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    Advances and Applications of DSmT for Information Fusion. Collected Works, Volume 5

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    This fifth volume on Advances and Applications of DSmT for Information Fusion collects theoretical and applied contributions of researchers working in different fields of applications and in mathematics, and is available in open-access. The collected contributions of this volume have either been published or presented after disseminating the fourth volume in 2015 in international conferences, seminars, workshops and journals, or they are new. The contributions of each part of this volume are chronologically ordered. First Part of this book presents some theoretical advances on DSmT, dealing mainly with modified Proportional Conflict Redistribution Rules (PCR) of combination with degree of intersection, coarsening techniques, interval calculus for PCR thanks to set inversion via interval analysis (SIVIA), rough set classifiers, canonical decomposition of dichotomous belief functions, fast PCR fusion, fast inter-criteria analysis with PCR, and improved PCR5 and PCR6 rules preserving the (quasi-)neutrality of (quasi-)vacuous belief assignment in the fusion of sources of evidence with their Matlab codes. Because more applications of DSmT have emerged in the past years since the apparition of the fourth book of DSmT in 2015, the second part of this volume is about selected applications of DSmT mainly in building change detection, object recognition, quality of data association in tracking, perception in robotics, risk assessment for torrent protection and multi-criteria decision-making, multi-modal image fusion, coarsening techniques, recommender system, levee characterization and assessment, human heading perception, trust assessment, robotics, biometrics, failure detection, GPS systems, inter-criteria analysis, group decision, human activity recognition, storm prediction, data association for autonomous vehicles, identification of maritime vessels, fusion of support vector machines (SVM), Silx-Furtif RUST code library for information fusion including PCR rules, and network for ship classification. Finally, the third part presents interesting contributions related to belief functions in general published or presented along the years since 2015. These contributions are related with decision-making under uncertainty, belief approximations, probability transformations, new distances between belief functions, non-classical multi-criteria decision-making problems with belief functions, generalization of Bayes theorem, image processing, data association, entropy and cross-entropy measures, fuzzy evidence numbers, negator of belief mass, human activity recognition, information fusion for breast cancer therapy, imbalanced data classification, and hybrid techniques mixing deep learning with belief functions as well

    Enhancing the Structural Stability of α-phase Hybrid Perovskite Films through Defect Engineering Approaches under Ambient Conditions

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    This thesis investigates methods whereby perovskite solar cell power conversion efficiency and material stability may be improved. Hybrid perovskites have gained increased attention for optoelectronic applications due to favourable properties such as strong absorption, facile processing, and changeable band-gap. Despite excellent improvements in power conversion efficiency of devices, perovskite films are unstable, degrading with relative ease in the presence of moisture, oxygen, light, heat, and electric fields. The focus of this thesis is on ambient atmosphere stability, concerned with the influence of moisture in particular on perovskite film fabrication, degradation, and device functionality. In order to shed light on the impact of ambient atmosphere on perovskite films, experiments are designed to investigate films during fabrication and degradation. The influences firstly of stoichiometry during ambient fabrication, and then ionic substitution (with caesium and formadinium) upon moisture-induced degradation are investigated. Finally, films and devices with a novel composition incorporating Zn are fabricated under ambient conditions to investigate the effect of Zn addition on perovskite film stability

    Gratitude in Healthcare an interdisciplinary inquiry

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    The expression and reception of gratitude is a significant dimension of interpersonal communication in care-giving relationships. Although there is a growing body of evidence that practising gratitude has health and wellbeing benefits for the giver and receiver, gratitude as a social emotion made in interaction has received comparatively little research attention. To address this gap, this thesis draws on a portfolio of qualitative methods to explore the ways in which gratitude is constituted in care provision in personal, professional, and public discourse. This research is informed by a discursive psychology approach in which gratitude is analysed, not as a morally virtuous character trait, but as a purposeful, performative social action that is mutually co-constructed in interaction.I investigate gratitude through studies that approach it on a meta, meso, macro, and micro level. Key intellectual traditions that underpin research literature on gratitude in healthcare are explored through a metanarrative review. Six underlying metanarratives were identified: social capital; gifts; care ethics; benefits of gratitude; staff wellbeing; and gratitude as an indicator of quality of care. At the meso (institutional) level, a narrative analysis of an archive of letters between patients treated for tuberculosis and hospital almoners positions gratitude as participating in a Maussian gift-exchange ritual in which communal ties are created and consolidated.At the macro (societal) level, a discursive analysis of tweets of gratitude to the National Health Service at the outset of the Covid-19 pandemic shows that attitudes to gratitude were dynamic in response to events, with growing unease about deflecting attention from risk reduction for those working in the health and social care sectors. A follow-up analysis of the clap-for-carers movement implicates gratitude in embodied, symbolic, and imagined performances in debates about care justice. At the micro (interpersonal) level, an analysis of gratitude encounters broadcast in the BBC documentary series, Hospital, uses pragmatics and conversation analysis to argue that gratitude is an emotion made in talk, with the uptake of gratitude opportunities influencing the course of conversational sequencing. The findings challenge the oftenmade distinction between task-oriented and relational conversation in healthcare.Moral economics are paradigmatic in the philosophical conceptualisation of gratitude. My research shows that, although balance-sheet reciprocity characterised the institutional culture of the voluntary hospital, it is hardly ever a feature ofinterpersonal gratitude encounters. Instead, gratitude is accomplished as shared moments of humanity through negotiated encounters infused with affect. Gratitude should never be instrumentalised as compensating for unsafe, inadequatelyrenumerated work. Neither should its potential to enhance healthcare encounters be underestimated. Attention to gratitude can participate in culture change by affirming modes of acting, emoting, relating, expressing, and connecting that intersect with care justice.This thesis speaks to gratitude as a culturally salient indicator of what people express as worthy of appreciation. It calls for these expressions to be more closely attended to, not only as useful feedback that can inform change, but also because gratitude is a resource on which we can draw to enhance and enrich healthcare as a communal, collaborative, cooperative endeavour

    Growth of Group IV and III-V Semiconductor Materials for Silicon Photonics: Buffer Layer and Light Source Development

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    High data transmission speeds, high levels of integration, and low manufacturing costs have established Si photonics as a crucial technology for next-generation data interconnects and communications systems. It involves a variety of components including light emitters, photodetectors, amplifiers, waveguides, modulators, and more. Because of its indirect bandgap, silicon is unable to serve as an efficient light source on a chip, hence this has been one of the formidable challenges. Within the framework of the monolithic approach, this thesis presents the study of two essential aspects of this challenge, the optimisation of buffer layers and development of light sources, by incorporating and improving different systems of Group IV thin films and III-V quantum dots (QDs) semiconductor materials. The monolithic approach focuses on the direct epitaxial growth of highly efficient light sources, usually by the epitaxy of III-V semiconductors lasers on a single Si chip. However, because of the material dissimilarities between III-V materials and Si, during the heteroepitaxy, a high density of crystalline defects such as threading dislocations (TDs), thermal cracks and anti-phase domains are introduced, severely impeding the performance and yield of the laser. For instance, TDs act as non-radiative recombination centres, while thermal cracks cause issues with the efficient evanescent coupling of the emitted light with Si waveguide. To address these defects, typically complex buffer growth techniques with micron-scale thickness are employed. The research in this thesis is divided into two parts, namely buffer layer optimisation and light source development. Each part outlines alternative strategies for overcoming the above-mentioned hurdles for monolithic growth. The first part highlights the optimisation of buffer layer growth to reduce threading dislocations for the monolithic integration of high-performance direct-bandgap III-V and group IV light sources on Si. The growth optimisation of low defect-density Ge buffer layers epitaxially grown on Si was first investigated. Defect elimination in Ge buffers with doped and undoped seed layers of increasing total thickness is studied under a variety of growth regimes, doping techniques, and annealing processes. This study demonstrates that a 500 nm thin Ge achieves the same defect level (1.3 × 108 cm -2) as 2.2 μm GaAs grown on Si, which greatly increases the thickness budget for the subsequent dislocation filter layers (DFLs) and laser structure growth before the formation of thermal cracks. Meanwhile, a low threading dislocation density of 3.3 × 107 cm -2 is obtained for 1 μm Ge grown on Si. The second part places emphasis on the development of light sources in the near-infrared wavelength range for Si photonics. 1) The development of GeSn, an emerging direct bandgap light source for Si photonics, is shown, which has wide bandgap tuneability and full compatibility with Si complementary metal-oxide semiconductor (CMOS). Growing the high Sn composition of GeSn required for efficient light generation is challenging and its growth generally severely affected by large surface roughness and Sn segregation. In this work, first, ex-situ rapid thermal annealing for the grown GeSn layer is investigated, showing that by proper annealing the strain can be relaxed by 90% without intriguing Sn segregation. This method shows its potential for both material growth and device fabrication. Besides, strain compensated layer and in-situ annealing techniques have been developed. Significantly improved surface quality has been confirmed by in-situ reflection high-energy electron diffraction (RHEED) observations and atomic force microscopy (AFM) images. Transmission electron microscopy (TEM) results reveal the high crystal quality of the multiple quantum wells (MQWs) grown on such buffer layers. 2) The final section details the development of InAs/InP QDs emitting near the strategic 1.55 μm, the lowest optical fibre loss window. The InAs/InP QDs growth is prone to inhomogeneous quantum dash morphologies which broaden the photoluminescence (PL) spectra and degrade the carrier confinement. Research has been conducted on growth parameters and techniques including deposition thickness, growth temperature and Indium-flush technique is applied to improve the uniformity of the dots, and narrow room temperature PL linewidths of 47.9 meV and 50.9 meV have been achieved for single-layer and five-layer quantum dot samples, respectively. The structures enable the fabrication of small footprint microdisk lasers with lasing thresholds as low as 30 μW

    Beam scanning by liquid-crystal biasing in a modified SIW structure

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    A fixed-frequency beam-scanning 1D antenna based on Liquid Crystals (LCs) is designed for application in 2D scanning with lateral alignment. The 2D array environment imposes full decoupling of adjacent 1D antennas, which often conflicts with the LC requirement of DC biasing: the proposed design accommodates both. The LC medium is placed inside a Substrate Integrated Waveguide (SIW) modified to work as a Groove Gap Waveguide, with radiating slots etched on the upper broad wall, that radiates as a Leaky-Wave Antenna (LWA). This allows effective application of the DC bias voltage needed for tuning the LCs. At the same time, the RF field remains laterally confined, enabling the possibility to lay several antennas in parallel and achieve 2D beam scanning. The design is validated by simulation employing the actual properties of a commercial LC medium

    Soundscape in Urban Forests

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    This Special Issue of Forests explores the role of soundscapes in urban forested areas. It is comprised of 11 papers involving soundscape studies conducted in urban forests from Asia and Africa. This collection contains six research fields: (1) the ecological patterns and processes of forest soundscapes; (2) the boundary effects and perceptual topology; (3) natural soundscapes and human health; (4) the experience of multi-sensory interactions; (5) environmental behavior and cognitive disposition; and (6) soundscape resource management in forests

    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 zelluläre Redox-Homöostase hängt 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 über Redox-Schalter in Substratproteinen lebenswichtige zelluläre Funktionen steuern und so an der Redox-Regulation und -Signalübertragung beteiligt sind. Persistente Veränderungen des Redoxmilieus in pathologischen Zuständen, wie z. B. bei Krebs, sind in hohem Maße mit dem Trx-System verbunden. Eine Hochregulierung und/oder Überaktivität des Trx-Systems, die bei vielen Krebsarten auftreten, unterstützt zudem das Fortschreiten des Krebswachstums, was TrxR/Trx zu vielversprechenden Zielproteinen für die Entwicklung neuer Krebsmedikamente macht. Um die biochemischen Prozesse dahinter zu erforschen, sind spezielle Techniken zur Visualisierung und Messung enzymatischer Aktivität nötig. Die hierzu geeigneten, meist genetischen Sensoren messen ratiometrisch das Verhältnis reduzierter/oxidierter Spezies in zellulärem Umfeld oder spezifisch ausgewählte 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 für TrxR/Trx in Zellen und deren potenziellen Verwendung als Krebsmittel von großem Interesse. Bislang gibt es keinen selektiven zellulären 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) für Oxidoreduktasen so mit molekularen Wirkstoffen (Cargo) verknüpft, dass dabei die Wirkstoffaktivität 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 stärksten Reduktasen gespalten werden; und (ii) die zyklische Topologie ermöglicht die kinetische Reversibilität der zwei Thiol-Disulfid-Austauschreaktionen, die eine erste Reaktion mit Monothiolen, wie z. B. GSH, sofort umkehrt und so eine vollständige Reduktion verhindert. Die meisten früheren Arbeiten auf diesem Gebiet verwendeten ein zyklisches, fünfgliedriges Disulfid (1,2 Dithiolan) als Substrat für TrxR. Das gleiche Strukturmotiv wurde jedoch an anderer Stelle als thermodynamisch instabil beschrieben und aufgrund dieser Eigenschaft explizit für dynamische Kaskadenreaktionen verwendet. Deshalb vergleicht diese Arbeit zu Beginn einen neuen 1,2 Dithiolan basierten fluorogenen Indikator mit bestehenden, z. T. kommerziellen, Redox Sonden für TrxR in einer Reihe von Zellkultur-Experimenten unter Modulation der zellulären TrxR Aktivität und stellt so einen Widerspruch in der Literatur klar: 1,2 Dithiolane eignen sich nicht als selektive Substrate für 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 Enzymspezifität, durch seine zyklische Natur und die Annelierung, auch unter Verwendung unterschiedlicher Farb-/Wirkstoffe. Auf dieser Grundlage konnte die molekulare Struktur durch einen weiteren Modifikationspunkt für die flexible Verwendung weiterer funktioneller Einheiten ergänzt werden. Obwohl zelluläre 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 Moleküle wertvoll, um den katalytischen Umsatz zellulärer Dithiol-Reduktasen, der sogenannten Trx Superfamilie, selektiv anzuzeigen (Preprint 2023). Begünstigt durch das modulare Moleküldesign stellt diese Arbeit zudem das erste Reportersystem RX1 zum selektiven Nachweis der TrxR-Aktivität 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 für eine Hochdurchsatz-Validierung bestehender TrxR Inhibitoren und unterstreicht dadurch den kommerziellen Nutzen derartiger Diagnostika (Chem 2022). Das zentrale Trigger-Cargo Konzept dieser Arbeit wurde für 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 für Trx; 1,2 Thiaselenan für TrxR) reagierten signifikant auf TrxR-Modulation in Zellen. Sie wurden darüber hinaus durch das Referenzieren ihrer Aktivität gegenüber nicht-reduzierbaren Kontrollmoleküle für die Erstellung zelllinienabhängiger Profile der Reduktaseaktivität in 177 Zelllinien genutzt. Schließlich waren diese neuen Krebsmittel im Tiermodell gut verträglich und zeigten in zwei verschiedenen Mausmodellen eine krebshemmende Wirkung (Preprint 2022b). Zusammenfassend präsentiert diese Dissertation monothiol-resistente reduzierbare Trigger-Einheiten für das zelluläre 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 zellulärer Proteinaktivität oder zum Einsatz als Antikrebsmittel Verwendung. Es wurden chemokompatible Motive sowohl für TrxR als auch für 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 zusätzliche 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 zellulären Redox-Maschinerie analog umgesetzt werden, und dadurch Schlussfolgerungen aus der Diagnostik direkt auf eine Therapie übertragbar machen. Dies birgt großes Potenzial für künftige Entwicklungen bei einer potenziellen Übertragung des modularen Konzepts auf andere Enzymklassen und therapeutische Einsatzgebiete
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