Molecular Computing: from conformational pattern recognition to complex processing networks

Natural biomolecular systems process information in a radically different manner than programmable machines. Conformational interactions, the basis of specificity and self-assembly, are of key importance. A gedanken device is presented that illustrates how the fusion of information through conformational self-organization can serve to enhance pattern processing at the cellular level. The device is used to highlight general features of biomolecular information processing. We briefly outline a simulation system designed to address the manner in which conformational processing interacts with kinetic and higher level structural dynamics in complex biochemical networks. Virtual models that capture features of biomolecular information processing can in some instances have artificial intelligence value in their own right and should serve as design tools for future computers built from real molecules

Prethermalization and Persistent Order in the Absence of a Thermal Phase Transition

We numerically study the dynamics after a parameter quench in the one-dimensional transverse-field Ising model with long-range interactions ($\propto 1/r^\alpha$ with distance $r$), for finite chains and also directly in the thermodynamic limit. In nonequilibrium, i.e., before the system settles into a thermal state, we find a long-lived regime that is characterized by a prethermal value of the magnetization, which in general differs from its thermal value. We find that the ferromagnetic phase is stabilized dynamically: as a function of the quench parameter, the prethermal magnetization shows a transition between a symmetry-broken and a symmetric phase, even for those values of $\alpha$ for which no finite-temperature transition occurs in equilibrium. The dynamical critical point is shifted with respect to the equilibrium one, and the shift is found to depend on $\alpha$ as well as on the quench parameters.Comment: 6 pages, 4 figure

Von der Subvention zum Leistungsvertrag. Neue Koordinations- und Steuerungsformen zwischen NPOs und dem öffentlichen Sektor und ihre Konsequenzen für NPOs.

In den Beziehungen und in der Zusammenarbeit zwischen Nonprofit Organisationen und öffentlichen Verwaltungen sind in Österreich markante Veränderungen zu beobachten. "Leere Kassen" und Sparprogramme gelten als Argument umfassender finanzpolitischer Restriktionen der öffentlichen Hand. Die Finanzierung der von NPOs erbrachten gesellschaftlichen Leistungen wird prekär. Eine theoretische Legitimation erhält diese Entwicklung durch die Diskussion zur gesellschaftlichen Verantwortung des öffentlichen und des NPO Sektors unter den Stichworten "New Public Management" und "Zivilgesellschaft". Auch supranationale Einflüsse - insbesondere jene der EU - schaffen neue Rahmenbedingungen für die Arbeit der NPOs. Die Konfrontation mit veränderten Spielregeln bedeutet für beide Sektoren eine Herausforderung. Insbesondere der anhaltende Druck in Richtung Sparsamkeit und Effizienz der öffentlichen Mittelverwendung hat erhebliche Auswirkungen auf das Verhältnis zwischen NPOs und öffentlicher Hand. Ein Kernelement dieser Entwicklung ist der Positionswandel vieler NPOs von der Rolle eines in seinen Aktivitäten weitgehend freien Subventionsempfängers, der durch persönliche Vertrauensbeziehungen gestützt wird, hin zum vertraglich gebundenen Dienstleister. Resultat sind widersprüchliche Forderungen, die zu wechselseitigen Fehleinschätzungen führen und den Eindruck einer "falschen Verbindung" entstehen lassen. Einige Beispiele sollen dies verdeutlichen: 1. Zum einen wird eine verstärkte Eigeninitiative von NPOs gefordert, zum anderen unterbinden enge Ausschreibungen jeglichen Spielraum. 2. Einerseits wird im Rahmen einer Zivilgesellschaft die Beteiligung der Ehrenamtlichen hoch gelobt, andererseits machen die Einklagbarkeit von Verträgen und die Vorgabe strikter Kriterien den Einsatz von Ehrenamtlichen zum Risiko. 3. Auf der einen Seite sollen NPOs wie professionelle Unternehmen agieren, auf der anderen Seite will man von der Tradition der Bevormundung und Detailkontrolle nicht lassen. Bislang durchgeführte qualitative Interviews mit Führungskräften des NPO-Sektors und der Geldgeber sprechen u.a. folgenden Forschungsannahmen hohe Plausibilität zu: - NPOs müssen für öffentliche Geldgeber berechenbar sein. Gründete die Berechenbarkeit früher dominant im politisch-werthaften Vertrauen in bestimmte Personen, so stützt sie sich heute zunehmend auf die Professionalität und auf das Wissenspotential der NPO. Die Steuerungsmedien Macht und persönliches Vertrauen werden überlagert durch jene von Geld und Wissen. - Leistungsvertragliche Beziehungen erfordern Entscheidungen und erzwingen Organisation: In Abgrenzung von informellen Handlungsmustern gewinnt formales Handeln in NPOs an Bedeutung. Auch basisnahen NPOs stehen unter Druck, sich vom Ideal und den Fesseln der Basisdemokratie zu verabschieden. - Es gibt eine Tendenz zur Professionalisierung sowohl im einschlägig-fachlichen wie auch im betriebswirtschaftlich-instrumentellen Bereich. Innerbetrieblich führt dies nicht selten zu einer symbolische Polarisierung zwischen Fachexperten einerseits und Betriebswirten andererseits. (Autorenref.)Series: WU-Jahrestagung 200

On quaternary complex Hadamard matrices of small orders

One of the main goals of design theory is to classify, characterize and count various combinatorial objects with some prescribed properties. In most cases, however, one quickly encounters a combinatorial explosion and even if the complete enumeration of the objects is possible, there is no apparent way how to study them in details, store them efficiently, or generate a particular one rapidly. In this paper we propose a novel method to deal with these difficulties, and illustrate it by presenting the classification of quaternary complex Hadamard matrices up to order 8. The obtained matrices are members of only a handful of parametric families, and each inequivalent matrix, up to transposition, can be identified through its fingerprint.Comment: 7 page

A cancer stem cell-like phenotype is associated with miR-10b expression in aggressive squamous cell carcinomas

Background Cutaneous squamous cell carcinomas (cSCC) are the primary cause of premature deaths in patients suffering from the rare skin-fragility disorder recessive dystrophic epidermolysis bullosa (RDEB), which is in marked contrast to the rarely metastasizing nature of these carcinomas in the general population. This remarkable difference is attributed to the frequent development of chronic wounds caused by impaired skin integrity. However, the specific molecular and cellular changes to malignancy, and whether there are common players in different types of aggressive cSCCs, remain relatively undefined. Methods MiRNA expression profiling was performed across various cell types isolated from skin and cSCCs. Microarray results were confirmed by qPCR and by an optimized in situ hybridization protocol. Functional impact of overexpression or knock-out of a dysregulated miRNA was assessed in migration and 3D-spheroid assays. Sample-matched transcriptome data was generated to support the identification of disease relevant miRNA targets. Results Several miRNAs were identified as dysregulated in cSCCs compared to control skin. These included the metastasis-linked miR-10b, which was significantly upregulated in primary cell cultures and in archival biopsies. At the functional level, overexpression of miR-10b conferred the stem cell-characteristic of 3D-spheroid formation capacity to keratinocytes. Analysis of miR-10b downstream effects identified a novel putative target of miR-10b, the actin- and tubulin cytoskeleton-associated protein DIAPH2. Conclusion The discovery that miR-10b mediates an aspect of cancer stemness – that of enhanced tumor cell adhesion, known to facilitate metastatic colonization – provides an important avenue for future development of novel therapies targeting this metastasis-linked miRNA

Complex chloroplast RNA metabolism: just debugging the genetic programme?

<p>Abstract</p> <p>Background</p> <p>The gene expression system of chloroplasts is far more complex than that of their cyanobacterial progenitor. This gain in complexity affects in particular RNA metabolism, specifically the transcription and maturation of RNA. Mature chloroplast RNA is generated by a plethora of nuclear-encoded proteins acquired or recruited during plant evolution, comprising additional RNA polymerases and sigma factors, and sequence-specific RNA maturation factors promoting RNA splicing, editing, end formation and translatability. Despite years of intensive research, we still lack a comprehensive explanation for this complexity.</p> <p>Results</p> <p>We inspected the available literature and genome databases for information on components of RNA metabolism in land plant chloroplasts. In particular, new inventions of chloroplast-specific mechanisms and the expansion of some gene/protein families detected in land plants lead us to suggest that the primary function of the additional nuclear-encoded components found in chloroplasts is the transgenomic suppression of point mutations, fixation of which occurred due to an enhanced genetic drift exhibited by chloroplast genomes. We further speculate that a fast evolution of transgenomic suppressors occurred after the water-to-land transition of plants.</p> <p>Conclusion</p> <p>Our inspections indicate that several chloroplast-specific mechanisms evolved in land plants to remedy point mutations that occurred after the water-to-land transition. Thus, the complexity of chloroplast gene expression evolved to guarantee the functionality of chloroplast genetic information and may not, with some exceptions, be involved in regulatory functions.</p

Integrative epigenomics in Sjögren´s syndrome reveals novel pathways and a strong interaction between the HLA, autoantibodies and the interferon signature

Primary Sjögren's syndrome (SS) is a systemic autoimmune disease characterized by lymphocytic infiltration and damage of exocrine salivary and lacrimal glands. The etiology of SS is complex with environmental triggers and genetic factors involved. By conducting an integrated multi-omics study, we confirmed a vast coordinated hypomethylation and overexpression effects in IFN-related genes, what is known as the IFN signature. Stratified and conditional analyses suggest a strong interaction between SS-associated HLA genetic variation and the presence of Anti-Ro/SSA autoantibodies in driving the IFN epigenetic signature and determining SS. We report a novel epigenetic signature characterized by increased DNA methylation levels in a large number of genes enriched in pathways such as collagen metabolism and extracellular matrix organization. We identified potential new genetic variants associated with SS that might mediate their risk by altering DNA methylation or gene expression patterns, as well as disease-interacting genetic variants that exhibit regulatory function only in the SS population. Our study sheds new light on the interaction between genetics, autoantibody profiles, DNA methylation and gene expression in SS, and contributes to elucidate the genetic architecture of gene regulation in an autoimmune population