Simulation und Darstellung eines Copolymers aus Styrol, n-Butylacrylat, Hydroxyethylmethacrylat und Acrylsäure mit besonderen Struktrurmerkmalen

Mit Unterstützung von Simulationen wurde radikalisch in tech. Xylol ein ternäres Acrylat-Copolymer aus den Monomeren Styrol (S), n-Butylacrylat (n-BA) und Hydroxyethylmethacrylat (HEMA) hergestellt, welches neue Strukturmerkmale (hart/weich Segmente) aufweist. Das hergestellte Copolymer besitzt eine große mittlere Sequenzlänge der Monomeren Styrol und n-BA. Zusätzlich besitzt das Copolymer eine sehr enge Molekulargewichtsverteilung und ein sehr niedriges Molekulargewicht (Mn < 3000 g/mol). Um die mittlere Sequenzlänge von Styrol und von n-BA weiter zu vergrößern, wurde die Reaktionstemperatur erhöht und das ursprüngliche ternäre Copolymer in zwei ineinander lösliche binäre Copolymere aufgetrennt. Des weiteren wurden die kinetische Daten der Homopolymerisation des Monomers HEMA bei 60°C und bei 180°C in verschiedenen Lösungsmitteln (Dioxan, DMF, DMSO, Ethanol, tech. Xylol (Ethylbenzol, o- und p ?Xylol) bei 60°C und Decahydronaphtalin (Decalin), Diphenylether, Diphenylmetan, Isodurol, Tetrahydronaphtalin (THN) bei 180°C ermittelt. Außerdem wurden die Copolymerisationsparameter von HEMA - Styrol und von HEMA - n-BA in tech. Xylol bei 180°C nach Kélen-Tüdös bestimmt. Beide Copolymere wurden anschließend in einer Kleintechnikumsanlage in tech. Xylol synthetisiert und miteinander gemischt. Der hergestellte Lackrohstoff erwies sich als kratz- und schlagfest, was auf die neuen Strukturmerkmale zurückzuführen ist

Ein Fall von Paratyphus-B-Meningitis

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Concurrent detection of autolysosome formation and lysosomal degradation by flow cytometry in a high-content screen for inducers of autophagy

<p>Abstract</p> <p>Background</p> <p>Autophagy mediates lysosomal degradation of cytosolic components. Recent work has associated autophagic dysfunction with pathologies, including cancer and cardiovascular disease. To date, the identification of clinically-applicable drugs that modulate autophagy has been hampered by the lack of standardized assays capable of precisely reporting autophagic activity.</p> <p>Results</p> <p>We developed and implemented a high-content, flow-cytometry-based screening approach for rapid, precise, and quantitative measurements of pharmaceutical control over autophagy. Our assay allowed for time-resolved individual measurements of autolysosome formation and degradation, and endolysosomal activities under both basal and activated autophagy conditions. As proof of concept, we analyzed conventional autophagy regulators, including cardioprotective compounds aminoimidazole carboxamide ribonucleotide (AICAR), rapamycin, and resveratrol, and revealed striking conditional dependencies of rapamycin and autophagy inhibitor 3-methyladenine (3-MA). To identify novel autophagy modulators with translational potential, we screened the Prestwick Chemical Library of 1,120 US Food and Drug Administration (FDA)-approved compounds for impact on autolysosome formation. In all, 38 compounds were identified as potential activators, and 36 as potential inhibitors of autophagy. Notably, amongst the autophagy enhancers were cardiac glycosides, from which we selected digoxin, strophanthidin, and digoxigenin for validation by standard biochemical and imaging techniques. We report the induction of autophagic flux by these cardiac glycosides, and the concentrations allowing for specific enhancement of autophagic activities without impact on endolysosomal activities.</p> <p>Conclusions</p> <p>Our systematic analysis of autophagic and endolysosomal activities outperformed conventional autophagy assays and highlights the complexity of drug influence on autophagy. We demonstrate conditional dependencies of established regulators. Moreover, we identified new autophagy regulators and characterized cardiac glycosides as novel potent inducers of autophagic flux.</p

Die individuelle Aktivität des Interferon-Typ-I-Signalwegs in Immunzellen von Patienten mit Multipler Sklerose in Assoziation mit dem Krankheitsverlauf unter Therapie

Interferon-beta (IFN-ß) ist ein Basistherapeutikum bei schubförmiger Multipler Sklerose (MS). Einige Patienten zeigen vor Therapie vermehrte IFN-ähnliche Aktivität gemessen an der Expression des IFN-stimulierten MX1-Gens. Diese Arbeit evaluiert das prognostische Potential endogen erhöhter MX1-Expression für den individuellen MS-Krankheitsverlauf unter IFN-ß-Therapie. Es wurden molekulare Ursachen endogener IFN-Aktivität eruiert und genregulatorische Therapieeffekte aufgezeigt. Hierzu wurden longitudinale Genexpressionsdaten zu 61 Patienten und deren Krankheitsverlauf über 5 Jahre analysiert

Two-Buffer Simulation Games

We consider simulation games played between Spoiler and Duplicator on two Büchi automata in which the choices made by Spoiler can be buffered by Duplicator in two different buffers before she executes them on her structure. Previous work on such games using a single buffer has shown that they are useful to approximate language inclusion problems. We study the decidability and complexity and show that games with two buffers can be used to approximate corresponding problems on finite transducers, i.e. the inclusion problem for rational relations over infinite words

Following autophagy step by step

Autophagy is an evolutionarily conserved lysosomal degradation route for soluble components of the cytosol and organelles. There is great interest in identifying compounds that modulate autophagy because they may have applications in the treatment of major diseases including cancer and neurodegenerative disease. Hundeshagen and colleagues describe this month in BMC Biology a screening assay based on flow cytometry that makes it possible to track distinct steps in the autophagic process and thereby identify novel modulators of autophagy

The surgical patient of yesterday, today, and tomorrow — a time-trend analysis based on a cohort of 8.7 million surgical patients

Background: Global healthcare delivery is challenged by the aging population and the increase in obesity and type 2 diabetes. The extent to which such trends affect the cohort of patients the authors surgically operate on remains to be elucidated. Comprising of 8.7 million surgical patients, the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) database can be analyzed to investigate the echo of general population dynamics and forecast future trends. Material and methods: The authors reviewed the ACS-NSQIP database (2008–2020) in its entirety, extracting patient age, BMI, and diabetes prevalence. Based on these data, the authors forecasted future trends up to 2030 using a drift model. Results: During the review period, median age increased by 3 years, and median BMI by 0.9 kg/m2. The proportion of patients with overweight, obesity class I, and class II rates increased. The prevalence of diabetes rose between 2008 (14.9%) and 2020 (15.3%). The authors forecast the median age in 2030 to reach 61.5 years and median BMI to climb to 29.8 kg/m2. Concerningly, in 2030, eight of ten surgical patients are projected to have a BMI above normal. Diabetes prevalence is projected to rise to 15.6% over the next decade. Conclusion: General population trends echo in the field of surgery, with the surgical cohort aging at an alarmingly rapid rate and increasingly suffering from obesity and diabetes. These trends show no sign of abating without dedicated efforts and call for urgent measures and fundamental re-structuring for improved future surgical care