestellt werden konnte, was m{\"o}glicherweise auf eine Ersch{\"o}pfung der metabolischen Kapazit{\"a}t der Zellen zur{\"u}ckzuf{\"u}hren ist. Insgesamt ist es den Ergebnissen zufolge wahrscheinlich, dass die Entstehung von Crosslinks durch Lasiocarpin und Riddelliin eher eine Rolle in der Genotoxizit{\"a}tsinduktion auf Huh6 Zellen spielen als oxidativer Stress. Doppelstrangbr{\"u}che konnten nicht als sicherer Induktor von Genotoxizit{\"a}t identifiziert werden. Die Besonderheiten der Stoffwechselwege einzelner PA und die Spezifizierung einzelner, f{\"u}r die Metabolisierung relevanter Enzyme sollte in Zukunft Gegenstand der Forschung sein, um die kumulativen Wirkungen von PA besser nachzuvollziehen und die f{\"u}r den Menschen entstehenden Risiken durch die Aufnahme von PA konkretisieren zu k{\"o}nnen.}, subject = {Pyrrolizidinalkaloide}, language = {de} } @article{GrueneLondiGillettetal.2023, author = {Gr{\"u}ne, Jeannine and Londi, Giacomo and Gillett, Alexander J. and St{\"a}hly, Basil and Lulei, Sebastian and Kotova, Maria and Olivier, Yoann and Dyakonov, Vladimir and Sperlich, Andreas}, title = {Triplet Excitons and Associated Efficiency-Limiting Pathways in Organic Solar Cell Blends Based on (Non-) Halogenated PBDB-T and Y-Series}, series = {Advanced Functional Materials}, volume = {33}, journal = {Advanced Functional Materials}, number = {12}, doi = {10.1002/adfm.202212640}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312164}, year = {2023}, abstract = {The great progress in organic photovoltaics (OPV) over the past few years has been largely achieved by the development of non-fullerene acceptors (NFAs), with power conversion efficiencies now approaching 20\%. To further improve device performance, loss mechanisms must be identified and minimized. Triplet states are known to adversely affect device performance, since they can form energetically trapped excitons on low-lying states that are responsible for non-radiative losses or even device degradation. Halogenation of OPV materials has long been employed to tailor energy levels and to enhance open circuit voltage. Yet, the influence on recombination to triplet excitons has been largely unexplored. Using the complementary spin-sensitive methods of photoluminescence detected magnetic resonance and transient electron paramagnetic resonance corroborated by transient absorption and quantum-chemical calculations, exciton pathways in OPV blends are unravelled employing the polymer donors PBDB-T, PM6, and PM7 together with NFAs Y6 and Y7. All blends reveal triplet excitons on the NFA populated via non-geminate hole back transfer and, in blends with halogenated donors, also by spin-orbit coupling driven intersystem crossing. Identifying these triplet formation pathways in all tested solar cell absorber films highlights the untapped potential for improved charge generation to further increase plateauing OPV efficiencies.}, language = {en} } @techreport{Stanka2023, type = {Working Paper}, author = {Stanka, Hans}, title = {Autonomy Reconsidered: Conceptualising a Phenomenon on the Verges of Self-Government and Self-Governance}, issn = {2698-2684}, doi = {10.25972/OPUS-32077}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-320771}, pages = {28}, year = {2023}, abstract = {For decades autonomy has been utilised as a concept in various social sciences, like sociology, political science, law and philosophy. Certain concepts of autonomy have always reflected the needs of the respective disciplines that made use of the term, but also ever infringed on the interpretation of autonomy in other disciplines. Most notably, conceptualisations of international and constitutional law have found their way into bordering sciences, like political science. The result: a legal positivist view prevailing in the conceptualisations of autonomy within political and administrative sciences. As this working paper points out, this perspective does not do justice to the complex phenomenon autonomy is or may be in social and political reality. Hence, the paper argues for a differentiated concept of autonomy, splitting it into autonomy claims, actors, process, rights and powers, regimes, and their institutions. The empirical world suggests a salience of formally and informally lived types of autonomy, especially in Latin America, due to the region's indigenous population often living outside of, or within the limited reach of the state. Therefore, the paper aims to incorporate the dimension of informality - lacking in previous legal positivist approaches. Autonomy regimes could be entrenched in international, constitutional, or secondary law, or they could be tolerated by the state or seized by autonomy claimants by force. From a theoretical or conceptual perspective, the dimension of (in)formality facilitates the incorporation of autonomy into the discussion on governance and government, mostly on the local or regional level. Thus, the paper establishes autonomy regimes as a concept located at the verges of (self-)government and (self-)governance.}, subject = {Staat}, language = {en} } @article{Kestler2023, author = {Kestler, Thomas}, title = {Exploring the Relationship Between Social Movement Organizations and the State in Latin America}, series = {Politics and Governance}, volume = {11}, journal = {Politics and Governance}, number = {2}, issn = {2183-2463}, doi = {10.17645/pag.v11i2.6383}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-321152}, pages = {346-356}, year = {2023}, abstract = {Under conditions of weak statehood, societal actors are supposed to assume functions usually attributed to the state. Social self-organization is expected to emerge when the state leaves important social problems unattended. Should social self-organization, therefore, be regarded as a reaction to state weakness and as compensation for state failure in the provision of basic services? Does society organize itself on its own in areas where the state is absent or ineffective? By the example of two Latin American social movements, this article aims to show that social self-organization—at least on a larger scale—is not independent of the state, but rather a result of a dynamic interaction with the state. The two examples this article explores are the middle-class Venezuelan neighborhood movement and the Argentine piquetero movement of unemployed workers. Both movements emerged as reactions to the state's failure and retreat from essential social functions and both developed into extensive and influential social actors. For that reason, they can be regarded as crucial cases for observing the patterns and conditions of social self-organization and autonomous collective action within the specific Latin American context. Despite their different backgrounds and social bases, the two cases reveal remarkable similarities. They show that the emergence and development of self-organized social groups cannot be conceived simply as a reaction to state weakness, but rather should be viewed as a dynamic interaction with the state.}, language = {en} } @misc{Schilling2023, type = {Master Thesis}, author = {Schilling, Sheila Elisabeth}, title = {Schaf-Woll-Geschichten. Multispezies-Perspektiven auf die Beziehung von Schafen und Menschen}, doi = {10.25972/OPUS-31959}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-319595}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {Schafe leben seit einigen Jahrtausenden mit Menschen zusammen und mit ihnen durchwandert ihre Wolle unsere Kulturen und Gesellschaften. Ausgangspunkt der vorliegenden Arbeit ist der gegenw{\"a}rtig geringe monet{\"a}re Wert von Schafwolle, der in den letzten dreißig Jahren in Deutschland stark gesunken ist. Basierend auf ethnografischen Methoden der Feldforschung, teilnehmende Beobachtung und Interviews, verfolgt die vorliegende Arbeit Spuren von Schafwolle und fragt dabei nach den Ber{\"u}hrungs- und Kontaktpunkten, die im Alltag zwischen Schafen, Menschen und Wolle entstehen. Menschen, die mit Schafen leben, werfen verschiedene Perspektiven auf die sogenannte Nutztierhaltung sowie auf l{\"a}ndliches Wirtschaften und Leben. Schafe und Schafwolle werden hier als Miterz{\"a}hlende und Mitgestaltende im Prozess der Entstehung von Schaf-Woll-Geschichten betrachtet. Besonders die Perspektiven auf Schafwolle regen an, tierliche Materialit{\"a}ten im Allgemeinen neu zu denken und zu reflektieren. So l{\"a}dt die vorliegende Arbeit dazu ein, Menschen, Tiere und Materialit{\"a}ten st{\"a}rker in den Wissensgenerierungsprozess zu integrieren sowie nach dem besonderen Wissen zu suchen, das eben jene mehr-als-menschliche Akteur*innen mit uns teilen.}, subject = {Europ{\"a}ische Ethnologie}, language = {de} }