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From Planning to Publication: Effective Management of Research Data
No full textWhether it's planning research projects, documenting data collection or publishing data - the responsible and sustainable handling of research data throughout the entire research cycle is becoming increasingly important. At this event, we will demonstrate how to carry out effective research data management and explain which digital services are useful and what support the UR offers
Interplay of IL‐6, GDF‐15 and Sarcopenia in Patients With Bladder Cancer Undergoing Radical Cystectomy and Its Implications on Survival
No full textBackground:
Sarcopenia has emerged as a significant predictor of adverse outcomes in cancer. Specifically, this is also true for patients with bladder cancer undergoing radical cystectomy (RC). This retrospective study investigates the roles of the biomarkers interleukin-6 (IL-6) and growth differentiation factor-15 (GDF-15), in the context of sarcopenia, assessing their impact on oncological and survival outcomes.
Methods:
Preoperative serum IL-6 and GDF-15 levels were analysed in 179 patients undergoing RC. Their association with sarcopenia, adverse pathological features and survival outcomes was investigated.
Results:
Elevated IL-6 and GDF-15 levels were significantly correlated with the presence of sarcopenia (p = 0.04 and p = 0.03, respectively). IL-6 and GDF-15 levels in serum showed a positive correlation (Spearman r = 0.45, 95%CI 0.32–0.56, p < 0.01). Higher IL-6 and GDF-15 levels were also associated with higher tumour stages (both p < 0.01), positive lymph nodes (p = 0.02 and p < 0.01) and unfavourable surgical margins (both p < 0.01). Patients with both sarcopenia and high IL-6 or GDF-15 levels exhibited significantly worse overall survival and cancer-specific survival in multivariate Cox regression analysis.
Conclusions:
These findings highlight the interplay between IL-6, GDF-15, sarcopenia and tumour progression, suggesting that IL-6 and GDF-15 may serve as valuable prognostic biomarkers and potential therapeutic targets. Further research is warranted to explore targeted therapeutic strategies aimed at mitigating sarcopenia and systemic inflammation in this patient population
Einfluss von Bewegung auf die Lebensqualität bei Patienten mit gastrointestinalen Tumorerkrankungen im Stadium IV unter Chemotherapie
No full textHintergrund: Obwohl gastrointestinale Tumoren unter den häufigsten Krebsarten sind, gibt es bislang kaum Forschungsergebnisse zu den Auswirkungen von Bewegung auf Patienten mit gastrointestinalen Tumoren im Stadium IV, die sich einer Chemotherapie unterziehen. Ziel dieser Studie ist es daher, die Auswirkungen alltäglicher Aktivitäten auf die Lebensqualität dieser Patienten aufzuzeigen.
Methoden: Die Studie wurde als nicht-interventionelle prospektive Beobachtungsstudie durchgeführt. Mithilfe von Schrittzählern und Aktivitätstagebüchern dokumentierten die Patienten ihre tägliche Schrittzahl dreimal über einen Zeitraum von zwei Wochen in Abständen von drei Monaten. Am Ende dieser 14 Tage erhielten sie EORTC-QLQ-C30-Fragebögen zur Bewertung ihrer Lebensqualität. Für die abschließende Analyse wurden die Patienten entsprechend ihrer Bewegungsmenge (geringe Menge, durchschnittliche Menge, hohe Menge) in drei Gruppen eingeteilt.
Ergebnisse: Die Ergebnisse zeigten signifikante Veränderungen zwischen den Gruppen zu Beginn der Studie und nach 3 Monaten für die Subskalen körperliche Funktionsfähigkeit, Rollenfunktion, Fatigue und Appetitlosigkeit. Bei der allgemeinen Gesundheit/Lebensqualität sowie Übelkeit und Erbrechen erreichten die Unterschiede zwischen den Gruppen nur zu Beginn der Studie ein signifikantes Niveau.
Schlussfolgerung: Diese Studie zeigt, dass selbst Patienten mit gastrointestinalen Tumoren im Stadium IV, die sich einer Chemotherapie unterziehen, von Bewegung während ihrer Behandlung profitieren können. Dies könnte den Patienten ein Gefühl der Kontrolle vermitteln, indem sie ihre Lebensqualität durch tägliche Bewegung verbessern. Patienten sollten daher über diese Vorteile informiert werden. Weitere Studien mit größeren Stichproben sind erforderlich, um die verschiedenen Subtypen von Magen-Darm-Krebs zu evaluieren
Quantum Chaos as an Essential Resource for Full Quantum State Controllability
No full textUsing the key properties of chaos, i.e.~ergodicity and exponential instability, as a resource to control classical dynamics has a long and considerable history. However, in the context of controlling ``chaotic'' quantum unitary dynamics, the situation is far more tenuous. The classical concepts of exponential sensitivity to trajectory initial conditions and ergodicity do not directly translate into quantum unitary evolution. Nevertheless properties inherent to quantum chaos can take on those roles: i) the dynamical sensitivity to weak perturbations, measured by the fidelity decay, serves a similar purpose as the classical sensitivity to initial conditions; and ii) paired with the fact that quantum chaotic systems are conjectured to be statistically described by random matrix theory, implies a method to translate the ergodic feature into the control of quantum dynamics. With those two properties, it can be argued that quantum chaotic dynamical systems, in principle, allow for full controllability beyond a characteristic time that scales only logarithmically with system size and . In the spirit of classical targeting, it implies that it is possible to fine tune the immense quantum interference with weak perturbations and steer the system from any initial state into any desired target state, subject to constraints imposed by conserved quantities. In contrast, integrable dynamics possess neither ergodicity nor exponential instability, and thus the weak perturbations apparently must break the integrability for control purposes. The main ideas are illustrated with the quantum kicked rotor. The production of revivals, cat-like entangled states, and the transition from any random state to any other random state is possible as demonstrated
Ordalien im spätantiken und frühmittelalterlichen Westen: Deutungen und Praktiken zwischen Recht, Ritual und Gesellschaft
No full textDie vorliegende Studie widmet sich dem iudicium Dei im Transformationsprozess von der Spätantike zum Frühmittelalter und analysiert es als ein Phänomen, in dem sich Rechtsautorität, rituelle Performanz und narrative Legitimierungsstrategien überschneiden. Jenseits älterer Forschungsansätze, die das Gottesurteil lediglich als „irrationales Relikt“ marginalisieren, rekonstruiert die Arbeit jene diskursiven und pragmatischen Bedingungen, unter denen ein Ordal überhaupt erst den Status eines validen Beweismittels erlangen konnte. Im Fokus steht dabei die Frage nach den Autorisierungsinstanzen, der topographischen Verortung sowie den Verfahren, die das Ergebnis sowohl sozial als auch textuell bindend machten.
Methodisch verschränkt die Untersuchung eine rechtsgeschichtliche Analyse mit performanztheoretischen Ansätzen und einer raumsoziologischen Perspektive auf sakrale Settings. Das Quellenkorpus umfasst dabei eine komparatistische Lektüre normativer Textsorten, Leges, Kapitularien, kirchenrechtliche Kanones und liturgische Ordines, und kontrastiert diese mit der interpretativen Evidenz hagiographischer und narrativer Quellen.
Eine zentrale These der Arbeit ist die Neukonturierung des Bischofs als Scharnierfigur dieses Prozesses: Er tritt nicht bloß als moralischer Kommentator in Erscheinung, sondern als entscheidender juridischer Akteur, der den Zugriff auf den sakralen Raum reglementiert, die Semantik des Rituals rahmt und die öffentliche Glaubwürdigkeit des Ergebnisses stabilisiert. Das Gottesurteil erweist sich in dieser Perspektive weniger als spontane „Glaubensprobe“, denn als eine liturgisch skriptierte und räumlich streng eingehegte Sequenz, deren Beweiskraft maßgeblich von ihrer orchestralen Inszenierung und der anschließenden narrativen Fixierung abhängt
Optimal marker genes for c-separated cell types with SepSolve
No full textThe identification of cell types in single-cell RNA-seq studies relies on the distinct expression signature of marker genes. A small set of target genes is also needed to design probes for targeted spatial transcriptomic experiments and to target proteins in single-cell spatial proteomics or for cell sorting. Although traditional approaches have relied on testing one gene at a time for differential expression between a given cell type and the rest, more recent methods have highlighted the benefits of a joint selection of markers that together distinguish all pairs of cell types simultaneously. However, existing methods either consider all pairs of individual cells, which becomes intractable even for medium-sized data sets, or ignore intra-cell-type expression variation entirely by collapsing all cells of a given type to a single representative. Here, we address these limitations and propose to find a small set of genes such that cell types are c-separated in the selected dimensions, a notion introduced previously in learning a mixture of Gaussians. To this end, we formulate a linear program that naturally takes into account expression variation within cell types without including each pair of individual cells in the model, leading to a highly stable set of marker genes that allow to accurately discriminate between cell types and that can be computed to optimality efficiently
Toward a more sustainable photocatalysis using copper and iron
Get PDFShifting from rare and precious metal catalysts in photochemical systems, such as ruthenium and iridium, to abundant and sustainable ones is still challenging. Copper and iron are fascinating, given their relative abundance and economic advantage. While the conception of copper and iron luminophores for the application in catalysis is faced with the undesirable rapid deactivation of photoactive states, making intermolecular redox exchange inefficient, the harnessing of copper and iron's propensity to perform fast ligand exchange and accommodation of radical intermediates enabled their successful implementation in photocatalysis. This review underscores the rapid growth of copper and iron in photocatalysis as green and sustainable alternatives, highlighting the unique catalytic features they offer
Klinisch-endoskopische Charakterisierung von Patientinnen und Patienten mit sekundär sklerosierender Cholangitis
Get PDFDie sekundär sklerosierende Cholangitis (SSC) ist eine chronisch cholestatische Erkrankung der Gallengänge, die durch verschiedene Ereignisse ausgelöst werden kann. Es existieren unterschiedliche Formen der SSC, wobei die SSC-CIP (secondary sclerosing cholangitis in critically ill patients) bei schwer erkrankten Patientinnen und Patienten oftmals im Rahmen eines akuten Auslöseereignisses wie Polytrauma, Sepsis oder nach großen Operationen mit Intensivaufenthalt auftritt. Die SSC-CIP verläuft deutlich aggressiver und protrahierter als andere SSC-Formen und insbesondere auch im Vergleich zur PSC.
Eine der bislang wichtigsten Annahmen zur Ätiopathogenese stellen ischämisch-hypoxische Gallengangläsionen dar, die oftmals bei schwer erkrankten und intensivmedizinisch therapierten Patientinnen und Patienten auftreten und zudem durch septische Krankheitsverläufe unterhalten werden können. Auch für die ITBL als morphologisches Korrelat einer SSC nach Lebertransplantation werden ischämische Prozesse als Auslöser diskutiert.
Diagnostisch stellt die ERC die wichtigste diagnostische und therapeutische Modalität der SSC dar. Die ERC bietet neben bildgebender Darstellung zugleich die Möglichkeit, therapeutisch am Gallengangsystem zu intervenieren. Typische Untersuchungsbefunde sind Sludge, Castformationen, Gallengangrarefizierungen, multiple Stenosierungen und prästenostische Dilatationen der Gallenwege.
Im Laufe der Erkrankung kommt es zu Komplikationen, die überwiegend durch die sich rasch entwickelnde sekundär biliäre Zirrhose bedingt sind.
Die Lebertransplantation ist bei manifester Zirrhose die einzige kurative Therapieoption.
Die weiteren Therapiemöglichkeiten sind begrenzt und basieren auf endoskopischen Therapiemaßnahmen wie Gallengangdilatationen, Stenteinlagen und Castextraktionen. Der Stellenwert der medikamentösen Behandlung der SSC wurde bislang nicht kontrolliert untersucht.
Um die Erkrankung in Zukunft besser verstehen und behandeln zu können, wurden in dieser Arbeit Überlebenszeitanalysen durchgeführt und prognostische Parameter analysiert, die mit höheren oder niedrigeren Überlebensraten assoziiert werden. So konnten das Vorhandensein biliärer Casts, ein MELD-Score ≥ 15 Punkte bei Erstdiagnose, ein CRP ≥ 8 mg/l bei Erstdiagnose und eine initiale Dialysepflichtigkeit als negative prognostische Faktoren identifiziert werden. Die endoskopische Dilatationstherapie sowie das weibliche Geschlecht waren mit einer längeren Überlebensdauer des Kollektivs vergesellschaftet.
Somit kann diese Arbeit einen Anhaltspunkt bieten, Vorhersagen über den Verlauf SSC-Erkrankter zu treffen. Hervorzuheben ist insbesondere der positive Effekt der endoskopischen Dilatationstherapie auf das transplantatfreie Überleben, was einen direkten Einfluss auf das Management der Patientinnen und Patienten mit SSC im klinischen Alltag haben kann
Small Inorganic Ring Systems: Understanding Cyclization and Bond Activation Processes
Get PDFWithin this work, the modification of the substituents at silicon of heterocyclic four-membered silyl phosphonium ions was investigated. In chapter 1 a general overview of the current state of research, and the design principles, to which the structure of the four-membered phosphonium ions adhere, are presented. The focus of chapter 3 is the modification of previously known silyl phosphine chalcogenides with different substituents and Lewis basic chalcogenides. New synthesis routes towards these novel compounds were developed, the structures synthesized and thoroughly investigated by means of single-crystal X-ray diffraction analysis, NMR analysis and DFT calculations. Through this procedure a deep understanding of the governing principles of steric and electronic effects within these four-membered silyl phosphonium chalcogenides was obtained. When all substituents are replaced by sterically demanding tert-butyl substituents, the choice of chalcogen used as a Lewis base becomes crucial for successful ring formation. The angular strain within the four-membered rings was found to be well balanced in all four-membered CPChSi rings investigated. Thermochemical investigations showed that the substituents on the silicon and phosphorus atoms play an important role for the strength of the intramolecular Ch–Si coordination. In the absence of large steric repulsions through bulky substituents (methyl groups on silicon, tert-butyl groups on phosphorus), a stability sequence depending on the chalcogen atom in the direction Se ≤ S < O can be observed. However, the order is reversed (O < S < Se) in case of strong repulsions between sterically demanding substituents (tert-butyl groups on both silicon and phosphorus atoms). Due to the shorter Si–O bond length compared to the Si–S and Si–Se bond lengths, the substituents of the phosphorus and silicon atom are forced in closer proximity in the four-membered cations. In the case of all-tert-butyl substituted compound I this leads to a significant increase in steric repulsion in this cation, therefore hampering its synthesis. Building upon this knowledge, another second-row element, nitrogen, was investigated as a donor in chapter 4. The nitrogen atom was introduced as a phosphinimine moiety into the systems. In contrast to phosphine chalcogenides, phosphinimine donor moieties allow for further modification of donor strength by the influence of steric or electronic parameters. The introduction of either a trimethylsilyl or a bis(3,5-trifluoromethylphenyl)boryl moiety allows for additional ring strain in these systems. Furthermore, an electronic destabilization of the Si–N bond was expected to be achieved by either resonance stabilization by the bis(3,5-trifluoromethylphenyl)boryl moiety or by hyperconjugative n(N)→σ*(SiMe) interactions from the –SiMe3 moiety. Taken together, these effects are expected to facilitate ring opening and enable small molecule activation or even catalytic transformations. The rational synthesis of these systems, the influence of steric and electronic factors, and the reactivity in terms of catalytic applications and FLP-like behavior were investigated. The silylated phosphinimines can be easily obtained in moderate to good yields. The ring-closure reactions of the methyl- and iso-propyl-substituted silanes (X, XI) proceeded smoothly, however the case of the all tert-butyl substituted silyl phosphinimine IX no ring closure was possible. Like the P–O bond length [1.4958(8) Å] in compound I the P–N bond length [1.538(2) Å] in compound IX is also very short, therefore the same effects hampering the ring formation in compound I were found to also affect the ring formation in compound IX. The Si–N bonds in the SiMe3-substituted four-membered phosphonium ions XII[B(C6F5)4] and XIII[B(C6F5)4] were found to be covalent in nature, and did not possess the ability to reversibly open as anticipated. Nevertheless, we were able to gain valuable insights from these results and therefore we set out to design a new system with a maximum of steric hinderance, while also preserving the desired ability to remove the hydride from the Si¬–H moiety. Therefore, an electrophilic boryl moiety was introduced to study the effect of electron-withdrawing groups on the reversible opening ability of these ring systems. With the zwitterionic compound XIV reversibility was finally achieved which was evidenced by the ability of compound XIV to catalyze the hydrosilylation of nitriles. This validated our approach of combining steric and electronic factors to weaken the Si¬–N bond in compound XIV. Upon receiving preliminary confirmation through this experiment, that reversibility is in principle possible within these systems our attention shifted away from the strongly Lewis acidic silylium-based Lewis acids towards neutral silicon-based Lewis acids. The rational was, that neutral silicon-based Lewis acids are of lower Lewis acidity compared to silylium ions, and therefore reversibility within these systems can be easier achieved. The question whether this really is the case was addressed in chapter 5. Several novel neutral Lewis acidic silanes were prepared and incorporated within the previously described CPSSi cycles (chapter 3). By varying the electron-withdrawing groups from pentafluorophenyl [-C6F5] over pentafluorophenoxy [-OC6F5] to tetrafluorocatecholato [-O2C6F4] moieties, a discernible difference in Lewis acidity at the silicon center was observed (Scheme 8.3). While the pentafluorophenyl [-C6F5] substituted compound showed no Lewis acidity, the tetrafluorocatecholato [-O2C6F4] substituted silane was strongly prone towards formation of the pentacoordinate state making the desired Si–H substituted tetravalent silane inaccessible. A good balance between Lewis acidity and stability of the tetravalent state was found with the pentafluorophenoxy [-OC6F5] substituted compound XV. Through in depth NMR spectroscopic experiments a equilibrium between compounds XV and XVI could be observed. Compound XV represents an intriguing structure as it combines a highly reducing anionic Si–H function, aswell as a protic cationic N–H function in close proximity to each other. To the best of our knowledge this is the only example were both motifs can be found within one molecule. Through additional time resolved NMR experiments it was also found that compound XV is not stable over a prolonged amount of time and slowly reacts with the loss of dihydrogen towards compound XVII. In conclusion the introduction of neutral Lewis acidic silanes indeed proved to ease the ability of the silicon Lewis acids to reversibly attach to Lewis bases.
In a second part of this doctoral project, chiral silanethiols were synthesized and investigated as enantioselective hydrogen-atom transfer (HAT) catalysts together with the group of Prof. König. The deracemization was achieved by a sequence of photocatalytic hydrogen-atom transfer, reductive radical-polar crossover (RRPCO), and protonation. Our goal was to design silanethiols which were able to act as potent and enantioselective HAT-catalysts. To achieve this goal, different strategies were employed. The first attempt was made with a silanethiol which was equipped with chiral substituents. Therefore the (–)-menthol substituted silanethiol XVIII was prepared and tested, and while compound XVIII performed well as a HAT-catalysts no enantioselectivity was observed. Next, the Si-chiral silanethiol XIX was prepared and tested. The idea was to bring the chiral information closer to the reactive Si¬–S– function, and therefore enhance enantioselectivity. This approach was successful and compound XIX performed well as a HAT catalyst and gave an enantiomeric excess of 16 % in the final product. While this finding served as proof that chiral silanethiols can indeed be used as enantioselective HAT-catalysts, the enantiomeric excess obtained was not good enough for practical use. In order to increase the enantioselectivity even further, the successful concept of using Si-chiral silanethiols was combined with a chiral backbone. A suitable motif, which combined both desired features was found in a class of silanthiols with a ferrocene backbone [(SSi,SP)-XX and (SSi,SP)-XXI]. While both compounds are Si-stereogenic, they also exhibit planar chirality in the ferrocenyl backbone. However, when employing compounds (SSi,SP)-XX and (SSi,SP)-XXI in the RRPCO-HAT-protonation sequence, decomposition was observed. No catalytic activity nor enantioselectivity was observed for both compounds, therefore concluding that the ferrocene backbone is not suitable for this application. In summary, this lays the foundation for the design of silanethiol HAT catalysts based on the general structure of compound XIX