Modelling of Pyroelectric Response in Inhomogeneous Ferroelectric-Semiconductor Films

We have modified Landau-Khalatnikov approach and shown that the pyroelectric response of inhomogeneous ferroelectric-semiconductor films can be described by using six coupled equations for six order parameters: average displacement, its mean-square fluctuation and correlation with charge defects density fluctuations, average pyroelectric coefficient, its fluctuation and correlation with charge defects density fluctuations. Coupled equations demonstrate the inhomogeneous reversal of pyroelectric response in contrast to the equations of Landau-Khalatnikov type, which describe the homogeneous reversal with the sharp pyroelectric coefficient peak near the thermodynamic coercive field value. Within the framework of our model pyroelectric hysteresis loop becomes much smoother, thinner and lower as well as pyroelectric coefficient peaks near the coercive field completely disappear under the increase of disordering caused by defects. This effect is similar to the well-known "square to slim transition" of the ferroelectric hysteresis loops in relaxor ferroelectrics. Also the increase of defect concentration leads to the drastic decrease of the coercive field typical for disordered ferroelectrics. Usually pyroelectric hysteresis loops of doped and inhomogeneous ferroelectrics have typical smooth shape without any pyroelectric coefficient peaks and coercive field values much lower than the thermodynamic one. Therefore our approach qualitatively explains available experimental results. Rather well quantitative agreement between our modelling and typical Pb(Zr,Ti)O3-film pyroelectric and ferroelectric loops has been obtained.Comment: 14 pages, 5 figure

Nonlinear dynamics in gene regulation promote robustness and evolvability of gene expression levels

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

Phosphate sink containing two-component signaling systems as tunable threshold devices.

Published onlineJournal ArticleResearch Support, Non-U.S. Gov'tSynthetic biology aims to design de novo biological systems and reengineer existing ones. These efforts have mostly focused on transcriptional circuits, with reengineering of signaling circuits hampered by limited understanding of their systems dynamics and experimental challenges. Bacterial two-component signaling systems offer a rich diversity of sensory systems that are built around a core phosphotransfer reaction between histidine kinases and their output response regulator proteins, and thus are a good target for reengineering through synthetic biology. Here, we explore the signal-response relationship arising from a specific motif found in two-component signaling. In this motif, a single histidine kinase (HK) phosphotransfers reversibly to two separate output response regulator (RR) proteins. We show that, under the experimentally observed parameters from bacteria and yeast, this motif not only allows rapid signal termination, whereby one of the RRs acts as a phosphate sink towards the other RR (i.e. the output RR), but also implements a sigmoidal signal-response relationship. We identify two mathematical conditions on system parameters that are necessary for sigmoidal signal-response relationships and define key parameters that control threshold levels and sensitivity of the signal-response curve. We confirm these findings experimentally, by in vitro reconstitution of the one HK-two RR motif found in the Sinorhizobium meliloti chemotaxis pathway and measuring the resulting signal-response curve. We find that the level of sigmoidality in this system can be experimentally controlled by the presence of the sink RR, and also through an auxiliary protein that is shown to bind to the HK (yielding Hill coefficients of above 7). These findings show that the one HK-two RR motif allows bacteria and yeast to implement tunable switch-like signal processing and provides an ideal basis for developing threshold devices for synthetic biology applications.Exeter University Science Strateg

Wavelet based flickering flame detector using differential PIR sensors

Cataloged from PDF version of article.A Pyro-electric Infrared (PIR) sensor based flame detection system is proposed using a Markovian decision algorithm. A differential PIR sensor is only sensitive to sudden temperature variations within its viewing range and it produces a time-varying signal. The wavelet transform of the PIR sensor signal is used for feature extraction from sensor signal and wavelet parameters are fed to a set of Markov models corresponding to the flame flicker process of an uncontrolled fire, ordinary activity of human beings and other objects. The final decision is reached based on the model yielding the highest probability among others. Comparative results show that the system can be used for fire detection in large rooms. (C) 2012 Elsevier Ltd. All rights reserved

Metabolic modelling in a dynamic evolutionary framework predicts adaptive diversification of bacteria in a long-term evolution experiment

Background: Predicting adaptive trajectories is a major goal of evolutionary biology and useful for practical applications. Systems biology has enabled the development of genome-scale metabolic models. However, analysing these models via flux balance analysis (FBA) cannot predict many evolutionary outcomes including adaptive diversification, whereby an ancestral lineage diverges to fill multiple niches. Here we combine in silico evolution with FBA and apply this modelling framework, evoFBA, to a long-term evolution experiment with Escherichia coli. Results: Simulations predicted the adaptive diversification that occurred in one experimental population and generated hypotheses about the mechanisms that promoted coexistence of the diverged lineages. We experimentally tested and, on balance, verified these mechanisms, showing that diversification involved niche construction and character displacement through differential nutrient uptake and altered metabolic regulation. Conclusion: The evoFBA framework represents a promising new way to model biochemical evolution, one that can generate testable predictions about evolutionary and ecosystem-level outcomes

A Genetic Screen Identifies Hypothalamic Fgf15 as a Regulator of Glucagon Secretion.

The counterregulatory response to hypoglycemia, which restores normal blood glucose levels to ensure sufficient provision of glucose to the brain, is critical for survival. To discover underlying brain regulatory systems, we performed a genetic screen in recombinant inbred mice for quantitative trait loci (QTL) controlling glucagon secretion in response to neuroglucopenia. We identified a QTL on the distal part of chromosome 7 and combined this genetic information with transcriptomic analysis of hypothalami. This revealed Fgf15 as the strongest candidate to control the glucagon response. Fgf15 was expressed by neurons of the dorsomedial hypothalamus and the perifornical area. Intracerebroventricular injection of FGF19, the human ortholog of Fgf15, reduced activation by neuroglucopenia of dorsal vagal complex neurons, of the parasympathetic nerve, and lowered glucagon secretion. In contrast, silencing Fgf15 in the dorsomedial hypothalamus increased neuroglucopenia-induced glucagon secretion. These data identify hypothalamic Fgf15 as a regulator of glucagon secretion

Cost-Effective Use of Silver Dressings for the Treatment of Hard-to-Heal Chronic Venous Leg Ulcers

Aim To estimate the cost-effectiveness of silver dressings using a health economic model based on time-to-wound-healing in hard-to-heal chronic venous leg ulcers (VLUs). Background Chronic venous ulceration affects 1–3% of the adult population and typically has a protracted course of healing, resulting in considerable costs to the healthcare system. The pathogenesis of VLUs includes excessive and prolonged inflammation which is often related to critical colonisation and early infection. The use of silver dressings to control this bioburden and improve wound healing rates remains controversial. Methods A decision tree was constructed to evaluate the cost-effectiveness of treatment with silver compared with non-silver dressings for four weeks in a primary care setting. The outcomes: ‘Healed ulcer’, ‘Healing ulcer’ or ‘No improvement’ were developed, reflecting the relative reduction in ulcer area from baseline to four weeks of treatment. A data set from a recent meta-analysis, based on four RCTs, was applied to the model. Results Treatment with silver dressings for an initial four weeks was found to give a total cost saving (£141.57) compared with treatment with non-silver dressings. In addition, patients treated with silver dressings had a faster wound closure compared with those who had been treated with non-silver dressings. Conclusion The use of silver dressings improves healing time and can lead to overall cost savings. These results can be used to guide healthcare decision makers in evaluating the economic aspects of treatment with silver dressings in hard-to-heal chronic VLUs

Anisotropic coarse-grained statistical potentials improve the ability to identify native-like protein structures

We present a new method to extract distance and orientation dependent potentials between amino acid side chains using a database of protein structures and the standard Boltzmann device. The importance of orientation dependent interactions is first established by computing orientational order parameters for proteins with alpha-helical and beta-sheet architecture. Extraction of the anisotropic interactions requires defining local reference frames for each amino acid that uniquely determine the coordinates of the neighboring residues. Using the local reference frames and histograms of the radial and angular correlation functions for a standard set of non-homologue protein structures, we construct the anisotropic pair potentials. The performance of the orientation dependent potentials was studied using a large database of decoy proteins. The results demonstrate that the new distance and orientation dependent residue-residue potentials present a significantly improved ability to recognize native folds from a set of native and decoy protein structures.Comment: Submitted to "The Journal of Chemical Physics

Physicians' perception of childhood asthma in Turkey: more appropriate practice among female physicians

<p>Abstract</p> <p>Background</p> <p>Low levels of asthma control worldwide point to the possibility of sub-optimal management; therefore, documentation of physicians' perception is critical for future interventions. Our aim was to examine self-reported management abilities of Turkish physicians dealing with children with asthma, document the factors affecting appropriate decisions and compare the results with those of a previous survey.</p> <p>Methods</p> <p>Physicians were surveyed via a questionnaire aimed to document self-perceived asthma knowledge and attitudes in asthma management.</p> <p>Results</p> <p>The majority of physicians were male (63%) and examined 234 ± 9 patients per week. Infrequent use of objective parameters in asthma diagnosis and attack severity assessment was reported and most preferred nebulized corticosteroids to the systemic form in acute asthma. Even though self-perceived overall asthma knowledge did not differ between genders (p = 0.098), male physicians scored higher than females for inhaled steroids for acute asthma (2.8 ± 0.12 vs 2.17 ± 0.2, respectively, p = 0.007), while female physicians recorded more frequent use of inhaled steroids for chronic asthma (3.72 ± 0.08 vs 3.43 ± 0.07, respectively, p = 0.006). Female physicians' scoring for "symptom control" as the main aim of asthma management was higher than that of their male counterparts (3.88 ± 0.04 vs 3.65 ± 0.06, respectively, p = 0.002).</p> <p>Conclusion</p> <p>Although there were some discrepancies between guidelines and clinical practice, most applications of Turkish physicians dealing with children with asthma were appropriate. Interestingly, when scores of female versus male physicians were compared, it can be suggested that female physicians have a more appropriate perception of asthma, indicating a significant contribution of gender-related factors in clinical attitudes and beliefs.</p