92 research outputs found

    A hidden integral structure endows absolute concentration robust systems with resilience to dynamical concentration disturbances: A hidden integral structure endows absolute concentration robust systems with resilience to dynamical concentration disturbances

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    Biochemical systems that express certain chemical species of interest at the same level at any positive steady state are called 'absolute concentration robust' (ACR). These species behave in a stable, predictable way, in the sense that their expression is robust with respect to sudden changes in the species concentration, provided that the system reaches a (potentially new) positive steady state. Such a property has been proven to be of importance in certain gene regulatory networks and signaling systems. In the present paper, we mathematically prove that a well-known class of ACR systems studied by Shinar and Feinberg in 2010 hides an internal integral structure. This structure confers these systems with a higher degree of robustness than was previously known. In particular, disturbances much more general than sudden changes in the species concentrations can be rejected, and robust perfect adaptation is achieved. Significantly, we show that these properties are maintained when the system is interconnected with other chemical reaction networks. This key feature enables the design of insulator devices that are able to buffer the loading effect from downstream systems - a crucial requirement for modular circuit design in synthetic biology. We further note that while the best performance of the insulators are achieved when these act at a faster timescale than the upstream module (as typically required), it is not necessary for them to act on a faster timescale than the downstream module in our construction

    TESTING USED ROLLER BEARINGS FOR QUALITY AND SERVICE LIFE

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    Synthetic biology is a rapidly expanding field at the interface of the engineering and biological sciences which aims to apply rational design principles in biological contexts. Many natural processes utilise regulatory architectures that parallel those found in control and electrical engineering, which has motivated their implementation as part of synthetic biological constructs. Tools based upon control theoretical concepts can be used to design such systems, as well as to guide their experimental realisation. In this paper we provide examples of biological implementations of negative feedback systems, and discuss progress made toward realisation of other feedback and control architectures. We then outline major challenges posed by the design of such systems, particularly focusing on those which are specific to biological contexts and on which feedback control can have a significant impact. We explore future directions for work in the field, including new approaches for theoretical design of biological control systems, the utilisation of novel components for their implementation, and the potential for application of automation and machine-learning approaches to accelerate synthetic biological research

    Coding Matrices for Wreath Products of Groups

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    Wreath product, a powerful construction in group theory, has found extensive applications in various areas of mathematics and computer science. In this paper, we present a comprehensive analysis of coding matrices associated with wreath products. The coding matrices for the wreath product of two cyclic finite groups were given for the first time. It gives a generalization of the coding matrices for the semi-direct product. We found out that the coding matrix of wreath product really has the same shape as the one for semidirect product and gave the RW-matrix for the coding matrix. An example was showed to illustrate the assertions. Conditions were also given for different wreath products of cyclic groups and that gives different orders for the wreath products

    Improving newborn health in countries exposed to political violence: an assessment of the availability, accessibility, and distribution of neonatal health services at Palestinian hospitals

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    Introduction: Geopolitical segregation of Palestine has left a fragile healthcare system with an unequal distribution of services. Data from the Gaza Strip reflect an increase in infant mortality that coincided with a significant increase in neonatal mortality (12.0 to 20.3 per 1,000 live births). Objective: A baseline study was carried out to evaluate available resources in neonatal units throughout Palestine. Study Design: A cross-sectional, hospital-based study was conducted in 2017 using the World Health Organization's "Hospital care for mothers and newborn babies: quality assessment and improvement tool." Data on the main indicators were updated in 2018. Results: There were 38 neonatal units in Palestine: 27 in the West Bank, 3 in East Jerusalem, and 8 in the Gaza Strip. There was an uneven geographic distribution of incubators in relation to population and births that was more marked in the Gaza Strip; 79% of neonatal units and 75% of incubators were in the West Bank. While almost all hospitals with neonatal units accepted very and extremely low birth weight and admitted out-born neonatal cases, there was a shortage in the availability of incubators with humidifiers, high-frequency oscillatory ventilation, mechanical ventilators with humidifiers and isolation wards. There was also a considerable shortage in neonatologists, neonatal nurses, and pediatric subspecialties. Conclusion: Almost all the neonatal units accepted extremely low birth weight neonatal cases despite not being ready to receive these newborns due to considerable shortages in human resources, equipment, drugs, and essential blood tests, as well as frequent disruptions in the availability of based amenities. Together, these factors contribute to the burden of providing quality care to newborns, which is further exacerbated by the lack of referral guidelines and challenges to timely referrals resulting from Israeli measures. Ultimately, this contributes to suboptimal care for neonates and negatively impacts future health outcomes

    Examining Neolithic Building and Activity Areas through Historic Cultural Heritage in Jordan: A Combined Ethnographic, Phytolith and Geochemical Investigation

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    The INEA project (Identifying activity areas in Neolithic sites through Ethnographic Analysis of phytoliths and geochemical residues, https://research.bournemouth. ac.uk/2014/07/inea-project-2/) develops and applies a method that combines the analysis of plant remains (silica phytoliths) and geochemical residues to inform on construction methods and the use of space in recently abandoned historical villages and Neolithic settlements. It is a collaborative project based at Bournemouth University, in partnership with the Council for British Research in the Levant

    Advanced Methods and Algorithms for Biological Networks Analysis

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    Module-Based Analysis of Robustness Tradeoffs in the Heat Shock Response System

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    Biological systems have evolved complex regulatory mechanisms, even in situations where much simpler designs seem to be sufficient for generating nominal functionality. Using module-based analysis coupled with rigorous mathematical comparisons, we propose that in analogy to control engineering architectures, the complexity of cellular systems and the presence of hierarchical modular structures can be attributed to the necessity of achieving robustness. We employ the Escherichia coli heat shock response system, a strongly conserved cellular mechanism, as an example to explore the design principles of such modular architectures. In the heat shock response system, the sigma-factor σ(32) is a central regulator that integrates multiple feedforward and feedback modules. Each of these modules provides a different type of robustness with its inherent tradeoffs in terms of transient response and efficiency. We demonstrate how the overall architecture of the system balances such tradeoffs. An extensive mathematical exploration nevertheless points to the existence of an array of alternative strategies for the existing heat shock response that could exhibit similar behavior. We therefore deduce that the evolutionary constraints facing the system might have steered its architecture toward one of many robustly functional solutions

    Analysis of Stochastic Strategies in Bacterial Competence: A Master Equation Approach

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    Competence is a transiently differentiated state that certain bacterial cells reach when faced with a stressful environment. Entrance into competence can be attributed to the excitability of the dynamics governing the genetic circuit that regulates this cellular behavior. Like many biological behaviors, entrance into competence is a stochastic event. In this case cellular noise is responsible for driving the cell from a vegetative state into competence and back. In this work we present a novel numerical method for the analysis of stochastic biochemical events and use it to study the excitable dynamics responsible for competence in Bacillus subtilis. Starting with a Finite State Projection (FSP) solution of the chemical master equation (CME), we develop efficient numerical tools for accurately computing competence probability. Additionally, we propose a new approach for the sensitivity analysis of stochastic events and utilize it to elucidate the robustness properties of the competence regulatory genetic circuit. We also propose and implement a numerical method to calculate the expected time it takes a cell to return from competence. Although this study is focused on an example of cell-differentiation in Bacillus subtilis, our approach can be applied to a wide range of stochastic phenomena in biological systems
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