Gene Expression Noise Facilitates Adaptation and Drug Resistance Independently of Mutation

We show that the effect of stress on the reproductive fitness of noisy cell populations can be modelled as first-passage time problem, and demonstrate that even relatively short-lived fluctuations in gene expression can ensure long-term survival of a drug-resistant population. We examine how this effect contributes to the development of drug-resistant cancer cells, and demonstrate that permanent immunity can arise independently of mutations.Comment: 5 pages, 3 figure

Materialien zum Aufsatz "Zwei Pater noster-Vertonungen von Melchior Vulpius und die Missa V. vocum super Pater noster qui es in Coelis Melchioris Vulpii von Georg Vintz" - Begleitmaterial zum Aufsatz im Tagungsband

Im Aufsatz "Zwei Pater noster-Vertonungen von Melchior Vulpius und die Missa V. vocum super Pater noster qui es in Coelis Melchioris Vulpii von Georg Vintz" werden Pater noster-Vertonungen aus dem OPUSCULUM NOVUM SELECTISSIMARVUM CANTIONVM SACRARVM (Erfurt 1610) und aus der PARS PRIMA CANTIONVM SACRARVM (Jena 1602) des Weimarer Kantors und Komponisten Melchior Vulpius (1570 - 1615) besprochen und miteinander verglichen. Ebenso wird untersucht, in welcher Weise der Naumburger Organist Georg Vintz (ca. 1580 - ca. 1635) eine dieser Motetten als Grundlage für die Parodiemesse "MISSA V. VOCUM,Super Pater noster [...] Melchioris Vulpii" genutzt und bearbeitet hat. Der Aufsatz beruht auf einem Vortrag bei einer Tagung über Vulpius, die 2015 in Meiningen stattfand. Der Tagungsband, den Maren Goltz herausgeben wird, erscheint vermutlich 2018. Da im Band nicht genügend Platz für ausführliche Notenbeispiele ist, werden die besprochenen Kompositionen vollständig als Noten- und Klangdateien durch diesen Permalink zur Verfügung gestellt

Beethovens Instrumentation als Mittel der Formbildung und der musikalischen Dramaturgie

Das Hauptinteresse des Beitrags gilt einer zentralen Charakteristik von Beethovens Orchestersatz, nämlich der engen Verknüpfung seiner Instrumentationstechnik mit seinem kompositorischen Denken

Begleitmaterial zum Aufsatz im Tagungsband, Ortus Musikverlag. 2014

Dieser Aufsatz, der im von Maren Goltz herausgegebenen Tagungsband JOHANN STEURLEIN (1546–1613) – Amtsdiener, Komponist und Poet zwischen Tradition und Innovation (Ortus Musikverlag, Beeskow 2014) erschienen ist, untersucht die 1576 entstandene Deutsche Passion (bzw. Johannespassion) von Johann Steuerlein insbesondere mit Blick auf dessen vermutete kompositorische Strategien zur dramaturgischen Gestaltung des langen Passionstextes innerhalb einer vierstimmigen, motettischen Passionsvertonung, die – wie auch der traditionelle liturgische Passionston – durchgängig in einem F-lydischen Modus steht, daher wenig Gelegenheit zu klanglicher Abwechslung bietet. Dabei ist Steuerleins Komposition ein Beispiel dafür (wenn auch wohl nicht das erste oder einzige), wie sich der Satz – entgegen früherer kompositorischer Traditionen – von der Struktur des Passionstones löst, in welchem die verschiedenen Handlungsebenen des Passionsgeschehens (Evangelist, Jesus, Soliloquenten und Volk) in festgelegten Tonräumen singen. Bei Steuerlein ist zu beobachten, wie sich der modale Tonraum, in welchem sich der Satz an jedweder Stelle des Textes ausbreitet, nicht mehr sprunghaft nach dessen Erzählebenen richtet, sondern großflächiger in den Dienst einer dramaturgischen, energetisch durchgeformten Textgestaltung gestellt wird. Der differenzierte Umgang mit den zeittypischen Mitteln der Klausellehre und einer daraus resultierenden Vielfalt von Kadenzformen zeigt das rhetorischen Bewusstsein, mit dem der musikalische Fluss als komponierte Interpunktion gegliedert und ebenfalls zu dramaturgischen Zwecken nutzbar gemacht wird. Die online verfügbar gemachten Materialien legen alle dem Aufsatz zugrunde liegenden Analysen offen, um die gemachten statistischen Aussagen transparent und nachvollziehbar zu machen

Experimental Results For Hydrocarbon Refrigerant Vaporization In Brazed Plate Heat Exchangers at High Pressure

In this contribution, the experimental heat transfer coefficient  and the pressure drop measured during HFC refrigerants vaporization inside small brazed plate heat exchanger (PHE) at typical evaporation temperature for organic Rankine cycle systems for low thermal energy quality applications are presented. Scientific work focusing on the heat transfer in PHEs has been carried out since the late 19th century. More recent publications have been focusing on vaporization and condensation of refrigerants at heat-pump like operation. Despite PHEs are largely used for small to medium organic Rankine cycle (ORC) systems (5-250 kWel), literature covering the heat exchanger performance at temperatures and pressures suitable for ORCs is scarce. In order to fill the lack of experimental data for heat transfer in ORC-like operation, a dedicated heat transfer test installation has been designed and built at the Technical University of Denmark. The rig features six small brazed PHEs installed in series which allow simulating various heat transfer conditions. The first measured experimental results are presented. The tests include vaporization runs carried out at three different saturation temperatures (70, 80, and 90 °C) and different evaporator outlet conditions (outlet vapor quality around 0.4 and 1.00) and  various inlet sub-cooling around 5 and 10 °C for HFC-134a. The recorded data are compared with available two-phase correlations in the literature. Furthermore a correlation for frictional pressure drop is proposed

Rules for biological regulation based on error minimization

The control of gene expression involves complex mechanisms that show large variation in design. For example, genes can be turned on either by the binding of an activator (positive control) or the unbinding of a repressor (negative control). What determines the choice of mode of control for each gene? This study proposes rules for gene regulation based on the assumption that free regulatory sites are exposed to nonspecific binding errors, whereas sites bound to their cognate regulators are protected from errors. Hence, the selected mechanisms keep the sites bound to their designated regulators for most of the time, thus minimizing fitness-reducing errors. This offers an explanation of the empirically demonstrated Savageau demand rule: Genes that are needed often in the natural environment tend to be regulated by activators, and rarely needed genes tend to be regulated by repressors; in both cases, sites are bound for most of the time, and errors are minimized. The fitness advantage of error minimization appears to be readily selectable. The present approach can also generate rules for multi-regulator systems. The error-minimization framework raises several experimentally testable hypotheses. It may also apply to other biological regulation systems, such as those involving protein-protein interactions.Comment: biological physics, complex networks, systems biology, transcriptional regulation http://www.weizmann.ac.il/complex/tlusty/papers/PNAS2006.pdf http://www.pnas.org/content/103/11/3999.ful

Evolutionary dynamics of tumor progression with random fitness values

Most human tumors result from the accumulation of multiple genetic and epigenetic alterations in a single cell. Mutations that confer a fitness advantage to the cell are known as driver mutations and are causally related to tumorigenesis. Other mutations, however, do not change the phenotype of the cell or even decrease cellular fitness. While much experimental effort is being devoted to the identification of the different functional effects of individual mutations, mathematical modeling of tumor progression generally considers constant fitness increments as mutations are accumulated. In this paper we study a mathematical model of tumor progression with random fitness increments. We analyze a multi-type branching process in which cells accumulate mutations whose fitness effects are chosen from a distribution. We determine the effect of the fitness distribution on the growth kinetics of the tumor. This work contributes to a quantitative understanding of the accumulation of mutations leading to cancer phenotypes.Comment: 33 pages, 2 Figure

Cross-talk and interference enhance information capacity of a signaling pathway

A recurring motif in gene regulatory networks is transcription factors (TFs) that regulate each other, and then bind to overlapping sites on DNA, where they interact and synergistically control transcription of a target gene. Here, we suggest that this motif maximizes information flow in a noisy network. Gene expression is an inherently noisy process due to thermal fluctuations and the small number of molecules involved. A consequence of multiple TFs interacting at overlapping binding-sites is that their binding noise becomes correlated. Using concepts from information theory, we show that in general a signaling pathway transmits more information if 1) noise of one input is correlated with that of the other, 2) input signals are not chosen independently. In the case of TFs, the latter criterion hints at up-stream cross-regulation. We demonstrate these ideas for competing TFs and feed-forward gene regulatory modules, and discuss generalizations to other signaling pathways. Our results challenge the conventional approach of treating biological noise as uncorrelated fluctuations, and present a systematic method for understanding TF cross-regulation networks either from direct measurements of binding noise, or bioinformatic analysis of overlapping binding-sites.Comment: 28 pages, 5 figure