121 research outputs found

    Active topolectrical circuits

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    The transfer of topological concepts from the quantum world to classical mechanical and electronic systems has opened fundamentally new approaches to protected information transmission and wave guidance. A particularly promising technology are recently discovered topolectrical circuits that achieve robust electric signal transduction by mimicking edge currents in quantum Hall systems. In parallel, modern active matter research has shown how autonomous units driven by internal energy reservoirs can spontaneously self-organize into collective coherent dynamics. Here, we unify key ideas from these two previously disparate fields to develop design principles for active topolectrical circuits (ATCs) that can self-excite topologically protected global signal patterns. Realizing autonomous active units through nonlinear Chua diode circuits, we theoretically predict and experimentally confirm the emergence of self-organized protected edge oscillations in one- and two-dimensional ATCs. The close agreement between theory, simulations and experiments implies that nonlinear ATCs provide a robust and versatile platform for developing high-dimensional autonomous electrical circuits with topologically protected functionalities.Comment: 10 pages, 4 figures, includes supplementary material. This version adds 2D experiment

    Universality of Hofstadter butterflies on hyperbolic lattices

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    Motivated by recent experimental breakthroughs in realizing hyperbolic lattices in superconducting waveguides and electric circuits, we compute the Hofstadter butterfly on regular hyperbolic tilings. By utilizing large hyperbolic lattices with periodic boundary conditions, we obtain the true hyperbolic bulk spectrum that is unaffected by contributions from boundary states. Our results reveal that the butterfly spectrum with large extended gapped regions prevails and that its shape is universally determined by the number of edges of the fundamental tile, while the fractal structure is lost in such a non-Euclidean case. We explain how these intriguing features are related to the nature of Landau levels in hyperbolic space, and how they could be verified experimentally.Comment: 4 pages, 3 figures + supplementar

    Short sequence motifs, overrepresented in mammalian conserved non-coding sequences

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    <p>Abstract</p> <p>Background</p> <p>A substantial fraction of non-coding DNA sequences of multicellular eukaryotes is under selective constraint. In particular, ~5% of the human genome consists of conserved non-coding sequences (CNSs). CNSs differ from other genomic sequences in their nucleotide composition and must play important functional roles, which mostly remain obscure.</p> <p>Results</p> <p>We investigated relative abundances of short sequence motifs in all human CNSs present in the human/mouse whole-genome alignments <it>vs</it>. three background sets of sequences: (i) weakly conserved or unconserved non-coding sequences (non-CNSs); (ii) near-promoter sequences (located between nucleotides -500 and -1500, relative to a start of transcription); and (iii) random sequences with the same nucleotide composition as that of CNSs. When compared to non-CNSs and near-promoter sequences, CNSs possess an excess of AT-rich motifs, often containing runs of identical nucleotides. In contrast, when compared to random sequences, CNSs contain an excess of GC-rich motifs which, however, lack CpG dinucleotides. Thus, abundance of short sequence motifs in human CNSs, taken as a whole, is mostly determined by their overall compositional properties and not by overrepresentation of any specific short motifs. These properties are: (i) high AT-content of CNSs, (ii) a tendency, probably due to context-dependent mutation, of A's and T's to clump, (iii) presence of short GC-rich regions, and (iv) avoidance of CpG contexts, due to their hypermutability. Only a small number of short motifs, overrepresented in all human CNSs are similar to binding sites of transcription factors from the FOX family.</p> <p>Conclusion</p> <p>Human CNSs as a whole appear to be too broad a class of sequences to possess strong footprints of any short sequence-specific functions. Such footprints should be studied at the level of functional subclasses of CNSs, such as those which flank genes with a particular pattern of expression. Overall properties of CNSs are affected by patterns in mutation, suggesting that selection which causes their conservation is not always very strong.</p

    Der Arbeitskräftebedarf in Deutschland 2006 bis 2011: Nachfrage, Rekrutierungsprozesse und Engpässe aus Sicht der Betriebe

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    Das Thema Fachkräftebedarf wird in Wissenschaft und Öffentlichkeit intensiv und kontrovers diskutiert. Der Bericht analysiert die Arbeitskräftenachfrage der Betriebe und versucht, aktuelle Engpässe auf dem Arbeitsmarkt zu identifizieren. Zunächst wird die Entwicklung der Betriebs- und Beschäftigungsstruktur sowie der offenen Stellen differenziert für verschiedene Teilarbeitsmärkte dargestellt. Weiterhin werden verschiedene Indikatoren diskutiert, die Hinweise auf Arbeitskräfteengpässe geben können. Insgesamt zeigen die Ergebnisse, dass in Deutschland derzeit kein allgemeiner, flächendeckender Fachkräftemangel besteht. Dennoch sind bestimmte Berufe, Regionen und Branchen zu erkennen, in denen die Engpässe zugenommen haben. Dies gilt etwa für Berufe aus dem Gesundheits- und Sozial-, aber auch dem Elektrobereich. Auf regionaler Ebene treten Fachkräfteengpässe am ehesten in den süddeutschen Bundesländern auf, im Branchenvergleich scheinen Engpässe vornehmlich in einzelnen Dienstleistungsbereichen zu bestehen.The topic of skilled labour requirements is discussed intensively and controversially in sciences and in public. The publication analyses the labour force requirements of companies and attempts to identify current shortage trends on the labour market. Initially, the development of company and employment structures as well as of vacancies is presented in relation to various partial employment markets. Furthermore, the different indicators providing clues for labour force shortages are discussed. Overall, the results show that currently there is no general, extensive shortage of skilled labour in Germany. However, there are trends visible in certain professions, areas and sectors where the shortages have increased. This applies, for example, to professions in the health care system, the social care system and the electrical sector. As for local divergences, the skilled labour shortages are most likely in the Southern German states, whilst the comparison of sectors suggests that above all the individual service providing sectors seem to experience shortages

    Realizing efficient topological temporal pumping in electrical circuits

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    Quantized adiabatic transport can occur when a system is slowly modulated over time. In most realizations however, the efficiency of such transport is reduced by unwanted dissipation, back-scattering, and non-adiabatic effects. In this work, we realize a topological adiabatic pump in an electrical circuit network that supports remarkably stable and long-lasting pumping of a voltage signal. We further characterize the topology of our system by deducing the Chern number from the measured edge band structure. To achieve this, the experimental setup makes use of active circuit elements that act as time-variable voltage-controlled inductors.Comment: main (5 pages, 3 figures) plus supplement (8 pages, 4 figures

    Betriebe im Wettbewerb um Arbeitskräfte: Bedarf, Engpässe und Rekrutierungsprozesse in Deutschland

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    Welche Arbeitskräfte werden in Deutschland gesucht? Gibt es bereits Schwierigkeiten, den Bedarf zu decken? Wenn ja, welche Branchen und Regionen sind betroffen? Und: In welchen Berufen sind Fachkräfte besonders knapp? Der Band gibt einen Überblick über die aktuelle Arbeitskräftenachfrage und bestehende Engpässe am deutschen Arbeitsmarkt. Dabei steht der betriebliche Fachkräftebedarf im Fokus. Außerdem greifen Schwerpunktkapitel wesentliche Aspekte des Fachkräftethemas auf und beantworten folgende Fragen auf Basis vertiefender Analysen: Haben kleine und mittlere Betriebe im Wettbewerb um die besten Köpfe eine Chance gegen die Großen? Welche Bedeutung kommt Frauen und Älteren bei der Deckung des Fachkräftebedarfs zu? Wie steht es um die Bereitschaft der Betriebe, ihre benötigten Fachkräfte selbst aus- oder weiterzubilden? Haben Betriebe mit hoher Innovationsaktivität besonderen Bedarf an bestimmten Arbeitskräften? Welche Rolle spielen Arbeitsbedingungen für die Attraktivität von Stellen?What kind of labour is being sought in Germany? Are there already difficulties in meeting the demand? If so, which branches and regions does this concern? And: In which professions are qualified workers especially scarce? This volume provides an overview of the current demand for labour and the shortages that exist on the German labour market. The focus is on the in-house requirement for qualified labour. In addition, topical chapters deal with key aspects of the topic of qualified labour and attempt to answer the following questions on the basis of deeper analyses: Do small and medium-sized establishments have a chance when competing with large establishments for the best employees? What significance is placed on women and older employees when covering the demand for qualified workers? How willing are establishments to train or further train the qualified labour that they need? Do establishments with a higher degree of innovative activity have a special need for particular kinds of workers? What role do working conditions play in the attractivity of jobs

    Simulating hyperbolic space on a circuit board

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    The Laplace operator encodes the behavior of physical systems at vastly different scales, describing heat flow, fluids, as well as electric, gravitational, and quantum fields. A key input for the Laplace equation is the curvature of space. Here we discuss and experimentally demonstrate that the spectral ordering of Laplacian eigenstates for hyperbolic (negatively curved) and flat two-dimensional spaces has a universally different structure. We use a lattice regularization of hyperbolic space in an electric-circuit network to measure the eigenstates of a ‘hyperbolic drum’, and in a time-resolved experiment we verify signal propagation along the curved geodesics. Our experiments showcase both a versatile platform to emulate hyperbolic lattices in tabletop experiments, and a set of methods to verify the effective hyperbolic metric in this and other platforms. The presented techniques can be utilized to explore novel aspects of both classical and quantum dynamics in negatively curved spaces, and to realise the emerging models of topological hyperbolic matter

    Role of Phagocytosis in the Pro-Inflammatory Response in LDL-Induced Foam Cell Formation; a Transcriptome Analysis

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    Excessive accumulation of lipid inclusions in the arterial wall cells (foam cell formation) caused by modified low-density lipoprotein (LDL) is the earliest and most noticeable manifestation of atherosclerosis. The mechanisms of foam cell formation are not fully understood and can involve altered lipid uptake, impaired lipid metabolism, or both. Recently, we have identified the top 10 master regulators that were involved in the accumulation of cholesterol in cultured macrophages induced by the incubation with modified LDL. It was found that most of the identified master regulators were related to the regulation of the inflammatory immune response, but not to lipid metabolism. A possible explanation for this unexpected result is a stimulation of the phagocytic activity of macrophages by modified LDL particle associates that have a relatively large size. In the current study, we investigated gene regulation in macrophages using transcriptome analysis to test the hypothesis that the primary event occurring upon the interaction of modified LDL and macrophages is the stimulation of phagocytosis, which subsequently triggers the pro-inflammatory immune response. We identified genes that were up- or downregulated following the exposure of cultured cells to modified LDL or latex beads (inert phagocytosis stimulators). Most of the identified master regulators were involved in the innate immune response, and some of them were encoding major pro-inflammatory proteins. The obtained results indicated that pro-inflammatory response to phagocytosis stimulation precedes the accumulation of intracellular lipids and possibly contributes to the formation of foam cells. In this way, the currently recognized hypothesis that the accumulation of lipids triggers the pro-inflammatory response was not confirmed. Comparative analysis of master regulators revealed similarities in the genetic regulation of the interaction of macrophages with naturally occurring LDL and desialylated LDL. Oxidized and desialylated LDL affected a different spectrum of genes than naturally occurring LDL. These observations suggest that desialylation is the most important modification of LDL occurring in vivo. Thus, modified LDL caused the gene regulation characteristic of the stimulation of phagocytosis. Additionally, the knock-down effect of five master regulators, such as IL15, EIF2AK3, F2RL1, TSPYL2, and ANXA1, on intracellular lipid accumulation was tested. We knocked down these genes in primary macrophages derived from human monocytes. The addition of atherogenic naturally occurring LDL caused a significant accumulation of cholesterol in the control cells. The knock-down of the EIF2AK3 and IL15 genes completely prevented cholesterol accumulation in cultured macrophages. The knock-down of the ANXA1 gene caused a further decrease in cholesterol content in cultured macrophages. At the same time, knock-down of F2RL1 and TSPYL2 did not cause an effect. The results obtained allowed us to explain in which way the inflammatory response and the accumulation of cholesterol are related confirming our hypothesis of atherogenesis development based on the following viewpoints: LDL particles undergo atherogenic modifications that, in turn, accompanied by the formation of self-associates; large LDL associates stimulate phagocytosis; as a result of phagocytosis stimulation, pro-inflammatory molecules are secreted; these molecules cause or at least contribute to the accumulation of intracellular cholesterol. Therefore, it became obvious that the primary event in this sequence is not the accumulation of cholesterol but an inflammatory response

    Walking pathways with positive feedback loops reveal DNA methylation

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    Background: the search for molecular biomarkers of early-onset colorectal cancer (CRC) is an important but still quite challenging and unsolved task. Detection of CpG methylation in human DNA obtained from blood or stool has been proposed as a promising approach to a noninvasive early diagnosis of CRC. Thousands of abnormally methylated CpG positions in CRC genomes are often located in non-coding parts of genes. Novel bioinformatic methods are thus urgently needed for multi-omics data analysis to reveal causative biomarkers with a potential driver role in early stages of cancer. Methods: we have developed a method for finding potential causal relationships between epigenetic changes (DNA methylations) in gene regulatory regions that affect transcription factor binding sites (TFBS) and gene expression changes. This method also considers the topology of the involved signal transduction pathways and searches for positive feedback loops that may cause the carcinogenic aberrations in gene expression. We call this method 'Walking pathways', since it searches for potential rewiring mechanisms in cancer pathways due to dynamic changes in the DNA methylation status of important gene regulatory regions ('epigenomic walking'). Results: in this paper, we analysed an extensive collection of full genome gene-expression data (RNA-seq) and DNA methylation data of genomic CpG islands (using Illumina methylation arrays) generated from a sample of tumor and normal gut epithelial tissues of 300 patients with colorectal cancer (at different stages of the disease) (data generated in the EU-supported SysCol project). Identification of potential epigenetic biomarkers of DNA methylation was performed using the fully automatic multi-omics analysis web service 'My Genome Enhancer' (MGE) (my-genome-enhancer.com). MGE uses the database on gene regulation TRANSFAC®, the signal transduction pathways database TRANSPATH®, and software that employs AI (artificial intelligence) methods for the analysis of cancer-specific enhancers. Conclusions: the identified biomarkers underwent experimental testing on an independent set of blood samples from patients with colorectal cancer. As a result, using advanced methods of statistics and machine learning, a minimum set of 6 biomarkers was selected, which together achieve the best cancer detection potential. The markers include hypermethylated positions in regulatory regions of the following genes: CALCA, ENO1, MYC, PDX1, TCF7, ZNF43
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