Contexts of social action: guest editors' introduction

Cataloged from PDF version of article.In traditional linguistic accounts of context, one thinks of the immediate features of a speech situation, that is, a situation in which an expression is uttered. Thus, features such as time, location, speaker, hearer and preceding discourse are all parts of context. But context is a wider and more transcendental notion than what these accounts imply. For one thing, context is a relational concept relating social actions and their surroundings, relating social actions, relating individual actors and their surroundings, and relating the set of individual actors and their social actions to their surroundings

Robustness from flexibility in the fungal circadian clock

Background Robustness is a central property of living systems, enabling function to be maintained against environmental perturbations. A key challenge is to identify the structures in biological circuits that confer system-level properties such as robustness. Circadian clocks allow organisms to adapt to the predictable changes of the 24-hour day/night cycle by generating endogenous rhythms that can be entrained to the external cycle. In all organisms, the clock circuits typically comprise multiple interlocked feedback loops controlling the rhythmic expression of key genes. Previously, we showed that such architectures increase the flexibility of the clock's rhythmic behaviour. We now test the relationship between flexibility and robustness, using a mathematical model of the circuit controlling conidiation in the fungus Neurospora crassa. Results The circuit modelled in this work consists of a central negative feedback loop, in which the frequency (frq) gene inhibits its transcriptional activator white collar-1 (wc-1), interlocked with a positive feedback loop in which FRQ protein upregulates WC-1 production. Importantly, our model reproduces the observed entrainment of this circuit under light/dark cycles with varying photoperiod and cycle duration. Our simulations show that whilst the level of frq mRNA is driven directly by the light input, the falling phase of FRQ protein, a molecular correlate of conidiation, maintains a constant phase that is uncoupled from the times of dawn and dusk. The model predicts the behaviour of mutants that uncouple WC-1 production from FRQ's positive feedback, and shows that the positive loop enhances the buffering of conidiation phase against seasonal photoperiod changes. This property is quantified using Kitano's measure for the overall robustness of a regulated system output. Further analysis demonstrates that this functional robustness is a consequence of the greater evolutionary flexibility conferred on the circuit by the interlocking loop structure. Conclusions Our model shows that the behaviour of the fungal clock in light-dark cycles can be accounted for by a transcription-translation feedback model of the central FRQ-WC oscillator. More generally, we provide an example of a biological circuit in which greater flexibility yields improved robustness, while also introducing novel sensitivity analysis techniques applicable to a broader range of cellular oscillators

Pengaruh Faktor Internal dan Eksternal Motivasi terhadap Mutu Pendidikan di Universitas Al Washliyah (UNIVA) Medan

Secara umum penelitian ini bertujuan untuk mengetahui pengaruh motivasi dalam meningkatkan mutu pendidikan di Universitas Al Washliyah (UNIVA) Medan. Penelitian ini termasuk Metode penelitian yang digunakan penulis dalam menyusun laporan tugas akhir ini menggunakan metode deskriptif, yaitu yang mengungkapkan gambaran masalah yang terjadi pada saat penelitian ini berlangsung dan metode kuantitatif, yaitu metode untuk menghitung seberapa besar pengaruh variabel bebas teradap variabel terikatnya. Dalam penelitian ini analisis data yang digunakan adalah analisis jalur dimaksudkan untuk mengetahui adakah pengaruh faktor-faktor internal dan eksternal yang mempengaruhi Perubahan Mutu Pendidikan Universitas Al Washliyah Medan dengan persamaan. Berdasarkan hubungan antar variabel diketahui bahwa ketiga hubungan yang memiliki hubungan yang tidak signifikan yaitu antara Mutu Pendidikan (Y) dengan Faktor Internal (X1), Mutu Pendidikan (Y) dengan Faktor Eksternal (X2) dan Faktor Internal (X1) dengan Faktor Eksternal (X2). Dari aspek variabel Faktor Internal dan Faktor Eksternal secara simultan berpengaruh signifikan terhadap Mutu Pendidikan. Pada uji F, terdapat kecocokan antara model dengan data. Sehingga model analisis jalur yang didapat layak untuk digunakan. Secara parsial koefisien Faktor Internal berpengaruh signifikan terhadap Mutu Pendidikan dan Faktor Eksternal tidak berpengaruh secara signifikan. Pengaruh langsung variabel Faktor Internal (X1) terhadap Mutu Pendidikan (Y) adalah sebesar 0,032041 atau 3,2041% dan pengaruh tidak langsung melalui Faktor Internal (X2) adalah 0,00159847 atau 0,159847% sehingga total pengaruh yang diberikan variabel Faktor Internal (X1) adalah 0,03363947 atau sebesar 3,363947% terhadap Mutu Pendidikan (Y). Ini berarti Faktor Internal memiliki pengaruh yang kecil terhadap Mutu Pendidikan.Pengaruh langsung variabel Faktor Eksternal (X2) terhadap Mutu Pendidikan (Y) adalah sebesar 0,002209 atau 0,2209% dan pengaruh tidak langsung melalui Faktor Internal (X1) adalah 0,00159846 atau 0,159846% sehingga total pengaruh yang diberikan variabel Faktor Eksternal (X2) adalah 0,00380747 atau 0,380747% terhadap Mutu Pendidikan (Y). Ini berarti Faktor Ekstrnal memiliki pengaruh yang besar terhadap Mutu Pendidikan. Nilai R square sebesar 4%, ini menunjukkan bahwa dengan menggunakan model analisis jalur yang didapatkan dimana variabel eksogen yaitu Faktor Internal (X1) dan Faktor Eksternal (X2), memiliki pengaruh terhadap variabel Mutu Pendidikan (Y) sebesar 4%, namun pengaruhnya sangatlah kecil. Sedangkan sisanya (100%-4% = 96%) adalah kemungkinan terdapat aspek-aspek lain yang memiliki pengaruh terhadap Perubahan variabel Mutu Pendidikan (Y). Hal ini sesuai dengan nilai error yang muncul pada path diatas yaitu sebesar 0,63

Nonlinear Dynamics in Gene Regulation Promote Robustness and Evolvability of Gene Expression Levels

This is the final version of the article. Available from Public Library of Science via the DOI in this record.Cellular phenotypes underpinned by regulatory networks need to respond to evolutionary pressures to allow adaptation, but at the same time be robust to perturbations. This creates a conflict in which mutations affecting regulatory networks must both generate variance but also be tolerated at the phenotype level. Here, we perform mathematical analyses and simulations of regulatory networks to better understand the potential trade-off between robustness and evolvability. Examining the phenotypic effects of mutations, we find an inverse correlation between robustness and evolvability that breaks only with nonlinearity in the network dynamics, through the creation of regions presenting sudden changes in phenotype with small changes in genotype. For genotypes embedding low levels of nonlinearity, robustness and evolvability correlate negatively and almost perfectly. By contrast, genotypes embedding nonlinear dynamics allow expression levels to be robust to small perturbations, while generating high diversity (evolvability) under larger perturbations. Thus, nonlinearity breaks the robustness-evolvability trade-off in gene expression levels by allowing disparate responses to different mutations. Using analytical derivations of robustness and system sensitivity, we show that these findings extend to a large class of gene regulatory network architectures and also hold for experimentally observed parameter regimes. Further, the effect of nonlinearity on the robustness-evolvability trade-off is ensured as long as key parameters of the system display specific relations irrespective of their absolute values. We find that within this parameter regime genotypes display low and noisy expression levels. Examining the phenotypic effects of mutations, we find an inverse correlation between robustness and evolvability that breaks only with nonlinearity in the network dynamics. Our results provide a possible solution to the robustness-evolvability trade-off, suggest an explanation for the ubiquity of nonlinear dynamics in gene expression networks, and generate useful guidelines for the design of synthetic gene circuits.This work was funded by the UK Engineering and Physical Sciences Research Council, grant number EP/I017445/1

Complementary approaches to understanding the plant circadian clock

Circadian clocks are oscillatory genetic networks that help organisms adapt to the 24-hour day/night cycle. The clock of the green alga Ostreococcus tauri is the simplest plant clock discovered so far. Its many advantages as an experimental system facilitate the testing of computational predictions. We present a model of the Ostreococcus clock in the stochastic process algebra Bio-PEPA and exploit its mapping to different analysis techniques, such as ordinary differential equations, stochastic simulation algorithms and model-checking. The small number of molecules reported for this system tests the limits of the continuous approximation underlying differential equations. We investigate the difference between continuous-deterministic and discrete-stochastic approaches. Stochastic simulation and model-checking allow us to formulate new hypotheses on the system behaviour, such as the presence of self-sustained oscillations in single cells under constant light conditions. We investigate how to model the timing of dawn and dusk in the context of model-checking, which we use to compute how the probability distributions of key biochemical species change over time. These show that the relative variation in expression level is smallest at the time of peak expression, making peak time an optimal experimental phase marker. Building on these analyses, we use approaches from evolutionary systems biology to investigate how changes in the rate of mRNA degradation impacts the phase of a key protein likely to affect fitness. We explore how robust this circadian clock is towards such potential mutational changes in its underlying biochemistry. Our work shows that multiple approaches lead to a more complete understanding of the clock

A novel and robust parameter training approach for HMMs under noisy and partial access to states

Cataloged from PDF version of article.This paper proposes a new estimation algorithm for the parameters of an HMM as to best account for the observed data. In this model, in addition to the observation sequence, we have partial and noisy access to the hidden state sequence as side information. This access can be seen as "partial labeling" of the hidden states. Furthermore, we model possible mislabeling in the side information in a joint framework and derive the corresponding EM updates accordingly. In our simulations, we observe that using this side information, we considerably improve the state recognition performance, up to 70%, with respect to the "achievable margin" defined by the baseline algorithms. Moreover, our algorithm is shown to be robust to the training conditions. (C) 2013 Elsevier B.V. All rights reserved

Role of the amino terminal RHAU-specific motif in the recognition and resolution of guanine quadruplex-RNA by the DEAH-box RNA helicase RHAU

Under physiological conditions, guanine-rich sequences of DNA and RNA can adopt stable and atypical four-stranded helical structures called G-quadruplexes (G4). Such G4 structures have been shown to occur in vivo and to play a role in various processes such as transcription, translation and telomere maintenance. Owing to their high-thermodynamic stability, resolution of G4 structures in vivo requires specialized enzymes. RHAU is a human RNA helicase of the DEAH-box family that exhibits a unique ATP-dependent G4-resolvase activity with a high affinity and specificity for its substrate in vitro. How RHAU recognizes G4-RNAs has not yet been established. Here, we show that the amino-terminal region of RHAU is essential for RHAU to bind G4 structures and further identify within this region the evolutionary conserved RSM (RHAU-specific motif) domain as a major affinity and specificity determinant. G4-resolvase activity and strict RSM dependency are also observed with CG9323, the Drosophila orthologue of RHAU, in the amino terminal region of which the RSM is the only conserved motif. Thus, these results reveal a novel motif in RHAU protein that plays an important role in recognizing and resolving G4-RNA structures, properties unique to RHAU among many known RNA helicase

Quantitative analysis of regulatory flexibility under changing environmental conditions

The circadian clock controls 24-h rhythms in many biological processes, allowing appropriate timing of biological rhythms relative to dawn and dusk. Known clock circuits include multiple, interlocked feedback loops. Theory suggested that multiple loops contribute the flexibility for molecular rhythms to track multiple phases of the external cycle. Clear dawn- and dusk-tracking rhythms illustrate the flexibility of timing in Ipomoea nil. Molecular clock components in Arabidopsis thaliana showed complex, photoperiod-dependent regulation, which was analysed by comparison with three contrasting models. A simple, quantitative measure, Dusk Sensitivity, was introduced to compare the behaviour of clock models with varying loop complexity. Evening-expressed clock genes showed photoperiod-dependent dusk sensitivity, as predicted by the three-loop model, whereas the one- and two-loop models tracked dawn and dusk, respectively. Output genes for starch degradation achieved dusk-tracking expression through light regulation, rather than a dusk-tracking rhythm. Model analysis predicted which biochemical processes could be manipulated to extend dusk tracking. Our results reveal how an operating principle of biological regulators applies specifically to the plant circadian clock