Development of novel Near-Infrared fluorescent contrast agents for intraoperative imaging

Surgery is the primary treatment for most patients with solid tumors and can be curative if complete resection is achieved. While visual inspection and palpation are usually effective for identifying the bulk tumor intraoperatively, they often prove inadequate for the delineation of small tumor remnants or nerves, increasing the risk of recurrence or iatrogenic nerve injury. Fluorescence-guided surgery (FGS) aims to visualize these critical structures in real time. It involves the administration of fluorescent contrast agents, typically composed of a ligand targeting the tissue of interest, conjugated to a Near-Infrared (NIR) fluorescent fluorophore. However, preclinical findings suggest that frequently utilized heptamethine cyanines like IRDye800 are affected by instability towards nucleophiles and, furthermore, are associated with non-specific retention in vivo, which compromises the agent’s efficacy in generating contrast and delays imaging. In this PhD work, targeted contrast agents were developed that overcome the afore-mentioned limitations due to the incorporation of the NIR fluorophore “sNIR”, discovered by explorative studies on a Zincke salt-based approach toward substituted hep-tamethine cyanines. Besides reduced off-target retention in vivo, it also displays faster clearance and greater photostability compared to IRDye800. sNIR was excessively characterized for its optical and chemical properties. Conjugation to established ligands for targeting biomarkers in certain tissue types afforded contrast agents to overcome cancer- and anatomy-related surgical challenges. As the main project, a meningioma-specific contrast agent was developed, which addresses the overexpressed somatostatin receptor subtype 2 (SSTR2) using the octapeptide TATE. TATE sNIR was extensively validated against controls in vitro in SSTR2-expressing cells and in vivo in physiologically SSTR2-expressing mouse tissues and three tumor mouse models, yielding outstanding contrast ratios. Further translational work included a proof-of-concept study in a pig as well as compatibility assessments with NIR fluorescence imaging devices already established in clinical practice. Explorative studies on additional sNIR-based probes addressing a variety of molecular markers expressed by other tu-mor types further suggest that sNIR holds great potential for FGS, regardless of the size of the targeting moiety

Neues Konzept zur Entwicklung einer thermischen Freisetzungsstrategie von locked nucleic acids zur Gentherapie

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Auslandssemester in Italien?

[no abstract available

Illustration Of The Need For A Synergetic Factory Planning For Sustainable Factory Operations

The topic of sustainability has established itself as a global megatrend and requires comprehensive rethinking and action due to challenges such as climate change and resource scarcity. Companies are under increasing pressure from regulations and market demands from consumers. Manufacturing companies in particular are affected by these challenges. Factory planning offers a key starting point here, as it plays a decisive role in determining the sustainability of factory operations over their life cycle. For small and medium-sized enterprises in particular, factory planning offers a good starting point for implementing sustainable practices, since their resources are oftentimes limited. But there is often a lack of transparency about the early planning phases in which decisions can be made that lead to an increase in sustainability during operations. The aim of this article is to explain the requirements for such a factory planning process and to provide an outlook on a possible solution for the development of a process model for sustainable factory planning

Aus dem Hörsaal in die Gründung : … mit dem Student Accelerator – Engineering Innovations

In der heutigen dynamischen Welt der Technologie und der Unternehmensgründung ist es von entscheidender Bedeutung, dass Studierende bereits während ihres Studiums lernen, ihre Gründungsideen zu ent wickeln und praktisch um zusetzen. Koordiniert durch das Institut für Mechatronische Systeme der Fakultät Maschinenbau bietet der „Student Accelerator – Engineeing Innovations“ den Studierenden eben diese Möglichkeit, in einem geeigneten Umfeld ihre unternehmerischen Visionen zu verwirklichen

A new numerical concept for the prediction of cyclic deformation accumulation of foundation structure in non-cohesive soil

Zur Bemessung einer flachgegründeten Windenergieanlage wird in der Regel gefordert, dass unter der quasi-ständigen Einwirkung bzw. dem Lastniveau D.3 sowie der Annahme der linearen Sohlspannungsverteilung keine klaffende Fuge auftreten darf. Diese Regelung ist in der Praxis oft maßgebend und führt zur möglichen Überdimensionierung des Fundaments. Diese Forderung stammt aus der alten DIN 1054 (1976) Norm und geht zurück auf die Befürchtung, dass es bei Stützmauern unter ständiger Erddruckbelastung zu großen Kriechverformungen kommen kann, und ist daher kaum relevant für flachgegründete Windenergieanlagen, welche hauptsächlich auf annähernd kriechfreien nichtbindigen Baugrund gebaut wird. Ein möglicher Vorteil dieser Forderung ist die indirekte Begrenzung der zyklischen Verformungen der Flachgründung, insbesondere der zyklischen Schiefstellung. Vor diesem Hintergrund liegt der Fokus auf der Prognose der zyklischen Schiefstellung. Diese Dissertation widmet sich der Entwicklung einer neuen numerischen Methode, der zyklischen Dehnungsakkumulationsmethode (CSAM). Diese Methode ist in der Lage, das zyklische Verhalten nicht nur von Flachgründungen, sondern auch von Monopiles numerisch nachzubilden. Die CSAM wird zunächst kalibriert durch den Vergleich mit der Stiffness Degradation Method (SDM) für zyklisch belastete Monopiles. Anschließend wird die CSAM modifiziert und auf die Flachgründung angewendet, welches die Nachrechnungen der zyklischen Versuche aus der Literatur und eigener mittelmaßstäblicher Versuche umfasst. Basierend auf den kalibrierten Modellparametern aus dem eigenen mittelmaßstäblichen Versuch, wird eine Parameterstudie für hochskalierte Flachgründungmodelle durchgeführt, um einerseits das Kenntnis der exzentrisch zyklisch belasteten Flachgründung zu vertiefen und andererseits eine praktische einfache empirische Gleichung zur Prognose der zyklischen Schiefstellung abzuleiten. Es hat sich gezeigt, dass die klaffende Fuge nicht unmittelbar zum von Hettler (1981) definierten „schrittweisen Versagen“ führt und unter der klaffenden Fuge die zyklische Schiefstellung prognostizierbar ist, entweder über die CSAM oder die abgeleitete empirische Gleichung. Allgemein bieten die Untersuchungen dieser Dissertation mögliche theoretische Grundlagen zur Bemessung der Flachgründung unter exzentrischer zyklischer Last. Die entwickelte zyklische Dehnungsakkumulationsmethode (CSAM) ist eine vielversprechende numerische Methode, an der weiterhin geforscht und die für mehr Anwendungsfälle optimiert wird, um sie in der geotechnischen Praxis zu etablieren.In the design of wind turbine founded on shallow foundation, it is usually required that under the quasi-static or D.3 load case and the assumption of linear contact stress, no gapping shall occur between the foundation and subsoil. This criterion is often decisive in the practical design and leads to possible over-dimensioning of shallow foundation. This requirement, however, originated from the old DIN 1054 (1976) standard and comes from the caution, that considerable creep deformation could occur for the retaining walls, which are subjected to permanent earth pressure loads, and is therefore seldom relevant for the shallow foundation for wind turbine, which is mainly constructed on the non-creep non-cohesive subsoil. One possible favourable effect of limiting the gapping of shallow foundation is to limit cyclic deformation, especially the cyclic rotation indirectly. Under these circumstances, the focus is on prediction of the cyclic rotation. This dissertation is dedicated to develop a new numerical method, the Cyclic Strain Accumulation Method (CSAM). This method is able to to describe the cyclic behaviour of not only shallow foundation but also the monopile numerically. The CSAM is firstly calibrated through the comparison with the Stiffness Degradation Method (SDM) for cyclically loaded monopile. Then the CSAM is modified and applied on the shallow foundation, which includes the back-analyses of cyclic tests from the literature and own medium-scale test. Based on the calibrated model parameters from own medium-scale test, a parametric study is performed to extend the understanding of the eccentrically cyclically loaded shallow foundation and to derive a practical simple empirical equation for predicting the cyclic rotation. It has been shown that the gapping does not directly lead to "incremental collapse'' defined by Hettler (1981) and with the gapping, the cyclic rotation can be predicted either via CSAM or the derived empirical equation. In general, the investigations of this dissertation provide possible theoretical basis for the design of shallow foundation under eccentric cyclic load. The proposed Cyclic Strain Accumulation Method (CSAM) is a very promising numerical method that will be further researched and optimised for more applications in geotechnical practice

Der Andere

[no abstract available

Structure and dynamics of molecules with oxygen-containing groups and their clusters studied by microwave spectroscopy

Sauerstoffhaltige funktionelle Gruppen spielen eine entscheidende Rolle und haben breite Anwendungen in der Chemie. Der Einbau von Sauerstoffatomen verleiht diesen Gruppen eine hohe Polarität, die ihre umfangreiche Beteiligung an kovalenten Bindungen und vielfältigen nicht-kovalenten Wechselwirkungen ermöglicht, was sich erheblich auf Löslichkeit, molekulare Stabilität und chemische Reaktivität auswirkt. Die Kohärenztechniken in der modernen Mikrowellenspektroskopie sind eine leistungsstarke Methode, um Einblicke in die Struktur, nicht-kovalente Wechselwirkungen, großamplitudige Bewegungen und – über Feinstrukturen – spezielle Bindungssituationen eines Molekülsystems zu gewinnen. In dieser Arbeit wurden zunächst aromatische Aldehyde mit unterschiedlichen Seitenkettenlängen untersucht. Es konnte gezeigt werden, dass die intramolekulare Wasserstoffbrücke, die sich zwischen der Seitenkette und dem Phenylring bildet, die Struktur der Seitenkette bestimmt. Darüber hinaus dienten diese Moleküle als Partner für Wechselwirkungen mit H2O und H2S, wodurch unterschiedliche Eigenschaften zwischen H2O und H2S aufgedeckt wurden, wie Bindungspräferenzen, Solvatationseffekte und die Art der nicht-kovalenten Wechselwirkungen. Die Monomere beteiligten sich auch an der Bildung von CO2 Clustern, aus denen die untypische Bindungsweisen von CO2 und die entstehenden nicht-kovalenten Wechselwirkungen verstanden wurden. Die - in para-Stellung zu einer -OCH3 Gruppe – halogen-substituierten (F, Cl, Br, I) Monomere von Anisolderivaten wurden mittels Mikrowellenspektroskopie analysiert, um Benchmarks für quantenchemische Berechnungen bereit zu stellen. Die Quadrupolkupplungskonstanten wurden bestimmt und auch das Verhältnis von Q(35Cl)/Q(37Cl) und Q(79Br)/Q(81Br) abgeleitet. Schließlich, untersützt durch quantenchemischer Berechnungen, wurden die Wasserkonfigurationen von 4-Hydroxy-2-butanon, das sowohl -OH als auch C=O Gruppen enthält, mit bis zu fünf Wassermolekülen untersucht. Das faszinierende Gleichgewicht zwischen dem Konformationsverhalten von 4-Hydroxy-2-butanon und der Wasseraggregation in den Komplex erklärt, wie die Konformationsanpassungsfähigkeit flexibler Substrate Wasserstrukturen aufnimmt und die Präferenz für ein sequentielles Wachstum von Wassertropfen unterstützt.Oxygen-contammg functional groups play pivotal roles and have broad applications in chemistry. The inclusion of oxygen atom imparts high polarity to these groups, enabling extensive participation in covalent bonding, and diverse non-covalent interactions, which significantly influence solubility, molecular stability, and chemical reactivity. The coherence techniques in modern microwave spectroscopy are powerful tools for gaining insight into the structure, non-covalent interaction, large amplitude motion, and –bonding situations of a molecular system. via hyperfine structures –particular In this thesis, the first investigation targets aromatic aldehyde molecules with varying side-chain lengths. lt was found that the intramolecular hydrogen bond formed between the side-chain and the phenyl ring determines the structure of the side-chain in molecules. Additionally, they served as the partner molecules to interact with H20 and H2S, revealing distinct properties between H20 and H2S, such as the binding preference, solvation effect, and the nature of the non-covalent interactions. The monomers also participate in the formation of C02 clusters, from which the atypical binding ways of C02 and the emerging non-covalent interactions have been investigated. The - at the para-position of a -OCH3 group - halogen-substituted (F, Cl, Br, 1) monomers of anisole derivates were analyzed by microwave spectroscopy, providing benchmarks for quantum chemical calculation. The quadrupole coupling constants were determined, deriving also the ratio of Q(35Cl)/Q(37Cl) and Q(79Br)/Qs( 1Br). Finally, aided by the quantum chemical calculations, the water clusters ofl hydroxy-2-butanone, bearing both -OH and C=O group, were investigated with up to five water molecules. The intriguing balance of conformational behavior of 4 hydroxy-2-butanone and the water assembling in the complex explains how the conformational adaptability of flexible substrates hosts water scaffolds and supports the preference for a sequential droplet growth

CoastSnap – Experiences from the Case Study Langwarder Groden in Germany

CoastSnap is a citizen science initiative that engages the public in coastal monitoring by encouraging them to take photos of specific coastlines from fixed, designated locations. Due to its promising implementation on coastlines all around the world, CoastSnap was also used as part of the Gute Küste Niedersachsen real-worl-laboratory (GKN RwL). The main task was to monitor the daily dynamics of the tidal water influx, sediment movement and vegetation changes in the salt marshes of the restoration measure in the Langwarder Groden in Butjadingen. In this working paper we present the results of a survey among the CoastSnap users at Langwarder Groden. It revealed a high level of public interest in scientific research and a willingness to contribute with some options for improvements. Based on the results we summarize 5 key findings to support the performance of CoastSnap stations in Germany and elsewhere

Human-in-the-Loop Workflow for Systematic Creation of Content for Scientific Knowledge Graphs

As the volume of scientific literature continues to grow, efficient knowledge curation is becoming an increasingly challenging task. Traditional manual processes for structuring scientific content are time-consuming and require significant domain expertise, increasing the need for tool support. Our goal is to create a Human-in-the-Loop workflow that supports researchers in creating and structuring scientific knowledge for the integration into knowledge graphs, exemplary the Open Research Knowledge Graph (ORKG) in this paper. The workflow aims to automate key steps, including data extraction and knowledge structuring, while keeping user oversight through human validation points. A tool implementing the workflow is developed and evaluated along the Quality Improvement Paradigm (QIP) with 9 participants from the ORKG domain. The evaluation demonstrated that the tool offers practical support for the ORKG users, by significantly reducing the time required to transform a research interest into a structured knowledge graph representation. Furthermore, participants reported positive feedback regarding the usability of the tool. However, further work is needed to enhance the quality of the extracted data and provide more accurate entity linking for pre-existing resources