3,837 research outputs found

    A Unifying Theory for Graph Transformation

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    The field of graph transformation studies the rule-based transformation of graphs. An important branch is the algebraic graph transformation tradition, in which approaches are defined and studied using the language of category theory. Most algebraic graph transformation approaches (such as DPO, SPO, SqPO, and AGREE) are opinionated about the local contexts that are allowed around matches for rules, and about how replacement in context should work exactly. The approaches also differ considerably in their underlying formal theories and their general expressiveness (e.g., not all frameworks allow duplication). This dissertation proposes an expressive algebraic graph transformation approach, called PBPO+, which is an adaptation of PBPO by Corradini et al. The central contribution is a proof that PBPO+ subsumes (under mild restrictions) DPO, SqPO, AGREE, and PBPO in the important categorical setting of quasitoposes. This result allows for a more unified study of graph transformation metatheory, methods, and tools. A concrete example of this is found in the second major contribution of this dissertation: a graph transformation termination method for PBPO+, based on decreasing interpretations, and defined for general categories. By applying the proposed encodings into PBPO+, this method can also be applied for DPO, SqPO, AGREE, and PBPO

    Modeling and Analysis of ETC Control System with Colored Petri Net and Dynamic Slicing

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    Nowadays, an Electronic Toll Collection (ETC) control system in highways has been widely adopted to smoothen traffic flow. However, as it is a complex business interaction system, there are inevitably flaws in its control logic process, such as the problem of vehicle fee evasion. Even we find that there are more than one way for vehicles to evade fees. This shows that it is difficult to ensure the completeness of its design. Therefore, it is necessary to adopt a novel formal method to model and analyze its design, detect flaws and modify it. In this paper, a Colored Petri net (CPN) is introduced to establish its model. To analyze and modify the system model more efficiently, a dynamic slicing method of CPN is proposed. First, a static slice is obtained from the static slicing criterion by backtracking. Second, considering all binding elements that can be enabled under the initial marking, a forward slice is obtained from the dynamic slicing criterion by traversing. Third, the dynamic slicing of CPN is obtained by taking the intersection of both slices. The proposed dynamic slicing method of CPN can be used to formalize and verify the behavior properties of an ETC control system, and the flaws can be detected effectively. As a case study, the flaw about a vehicle that has not completed the payment following the previous vehicle to pass the railing is detected by the proposed method

    Information actors beyond modernity and coloniality in times of climate change:A comparative design ethnography on the making of monitors for sustainable futures in Curaçao and Amsterdam, between 2019-2022

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    In his dissertation, Mr. Goilo developed a cutting-edge theoretical framework for an Anthropology of Information. This study compares information in the context of modernity in Amsterdam and coloniality in Curaçao through the making process of monitors and develops five ways to understand how information can act towards sustainable futures. The research also discusses how the two contexts, that is modernity and coloniality, have been in informational symbiosis for centuries which is producing negative informational side effects within the age of the Anthropocene. By exploring the modernity-coloniality symbiosis of information, the author explains how scholars, policymakers, and data-analysts can act through historical and structural roots of contemporary global inequities related to the production and distribution of information. Ultimately, the five theses propose conditions towards the collective production of knowledge towards a more sustainable planet

    Natural and Technological Hazards in Urban Areas

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    Natural hazard events and technological accidents are separate causes of environmental impacts. Natural hazards are physical phenomena active in geological times, whereas technological hazards result from actions or facilities created by humans. In our time, combined natural and man-made hazards have been induced. Overpopulation and urban development in areas prone to natural hazards increase the impact of natural disasters worldwide. Additionally, urban areas are frequently characterized by intense industrial activity and rapid, poorly planned growth that threatens the environment and degrades the quality of life. Therefore, proper urban planning is crucial to minimize fatalities and reduce the environmental and economic impacts that accompany both natural and technological hazardous events

    LIPIcs, Volume 251, ITCS 2023, Complete Volume

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    LIPIcs, Volume 251, ITCS 2023, Complete Volum

    Undergraduate Catalog of Studies, 2022-2023

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    Deteção de intrusÔes de rede baseada em anomalias

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    Dissertação de mestrado integrado em EletrĂłnica Industrial e ComputadoresAo longo dos Ășltimos anos, a segurança de hardware e software tornou-se uma grande preocupação. À medida que a complexidade dos sistemas aumenta, as suas vulnerabilidades a sofisticadas tĂ©cnicas de ataque tĂȘm proporcionalmente escalado. Frequentemente o problema reside na heterogenidade de dispositivos conectados ao veĂ­culo, tornando difĂ­cil a convergĂȘncia da monitorização de todos os protocolos num Ășnico produto de segurança. Por esse motivo, o mercado requer ferramentas mais avançadas para a monitorizar ambientes crĂ­ticos Ă  vida humana, tais como os nossos automĂłveis. Considerando que existem vĂĄrias formas de interagir com os sistemas de entretenimento do automĂłvel como o Bluetooth, o Wi-fi ou CDs multimĂ©dia, a necessidade de auditar as suas interfaces tornou-se uma prioridade, uma vez que elas representam um sĂ©rio meio de aceeso Ă  rede interna do carro. Atualmente, os mecanismos de segurança de um carro focam-se na monitotização da rede CAN, deixando para trĂĄs as tecnologias referidas e nĂŁo contemplando os sistemas nĂŁo crĂ­ticos. Como exemplo disso, o Bluetooth traz desafios diferentes da rede CAN, uma vez que interage diretamente com o utilizador e estĂĄ exposto a ataques externos. Uma abordagem alternativa para tornar o automĂłvel num sistema mais robusto Ă© manter sob supervisĂŁo as comunicaçÔes que com este sĂŁo estabelecidas. Ao implementar uma detecção de intrusĂŁo baseada em anomalias, esta dissertação visa analisar o protocolo Bluetooth no sentido de identificar interaçÔes anormais que possam alertar para uma situação fora dos padrĂ”es de utilização. Em Ășltima anĂĄlise, este produto de software embebido incorpora uma grande margem de auto-aprendizagem, que Ă© vital para enfrentar quaisquer ameaças desconhecidas e aumentar os nĂ­veis de segurança globais. Ao longo deste documento, apresentamos o estudo do problema seguido de uma metodologia alternativa que implementa um algoritmo baseado numa LSTM para prever a sequĂȘncia de comandos HCI correspondentes a trĂĄfego Bluetooth normal. Os resultados mostram a forma como esta abordagem pode impactar a deteção de intrusĂ”es nestes ambientes ao demonstrar uma grande capacidade para identificar padrĂ”es anĂłmalos no conjunto de dados considerado.In the last few years, hardware and software security have become a major concern. As the systems’ complexity increases, its vulnerabilities to several sophisticated attack techniques have escalated likewise. Quite often, the problem lies in the heterogeneity of the devices connected to the vehicle, making it difficult to converge the monitoring systems of all existing protocols into one security product. Thereby, the market requires more refined tools to monitor life-risky environments such as personal vehicles. Considering that there are several ways to interact with the car’s infotainment system, such as Wi-fi, Bluetooth, or CD player, the need to audit these interfaces has become a priority as they represent a serious channel to reach the internal car network. Nowadays, security in car networks focuses on CAN bus monitoring, leaving behind the aforementioned technologies and not contemplating other non-critical systems. As an example of these concerns, Bluetooth brings different challenges compared to CAN as it interacts directly with the user, being exposed to external attacks. An alternative approach to converting modern vehicles and their set of computers into more robust systems is to keep track of established communications with them. By enforcing anomaly-based intrusion detection this dissertation aims to analyze the Bluetooth protocol to identify abnormal user interactions that may alert for a non conforming pattern. Ultimately, such embedded software product incorporates a self-learning edge, which is vital to face newly developed threats and increasing global security levels. Throughout this document, we present the study case followed by an alternative methodology that implements an LSTM based algorithm to predict a sequence of HCI commands corresponding to normal Bluetooth traffic. The results show how this approach can impact intrusion detection in such environments by expressing a high capability of identifying abnormal patterns in the considered data

    Medium Voltage Solid-State Transformer:An IEC60076-3 based design

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    Mathematical Modelling of Spread of Vector Borne Disease In Germany

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    Ziel dieser Doktorarbeit ist ein mathematisches Modell zu entwickeln, um eine mögliche Ausbreitung des West-Nil-Virus (WNV) in Deutschland zu simulieren und zu bewerten. Das entwickelte Werkzeug soll auch auf eine weitere, durch Zecken ĂŒbertragene Krankheit, dem Krim-Kongo-HĂ€morrhagischen Fieber (CCHFV) angewendet werden. Die durch den Klimawandel verursachte globalen ErwĂ€rmung unterstĂŒtzt auch die Verbreitung und Entwicklung verschiedener Vektorpopulationen. Dabei hat eine Temperaturerhöhung einen positiven Einfluss auf den Lebenszyklus des Vektors und die Zunahme der VektoraktivitĂ€t. In dieser Arbeit haben wir ein Differentialgleichungsmodell (ODE) entwickelt, um den Einfluss eines regelmĂ€ĂŸigen Eintrags von Infektionserregern auf die empfĂ€ngliche Population unter BerĂŒcksichtigung des Temperatureinflusses zu verstehen. Als Ergebnis haben wir einen analytischen Ausdruck der Basisreproduktionszahl und deren Wechselwirkung mit der Temperatur gefunden. Eine SensitivitĂ€tsanalyse zeigt, wie wichtig das VerhĂ€ltnis der anfĂ€lligen MĂŒcken zur lokalen Wirtspopulation ist. Als ein zentrales Ergebnis haben wir den zukĂŒnftigen Temperaturverlauf auf Basis der Modellergebnisse des IPCC in unser Modell integriert und Bedingungen gefunden, unter denen es zu einer dauerhaften Etablierung des West-Nil-Virus in Deutschland kommt. DarĂŒber hinaus haben wir die entwickelten mathematischen Modelle verwendet, um verschiedene Szenarien zu untersuchen, unter denen sich CCHFV möglicherweise in einer naiven Population etablieren kann, und wir haben verschiedene Kontrollszenarien mathematisch abgeleitet, um die Belastung von einer Infektion durch Zecken zu bewĂ€ltigen.The objective of this thesis is to develop the necessary mathematical model to assess the potential spread of West Nile Virus (WNV) in Germany and employ the developed tool to analyse another tick-borne disease Crimean- Congo Hemorrhagic Fever (CCHFV). Given the backdrop of global warming and the climate change, increasing temperature has benefitted the vector population. The increase in the temperature has a positive influence in the life cycle of the vector and the increase in its activities. In this thesis, we have developed an Ordinary Differential Equation (ODE) model system to understand the influence of the periodic introduction of infectious agents into the local susceptible population while taking account of influence of temperature. As results, we have found an analytic expression of the basic reproduction number and its interplay with the temperature. The sensitivity analysis shows us the importance of the ratio between the susceptible mosquitoes to the local host population. As a central result we have extrapolated the temperature trend under different IPCC conditions and found the condition under which the circulation of West Nile Virus will be permanent in Germany. Furthermore, we have utilised the developed mathematical models to examine different scenarios under which CCHFV can potentially establish in a naive population along with we mathematically derived different control scenarios to manage the burden of tick infection

    Rational development of stabilized cyclic disulfide redox probes and bioreductive prodrugs to target dithiol oxidoreductases

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    Countless biological processes allow cells to develop, survive, and proliferate. Among these, tightly balanced regulatory enzymatic pathways that can respond rapidly to external impacts maintain dynamic physiological homeostasis. More specifically, redox homeostasis broadly affects cellular metabolism and proliferation, with major contributions by thiol/disulfide oxidoreductase systems, in particular, the Thioredoxin Reductase Thioredoxin (TrxR/Trx) and the Glutathione Reductase-Glutathione-Glutaredoxin (GR/GSH/Grx) systems. These cascades drive vital cellular functions in many ways through signaling, regulating other proteins' activity by redox switches, and by stoichiometric reductant transfers in metabolism and antioxidant systems. Increasing evidence argues that there is a persistent alteration of the redox environment in certain pathological states, such as cancer, that heavily involve the Trx system: upregulation and/or overactivity of the Trx system may support or drive cancer progression, making both TrxR and Trx promising targets for anti-cancer drug development. Understanding the biochemical mechanisms and connections between certain redox cascades requires research tools that interact with them. The state-of-the-art genetic tools are mostly ratiometric reporters that measure reduced:oxidized ratios of selected redox pairs or the general thiol pool. However, the precise cellular roles of the central oxidoreductase systems, including TrxR and Trx, remain inaccessible due to the lack of probes to selectively measure turnover by either of these proteins. However, such probes would allow measuring their effective reductive activity apart from expression levels in native systems, including in cells, animals, or patient samples. They are also of high interest to identify chemical inhibitors for TrxR/Trx in cells and to validate their potential use as anti-cancer agents (to date, there is no selective cellular Trx inhibitor, and most known TrxR inhibitors were not comprehensively evaluated considering selectivity and potential off-targets). However, small molecule redox imaging tools are underdeveloped: their protein specificity, spectral properties, and applicability remain poorly precedented. This work aimed to address this opportunity gap and develop novel, small molecule diagnostic and therapeutic tools to selectively target the Trx system based on a modular trigger cargo design: artificial cyclic disulfide substrates (trigger) for oxidoreductases are tethered to molecular agents (cargo) such that the cargo’s activity is masked and is re-established only through reduction by a target protein. The rational design of these novel reduction sensors to target the cell's strongest disulfide-reducing enzymes was driven by the following principles: (i) cyclic disulfide triggers with stabilized ring systems were used to gain low reduction potentials that should resist reduction except by the strongest cellular reductases, such as Trx; and (ii) the cyclic topology also offers the potential for kinetic reversibility that should select for dithiol-type redox proteins over the cellular monothiol background. Creating imaging agents based on such two-component designs to selectively measure redox protein activity in native cells required to combine the correct trigger reducibility, probe activation kinetics, and imaging modalities and to consider the overall molecular architecture. The major prior art in this field has applied cyclic 5-membered disulfides (1,2 dithiolanes) as substrates for TrxR in a similar way to create such tools. However, this motif was described elsewhere as thermodynamically instable and was due to widely used for dynamic covalent cascade reactions. By comparing a novel 1,2 dithiolane-based probe to the state-of-the-art probes, including commercial TrxR sensors, by screening a conclusive assay panel of cellular TrxR modulations, I clarified that 1,2 dithiolanes are not selective substrates for TrxR in biological settings (Nat Commun 2022). Instead, aiming for more stable ring systems and thus more robust redox probes, during this work, I developed bicyclic 6 membered disulfides (piperidine fused 1,2 dithianes) with remarkably low reduction potentials. I showed that molecular probes using them as reduction sensors can be mostly processed by thioredoxins while being stable against reduction by GSH. The thermodynamically stabilized decalin like topology of the cis-annelated 1,2 dithianes requires particularly strong reductants to be cleaved. They also select for dithiol type redox proteins, like Trx, based on kinetic reversibility and offer fast cyclization due to the preorganization by annelation (JACS 2021). This work further expanded the system’s modularity with structural cores based on piperazine-fused 1,2 dithianes with the two amines allowing independent derivatization. Diagnostic tools using them as reduction sensors proved equally robust but with highly improved activation kinetics and were thus cellularly activated. Cellular studies evolved that they are substrates for both Trxs and their protein cousins Grxs, so measuring the cellular dithiol protein pool rather than solely Trx activity (preprint 2023). Finally, a trigger based on a slightly adapted reduction sensor, a desymmetrized 1,2 thiaselenane, was designed for selective reduction by TrxR’s selenol/thiol active site, then combined with a precipitating large Stokes’ shift fluorophore and a solubilizing group, to evolve the first selective probe RX1 to measure cellular TrxR activity, which even allowed high throughput inhibitor screening (Chem 2022). The central principle of this work was further advanced to therapeutic prodrugs based on the duocarmycin cargo (CBI) with tunable potency (JACS Au 2022) that can be used to create off-to-on therapeutic prodrugs. Such CBI prodrugs employing stabilized 1,2 dichalcogenide triggers proved to be cytotoxins that depend on Trx system activity in cells. They could further be exploited for cell-line dependent reductase activity profiling by screening their redox activation indices, the reduction-dependent part of total prodrug activation, in 177 cell lines. Beyond that, these prodrugs were well-tolerated in animals and showed anti-cancer efficacy in vivo in two distinct mouse tumor models (preprint 2022). Taken together, I introduced unique monothiol-resistant reducible motifs to target the cellular Trx system with chemocompatible units for each for TrxR and Trx/Grx, where the cyclic nature of the dichalcogenides avoids activation by GSH. By using them with distinct molecular cargos, I developed novel selective fluorescent reporter probes; and introduced a new class of bioreductive therapeutic constructs based on a common modular design. These were either applied to selectively measure cellular reductase activity or to deliver cytotoxic anti cancer agents in vivo. Ongoing work aims to differentiate between the two major redox effector proteins Trx and Grx, requiring additional layers of selectivity that may be addressed by tuned molecular recognition. The flexible use of various molecular cargos allows harnessing the same cellular redox machinery by either probes or prodrugs. This allows predictive conclusions from diagnostics to be directly translated into therapy and offers great potential for future adaptation to other enzyme classes and therapeutic venues.Die zellulĂ€re Redox-Homöostase hĂ€ngt von Thiol/Disulfid-Oxidoreduktasen ab, die den Stoffwechsel, die Proliferation und die antioxidative Antwort von Zellen beeinflussen. Die wichtigsten Netzwerke sind die Thioredoxin Reduktase-Thioredoxin (TrxR/Trx) und Glutathion Reduktase-Glutathion-Glutaredoxin (GR/GSH/Grx) Systeme, die ĂŒber Redox-Schalter in Substratproteinen lebenswichtige zellulĂ€re Funktionen steuern und so an der Redox-Regulation und -SignalĂŒbertragung beteiligt sind. Persistente VerĂ€nderungen des Redoxmilieus in pathologischen ZustĂ€nden, wie z. B. bei Krebs, sind in hohem Maße mit dem Trx-System verbunden. Eine Hochregulierung und/oder ÜberaktivitĂ€t des Trx-Systems, die bei vielen Krebsarten auftreten, unterstĂŒtzt zudem das Fortschreiten des Krebswachstums, was TrxR/Trx zu vielversprechenden Zielproteinen fĂŒr die Entwicklung neuer Krebsmedikamente macht. Um die biochemischen Prozesse dahinter zu erforschen, sind spezielle Techniken zur Visualisierung und Messung enzymatischer AktivitĂ€t nötig. Die hierzu geeigneten, meist genetischen Sensoren messen ratiometrisch das VerhĂ€ltnis reduzierter/oxidierter Spezies in zellulĂ€rem Umfeld oder spezifisch ausgewĂ€hlte Redoxpaare. Die weitere Erforschung der exakten Funktion von TrxR/Trx und deren Substrate ist jedoch durch mangelnde Nachweismethoden limitiert. Diese sind außerdem zur Validierung chemischer Hemmstoffe fĂŒr TrxR/Trx in Zellen und deren potenziellen Verwendung als Krebsmittel von großem Interesse. Bislang gibt es keinen selektiven zellulĂ€ren Trx-Inhibitor und potenzielle Off-Target-Effekte der bekannten TrxR-Inhibitoren wurden nicht abschließend bewertet. Ziel dieser Arbeit ist die Entwicklung niedermolekularer, diagnostischer und therapeutischer Werkzeuge, die selektiv auf das Trx-System abzielen und auf einem modularen Trigger-Cargo Design basieren. Hierzu werden zyklische Disulfid-Substrate (Trigger) fĂŒr Oxidoreduktasen so mit molekularen Wirkstoffen (Cargo) verknĂŒpft, dass dabei die WirkstoffaktivitĂ€t maskiert, und erst nach Reduktion durch ein Zielprotein wiederhergestellt wird. Diese neuartigen, synthetischen Reduktionssensoren basieren auf den folgenden Grundprinzipien: (i) Zyklische Disulfide sind thermodynamisch stabilisiert und können nur durch die stĂ€rksten Reduktasen gespalten werden; und (ii) die zyklische Topologie ermöglicht die kinetische ReversibilitĂ€t der zwei Thiol-Disulfid-Austauschreaktionen, die eine erste Reaktion mit Monothiolen, wie z. B. GSH, sofort umkehrt und so eine vollstĂ€ndige Reduktion verhindert. Die meisten frĂŒheren Arbeiten auf diesem Gebiet verwendeten ein zyklisches, fĂŒnfgliedriges Disulfid (1,2 Dithiolan) als Substrat fĂŒr TrxR. Das gleiche Strukturmotiv wurde jedoch an anderer Stelle als thermodynamisch instabil beschrieben und aufgrund dieser Eigenschaft explizit fĂŒr dynamische Kaskadenreaktionen verwendet. Deshalb vergleicht diese Arbeit zu Beginn einen neuen 1,2 Dithiolan basierten fluorogenen Indikator mit bestehenden, z. T. kommerziellen, Redox Sonden fĂŒr TrxR in einer Reihe von Zellkultur-Experimenten unter Modulation der zellulĂ€ren TrxR AktivitĂ€t und stellt so einen Widerspruch in der Literatur klar: 1,2 Dithiolane eignen sich nicht als selektive Substrate fĂŒr TrxR, da sie labil sowohl gegen die Reduktion durch andere Redoxproteine, als auch gegen den Monothiol Hintergrund in Zellen sind (Nat. Commun. 2022). Als alternatives Strukturmotiv wird in dieser Arbeit ein bizyklisches sechsgliedriges Disulfid (anneliertes 1,2 Dithian) etabliert. Durch sein niedriges Reduktionspotenzial, also seine hohe Resistenz gegen Reduktion, werden molekulare Sonden basierend auf diesem 1,2 Dithian als Reduktionssensor fast ausschließlich von Trx aktiviert, nicht aber von TrxR oder GSH (JACS 2021). Dieses Kernmotiv bestimmt dabei die Reduzierbarkeit, und damit die EnzymspezifitĂ€t, durch seine zyklische Natur und die Annelierung, auch unter Verwendung unterschiedlicher Farb-/Wirkstoffe. Auf dieser Grundlage konnte die molekulare Struktur durch einen weiteren Modifikationspunkt fĂŒr die flexible Verwendung weiterer funktioneller Einheiten ergĂ€nzt werden. Obwohl zellulĂ€re Studien ergaben, dass diese neuartigen 1,2 Dithian Einheiten in Zellen sowohl Trx als auch das strukturell verwandte Grx adressieren, sind die daraus resultierenden diagnostischen MolekĂŒle wertvoll, um den katalytischen Umsatz zellulĂ€rer Dithiol-Reduktasen, der sogenannten Trx Superfamilie, selektiv anzuzeigen (Preprint 2023). BegĂŒnstigt durch das modulare MolekĂŒldesign stellt diese Arbeit zudem das erste Reportersystem RX1 zum selektiven Nachweis der TrxR-AktivitĂ€t in Zellen vor. Es basiert auf der Verwendung eines zyklischen, unsymmetrischen Selenenylsulfid-Sensors (1,2 Thiaselenan), der selektiv von dem einzigartigen Selenolat der TrxR angegriffen wird, und dadurch letztlich nur von TrxR reduziert werden kann. RX1 eignete sich zudem fĂŒr eine Hochdurchsatz-Validierung bestehender TrxR Inhibitoren und unterstreicht dadurch den kommerziellen Nutzen derartiger Diagnostika (Chem 2022). Das zentrale Trigger-Cargo Konzept dieser Arbeit wurde fĂŒr therapeutische Zwecke weiterentwickelt und nutzt dabei den einzigartigen Wirkmechanismus der Duocarmycin-Naturstoffklasse (CBI) (JACS Au 2022) zur Entwicklung reduktiv aktivierbarer Therapeutika. CBI Prodrugs basierend auf stabilisierten Redox-Schaltern (1,2 Dithiane fĂŒr Trx; 1,2 Thiaselenan fĂŒr TrxR) reagierten signifikant auf TrxR-Modulation in Zellen. Sie wurden darĂŒber hinaus durch das Referenzieren ihrer AktivitĂ€t gegenĂŒber nicht-reduzierbaren KontrollmolekĂŒle fĂŒr die Erstellung zelllinienabhĂ€ngiger Profile der ReduktaseaktivitĂ€t in 177 Zelllinien genutzt. Schließlich waren diese neuen Krebsmittel im Tiermodell gut vertrĂ€glich und zeigten in zwei verschiedenen Mausmodellen eine krebshemmende Wirkung (Preprint 2022b). Zusammenfassend prĂ€sentiert diese Dissertation monothiol-resistente reduzierbare Trigger-Einheiten fĂŒr das zellulĂ€re Trx-System zur Entwicklung neuartiger, selektiver Reporter-Sonden, sowie eine neue Klasse reduktiv aktivierbarer Krebsmittel auf Basis eines adaptierbaren Trigger-Cargo Designs. Diese fanden entweder zur selektiven Messung zellulĂ€rer ProteinaktivitĂ€t oder zum Einsatz als Antikrebsmittel Verwendung. Es wurden chemokompatible Motive sowohl fĂŒr TrxR als auch fĂŒr Trx/Grx identifiziert, wobei deren zyklische Natur eine Aktivierung durch GSH verhindert. Eine weitere Differenzierung zwischen den beiden Redox-Proteinen Trx und Grx und anderen Proteinen der Trx-Superfamilie erfordert eine zusĂ€tzliche Ebene der Selektierung, z. B. durch molekulare Erkennung, und ist Gegenstand laufender Arbeiten. Die flexible Verwendung verschiedener molekularer Wirkstoffe ermöglicht dabei die „Pipeline-Entwicklung“ von Diagnostika und Therapeutika, die von der zellulĂ€ren Redox-Maschinerie analog umgesetzt werden, und dadurch Schlussfolgerungen aus der Diagnostik direkt auf eine Therapie ĂŒbertragbar machen. Dies birgt großes Potenzial fĂŒr kĂŒnftige Entwicklungen bei einer potenziellen Übertragung des modularen Konzepts auf andere Enzymklassen und therapeutische Einsatzgebiete
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