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Additional file 1: Supplementary Figure S1. Expression of lymphocyte markers in different passages. Supplementary Figure S2. In situ hybridization of EBV. Supplementary Table S1. RT-qPCR primers purchased from Sigma-Aldrich. Supplementary Table S2. Data of BI-12 growth curve. Supplementary Table S3. Data of HDM201 treatment in BI-12 cells.

The research aim of this review is a summary of the „oddball paradigm“. I will investigate its effects with a statistical analysis (p-curve) and discuss theoretical background. Also it is a goal to investigate certain factors that influence the effect, especially expectations.

In der Corona-Pandemie hat der Staat in Deutschland auf verschiedenen Ebenen eine zentrale Rolle eingenommen, wodurch mehrere aus der Pandemiebekämpfung resultierende Sondereffekte die Entwicklung der Staatsaggregate in den Volkswirtschaftlichen Gesamtrechnungen (VGR) beeinflussen. Dazu zählen Schließungen von Kindertageseinrichtungen, die Beschaffung von Impfstoffen oder die Verschiebung von nicht akut notwendigen Operationen. Dieser Aufsatz fokussiert spezielle Punkte, die sich im Laufe der Corona-Pandemie als Herausforderungen für die Berechnung und Interpretation von staatlichen Aggregaten herausstellten, und national oder international diskutiert wurden. Er zeigt, dass sich einige dieser Punkte erheblich auf den Verlauf und das Niveau von staatlichen Aggregaten in den VGR auswirken. General government has played a key role at various levels in Germany during the coronavirus pandemic. For that reason, the development of general government aggregates in national accounts has been influenced by several special effects resulting from the fight against the pandemic. This includes the closing of child day care centres, the procurement of vaccines and the postponement of non-urgent operations. This article focuses on special issues which have become a challenge for the calculation and interpretation of general government aggregates during the pandemic and have been discussed nationally or internationally. The article shows that some of these issues have had a significant impact on the trend and level of general government aggregates in national accounts.

Head and neck squamous cell carcinoma (HNSCC) is a highly malignant disease with a mortality rate of about 50%. It represents the sixth most common type of malignant tumor in the world. Risk factors include tobacco and alcohol usage and infection with the human papilloma virus (HPV). HPV-negative HNSCCs frequently display areas of cornification evident by keratin pearls in the tumor tissue. Cornification represents a natural differentiation path of keratinocytes in the normal epidermis and oral mucosa. To investigate the mechanisms of HNSCC cell differentiation we have established spheroid cell cultures from patient-derived HNSCC and parotid gland adenoid cystic carcinoma (ACC) tissue that grow in suspension under serum-free conditions. The use of a specific differentiation medium induced striking adhesion, loss of proliferation, and differentiation in tumor cells. Spheroid cells grew as single cell clones under serum-free conditions with a cloning efficiency of 40-60%, which was fully diminished under differentiating conditions. HNSCC cells cornified as indicated by the formation of lamellar bodies in the cytoplasm of adherent cells and an upregulation of cornification markers SPRR3 and involucrin. ACC cells upregulated parotid gland differentiation markers including α-amylase. RNA-seq analysis in HNSCC cells confirmed an upregulation of signaling pathways associated with cornification and epithelial cell differentiation. Conversely, pathways regulating the three-dimensional organization of the genome were downregulated upon differentiation. This was accompanied by the formation of ATRX-positive heterochromatin foci in the nucleus of differentiated ACC and HNSCC cells resembling those previously described to arise during therapy-induced senescence. Moreover, gas chromatography mass spectrometry analysis revealed a lack of essential amino acids including leucine to be implicated in the differentiation process. Altogether, our spheroid model of HNSCC and ACC cells is suitable to analyze the mechanisms underlying tumor cell differentiation and might lead to new therapeutic approaches that can drive long-term repopulating HNSCC and ACC cells into differentiation. Citation Format: Felix Oppel, Senyao Shao, Sarah Gendreizig, Philipp Kühnel, Vivien Przybycin, Carsten Hain, Pascal Schmidt, Matthias Schürmann, Peter Goon, Karsten Niehaus, Jörn Kalinowski, Holger Sudhoff. Head and neck cancer cells can differentiate and resemble their tissue of origin [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 111.

Dieser Artikel gibt einen frühen Überblick über die wichtigsten Entwicklungen in der deutschen Wirtschaft im Jahr 2020 unter dem Eindruck der Corona-Pandemie. Das Bruttoinlandsprodukt ist im Jahr 2020 nach ersten vorläufigen Ergebnissen um 5,0 % zurückgegangen. Die deutsche Wirtschaft ist somit nach einer zehnjährigen Wachstumsphase in eine tiefe Rezession geraten, ähnlich wie zuletzt während derFinanz- und Wirtschaftskrise 2008/2009. Dabei war die Entwicklung in den einzelnen Quartalen sehr unterschiedlich; sie stand jeweils in engem Zusammenhang mit den Maßnahmen, die zur Eindämmung der Pandemie ergriffen wurden This article provides an early overview of the major trends in Germany's economy during the coronavirus pandemic in 2020. The gross domestic product declined by 5.0% in 2020, according to first provisional results. After a ten-year growth period, the German economy has fallen into a deep recession similar to that of the 2008-2009 financial and economic crisis. Depending on the measures taken to contain the pandemic, the trends differed significantly in the individual quarters of 2020.

Der Workshop zeigt einen unterrichtspraktischen Weg auf, wie in das Thema “Lernende Algorithmen” am Beispiel von Entscheidungsbäumen im Informatikunterricht der Sekundarstufe II eingeführt werden kann.

One of the open challenges in chemical biology is to identify reactions that proceed with large rate constants in water at neutral pH values. Once assembled, these conjugates may be used for a broad variety of applications (e.g., therapeutics, imaging probes or as a catalytic system). Herein we describe a novel approach for the chemical modification of nucleic acids using guided organometallic-catalysts. Customized dirhodium complexes were prepared using modular ligands bearing various functional groups and connected to peptide nucleic acids through stable oxime linkages. The final constructs have been optimized for aqueous catalysis and were tested in preliminary alkylation studies of single-stranded DNA via dirhodium-carbenoids generated from alpha-diazocarbonyl compounds. During the course of optimizing the rather slow kinetics of oxime formation, we have developed two highly efficient methods for rapid oxime-based bioconjugations. (1) Dialdehydes were found to react with O-alkylhydroxylamines at rates of 500 M-1 s-1 in neutral aqueous buffer in the absence of a catalyst. The key to these conjugations is an unusually stable cyclic intermediate, which ultimately undergoes dehydration to yield an oxime. The scope and limitations of this method are outlined, as well as its application in bioconjugation with a DNA 41-mer and a mechanistic interpretation that will facilitate further developments of reactions with O-alkylhydroxylamines at low substrate concentrations. (2) Oximes proximal to boronic acids form in neutral aqueous buffer with rate constants of more than 104 M−1 s−1, the largest to date for any oxime condensation. The reaction tolerates a variety of biological interfering additives and is suitable for the rapid modification of short peptide sequences. Once formed, the oxime products are stable for days and undergo slow interconversion through a hydrolysis-based mechanism. Boron's dynamic coordination chemistry confers an adaptability that seems to aid a number of elementary steps in the oxime condensation. In conclusion both methods represent important improvements for oxime-based bioconjugations in water (pH 7) at low equimolar concentrations. The high reaction kinetics are achieved without the need for additional reagents, catalysts or variations of the reaction conditions. In addition, the possibility of using reacting pairs that are commercially available will greatly enhance the applicability of these methods for efficient conjugations of precious biomolecules in the future.

La planification automatique est un domaine de recherche de l’Intelligence Artificielle qui vise à calculer automatiquement une séquence d’actions menant d’un état initial donné à un but souhaité. Cependant, résoudre des problèmes réalistes est généralement difficile car trouver un chemin solution peut demander d’explorer un nombre d’états croissant exponentiellement avec le nombre de variables. Pour faire face à cette explosion combinatoire, les algorithmes performants ont recours aux heuristiques ou à des solutions hiérarchiques, décomposant le problème en sous-problèmes plus petits et plus simples. Dans une grande majorité des cas, le planificateur doit prendre en compte un certain nombre de contraintes telles que des phases d’actions prédéfinies ou des protocoles. Ces contraintes aident à résoudre le problème en élaguant un grand nombre de branches de l’arbre de recherche. Nous proposons alors une nouvelle méthode pour modéliser et résoudre des problèmes de planification déterministe en se basant sur une approche hiérarchique et heuristique. Nous nous sommes inspirés des formalismes de programmation structurée afin de fournir à l’utilisateur un cadre de travail plus intuitif pour la modélisation des domaines de planification hiérarchique. D’autre part, nous avons proposé un algorithme de planification capable d’exploiter ce formalisme et composer des stratégies à différents niveaux de granularité, ce qui lui permet de planifier rapidement une stratégie globale, tout en étant en mesure de pallier aux difficultés rencontrées à plus bas niveau. Cet algorithme a fait ses preuves face au principal planificateur HTN, SHOP2, sur des problèmes de planification classique. Automated planning is a field of Artificial Intelligence which aims at automatically computing a sequence of actions that lead to some goals from a given initial state. However, solving realistic problems is challenging because finding a solution path may require to explore an exponential number of states with regard to the number of state variables. To cope with this combinatorial explosion, efficient algorithms use heuristics, which guide the search towards optimistic or approximate solutions. Remarkably, hierarchical methods iteratively decompose the planning problem into smaller and much simpler ones. In a vast majority of problems, the planner must deal with constraints, such as multiple predefined phases or protocols. Such constraints generally help solving the planning problem, because they prune lots of search paths where these constraints do not hold. In this thesis, we assume that these constraints are known and given to the planner. We thus propose a new method to model and solve a deterministic planning problem, based on a hierarchical and heuristic approach and taking advantage of these constraints. We inspired ourselves from structured programming formalisms in order to offer a more intuitive modeling framework in the domain of hierarchical planning to the user. We also proposed a planning algorithm able to exploit this formalism and build strategies at various levels of granularity, thus allowing to plan quickly a global strategy, while still being able to overcome the difficulties at lower level. This algorithm showed its performances compared with the main HTN planner, SHOP2, on classical planning problems.