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In genome analysis, k-mer-based comparison methods have become standard tools. However, even though they are able to deliver reliable results, other algorithms seem to work better in some cases. To improve k-mer-based DNA sequence analysis and comparison, we successfully checked whether adding positional resolution is beneficial for finding and/or comparing interesting organizational structures. A simple but efficient algorithm for extracting and saving local k-mer spectra (frequency distribution of k-mers) was developed and used. The results were analyzed by including positional information based on visualizations as genomic maps and by applying basic vector correlation methods. This analysis was concentrated on small word lengths (1 ≤ k ≤ 4) on relatively small viral genomes of Papillomaviridae and Herpesviridae, while also checking its usability for larger sequences, namely human chromosome 2 and the homologous chromosomes (2A, 2B) of a chimpanzee. Using this alignment-free analysis, several regions with specific characteristics in Papillomaviridae and Herpesviridae formerly identified by independent, mostly alignment-based methods, were confirmed. Correlations between the k-mer content and several genes in these genomes have been found, showing similarities between classified and unclassified viruses, which may be potentially useful for further taxonomic research. Furthermore, unknown k-mer correlations in the genomes of Human Herpesviruses (HHVs), which are probably of major biological function, are found and described. Using the chromosomes of a chimpanzee and human that are currently known, identities between the species on every analyzed chromosome were reproduced. This demonstrates the feasibility of our approach for large data sets of complex genomes. Based on these results, we suggest k-mer analysis with positional resolution as a method for closing a gap between the effectiveness of alignment-based methods (like NCBI BLAST) and the high pace of standard k-mer analysis.

Localization microscopy, especially SPDM (Spectral Position Determination Microscopy), can scale optical resolution down almost to the electron microscopy level in the 10 nm range, which is important for biological and medical research and diagnosis. But these techniques produce image data in the range of GB/s and require the handling, processing and evaluation of image stacks of up to thousands of frames per single cell. These data have to be stored and made accessible for the research community, in diagnostic connotation for 30 years by law. To this end, we have designed a system for transmitting the data, adding meta data for characterization and retrieval, storing the data, and also offering programs and processing procedures for fast evaluation, on individual machines or in clusters. A Generic Client Service (GCS) API for connecting disparate services is designed and implemented seamlessly integrating with the KIT Data Manager and the Large Scale Data Storage. A structured metadata model based on Core Scientific Metadata Model (CSMD) is established for describing the extremely large datasets of localization microscopy research. Standardised descriptions of the workflow steps with an automated execution of the workflow, based on extended image analysis programs is achieved by a workflow management system (WfMS).

We review the process rates and energy intensities of various additive processing technologies and focus on recent progress in improving these metrics for laser powder bed fusion processing of metals, and filament and pellet extrusion processing of polymers and composites. Over the last decade, observed progress in raw build rates has been quite substantial, with laser metal processes improving by about 1 order of magnitude, and polymer extrusion processes by more than 2 orders of magnitude. We develop simple heat transfer models that explain these improvements, point to other possible strategies for improvement, and highlight rate limits. We observe a pattern in laser metal technologies that mimics the development of machine tools; an efficiency plateau, where faster rates require more power with no change in energy nor rate efficiency., Journal of Industrial Ecology, 21 (S1), ISSN:1088-1980, ISSN:1530-9290

International audience; Inactivation of the human CDKN2A tumor suppressor gene by mutation or epigenetic changes is a frequent signature of malignant melanoma. The locus encodes two transcripts, Ink4a and Arf, which are important regulators of the cell cycle. In teleost fish a gene has been identified, cdkn2ab, which represents the common ancestor of mammalian cdkn2a and cdkn2b genes. However, the cdkn2ab gene encodes only Ink4a. In platyfish and swordtails the cdkn2ab gene has been mapped to a genomic region that harbors a melanoma suppressor gene. However, an unexpected positive correlation of cdkn2ab and xmrk transcript levels has been reported. As high xmrk expression levels are a reliable molecular readout for melanoma malignancy, simultaneous high levels of a tumor suppressor gene are counterintuitive. To obtain a better understanding of the role of cdkn2ab in melanoma formation in fish we studied the effect of its expression levels in-vitro and in-vivo. First we analyzed cdkn2ab and xmrk expression levels in a large number of melanoma of varying degree of malignancy. Overexpression of cdkn2ab in a melanoma cell line led to decreased proliferation and induction of a senescence-like phenotype. This indicated an analogous melanoma-suppressive function as in mammals. Overexpression of Xiphophorus cdkn2ab under control of the medaka mitfa promoter did not affect pigment cell development in wildtype medaka. Coexpression of this construct in the mitf:xmrk trangenic medaka melanoma model resulted in full suppression of pigment cell tumor development. Interestingly, this occured also in the majority of fish with a p53 negative background. Using CRISPR/cas9 technology a cdkn2ab knock-out was produced, which is fully viable with no detectable major defects. However, unlike in humans, the cdkn2ab deficient medaka did not display spontaneous melanoma development so far. The mitf:xmrk melanoma inducing gene was crossed into the cdkn2a negative background to monitor the effect on melanoma development.

The present work addresses the question of to what extent a geometrical support acts as a physiological determining template in the setup of artificial cardiac tissue. Surface patterns with alternating concave to convex transitions of cell size dimensions were used to organize and orientate human-induced pluripotent stem cell (hIPSC)-derived cardiac myocytes and mouse neonatal cardiac myocytes. The shape of the cells, as well as the organization of the contractile apparatus recapitulates the anisotropic line pattern geometry being derived from tissue geometry motives. The intracellular organization of the contractile apparatus and the cell coupling via gap junctions of cell assemblies growing in a random or organized pattern were examined. Cell spatial and temporal coordinated excitation and contraction has been compared on plain and patterned substrates. While the α-actinin cytoskeletal organization is comparable to terminally-developed native ventricular tissue, connexin-43 expression does not recapitulate gap junction distribution of heart muscle tissue. However, coordinated contractions could be observed. The results of tissue-like cell ensemble organization open new insights into geometry-dependent cell organization, the cultivation of artificial heart tissue from stem cells and the anisotropy-dependent activity of therapeutic compounds.

Unter dem Einfluss von M-CSF und GM-CSF entwickeln sich CD14-positive periphere humane Blutmonozyten zu CD68-positiven M-CSF- bzw. GM-CSF-Makrophagen. M-CSF-Makrophagen lassen sich mit INFg und LPS zu klassisch aktivierten M1-Makrophagen, oder mit IL-4 und IL-10 zu alternativ aktivierten M2-Makrophagen differenzieren. Durch GM-CSF werden aus Monozyten GM-CSF-Makrophagen induziert. Im Gegensatz zu M1-Makrophagen sind GM1-Makrophagen bisher noch wenig untersucht. Mit INFg und LPS werden GM-CSF-Makrophagen zu GM1-Makrophagen aktivert. In der vorliegenden Arbeit wurde überprüft, wie groß die Übereinstimmung zwischen M-CSF- und M2-Makrophagen sowie zwischen GM-CSF- und M1-Makrophagen / GM1-Makrophagen ist. Im Gegensatz zu M-CSF- und GM-CSF stellt Laktat aber keinen Differenzierungsfaktor für Monozyten dar. Jedoch beeinflusst Laktat den Phänotyp von M2-Makrophagen und hemmt die Ausschüttung von IL-12 und NO durch M1- und GM1-Makrophagen., In the presence of M-CSF and GM-CSF CD14-positive human blood monocytes develop into CD68-pos M-CSF- or GM-CSF-macrophages. M-CSF-macrophages differentiate when incubated with INFg and LPS to classicly activated M1-marophages, when incubated with IL-4 and IL-10 zu alternativly activated M2-macrophages. Monocytes presented to GM-CSF eventually become GM-CSF-macrophages. There are only few examinations of GM-CSF-macrophages and classicly activated GM1-macrophages compared to M1-macrophages. In this study we focused on comparing the non-activated M-CSF-macrophages to alternativly activated M2-macrophages and non-activated GM-CSF-macrophages to classicly activated GM1-macrophages/M1-macrophages. Furthermore we point out that lactate is not a potential differentiation-signal für monocytes. But lactate does infact interfere with certain macrophage-phenotypes and the secretion of proinflammatory IL-12 and NO-molecules.

This study draws on and interprets an extensive corpus of archived materials, in particular from the Stadtmuseum Düsseldorf, to offer the first wide-ranging critical analysis of the written and visual images of the life and legend of Weimar Germany’s most important "modern" art dealers - Johanna Ey (1864-1947), commonly known as "Mutter Ey". Once feted by the press as the most portrayed woman in Germany, she contributed greatly to the careers of artists such as Max Ernst, Otto Dix, Gert Wollheim, Otto Pankok and many others and was a vital figure in the ‘modern’ Düsseldorf art scene until she was evicted from her gallery by the Nazis in 1934. This study opens with a factual overview of Ey’s biography. Chapters are then devoted to an analysis of the development, reception and prevalence of aspects of her legend: the use of the "Mutter Ey" image in the Weimar Period; an exploration of the notion of Ey’s modernity using the trope of the "Neue Frau"; an investigation into her attitude to politics in general and the Nazis in particular, in the first detailed reading of Ey’s 1936 memoirs and her correspondence from 1933-1947; and an analysis of the factors influencing the rise, fall and rise of her celebrity status and her memorialisation since her death.