In silico generation of novel, drug-like chemical matter using the LSTM neural network

The exploration of novel chemical spaces is one of the most important tasks of cheminformatics when supporting the drug discovery process. Properly designed and trained deep neural networks can provide a viable alternative to brute-force de novo approaches or various other machine-learning techniques for generating novel drug-like molecules. In this article we present a method to generate molecules using a long short-term memory (LSTM) neural network and provide an analysis of the results, including a virtual screening test. Using the network one million drug-like molecules were generated in 2 hours. The molecules are novel, diverse (contain numerous novel chemotypes), have good physicochemical properties and have good synthetic accessibility, even though these qualities were not specific constraints. Although novel, their structural features and functional groups remain closely within the drug-like space defined by the bioactive molecules from ChEMBL. Virtual screening using the profile QSAR approach confirms that the potential of these novel molecules to show bioactivity is comparable to the ChEMBL set from which they were derived. The molecule generator written in Python used in this study is available on request.Comment: in this version fixed some reference number

Verwendung von Scalable Vector Graphics und MathML in web-basierten Lernumgebungen

In web-basierten Lernumgebungen werden Rastergraphiken eingesetzt, um Skizzen und Formeln darzustellen. Dies erschwert den Austausch und die Wiederverwendung von Lehrmaterialien unter Lernenden und Lehrenden. Dieser Beitrag stellt das Vektorgraphikformat SVG (Scalable Vector Graphics) und MathML, das Format zur Beschreibung mathematischer Ausdrücke, vor. Die Möglichkeiten des SVG-Formats reichen von der Darstellung einfacher Graphikelemente bis hin zu komplexen Filtern und Beleuchtungseffekten. In MathML lässt sich der inhaltliche Zusammenhang oder die Darstellung von mathematischen Ausdrücken beschreiben. Das letzte Kapitel gibt einen Ausblick auf Anwendungsfelder von web-basierten Lernumgebungen mit SVG und MathML

Die Steuerreformen und die Wirkung der kalten Progression im Zeitraum 2016 bis 2025: Überblick über die IHS Studie und aktuelle Handlungsempfehlung

Die Diskussion um die kalte Progression in Österreich ist zunächst vergangenen Herbst, anlässlich der Ankündigung der ökosozialen Steuerreform durch die Bundesregierung, wieder aufgeflammt und hat durch den dramatischen Anstieg der Inflation seit Jahresbeginn nun zusätzlich an Aktualität gewonnen. Eine kürzlich veröffentlichte Studie des IHS (Reiter et al. (2022)), in der die Effekte der kalten Progression seit der letzten Steuerreform 2015/2016 sowie der steuerpolitischen Reformmaßnahmen im Beobachtungs- und Prognosezeitraum von 2016 bis 2025 geschätzt und gegenübergestellt wurden, kommt zu folgenden Ergebnissen: Ausgehend von den Inflationsprognosen vom Dezember des letzten Jahres übersteigt die Entlastung durch die Steuerreformen bei weitem die Effekte der kalten Progression. Über den betrachteten Zeithorizont liegt die Nettoentlastung in Summe bei fast 10 Milliarden Euro. Die Entlastung ist für Haushalte mit Kindern am stärksten, generell profitieren vor allem untere Einkommen, in geringem Ausmaß aber auch mittlere Einkommen, und Spitzeneinkommen deutlich weniger bis gar nicht. Der unerwartete Inflationsschub der vergangenen Monate hat das Bild allerdings drastisch geändert. Neue Schätzungen auf Basis aktualisierter Inflationsprognosen ergeben ab dem Jahr 2022 einen zussätzlichen Effekt der kalten Progression von etwa einer Milliarde Euro pro Jahr. Diese zusätzliche Steuerbelastung von Arbeits- und Pensionseinkommen könnte durch eine einmalige Anhebung der Tarifgrenzen der Lohn- und Einkommensteuer, zumindest auf aggregierter Ebene, fast vollständig ausgeglichen werden

Die Auswirkungen des von der EU beschlossenen Embargos russischer Ölimporte auf die österreichische Wirtschaft

Am 30. Mai 2022 beschlossen die 27 Staats- und Regierungschefs der EU-Mitgliedsstaaten ein Ölembargo gegen die Russische Föderation. Es ist wahrscheinlich, dass ein solches Embargo eine erhebliche Steigerung der Ölpreise auf dem Weltmarkt bewirken wird, oder dessen Antizipation eine solche Steigerung schon bewirkt hat. Ziel dieser Kurzstudie ist es, die Auswirkungen des Embargos auf die österreichische Wirtschaft abzuschätzen, wobei der Fokus auf den kurzfristigen Auswirkungen liegt

Monitoring of metabolic parameters of mammal cells cultures in microfluidic devices using integrated optical chemical sensors

Optical chemical sensors are well established in the chemical industry, life science, biotechnology and research laboratories. They are operate non-invasive, do not need any reference elements and can be read-out via contactless measurement. Moreover, it is possible to miniaturize and integrate them into microfluidic systems. Due to their simple composition, optical sensors can be produced at low price and therefore represent a good alternative compared to electrochemical sensors for their application in disposable microfluidics. The various possibilities of integrated optical oxygen sensors have already shown their potential in different microfluidic applications [1]. However, monitoring of further metabolic parameters is important for a better understanding of biological processes. Therefore, our group develops, next to oxygen sensors, also optical sensors for monitoring pH, glucose, CO2, ammonia and various ions. Still, integration in a Lab-on-a-chip format is a challenging task due to the state-of-the-art performances in terms of signal brightness, response times, optoelectronic read-out systems, fabrication and integration. Please click Additional Files below to see the full abstrac

Clinical examination and patients’ history are not suitable for neonatal hip screening

PURPOSE: To assess the percentage of missed developmental dysplasia of the hip, which escape the German criteria for newborn hip high-risk screening, we analyzed our data gained from the general neonatal sonographic hip screening performed at our department. The aim of the study was to determine the number of potentially belatedly treated developmental dysplasia of the hip. METHODS: The data from 1145 standardized newborn hip ultrasound examinations according to the Graf technique were analyzed retrospectively comparing findings for general neonatal sonographic hip screening and high-risk screening subgroups. RESULTS: We diagnosed developmental dysplasia of the hip in 18 of the 1145 newborns via ultrasound. A total of 10 out of 18 developmental dysplasia of the hip would have been missed by high-risk screening, which corresponds to a proportion of 55.6% false-negative results. The sensitivity of high-risk screening was only 44.4% and specificity, 78.3%. The positive predictive value was 3.2%. Family history as a screening criterion yielded false-negative results in 77.8% and false-positive results in 16.8%. In all, 83.3% of the children who were born with developmental dysplasia of the hip but not from breech position as a risk factor were false negative. The clinical examination was false negative in 88.9% and false positive in 0.6%. CONCLUSION: High-risk screening detected less than every second developmental dysplasia of the hip, rendering the first month as the most effective treatment window unavailable for inapparent dysplastic hips, potentially resulting in the need for more invasive treatment. Due to the high sensitivity of ultrasound in the detection of developmental dysplasia of the hip, we recommend to replace the current German high-risk screening guidelines with a general newborn screening for all neonates using Graf ultrasound in the first week of life. LEVEL OF EVIDENCE: Level II

Dietary calcium concentration and cereals differentially affect mineral balance and tight junction proteins expression in jejunum of weaned pigs

Ca plays an essential role in bone development; however, little is known about its effect on intestinal gene expression in juvenile animals. In the present study, thirty-two weaned pigs (9·5 (sem 0·11) kg) were assigned to four diets that differed in Ca concentration (adequate v. high) and cereal composition (wheat–barley v. maize) to assess the jejunal and colonic gene expression of nutrient transporters, tight junction proteins, cytokines and pathogen-associated molecular patterns, nutrient digestibility, Ca balance and serum acute-phase response. To estimate the impact of mucosal bacteria on colonic gene expression, Spearman's correlations between colonic gene expression and bacterial abundance were computed. Faecal Ca excretion indicated that more Ca was available along the intestinal tract of the pigs fed high Ca diets as compared to the pigs fed adequate Ca diets (P0·35; P< 0·05) indicated an association between operational taxonomic units assigned to the phyla Bacteroidetes, Firmicutes and Proteobacteria and bacterial metabolites and mucosal gene expression in the colon. The present results indicate that high Ca diets have the potential to modify the jejunal and colonic mucosal gene expression response which, in turn, interacts with the composition of the basal diet and mucosa-associated bacteria in weaned pigs