Spatially resolved immobilization of metallopolymers – Spiropyrans for light sensitive metal complexes and STED-inspired laser lithography

In the course of the present thesis, the first method for the spatially resolved surface immobilization of various metallopolymers on a single surface was developed, employing the versatile NITEC photochemistry. The in-depth analysis of the photoligation process identified crucial parameters for the successful immobilization of the metallopolymers, which are also valid for all other photo triggered surface ligation protocols. ToF-SIMS and spatially resolved XPS analysis of the prepared surfaces demonstrated the preserved chemical composition of the fabricated metallopolymer surfaces. In the second part of the thesis, the photochemistry of spiro(thio)pyrans was investigated for the formation of light-sensitive spiropyran-metal complexes, as well as the creation of a photoresist for the application in STED-inspired lithography. The irradiation of an NMR tube inside the NMR spectrometer in so-called LED-NMR experiments was introduced for the investigation of the prepared spiropyran-metal complexes. Finally, the photo triggered reaction of the spirothiopyran photoswitch with an electron deficient maleimide was used for the spatial encoding of surfaces for the first time. In addition, the preparation of a spirothiopyran-based photoresist enabled the writing of structures below the diffraction limit, with the thinnest lines written with STED-inspired lithography to date

Evaluation of an automated enzyme-linked fluorescent assay for thyroxine measurement in cat and dog sera

Measurement of total thyroxine (T4) is the first testing step in the work-up of thyroid disease in small animals. We evaluated an enzyme-linked fluorescent assay (ELFA) as an in-house method to measure T4 in cats and dogs. We compared the T4 concentration in sera of 122 cats and 176 dogs measured by the ELFA with an enzyme immunoassay (EIA) to assess the concordance of the 2 methods. Bias of the ELFA in cats was -11.4% and in dogs 1.4%. Using Bland-Altman plots, limits of agreement were -81.5 to 58.7% in cats and -71.4 to 74.4% in dogs. Imprecision was calculated for both methods. Intra- and interassay coefficients of variation (CVs) of the ELFA in feline sera were 0.7 and 3.4% and of the EIA 7.6 and 15.7%, respectively. Intra- and interassay CVs of both ELFA and EIA in canine sera were <9.5%. Reference intervals for the ELFA method were established and were 13.3-49.5 nmol/L for cats and 10.1-42.9 nmol/L for dogs. Accuracy of the EIA and ELFA was scored by assessing if the measured T4 value would identify the expected T4 range (low, normal, or elevated) of patients, based on history, clinical presentation, other diagnostic means, and response to therapy. This was possible for 75 cats and 50 dogs. Both methods yielded acceptable results, but the EIA was more accurate compared to the ELFA (percentage of true-positives in cats and dogs: EIA: 97% and 100%; ELFA: 92% and 94%)

Identifying Contact Risks for SARS-CoV-2 Transmission to Healthcare Workers during Outbreak on COVID-19 Ward

We assessed the risk for different exposures to SARS-CoV-2 during a COVID-19 outbreak among healthcare workers on a hospital ward in late 2020. We found working with isolated COVID-19 patients did not increase the risk of COVID-19 among workers, but working shifts with presymptomatic healthcare coworkers did

Efficient Blue Phosphorescence in Gold(I)‐Acetylide Functionalized Coinage Metal Bis(amidinate) Complexes

The synthesis of linear symmetric ethynyl‐ and acetylide‐amidinates of the coinage metals is presented. Starting with the desilylation of the complexes [{Me$_{3}$SiC≡CC(NDipp)$_{2}$}$_{2}$M$_{2}$] (Dipp=2,6‐diisopropylphenyl) (M=Cu, Au) it is demonstrated that this compound class is suitable to serve as a versatile metalloligand. Deprotonation with n‐butyllithium and subsequent salt metathesis reactions yield symmetric tetranuclear gold(I) acetylide complexes of the form [{(PPh$_{3}$)AuC≡CC(NDipp)$_{2}$}$_{2}$M$_{2}$] (M=Cu, Au). The corresponding Ag complex [{(PPh$_{3}$)AuC≡CC(NDipp)$_{2}$}$_{2}$Ag$_{2}$] was obtained by a different route via metal rearrangement. All compounds show bright blue or blue‐green microsecond long phosphorescence in the solid state, hence their photophysical properties were thoroughly investigated in a temperature range of 20–295 K. Emission quantum yields of up to 41 % at room temperature were determined. Furthermore, similar emissions with quantum yields of 15 % were observed for the two most brightly luminescent complexes in thf solution

Atlas of the clinical genetics of human dilated cardiomyopathy

[Abstract] Aim. Numerous genes are known to cause dilated cardiomyopathy (DCM). However, until now technological limitations have hindered elucidation of the contribution of all clinically relevant disease genes to DCM phenotypes in larger cohorts. We now utilized next-generation sequencing to overcome these limitations and screened all DCM disease genes in a large cohort. Methods and results. In this multi-centre, multi-national study, we have enrolled 639 patients with sporadic or familial DCM. To all samples, we applied a standardized protocol for ultra-high coverage next-generation sequencing of 84 genes, leading to 99.1% coverage of the target region with at least 50-fold and a mean read depth of 2415. In this well characterized cohort, we find the highest number of known cardiomyopathy mutations in plakophilin-2, myosin-binding protein C-3, and desmoplakin. When we include yet unknown but predicted disease variants, we find titin, plakophilin-2, myosin-binding protein-C 3, desmoplakin, ryanodine receptor 2, desmocollin-2, desmoglein-2, and SCN5A variants among the most commonly mutated genes. The overlap between DCM, hypertrophic cardiomyopathy (HCM), and channelopathy causing mutations is considerably high. Of note, we find that >38% of patients have compound or combined mutations and 12.8% have three or even more mutations. When comparing patients recruited in the eight participating European countries we find remarkably little differences in mutation frequencies and affected genes. Conclusion. This is to our knowledge, the first study that comprehensively investigated the genetics of DCM in a large-scale cohort and across a broad gene panel of the known DCM genes. Our results underline the high analytical quality and feasibility of Next-Generation Sequencing in clinical genetic diagnostics and provide a sound database of the genetic causes of DCM.Hôpitaux de Paris; PHRC AOM0414

Separation – integration – and now …? - An historical perspective on the relationship between German management accounting and financial accounting

German accounting has traditionally followed a dual ledger approach with strictly separated internal cost accounting, as the basis for management information, and external financial accounting focusing on creditor protection and based on the commercial law. However, the increased adoption of integrated accounting system implies a significant change in the relationship between financial and management accounting systems. We use Hegelian dialectic to trace the historical development of German accounting from separated systems towards antithetical propositions of full integration, and the emergence of partial integration as the synthesis of this transformation process. For this reason, our paper provides a comprehensive analysis of the literature on the relationship between financial and management accounting in Germany. On this basis, we elaborate how financial accounting in Germany has been shaped by its economic context and legislation, and how financial accounting – accompanied by institutional pressures – in turn influenced management accounting. We argue that the changing relationship between management and financial accounting in the German context illustrates how current accounting practice is shaped not only by its environment, but also by its historical path. Based on this reasoning, we discuss several avenues for future research

Untersuchungen zur Signaltransduktion in Zellinien der Akuten Myeloischen Leukämie mit Mutationen der Rezeptortyrosinkinase

In der vorliegenden Arbeit wurden von Leukämiepatienten abgeleitete permanente Zellinien mit Mutationen der Rezeptortyrosinkinase FLT3 untersucht. Dabei handelte es sich um die Zellinien MOLM-13 und MV4-11 mit einer internen Tandemduplikation (FLT3-ITD) sowie die Zellinie MONO-MAC-6 mit einer Punktmutation in der juxtamembranären Domäne der Rezeptortyrosinkinase. Als biologische Kontrolle wurde die Zellinie THP-1 untersucht, eine Zellinie mit FLT3-Wildtyp-Expression. Ziel der Arbeit war die Charakterisierung der Zellinien hinsichtlich Signaltransduktion, Zellzyklusverteilung, Differenzierungsinduktion sowie Apoptose- und Proliferationsverhalten nach vorangehender Inkubation mit dem Tyrosinkinaseinhibitor D-65476 sowie den beiden Substanzen All-trans-Retinsäure (ATRA) und G-CSF. Zusammenfassend konnte in der vorliegenden Arbeit die Bedeutung der Rezeptortyrosinkinase FLT3 auf Proliferation, Apoptose und Differenzierung in den genannten Modellsystemen gezeigt werden. Durch die Hemmung von FLT3 mittels des Inhibitors D-65476 konnte die Proliferation der untersuchten Zellinien gehemmt, Apoptose induziert und begleitend eine Zellzyklusumverteilung beobachtet werden. ATRA konnte insbesondere in den Zellinien mit FLT3-ITD-Mutation die Apoptoserate signifikant steigern. So erscheint es vielversprechend, konventionelle Chemotherapieregime durch derartige Substanzen zu ergänzen