Multivalent 1,2,3‐Triazole‐Linked Carbohydrate Mimetics by Huisgen–Meldal‐Sharpless Cycloadditions of an Azidopyran

Starting from an enantiopure 3‐azido‐substituted pyran derivative and various oligo‐alkynes a series of multivalent 1,2,3‐triazole‐linked carbohydrate mimetics was synthesized. The copper‐catalyzed Huisgen–Meldal‐Sharpless cycloaddition (CuAAC) served as key coupling reaction. Cu/C in the presence of triethylamine proved to be a good catalytic system in most cases. Tri‐, tetra‐, hexa‐, and octavalent compounds with typical rigid or flexible core units were prepared. The most complex compound contains a C60‐fullerene center leading to a dodecavalent carbohydrate mimetic. Only a few of the multivalent target compounds could be converted into pure O‐sulfated derivatives that are required for their evaluation as L‐ and P‐selectin ligands. Nevertheless, preliminary experiments suggest that the dodecavalent C60‐derived compound may be a promising ligand of these biologically important proteins with IC50 values in the low nanomolar range

Stickstoff- und Schwefelversorgung von Rapsbeständen im Ökologischen Landbau

In this study results of 3 experimental years, 4 locations (2009-2011) and additionally 12 fields in northern and eastern Germany (only in 2011) are presented with regard to the nitrogen and sulphur status of oil seed rape. The nitrogen and sulphur level was often not sufficient, so that the fertilisation regimes have to be optimised

Contradictory antecedent debugging in bounded model checking

In the context of formal verification Bounded Model Check-ing (BMC) has shown to be very powerful for large industrial designs. BMC is used to check whether a circuit satisfies a temporal property or not. Typically, such a property is for-mulated as an implication. In the antecedent of the property the verification engineer specifies the assumptions about the design environment and joins the respective expressions by logical AND. However, the overall conjunction may have no solution, i.e. the antecedent is contradictory. Since in this case a property trivially holds this situation has to be avoided. Furthermore, the root cause of a contradictory an-tecedent has to be identified which is a manual and very time-consuming process. In this paper we propose a fully automatic approach for presenting all reasons of a contradictory antecedent to the verification engineer, i.e. the approach pinpoints to the sub-expressions in the antecedent that form a contradiction. Hence, our approach reduces the debugging time of a con-tradictory antecedent significantly

Formal Verification of Integer Multipliers by Combining Gröbner Basis with Logic Reduction

Formal verification utilizing symbolic computer algebra has demonstrated the ability to formally verify large Galois field arithmetic circuits and basic architectures of integer arithmetic circuits. The technique models the circuit as Gröbner basis polynomials and reduces the polynomial equation of the circuit specification wrt. the polynomials model. However, during the Gröbner basis reduction, the technique suffers from exponential blow-up in the size of the polynomials, if it is applied on parallel adders and recoded multipliers. In this paper, we address the reasons of this blow-up and present an approach that allows to apply the technique on basic and complex parallel architectures of multipliers. The approach is based on applying a logic reduction rule during Gröbner basis rewriting. The rule uses structural circuit information to remove terms that evaluate to zero before their blow-up. The experiments show that the approach is applicable up to 128 bit multipliers

Schädlingsregulierung im ökologischen Winterrapsanbau

Die Versuche unter norddeutschen Praxisbedingungen sowie die Ergebnisse der Feldversuche belegen eine durchgehend höhere Attraktivität des Rübsens gegenüber Raps für den Rapsglanzkäfer. Damit werden die Beobachtungen aus der Praxis zunächst bestätigt. Durch den direkten Vergleich von Rapsfeldern mit und ohne Rübsen-Randstreifen sowie von Raps/Rübsen-Mischsaaten mit Rapsreinsaat in Praxis- sowie Feldversuchen war es möglich, den Erfolg dieser Maßnahme in seiner gesamten Wirkungsvielfalt zu untersuchen. Es hat sich gezeigt, dass entgegen den Erwartungen weder der Schädlingsbesatz noch der Schaden im Rapskernbestand durch den Rübsen-Fangstreifen wesentlich reduziert werden konnte. Ebenso erbrachte die flächige Mischsaat von Raps mit Rübsen keine deutliche Entlastung für die Schadensausprägung in der Hauptkomponente Raps. Die Wirkungsgrade der Fangpflanzen blieben damit deutlich hinter den Erwartungen der Praxis zurück und die Mehraufwendungen überstiegen den erwarteten Nutzen. Zusammenfassend muss festgestellt werden, dass der alleinige Fangpflanzenanbau als Randstreifen um den Rapsbestand herum oder als Mischsaat der Praxis als alleiniges Konzept für die Schädlingsregulierung nicht empfohlen werden kann und sogar das ökonomische Verlustrisiko erhöht. Diese Erkenntnis ist für die Praxis sehr wertvoll, da die Anwendung der Fangpflanzen zum Teil empfohlen wird und der Landwirt durch die stärkere Bindung der Rapsglanzkäfer an den Rübsen vermeintlich glaubt, erfolgreich den Schädlingsbefall zu regulieren und damit die Erträge zu erhöhen. Die praxisnahen Versuche haben noch einmal die Schwierigkeiten des ökologischen Rapsanbaus in seiner gesamten Breite aufgezeigt. Ausgehend von dem hohen Nährstoffbedarf reichen die Probleme bei der Unkraut- und Schädlingsregulierung bis zur Ernte, bei der zusätzlich durch ungleichmäßige Abreife und geringe Schotenfestigkeit, hohe Ernteverluste entstehen können. Die Untersuchungen zur Wirkung naturstofflicher Pflanzenschutzmittel konnten einen Hinweis darauf geben, welche Wirkstoffe eine wirksame Kontrolle der Rapsglanzkäfer ermöglichen. Dazu zählen Spinosad, ein Fermentationsprodukt aus einem Bodenmikroorganismus sowie Gesteinsmehle, die allerdings mehrfach angewendet werden müssen und deshalb nur für die Teilflächenbehandlung in Frage kommen. Während in der Schweiz Spinosad in einem Pflanzenschutzmittel im Raps zugelassen ist, fehlt eine derartige Zulassung bisher in Deutschland und darf nicht angewendet werden

HIV-Studien und HIV-Projekte am Robert Koch-Institut

Neben der gesetzlich geregelten Surveillance von HIV-Neudiagnosen in Deutschland erfolgt am RKI auch die Durchführung verschiedener Studienprojekte, die im Epidemiologischen Bulletin 49/2019 vorgestellt werden. Das Rückgrat der erweiterten HIV-Surveillance in Deutschland bilden vier Studien: das Monitoring rezenter HIV-Infektionen in Deutschland (InzSurv-HIV), die Molekulare Surveillance von HIV-Neudiagnosen (MolSurv-HIV), die HIV-1 Serokonverterstudie und die Klinische Surveillance der HIV-Erkrankung (ClinSurv-HIV). Bei InzSurv-HIV und MolSurv-HIV werden Proben von Patienten untersucht, die gerade neu diagnostiziert wurden. Bei der HIV-1 Serokonverterstudie und bei ClinSurv-HIV handelt es sich um Kohortenstudien. Ergänzend dazu wird am RKI auch das AIDS-Fallregister betrieben, in dem seit 1982 auf freiwilliger Basis anonym durch die behandelnden Ärzte berichtete AIDS-Erkrankungsfälle und -Todesfälle in Deutschland zusammengetragen und ausgewertet werden

Sex Differences in Cardiac Mitochondria in the New Zealand Obese Mouse

Background: Obesity is a risk factor for diseases including type 2 diabetes mellitus (T2DM) and cardiovascular disorders. Diabetes itself contributes to cardiac damage. Thus, studying cardiovascular events and establishing therapeutic intervention in the period of type T2DM onset and manifestation are of highest importance. Mitochondrial dysfunction is one of the pathophysiological mechanisms leading to impaired cardiac function.Methods: An adequate animal model for studying pathophysiology of T2DM is the New Zealand Obese (NZO) mouse. These mice were maintained on a high-fat diet (HFD) without carbohydrates for 13 weeks followed by 4 week HFD with carbohydrates. NZO mice developed severe obesity and only male mice developed manifest T2DM. We determined cardiac phenotypes and mitochondrial function as well as cardiomyocyte signaling in this model.Results: The development of an obese phenotype and T2DM in male mice was accompanied by an impaired systolic function as judged by echocardiography and MyH6/7 expression. Moreover, the mitochondrial function only in male NZO hearts was significantly reduced and ERK1/2 and AMPK protein levels were altered.Conclusions: This is the first report demonstrating that the cardiac phenotype in male diabetic NZO mice is associated with impaired cardiac energy function and signaling events

The ghost sex-life of the paedogenetic beetle Micromalthus debilis

Genetic and sexual systems can be evolutionarily dynamic within and among clades. However, identifying the processes responsible for switches between, for instance, sexual and asexual reproduction, or cyclic and non-cyclic life histories remains challenging. When animals evolve parthenogenetic reproduction, information about the sexual mating system becomes lost. Here we report an extraordinary case where we have been able to resurrect sexual adults in a species of beetle that reproduces by parthenogenetic paedogenesis, without the production of adults. Via heat treatment, we were able to artificially induce adult beetles of Micromalthus debilis in order to describe its pre-paedogenetic mating system. Adults showed a highly female biased sex ratio, out-breeding behaviour, and sex-role reversal. Paedogenetic larvae of Micromalthus are infected with the endosymbiotic bacteria Rickettsia and Wolbachia. Clear signs of vestigialization in adults are concurrent with the loss of adults. Our data suggest an ancient female sex ratio bias that predated the loss of adults, perhaps associated with endosymbionts. We propose a model for the transition from a haplodiploid cyclical parthenogenetic life history to parthenogenetic paedogenesis. Paedogenetic development induces a new mechanism of sex ratio bias in midges, wasps and beetles

On Assessing Trustworthy AI in Healthcare. Machine Learning as a Supportive Tool to Recognize Cardiac Arrest in Emergency Calls

Artificial Intelligence (AI) has the potential to greatly improve the delivery of healthcare and other services that advance population health and wellbeing. However, the use of AI in healthcare also brings potential risks that may cause unintended harm. To guide future developments in AI, the High-Level Expert Group on AI set up by the European Commission (EC), recently published ethics guidelines for what it terms “trustworthy” AI. These guidelines are aimed at a variety of stakeholders, especially guiding practitioners toward more ethical and more robust applications of AI. In line with efforts of the EC, AI ethics scholarship focuses increasingly on converting abstract principles into actionable recommendations. However, the interpretation, relevance, and implementation of trustworthy AI depend on the domain and the context in which the AI system is used. The main contribution of this paper is to demonstrate how to use the general AI HLEG trustworthy AI guidelines in practice in the healthcare domain. To this end, we present a best practice of assessing the use of machine learning as a supportive tool to recognize cardiac arrest in emergency calls. The AI system under assessment is currently in use in the city of Copenhagen in Denmark. The assessment is accomplished by an independent team composed of philosophers, policy makers, social scientists, technical, legal, and medical experts. By leveraging an interdisciplinary team, we aim to expose the complex trade-offs and the necessity for such thorough human review when tackling socio-technical applications of AI in healthcare. For the assessment, we use a process to assess trustworthy AI, called 1Z-Inspection® to identify specific challenges and potential ethical trade-offs when we consider AI in practice.</jats:p