Noise and information transmission in promoters with multiple internal states

Based on the measurements of noise in gene expression performed during the last decade, it has become customary to think of gene regulation in terms of a two-state model, where the promoter of a gene can stochastically switch between an ON and an OFF state. As experiments are becoming increasingly precise and the deviations from the two-state model start to be observable, we ask about the experimental signatures of complex multi-state promoters, as well as the functional consequences of this additional complexity. In detail, we (i) extend the calculations for noise in gene expression to promoters described by state transition diagrams with multiple states, (ii) systematically compute the experimentally accessible noise characteristics for these complex promoters, and (iii) use information theory to evaluate the channel capacities of complex promoter architectures and compare them to the baseline provided by the two-state model. We find that adding internal states to the promoter generically decreases channel capacity, except in certain cases, three of which (cooperativity, dual-role regulation, promoter cycling) we analyze in detail.Comment: 16 pages, 9 figure

IST Austria Thesis

The process of gene expression is central to the modern understanding of how cellular systems function. In this process, a special kind of regulatory proteins, called transcription factors, are important to determine how much protein is produced from a given gene. As biological information is transmitted from transcription factor concentration to mRNA levels to amounts of protein, various sources of noise arise and pose limits to the fidelity of intracellular signaling. This thesis concerns itself with several aspects of stochastic gene expression: (i) the mathematical description of complex promoters responsible for the stochastic production of biomolecules, (ii) fundamental limits to information processing the cell faces due to the interference from multiple fluctuating signals, (iii) how the presence of gene expression noise influences the evolution of regulatory sequences, (iv) and tools for the experimental study of origins and consequences of cell-cell heterogeneity, including an application to bacterial stress response systems

Stochastic proofreading mechanism alleviates crosstalk in transcriptional regulation

Gene expression is controlled primarily by interactions between transcription factor proteins (TFs) and the regulatory DNA sequence, a process that can be captured well by thermodynamic models of regulation. These models, however, neglect regulatory crosstalk: the possibility that non-cognate TFs could initiate transcription, with potentially disastrous effects for the cell. Here we estimate the importance of crosstalk, suggest that its avoidance strongly constrains equilibrium models of TF binding, and propose an alternative non-equilibrium scheme that implements kinetic proofreading to suppress erroneous initiation. This proposal is consistent with the observed covalent modifications of the transcriptional apparatus and would predict increased noise in gene expression as a tradeoff for improved specificity. Using information theory, we quantify this tradeoff to find when optimal proofreading architectures are favored over their equilibrium counterparts.Comment: 5 pages, 3 figure

Evaluating two methods of estimating error variances using simulated data sets with known errors

In this paper we compare two different methods of estimating the error variances of two or more independent data sets. One method, called the three-cornered hat (3CH) method, requires three data sets. Another method, which we call the two-cornered hat (2CH) method, requires only two data sets. Both methods have been used in previous studies to estimate the error variances associated with a number of physical and geophysical data sets. A key assumption in both methods is that the errors of the data sets are not correlated, although some studies have considered the effect of the partial correlation of representativeness errors in two or more of the data sets.We compare the 3CH and 2CH methods using a simple model to simulate three and two data sets with various error correlations and biases. With this model, we know the exact error variances and covariances, which we use to assess the accuracy of the 3CH and 2CH estimates. We examine the sensitivity of the estimated error variances to the degree of error correlation between two of the data sets as well as the sample size. We find that the 3CH method is less sensitive to these factors than the 2CH method and hence is more accurate. We also find that biases in one of the data sets has a minimal effect on the 3CH method, but can produce large errors in the 2CH method.</p

Dealing with the Past in Security Sector Reform

Security sector reform (SSR) and transitional justice processes often occur alongside each other in societies emerging from conflict or authoritarian rule, involve many of the same actors, are supported by some of the same partner countries and impact on each other. Yet the relationship between SSR and transitional justice, or â dealing with the pastâ (DwP) as it is also called, remains underexplored and is often marked by ignorance and resistance. While SSR and transitional justice processes can get into each otherâ s way, this paper argues that SSR and DwP are intrinsically linked and can complement each other. SSR can make for better transitional justice and vice versa. Transitional justice needs SSR to prevent a recurrence of abuses, an essential element of justice. SSR can learn from transitional justice not only that it is better to deal with rather than ignore an abusive past but also how to address an abusive legacy in the security sector. The validity of these assumptions is tested in two case studies: the police reform process in Bosnia and Herzegovina after 1995 and the SSR process in Nepal after 2006

Wertewandel in Schulbüchern?

In der vorliegenden Arbeit wurden Schulbücher als Massenmedien und die darin vermittelten Wertvorstellungen und Wirklichkeitsbilder von Beruf und Arbeit untersucht. Gerhard \citet{maletzke-1979} versteht unter „Massenmedium“ jede Kommunikationsform, bei welcher mittels einem technischen Verbreitungsmittel Aussagen öffentlich, indirekt und einseitig an ein disperses Publikum vermittelt werden. Unter Annahme dieser Definition können auch Schulbücher eindeutig als Massenmedien verstanden werden. Eine Besonderheit bei Schulbüchern ist auch die Tatsache, dass die Rezeption durch das Publikum zwangsläufig stattfindet. Im Laufe der schulischen Ausbildung kommen alle SchülerInnen bereits in sehr jungem Alter in Kontakt mit Lehrbüchern. Dadurch besitzen solche Medien ein großes Potential an sowohl Wissens- als auch Wertevermittlung. Zur vorliegenden Untersuchung wurden Lesebücher aus unterschiedlichen Schuljahren (1975/76, 1995/96 und aus dem aktuellen Schuljahr 2009/2010) herangezogen, die im Unterricht an österreichischen Volksschulen in Verwendung waren bzw. sind. Als eines von mehreren Elementen im gesellschaftlichen Teilsystem „Bildung“ haben Schul- bzw. Lesebücher unter anderem auch die Funktion der Sozialisation in ein bestehendes soziokulturelles Gesellschaftssystem. Ein wichtiger Bestandteil dieser Vorbereitung auf das spätere Leben stellt natürlich die Thematisierung und Reflektierung von realen gesellschaftlichen Gegebenheiten dar. Ganz zu Beginn der schulischen Ausbildung, das heißt in der Volksschule, können natürlich nicht alle realen Sachverhalte in ihrer ganzen Komplexität vermittelt bzw. erklärt werden, trotzdem ist es wichtig, dass den SchülerInnen bereits in diesem Alter keine völlig falschen und verzerrten Vorstellungen der Wirklichkeit kommuniziert werden \citep{arnold-1973}. Das Forschungsinteresse dieser Arbeit lag nun darin, die Thematisierung eines speziellen Aspekts der Realität zu untersuchen, und zwar die der Berufs- und Arbeitswelt. Arbeit dient heutzutage nicht mehr nur der Sicherung des Lebensunterhalts, sondern wird oftmals als persönliche Sinngebung und Daseinserfüllung verstanden und ist somit eine „Grundfunktion menschlicher Existenz“ \citet{perner-1977}. Genau aus diesem Grund wäre es auch wichtig, dass Schulbücher bezüglich der Berufs- und Arbeitswelt möglichst aktuelle und keine utopischen Vorstellung dieses relevanten Lebensbereichs vermitteln. Eine Kombination aus qualitativer und quantitativer Inhaltsanalyse hat gezeigt, dass in den Volksschullesebüchern seit den 1970er Jahren bis heute sehr wohl eine Entwicklung bezüglich der Thematisierung von Berufs- und Arbeitswelt erkennbar ist. Diese historischen Veränderungen entsprechen in gewissen Aspekten auch dem realen Wandel, wie z.B. der Häufigkeiten unterschiedlicher Berufe oder der Verteilung der verschiedenen Wirtschaftssektoren. Antiquierte bzw. stereotype Vorstellungen konnten hingegen bei der Thematisierung von Geschlechterrollen im öffentlichen und privaten Arbeitsleben aufgezeigt werden.According to Gerhard Maletzke "mass media" are any form of communication, which are distributed publicly, indirectly and unilaterally to a dispersed audience. Assuming this definition, school textbooks are clearly understood as mass media. A special feature of school books is the fact that the audience is forced to absorb this media. During school education every pupil comes in contact with textbooks. Because of this such media have a great potential not only to inform, but also to transport values. As one of several elements in the social subsystem "education" reading books have the function of socialization into an existing socio-cultural system of society. An important component of this preparation for later life is, of course, the theming and reflection of real-world social conditions. The research focus of this work is to analyze the theming of work and professionals. Today people don't work for the money only, but work is often understood as a personal meaning and existential fulfillment and thus as a "basic function of human existence". A content analysis has shown that the development of work and professionals is reflected also in primary school textbooks. These historic changes are even in accordance with certain real aspects, such as the quantity of different professions. However, antiquated views and stereotypes have been found in the theming of gender roles in public and private employment

Du darfst nicht mitspielen

Diese Diplomarbeit beschäftigt sich mit einer der berühmtesten und meistkommentierten Stellen in Wittgensteins Philosophischen Untersuchungen - dem Privatsprachenargument ([PU] §§243 ff.). Den ersten Teil dieser Arbeit (Kapitel 2) bildet eine einführende Erklärung der für die weiteren Unternehmungen wichtigen Begriffe des Sprachspiels, der Familienähnlichkeit, der Grammatik und der Lebensform. Dabei wird bereits stets deren Wichtigkeit für die Untersuchungen zur Möglichkeit von Privatsprachen betont. Der zweite Teil dieser Arbeit (Kapitel 3) beinhaltet ein Privatsprachenargument. Dessen Darstellung ist zu Beginn an jene Wittgensteins angelehnt, entfernt sich aber zunehmend von dieser, um schließlich durch den Entwurf einer Art von tatsächlich möglichen Privatsprachen einen neuen Blick auf das Thema zu bieten. Es handelt sich dabei um eine Untersuchung darüber, inwieweit unser Begriff von Sprache zu dehnen ist, damit Privatsprachen möglich sind. Der dritten Teil dieser Arbeit (Kapitel 4) bietet eine kurze Darstellung der Verwandschaft einiger Aspekte des Privatsprachenarguments mit anderen Stellen in Wittgensteins Spätwerk (Bemerkungen über die Grundlagen der Mathematik, Bemerkungen über die Farben, Bemerkungen über die Philosophie der Psychologie, Über Gewissheit)

Memory and wholeness in the work of Andrei Platonov, Valentin Rasputin and Andrei Tarkovskii

This thesis explores how wholeness (tselostnost' or tsel'nost'), a central theme and impulse of Russian nineteenth-century philosophy, is expressed in the work of three different twentieth-century Russian artists. Tselostnost' is understood here as Russian philosophy‘s enduring preoccupation with the essential, original wholeness of the universe, an ideal state from which the human world has fallen and which man seeks to regain. Particular attention is paid to the way in which this idea was taken up and developed by a range of nineteenth-century Russian thinkers: Petr Chaadaev, Aleksei Khomiakov, Ivan Kireevskii, Nikolai Fedorov, Vladimir Solov‘ev and Fedor Dostoevskii. In their works, the vision of the universe as an ideal tselostnost' is connected with a number of key key concepts from Russian philosophy, among which are: tsel'noe znanie, sobornost', and vseedinstvo. The main body of the thesis bases its analysis on selected writings by Andrei Platonov (1899-1951) and Valentin Rasputin (1937- ), and on the cinematic oeuvre of Andrei Tarkovskii (1932-1986). It explores how in the work of all three artists, tselostnost' is repeatedly linked with the theme of memory, framing the worldviews they express and influencing their aesthetic. The work of these three men, crossing two artistic media and realised with different levels of complexity, also spans a historical period which stretches from the 1920s to the present. The choice of these three very different artists to explore these ideas is integral to the wider aim of this study, which is to investigate the pervasiveness and longevity of the ideal of the whole in Russian culture, as well as the consistency with which it has been expressed. In addition, the examination of the three artists' work is a contribution to the wider critical discussion about the close links between the Russian philosophical and literary traditions

The effect of tunnel construction on future underground railway vibrations

This paper investigates the effect of initial tunnel construction on the future ground vibration levels generated during underground railway line operation. This is important because tunnel construction results in soil disturbance, thus inducing high soil strain levels near the tunnel lining. The resulting soil stiffness degradation impacts the future generation of ground-borne traffic vibration and it's propagation to the foundations of nearby buildings, however has never been investigated. Therefore, to address this, this work develops a novel hybrid modelling approach, consisting of a construction simulation model and an elastodynamics model. First the convergence-confinement method is used to determine the stress state induced during tunnel construction using a tunnel boring machine (TBM). Next a 2.5D FEM-PML model consisting of vehicle-track-tunnel-soil is used to predict the vibration fields induced by underground trains. To link the approaches, the soil stiffness degradation contours computed from the tunnelling simulation act as inputs for the 2.5D underground railway model. This facilitates the assessment of the effect of tunnel construction on vibration levels. It is found that railway ground-borne vibration levels are underestimated if construction effects are ignored, with discrepancies of up to 10 dB found at higher frequencies. Therefore, when estimating future vibration levels during the underground railway design stage (e.g. for subway, metro, high-speed lines … etc), tunnel construction should be considered as an operational source of uncertainty