WorldWideScience

Sample records for complex biological system

  1. Systems Biology and Health Systems Complexity in;

    NARCIS (Netherlands)

    Donald Combs, C.; Barham, S.R.; Sloot, P.M.A.

    2016-01-01

    Systems biology addresses interactions in biological systems at different scales of biological organization, from the molecular to the cellular, organ, organism, societal, and ecosystem levels. This chapter expands on the concept of systems biology, explores its implications for individual patients

  2. Mathematical Modeling of Complex Biological Systems

    OpenAIRE

    Fischer, Hans Peter

    2008-01-01

    To understand complex biological systems such as cells, tissues, or even the human body, it is not sufficient to identify and characterize the individual molecules in the system. It also is necessary to obtain a thorough understanding of the interaction between molecules and pathways. This is even truer for understanding complex diseases such as cancer, Alzheimer’s disease, or alcoholism. With recent technological advances enabling researchers to monitor complex cellular processes on the mole...

  3. Life: An Introduction to Complex Systems Biology

    CERN Document Server

    Kaneko, Kunihiko

    2006-01-01

    What is life? Has molecular biology given us a satisfactory answer to this question? And if not, why, and how to carry on from there? This book examines life not from the reductionist point of view, but rather asks the question: what are the universal properties of living systems and how can one construct from there a phenomenological theory of life that leads naturally to complex processes such as reproductive cellular systems, evolution and differentiation? The presentation has been deliberately kept fairly non-technical so as to address a broad spectrum of students and researchers from the natural sciences and informatics.

  4. Complex biological and bio-inspired systems

    Energy Technology Data Exchange (ETDEWEB)

    Ecke, Robert E [Los Alamos National Laboratory

    2009-01-01

    The understanding and characterization ofthe fundamental processes of the function of biological systems underpins many of the important challenges facing American society, from the pathology of infectious disease and the efficacy ofvaccines, to the development of materials that mimic biological functionality and deliver exceptional and novel structural and dynamic properties. These problems are fundamentally complex, involving many interacting components and poorly understood bio-chemical kinetics. We use the basic science of statistical physics, kinetic theory, cellular bio-chemistry, soft-matter physics, and information science to develop cell level models and explore the use ofbiomimetic materials. This project seeks to determine how cell level processes, such as response to mechanical stresses, chemical constituents and related gradients, and other cell signaling mechanisms, integrate and combine to create a functioning organism. The research focuses on the basic physical processes that take place at different levels ofthe biological organism: the basic role of molecular and chemical interactions are investigated, the dynamics of the DNA-molecule and its phylogenetic role are examined and the regulatory networks of complex biochemical processes are modeled. These efforts may lead to early warning algorithms ofpathogen outbreaks, new bio-sensors to detect hazards from pathomic viruses to chemical contaminants. Other potential applications include the development of efficient bio-fuel alternative-energy processes and the exploration ofnovel materials for energy usages. Finally, we use the notion of 'coarse-graining,' which is a method for averaging over less important degrees of freedom to develop computational models to predict cell function and systems-level response to disease, chemical stress, or biological pathomic agents. This project supports Energy Security, Threat Reduction, and the missions of the DOE Office of Science through its efforts to

  5. Integrative Systems Biology: Elucidating Complex Traits

    DEFF Research Database (Denmark)

    Pers, Tune Hannes

    Risk-phenotypes and diseases are oen caused by perturbed cellular networks, as biological processes depend on an overwhelming number of heavily intertwined components. e impact of a genetically altered gene may ripple through its molecular neighborhood instead of being confined to the gene...... product itself. My doctoral studies have been focused on the development of integrative approaches to identify systemic risk-modifying and disease-causing patterns. ey have been rooted in the hypothesis that data integration of complementary data sets may yield additional etiologic insights compared...... to analyses conducted within a single type of data. e first line of research presented here outlines two integrative methodologies designed to identify etiological pathways and susceptibility genes. In Paper I, my coworkers and I present an integrative approach that interrogates protein complexes...

  6. Complexity, Analysis and Control of Singular Biological Systems

    CERN Document Server

    Zhang, Qingling; Zhang, Xue

    2012-01-01

    Complexity, Analysis and Control of Singular Biological Systems follows the control of real-world biological systems at both ecological and phyisological levels concentrating on the application of now-extensively-investigated singular system theory. Much effort has recently been dedicated to the modelling and analysis of developing bioeconomic systems and the text establishes singular examples of these, showing how proper control can help to maintain sustainable economic development of biological resources. The book begins from the essentials of singular systems theory and bifurcations before tackling  the use of various forms of control in singular biological systems using examples including predator-prey relationships and viral vaccination and quarantine control. Researchers and graduate students studying the control of complex biological systems are shown how a variety of methods can be brought to bear and practitioners working with the economics of biological systems and their control will also find the ...

  7. Complex fluids in biological systems experiment, theory, and computation

    CERN Document Server

    2015-01-01

    This book serves as an introduction to the continuum mechanics and mathematical modeling of complex fluids in living systems. The form and function of living systems are intimately tied to the nature of surrounding fluid environments, which commonly exhibit nonlinear and history dependent responses to forces and displacements. With ever-increasing capabilities in the visualization and manipulation of biological systems, research on the fundamental phenomena, models, measurements, and analysis of complex fluids has taken a number of exciting directions. In this book, many of the world’s foremost experts explore key topics such as: Macro- and micro-rheological techniques for measuring the material properties of complex biofluids and the subtleties of data interpretation Experimental observations and rheology of complex biological materials, including mucus, cell membranes, the cytoskeleton, and blood The motility of microorganisms in complex fluids and the dynamics of active suspensions Challenges and solut...

  8. From globally coupled maps to complex-systems biology

    Energy Technology Data Exchange (ETDEWEB)

    Kaneko, Kunihiko, E-mail: kaneko@complex.c.u-tokyo.ac.jp [Research Center for Complex Systems Biology, Graduate School of Arts and Sciences, The University of Tokyo 3-8-1 Komaba, Meguro-ku, Tokyo 153-8902 (Japan)

    2015-09-15

    Studies of globally coupled maps, introduced as a network of chaotic dynamics, are briefly reviewed with an emphasis on novel concepts therein, which are universal in high-dimensional dynamical systems. They include clustering of synchronized oscillations, hierarchical clustering, chimera of synchronization and desynchronization, partition complexity, prevalence of Milnor attractors, chaotic itinerancy, and collective chaos. The degrees of freedom necessary for high dimensionality are proposed to equal the number in which the combinatorial exceeds the exponential. Future analysis of high-dimensional dynamical systems with regard to complex-systems biology is briefly discussed.

  9. Toxicity of silver nanoparticles in biological systems: Does the complexity of biological systems matter?

    Science.gov (United States)

    Vazquez-Muñoz, Roberto; Borrego, Belen; Juárez-Moreno, Karla; García-García, Maritza; Mota Morales, Josué D; Bogdanchikova, Nina; Huerta-Saquero, Alejandro

    2017-07-05

    Currently, nanomaterials are more frequently in our daily life, specifically in biomedicine, electronics, food, textiles and catalysis just to name a few. Although nanomaterials provide many benefits, recently their toxicity profiles have begun to be explored. In this work, the toxic effects of silver nanoparticles (35nm-average diameter and Polyvinyl-Pyrrolidone-coated) on biological systems of different levels of complexity was assessed in a comprehensive and comparatively way, through a variety of viability and toxicological assays. The studied organisms included viruses, bacteria, microalgae, fungi, animal and human cells (including cancer cell lines). It was found that biological systems of different taxonomical groups are inhibited at concentrations of silver nanoparticles within the same order of magnitude. Thus, the toxicity of nanomaterials on biological/living systems, constrained by their complexity, e.g. taxonomic groups, resulted contrary to the expected. The fact that cells and virus are inhibited with a concentration of silver nanoparticles within the same order of magnitude could be explained considering that silver nanoparticles affects very primitive cellular mechanisms by interacting with fundamental structures for cells and virus alike. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. A complex systems approach to computational molecular biology

    Energy Technology Data Exchange (ETDEWEB)

    Lapedes, A. [Los Alamos National Lab., NM (United States)]|[Santa Fe Inst., NM (United States)

    1993-09-01

    We report on the containing research program at Santa Fe Institute that applies complex systems methodology to computational molecular biology. Two aspects are stressed here are the use of co-evolving adaptive neutral networks for determining predictable protein structure classifications, and the use of information theory to elucidate protein structure and function. A ``snapshot`` of the current state of research in these two topics is presented, representing the present state of two major research thrusts in the program of Genetic Data and Sequence Analysis at the Santa Fe Institute.

  11. Complex systems of biological interest stability under ionising radiations

    International Nuclear Information System (INIS)

    Maclot, Sylvain

    2014-01-01

    This PhD work presents the study of stability of molecular systems of biological interest in the gas phase after interaction with ionising radiations. The use of ionising radiation can probe the physical chemistry of complex systems at the molecular scale and thus consider their intrinsic properties. Beyond the fundamental aspect, this work is part of the overall understanding of radiation effects on living organisms and in particular the use of ionizing radiation in radiotherapy. Specifically, this study focused on the use of low-energy multiply charged ions (tens of keV) provided by the GANIL (Caen), which includes most of the experiments presented. In addition, experiments using VUV photons were also conducted at synchrotron ELETTRA (Trieste, Italy). The bio-molecular systems studied are amino acids and nucleic acid constituents. Using an experimental crossed beams device allows interaction between biomolecules and ionising radiation leads mainly to the ionization and fragmentation of the system. The study of its relaxation dynamics is by time-of-flight mass spectrometry coupled to a coincidences measurements method. It is shown that an approach combining experiment and theory allows a detailed study of the fragmentation dynamics of complex systems. The results indicate that fragmentation is generally governed by the Coulomb repulsion but the intramolecular rearrangements involve specific relaxation mechanisms. (author) [fr

  12. The physics of complex systems in information and biology

    Science.gov (United States)

    Walker, Dylan

    study the interaction between popularity and quality, we introduce simple stochastic models of user behavior that approximate differing user quality and susceptibility to the common notion of popularity. We define a metric to quantify user reputation in a manner that is self-consistent, adaptable and content-blind and shows good correlation with the probability that a user behaves in an optimal fashion. We further construct a mechanism for ranking documents that take into account user reputation and provides substantial improvement in the time-critical performance of the system. The structure of complex systems have been well studied in the context of both information and biological systems. More recently, dynamics in complex systems that occur over the background of the underlying network has received a great deal of attention. In particular, the study of fluctuations in complex systems has emerged as an issue central to understanding dynamical behavior. We approach the problem of collective effects of the underlying network on dynamical fluctuations by considering the protein-protein interaction networks for the system of the living cell. We consider two types of fluctuations in the mass-action equilibrium in protein binding networks. The first type is driven by relatively slow changes in total concentrations (copy numbers) of interacting proteins. The second type, to which we refer to as spontaneous, is caused by quickly decaying thermodynamic deviations away from the mass-action equilibrium of the system. As such they are amenable to methods of equilibrium statistical mechanics used in our study. We investigate the effects of network connectivity on these fluctuations by comparing them to different scenarios in which the interacting pair is isolated form the rest of the network. Such comparison allows us to analytically derive upper and lower bounds on network fluctuations. The collective effects are shown to sometimes lead to relatively large amplification of

  13. Network Analyses in Systems Biology: New Strategies for Dealing with Biological Complexity

    DEFF Research Database (Denmark)

    Green, Sara; Serban, Maria; Scholl, Raphael

    2018-01-01

    The increasing application of network models to interpret biological systems raises a number of important methodological and epistemological questions. What novel insights can network analysis provide in biology? Are network approaches an extension of or in conflict with mechanistic research...

  14. Network biology: Describing biological systems by complex networks. Comment on "Network science of biological systems at different scales: A review" by M. Gosak et al.

    Science.gov (United States)

    Jalili, Mahdi

    2018-03-01

    I enjoyed reading Gosak et al. review on analysing biological systems from network science perspective [1]. Network science, first started within Physics community, is now a mature multidisciplinary field of science with many applications ranging from Ecology to biology, medicine, social sciences, engineering and computer science. Gosak et al. discussed how biological systems can be modelled and described by complex network theory which is an important application of network science. Although there has been considerable progress in network biology over the past two decades, this is just the beginning and network science has a great deal to offer to biology and medical sciences.

  15. How do precision medicine and system biology response to human body's complex adaptability?

    Science.gov (United States)

    Yuan, Bing

    2016-12-01

    In the field of life sciences, although system biology and "precision medicine" introduce some complex scientifific methods and techniques, it is still based on the "analysis-reconstruction" of reductionist theory as a whole. Adaptability of complex system increase system behaviour uncertainty as well as the difficulties of precise identifification and control. It also put systems biology research into trouble. To grasp the behaviour and characteristics of organism fundamentally, systems biology has to abandon the "analysis-reconstruction" concept. In accordance with the guidelines of complexity science, systems biology should build organism model from holistic level, just like the Chinese medicine did in dealing with human body and disease. When we study the living body from the holistic level, we will fifind the adaptability of complex system is not the obstacle that increases the diffificulty of problem solving. It is the "exceptional", "right-hand man" that helping us to deal with the complexity of life more effectively.

  16. Using systems biology to simplify complex disease: immune cartography.

    Science.gov (United States)

    Polpitiya, Ashoka D; McDunn, Jonathan E; Burykin, Anton; Ghosh, Bijoy K; Cobb, J Perren

    2009-01-01

    What if there was a rapid, inexpensive, and accurate blood diagnostic that could determine which patients were infected, identify the organism(s) responsible, and identify patients who were not responding to therapy? We hypothesized that systems analysis of the transcriptional activity of circulating immune effector cells could be used to identify conserved elements in the host response to systemic inflammation, and furthermore, to discriminate between sterile and infectious etiologies. We review herein a validated, systems biology approach demonstrating that 1) abdominal and pulmonary sepsis diagnoses can be made in mouse models using microarray (RNA) data from circulating blood, 2) blood microarray data can be used to differentiate between the host response to Gram-negative and Gram-positive pneumonia, 3) the endotoxin response of normal human volunteers can be mapped at the level of gene expression, and 4) a similar strategy can be used in the critically ill to follow septic patients and quantitatively determine immune recovery. These findings provide the foundation of immune cartography and demonstrate the potential of this approach for rapidly diagnosing sepsis and identifying pathogens. Further, our data suggest a new approach to determine how specific pathogens perturb the physiology of circulating leukocytes in a cell-specific manner. Large, prospective clinical trails are needed to validate the clinical utility of leukocyte RNA diagnostics (e.g., the riboleukogram).

  17. Approaching complexity by stochastic methods: From biological systems to turbulence

    Energy Technology Data Exchange (ETDEWEB)

    Friedrich, Rudolf [Institute for Theoretical Physics, University of Muenster, D-48149 Muenster (Germany); Peinke, Joachim [Institute of Physics, Carl von Ossietzky University, D-26111 Oldenburg (Germany); Sahimi, Muhammad [Mork Family Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, CA 90089-1211 (United States); Reza Rahimi Tabar, M., E-mail: mohammed.r.rahimi.tabar@uni-oldenburg.de [Department of Physics, Sharif University of Technology, Tehran 11155-9161 (Iran, Islamic Republic of); Institute of Physics, Carl von Ossietzky University, D-26111 Oldenburg (Germany); Fachbereich Physik, Universitaet Osnabrueck, Barbarastrasse 7, 49076 Osnabrueck (Germany)

    2011-09-15

    This review addresses a central question in the field of complex systems: given a fluctuating (in time or space), sequentially measured set of experimental data, how should one analyze the data, assess their underlying trends, and discover the characteristics of the fluctuations that generate the experimental traces? In recent years, significant progress has been made in addressing this question for a class of stochastic processes that can be modeled by Langevin equations, including additive as well as multiplicative fluctuations or noise. Important results have emerged from the analysis of temporal data for such diverse fields as neuroscience, cardiology, finance, economy, surface science, turbulence, seismic time series and epileptic brain dynamics, to name but a few. Furthermore, it has been recognized that a similar approach can be applied to the data that depend on a length scale, such as velocity increments in fully developed turbulent flow, or height increments that characterize rough surfaces. A basic ingredient of the approach to the analysis of fluctuating data is the presence of a Markovian property, which can be detected in real systems above a certain time or length scale. This scale is referred to as the Markov-Einstein (ME) scale, and has turned out to be a useful characteristic of complex systems. We provide a review of the operational methods that have been developed for analyzing stochastic data in time and scale. We address in detail the following issues: (i) reconstruction of stochastic evolution equations from data in terms of the Langevin equations or the corresponding Fokker-Planck equations and (ii) intermittency, cascades, and multiscale correlation functions.

  18. Approaching complexity by stochastic methods: From biological systems to turbulence

    International Nuclear Information System (INIS)

    Friedrich, Rudolf; Peinke, Joachim; Sahimi, Muhammad; Reza Rahimi Tabar, M.

    2011-01-01

    This review addresses a central question in the field of complex systems: given a fluctuating (in time or space), sequentially measured set of experimental data, how should one analyze the data, assess their underlying trends, and discover the characteristics of the fluctuations that generate the experimental traces? In recent years, significant progress has been made in addressing this question for a class of stochastic processes that can be modeled by Langevin equations, including additive as well as multiplicative fluctuations or noise. Important results have emerged from the analysis of temporal data for such diverse fields as neuroscience, cardiology, finance, economy, surface science, turbulence, seismic time series and epileptic brain dynamics, to name but a few. Furthermore, it has been recognized that a similar approach can be applied to the data that depend on a length scale, such as velocity increments in fully developed turbulent flow, or height increments that characterize rough surfaces. A basic ingredient of the approach to the analysis of fluctuating data is the presence of a Markovian property, which can be detected in real systems above a certain time or length scale. This scale is referred to as the Markov-Einstein (ME) scale, and has turned out to be a useful characteristic of complex systems. We provide a review of the operational methods that have been developed for analyzing stochastic data in time and scale. We address in detail the following issues: (i) reconstruction of stochastic evolution equations from data in terms of the Langevin equations or the corresponding Fokker-Planck equations and (ii) intermittency, cascades, and multiscale correlation functions.

  19. The ultimate complex system: networks in molecular biology

    Science.gov (United States)

    Schreiber, Andreas W.

    2010-07-01

    This contribution provides a brief survey of networks as they occur in molecular biology. It is intended as an introduction for a physics audience with no prior knowledge of molecular biology. References to key papers and reviews are included for the reader who wishes to explore this fascinating area further.

  20. Towards Complex Abiotic Systems for Chemical and Biological Sensing

    Science.gov (United States)

    2009-11-01

    properties. The most sensitive biodetector known today is the olfactory system of animal species, such as dogs and pigs,1 capable of detecting a few...the two ATP generating steps in Glycolysis . It is noteworthy that the above two reactions represent the sole source of de novo synthesis of ATP in the

  1. Complex Systems Biology Approach To Understanding Coordination of JAK-STAT Signaling

    OpenAIRE

    Soebiyanto, Radina P.; Sreenath, Sree N.; Qu, Cheng-Kui; Loparo, Kenneth A.; Bunting, Kevin D.

    2007-01-01

    In this work, we search for coordination as an organizing principle in a complex signaling system using a multilevel hierarchical paradigm. The objective is to explain the underlying mechanism of Interferon (IFNγ) induced JAK-STAT (specifically JAK1/JAK2-STAT1) pathway behavior. Starting with a mathematical model of the pathway from the literature, we modularize the system using biological knowledge via principles of biochemical cohesion, biological significance, and functionality. The modula...

  2. From Molecules to Life: Quantifying the Complexity of Chemical and Biological Systems in the Universe.

    Science.gov (United States)

    Böttcher, Thomas

    2018-01-01

    Life is a complex phenomenon and much research has been devoted to both understanding its origins from prebiotic chemistry and discovering life beyond Earth. Yet, it has remained elusive how to quantify this complexity and how to compare chemical and biological units on one common scale. Here, a mathematical description of molecular complexity was applied allowing to quantitatively assess complexity of chemical structures. This in combination with the orthogonal measure of information complexity resulted in a two-dimensional complexity space ranging over the entire spectrum from molecules to organisms. Entities with a certain level of information complexity directly require a functionally complex mechanism for their production or replication and are hence indicative for life-like systems. In order to describe entities combining molecular and information complexity, the term biogenic unit was introduced. Exemplified biogenic unit complexities were calculated for ribozymes, protein enzymes, multimeric protein complexes, and even an entire virus particle. Complexities of prokaryotic and eukaryotic cells, as well as multicellular organisms, were estimated. Thereby distinct evolutionary stages in complexity space were identified. The here developed approach to compare the complexity of biogenic units allows for the first time to address the gradual characteristics of prebiotic and life-like systems without the need for a definition of life. This operational concept may guide our search for life in the Universe, and it may direct the investigations of prebiotic trajectories that lead towards the evolution of complexity at the origins of life.

  3. Systems-synthetic biology in understanding the complexities and simple devices in immunology.

    Science.gov (United States)

    Soni, Bhavnita; Nimsarkar, Prajakta; Mol, Milsee; Saha, Bhaskar; Singh, Shailza

    2018-03-23

    Systems and synthetic biology in the coming era has the ability to manipulate, stimulate and engineer cells to counteract the pathogenic immune response. The inherent biological complexities associated with the creation of a device allow capitalizing the biotechnological resources either by simply administering a recombinant cytokine or just reprogramming the immune cells. The strategy outlined, adopted and discussed may mark the beginning with promising therapeutics based on the principles of synthetic immunology. Copyright © 2018 Elsevier Ltd. All rights reserved.

  4. Modeling complexity: cognitive constraints and computational model-building in integrative systems biology.

    Science.gov (United States)

    MacLeod, Miles; Nersessian, Nancy J

    2018-01-08

    Modern integrative systems biology defines itself by the complexity of the problems it takes on through computational modeling and simulation. However in integrative systems biology computers do not solve problems alone. Problem solving depends as ever on human cognitive resources. Current philosophical accounts hint at their importance, but it remains to be understood what roles human cognition plays in computational modeling. In this paper we focus on practices through which modelers in systems biology use computational simulation and other tools to handle the cognitive complexity of their modeling problems so as to be able to make significant contributions to understanding, intervening in, and controlling complex biological systems. We thus show how cognition, especially processes of simulative mental modeling, is implicated centrally in processes of model-building. At the same time we suggest how the representational choices of what to model in systems biology are limited or constrained as a result. Such constraints help us both understand and rationalize the restricted form that problem solving takes in the field and why its results do not always measure up to expectations.

  5. Using multi-criteria analysis of simulation models to understand complex biological systems

    Science.gov (United States)

    Maureen C. Kennedy; E. David. Ford

    2011-01-01

    Scientists frequently use computer-simulation models to help solve complex biological problems. Typically, such models are highly integrated, they produce multiple outputs, and standard methods of model analysis are ill suited for evaluating them. We show how multi-criteria optimization with Pareto optimality allows for model outputs to be compared to multiple system...

  6. On the analysis of complex biological supply chains: From Process Systems Engineering to Quantitative Systems Pharmacology.

    Science.gov (United States)

    Rao, Rohit T; Scherholz, Megerle L; Hartmanshenn, Clara; Bae, Seul-A; Androulakis, Ioannis P

    2017-12-05

    The use of models in biology has become particularly relevant as it enables investigators to develop a mechanistic framework for understanding the operating principles of living systems as well as in quantitatively predicting their response to both pathological perturbations and pharmacological interventions. This application has resulted in a synergistic convergence of systems biology and pharmacokinetic-pharmacodynamic modeling techniques that has led to the emergence of quantitative systems pharmacology (QSP). In this review, we discuss how the foundational principles of chemical process systems engineering inform the progressive development of more physiologically-based systems biology models.

  7. Systems Biology

    Indian Academy of Sciences (India)

    IAS Admin

    Systems biology seeks to study biological systems as a whole, contrary to the reductionist approach that has dominated biology. Such a view of biological systems emanating from strong foundations of molecular level understanding of the individual components in terms of their form, function and interactions is promising to ...

  8. From 'omics' to complex disease: a systems biology approach to gene-environment interactions in cancer

    Directory of Open Access Journals (Sweden)

    Knox Sarah S

    2010-04-01

    Full Text Available Abstract Background Cancer is a complex disease that involves a sequence of gene-environment interactions in a progressive process that cannot occur without dysfunction in multiple systems, including DNA repair, apoptotic and immune functions. Epigenetic mechanisms, responding to numerous internal and external cues in a dynamic ongoing exchange, play a key role in mediating environmental influences on gene expression and tumor development. Hypothesis The hypothesis put forth in this paper addresses the limited success of treatment outcomes in clinical oncology. It states that improvement in treatment efficacy requires a new paradigm that focuses on reversing systemic dysfunction and tailoring treatments to specific stages in the process. It requires moving from a reductionist framework of seeking to destroy aberrant cells and pathways to a transdisciplinary systems biology approach aimed at reversing multiple levels of dysfunction. Conclusion Because there are many biological pathways and multiple epigenetic influences working simultaneously in the expression of cancer phenotypes, studying individual components in isolation does not allow an adequate understanding of phenotypic expression. A systems biology approach using new modeling techniques and nonlinear mathematics is needed to investigate gene-environment interactions and improve treatment efficacy. A broader array of study designs will also be required, including prospective molecular epidemiology, immune competent animal models and in vitro/in vivo translational research that more accurately reflects the complex process of tumor initiation and progression.

  9. PeTTSy: a computational tool for perturbation analysis of complex systems biology models.

    Science.gov (United States)

    Domijan, Mirela; Brown, Paul E; Shulgin, Boris V; Rand, David A

    2016-03-10

    Over the last decade sensitivity analysis techniques have been shown to be very useful to analyse complex and high dimensional Systems Biology models. However, many of the currently available toolboxes have either used parameter sampling, been focused on a restricted set of model observables of interest, studied optimisation of a objective function, or have not dealt with multiple simultaneous model parameter changes where the changes can be permanent or temporary. Here we introduce our new, freely downloadable toolbox, PeTTSy (Perturbation Theory Toolbox for Systems). PeTTSy is a package for MATLAB which implements a wide array of techniques for the perturbation theory and sensitivity analysis of large and complex ordinary differential equation (ODE) based models. PeTTSy is a comprehensive modelling framework that introduces a number of new approaches and that fully addresses analysis of oscillatory systems. It examines sensitivity analysis of the models to perturbations of parameters, where the perturbation timing, strength, length and overall shape can be controlled by the user. This can be done in a system-global setting, namely, the user can determine how many parameters to perturb, by how much and for how long. PeTTSy also offers the user the ability to explore the effect of the parameter perturbations on many different types of outputs: period, phase (timing of peak) and model solutions. PeTTSy can be employed on a wide range of mathematical models including free-running and forced oscillators and signalling systems. To enable experimental optimisation using the Fisher Information Matrix it efficiently allows one to combine multiple variants of a model (i.e. a model with multiple experimental conditions) in order to determine the value of new experiments. It is especially useful in the analysis of large and complex models involving many variables and parameters. PeTTSy is a comprehensive tool for analysing large and complex models of regulatory and

  10. Biological design principles of complex feedback modules in the E. coli ammonia assimilation system.

    Science.gov (United States)

    Masaki, Koichi; Maeda, Kazuhiro; Kurata, Hiroyuki

    2012-01-01

    To synthesize natural or artificial life, it is critically important to understand the design principles of how biochemical networks generate particular cellular functions and evolve complex systems in comparison with engineering systems. Cellular systems maintain their robustness in the face of perturbations arising from environmental and genetic variations. In analogy to control engineering architectures, the complexity of modular structures within a cell can be attributed to the necessity of achieving robustness. To reveal such biological design, the E. coli ammonia assimilation system is analyzed, which consists of complex but highly structured modules: the glutamine synthetase (GS) activity feedback control module with bifunctional enzyme cascades for catalyzing reversible reactions, and the GS synthesis feedback control module with positive and negative feedback loops. We develop a full-scale dynamic model that unifies the two modules, and we analyze its robustness and fine tuning with respect to internal and external perturbations. The GS activity control is added to the GS synthesis module to improve its transient response to ammonia depletion, compensating the tradeoffs of each module, but its robustness to internal perturbations is lost. These findings suggest some design principles necessary for the synthesis of life.

  11. Systems Biology

    Energy Technology Data Exchange (ETDEWEB)

    Wiley, H S.

    2006-06-01

    The biology revolution over the last 50 years has been driven by the ascendancy of molecular biology. This was enthusiastically embraced by most biologists because it took us into increasingly familiar territory. It took mysterious processes, such as the replication of genetic material and assigned them parts that could be readily understood by the human mind. When we think of ''molecular machines'' as being the underlying basis of life, we are using a paradigm derived from everyday experience. However, the price that we paid was a relentless drive towards reductionism and the attendant balkanization of biology. Now along comes ''systems biology'' that promises us a solution to the problem of ''knowing more and more about less and less''. Unlike molecular biology, systems biology appears to be taking us into unfamiliar intellectual territory, such as statistics, mathematics and computer modeling. Not surprisingly, systems biology has met with widespread skepticism and resistance. Why do we need systems biology anyway and how does this new area of research promise to change the face of biology in the next couple of decades?

  12. Systems biology in psychiatric research: from complex data sets over wiring diagrams to computer simulations.

    Science.gov (United States)

    Tretter, Felix; Gebicke-Haerter, Peter J

    2012-01-01

    The classification of psychiatric disorders has always been a problem in clinical settings. The present debate about the major systems in clinical practice, DSM-IV and ICD-10, has resulted in attempts to improve and replace those schemes by some that include more endophenotypic and molecular features. However, these disorders not only require more precise diagnostic tools, but also have to be viewed more extensively in their dynamic behaviors, which require more precise data sets related to their origins and developments. This enormous challenge in brain research has to be approached on different levels of the biological system by new methods, including improvements in electroencephalography, brain imaging, and molecular biology. All these methods entail accumulations of large data sets that become more and more difficult to interpret. In particular, on the molecular level, there is an apparent need to use highly sophisticated computer programs to tackle these problems. Evidently, only interdisciplinary work among mathematicians, physicists, biologists, and clinicians can further improve our understanding of complex diseases of the brain.

  13. Systems Biology via Redescription and Ontologies (II): A Tool for Discovery in Complex Systems

    Science.gov (United States)

    Kleinberg, Samantha; Antoniotti, Marco; Tadepalli, Satish; Ramakrishnan, Naren; Mishra, Bud

    A complex system creates a "whole that is larger than the sum of its parts," by coordinating many interacting simpler component processes. Yet, each of these processes is difficult to decipher as their visible signatures are only seen in a syntactic background, devoid of the context. Examples of such visible datasets are time-course description of gene-expression abundance levels, neural spike-trains, or click-streams for web pages. It has now become rather effortless to collect voluminous datasets of this nature; but how can we make sense of them and draw significant conclusions? For instance, in the case of time-course gene-expression datasets, rather than following small sets of known genes, can we develop a holistic approach that provides a view of the entire system as it evolves through time?

  14. Evolution of Biological Complexity

    Science.gov (United States)

    Goldstein, Raymond E.

    It is a general rule of nature that larger organisms are more complex, at least as measured by the number of distinct types of cells present. This reflects the fitness advantage conferred by a division of labor among specialized cells over homogeneous totipotency. Yet, increasing size has both costs and benefits, and the search for understanding the driving forces behind the evolution of multicellularity is becoming a very active area of research. This article presents an overview of recent experimental and theoretical work aimed at understanding this biological problem from the perspective of physics. For a class of model organisms, the Volvocine green algae, an emerging hypothesis connects the transition from organisms with totipotent cells to those with terminal germ-soma differentiation to the competition between diffusion and fluid advection created by beating flagella. A number of challenging problems in fluid dynamics, nonlinear dynamics, and control theory emerge when one probes the workings of the simplest multicellular organisms.

  15. Perspective: Differential dynamic microscopy extracts multi-scale activity in complex fluids and biological systems

    Science.gov (United States)

    Cerbino, Roberto; Cicuta, Pietro

    2017-09-01

    Differential dynamic microscopy (DDM) is a technique that exploits optical microscopy to obtain local, multi-scale quantitative information about dynamic samples, in most cases without user intervention. It is proving extremely useful in understanding dynamics in liquid suspensions, soft materials, cells, and tissues. In DDM, image sequences are analyzed via a combination of image differences and spatial Fourier transforms to obtain information equivalent to that obtained by means of light scattering techniques. Compared to light scattering, DDM offers obvious advantages, principally (a) simplicity of the setup; (b) possibility of removing static contributions along the optical path; (c) power of simultaneous different microscopy contrast mechanisms; and (d) flexibility of choosing an analysis region, analogous to a scattering volume. For many questions, DDM has also advantages compared to segmentation/tracking approaches and to correlation techniques like particle image velocimetry. The very straightforward DDM approach, originally demonstrated with bright field microscopy of aqueous colloids, has lately been used to probe a variety of other complex fluids and biological systems with many different imaging methods, including dark-field, differential interference contrast, wide-field, light-sheet, and confocal microscopy. The number of adopting groups is rapidly increasing and so are the applications. Here, we briefly recall the working principles of DDM, we highlight its advantages and limitations, we outline recent experimental breakthroughs, and we provide a perspective on future challenges and directions. DDM can become a standard primary tool in every laboratory equipped with a microscope, at the very least as a first bias-free automated evaluation of the dynamics in a system.

  16. Systems Biology of Metabolism.

    Science.gov (United States)

    Nielsen, Jens

    2017-06-20

    Metabolism is highly complex and involves thousands of different connected reactions; it is therefore necessary to use mathematical models for holistic studies. The use of mathematical models in biology is referred to as systems biology. In this review, the principles of systems biology are described, and two different types of mathematical models used for studying metabolism are discussed: kinetic models and genome-scale metabolic models. The use of different omics technologies, including transcriptomics, proteomics, metabolomics, and fluxomics, for studying metabolism is presented. Finally, the application of systems biology for analyzing global regulatory structures, engineering the metabolism of cell factories, and analyzing human diseases is discussed.

  17. Bayesian uncertainty analysis for complex systems biology models: emulation, global parameter searches and evaluation of gene functions.

    Science.gov (United States)

    Vernon, Ian; Liu, Junli; Goldstein, Michael; Rowe, James; Topping, Jen; Lindsey, Keith

    2018-01-02

    Many mathematical models have now been employed across every area of systems biology. These models increasingly involve large numbers of unknown parameters, have complex structure which can result in substantial evaluation time relative to the needs of the analysis, and need to be compared to observed data of various forms. The correct analysis of such models usually requires a global parameter search, over a high dimensional parameter space, that incorporates and respects the most important sources of uncertainty. This can be an extremely difficult task, but it is essential for any meaningful inference or prediction to be made about any biological system. It hence represents a fundamental challenge for the whole of systems biology. Bayesian statistical methodology for the uncertainty analysis of complex models is introduced, which is designed to address the high dimensional global parameter search problem. Bayesian emulators that mimic the systems biology model but which are extremely fast to evaluate are embeded within an iterative history match: an efficient method to search high dimensional spaces within a more formal statistical setting, while incorporating major sources of uncertainty. The approach is demonstrated via application to a model of hormonal crosstalk in Arabidopsis root development, which has 32 rate parameters, for which we identify the sets of rate parameter values that lead to acceptable matches between model output and observed trend data. The multiple insights into the model's structure that this analysis provides are discussed. The methodology is applied to a second related model, and the biological consequences of the resulting comparison, including the evaluation of gene functions, are described. Bayesian uncertainty analysis for complex models using both emulators and history matching is shown to be a powerful technique that can greatly aid the study of a large class of systems biology models. It both provides insight into model behaviour

  18. 7th Annual Systems Biology Symposium: Systems Biology and Engineering

    Energy Technology Data Exchange (ETDEWEB)

    Galitski, Timothy P.

    2008-04-01

    Systems biology recognizes the complex multi-scale organization of biological systems, from molecules to ecosystems. The International Symposium on Systems Biology has been hosted by the Institute for Systems Biology in Seattle, Washington, since 2002. The annual two-day event gathers the most influential researchers transforming biology into an integrative discipline investingating complex systems. Engineering and application of new technology is a central element of systems biology. Genome-scale, or very small-scale, biological questions drive the enigneering of new technologies, which enable new modes of experimentation and computational analysis, leading to new biological insights and questions. Concepts and analytical methods in engineering are now finding direct applications in biology. Therefore, the 2008 Symposium, funded in partnership with the Department of Energy, featured global leaders in "Systems Biology and Engineering."

  19. Entropy as a method to investigate complex biological systems. An alternative view on the biological transition from healthy aging to frailty

    Directory of Open Access Journals (Sweden)

    Roberto Siciliano

    2017-07-01

    Full Text Available Everyone is subject to a process of progressive deterioration of control mechanisms, which supervise the complex network of human physiological functions, reducing the individual ability to adapt to emerging situations of stress or change. In the light of results obtained during the last years, it appears that some of the tools of nonlinear dynamics, first developed for the physical sciences are well suited for studies of biological systems. We believe that, considering the level of order or complexity of the anatomical apparatus by measuring a physical quantity, which is the entropy, we can evaluate the health status or vice versa fragility of a biological system. In particular, a reduction in the entropy value, indicates modification of the structural order with a progressive reduction of functional reserve of the individual, which is associated with a failure to adapt to stress conditions, difficult to be analyzed and documented with a unique traditional biochemical or biomolecular vision. Therefore, in this paper, we present a method that, conceptually combines complexity, disease and aging, alloys Poisson statistics, predictive of the personal level of health, to the entropy value indicating the status of bio-dynamic and functional body, seen as a complex and open thermodynamic system.

  20. Genomewide effects of peroxisome proliferator-activated receptor gamma in macrophages and dendritic cells--revealing complexity through systems biology.

    Science.gov (United States)

    Cuaranta-Monroy, Ixchelt; Kiss, Mate; Simandi, Zoltan; Nagy, Laszlo

    2015-09-01

    Systems biology approaches have become indispensable tools in biomedical and basic research. These data integrating bioinformatic methods gained prominence after high-throughput technologies became available to investigate complex cellular processes, such as transcriptional regulation and protein-protein interactions, on a scale that had not been studied before. Immunology is one of the medical fields that systems biology impacted profoundly due to the plasticity of cell types involved and the accessibility of a wide range of experimental models. In this review, we summarize the most important recent genomewide studies exploring the function of peroxisome proliferator-activated receptor γ in macrophages and dendritic cells. PPARγ ChIP-seq experiments were performed in adipocytes derived from embryonic stem cells to complement the existing data sets and to provide comparators to macrophage data. Finally, lists of regulated genes generated from such experiments were analysed with bioinformatics and system biology approaches. We show that genomewide studies utilizing high-throughput data acquisition methods made it possible to gain deeper insights into the role of PPARγ in these immune cell types. We also demonstrate that analysis and visualization of data using network-based approaches can be used to identify novel genes and functions regulated by the receptor. The example of PPARγ in macrophages and dendritic cells highlights the crucial importance of systems biology approaches in establishing novel cellular functions for long-known signaling pathways. © 2015 Stichting European Society for Clinical Investigation Journal Foundation.

  1. Top-down models in biology: explanation and control of complex living systems above the molecular level.

    Science.gov (United States)

    Pezzulo, Giovanni; Levin, Michael

    2016-11-01

    It is widely assumed in developmental biology and bioengineering that optimal understanding and control of complex living systems follows from models of molecular events. The success of reductionism has overshadowed attempts at top-down models and control policies in biological systems. However, other fields, including physics, engineering and neuroscience, have successfully used the explanations and models at higher levels of organization, including least-action principles in physics and control-theoretic models in computational neuroscience. Exploiting the dynamic regulation of pattern formation in embryogenesis and regeneration requires new approaches to understand how cells cooperate towards large-scale anatomical goal states. Here, we argue that top-down models of pattern homeostasis serve as proof of principle for extending the current paradigm beyond emergence and molecule-level rules. We define top-down control in a biological context, discuss the examples of how cognitive neuroscience and physics exploit these strategies, and illustrate areas in which they may offer significant advantages as complements to the mainstream paradigm. By targeting system controls at multiple levels of organization and demystifying goal-directed (cybernetic) processes, top-down strategies represent a roadmap for using the deep insights of other fields for transformative advances in regenerative medicine and systems bioengineering. © 2016 The Author(s).

  2. Introduction to symposium: Arthropods and wildlife conservation: synergy in complex biological systems

    Science.gov (United States)

    The symposium will discuss the effects of arthropods and other stressors on wildlife conservation programs. Speakers with affiliations in wildlife biology, parasitology and entomology will be included in the program. Research of national and international interest will be presented....

  3. Detecting critical state before phase transition of complex biological systems by hidden Markov model.

    Science.gov (United States)

    Chen, Pei; Liu, Rui; Li, Yongjun; Chen, Luonan

    2016-07-15

    Identifying the critical state or pre-transition state just before the occurrence of a phase transition is a challenging task, because the state of the system may show little apparent change before this critical transition during the gradual parameter variations. Such dynamics of phase transition is generally composed of three stages, i.e. before-transition state, pre-transition state and after-transition state, which can be considered as three different Markov processes. By exploring the rich dynamical information provided by high-throughput data, we present a novel computational method, i.e. hidden Markov model (HMM) based approach, to detect the switching point of the two Markov processes from the before-transition state (a stationary Markov process) to the pre-transition state (a time-varying Markov process), thereby identifying the pre-transition state or early-warning signals of the phase transition. To validate the effectiveness, we apply this method to detect the signals of the imminent phase transitions of complex systems based on the simulated datasets, and further identify the pre-transition states as well as their critical modules for three real datasets, i.e. the acute lung injury triggered by phosgene inhalation, MCF-7 human breast cancer caused by heregulin and HCV-induced dysplasia and hepatocellular carcinoma. Both functional and pathway enrichment analyses validate the computational results. The source code and some supporting files are available at https://github.com/rabbitpei/HMM_based-method lnchen@sibs.ac.cn or liyj@scut.edu.cn Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  4. New Insights Into the Mechanisms and Biological Roles of D-Amino Acids in Complex Eco-Systems

    Science.gov (United States)

    Aliashkevich, Alena; Alvarez, Laura; Cava, Felipe

    2018-01-01

    In the environment bacteria share their habitat with a great diversity of organisms, from microbes to humans, animals and plants. In these complex communities, the production of extracellular effectors is a common strategy to control the biodiversity by interfering with the growth and/or viability of nearby microbes. One of such effectors relies on the production and release of extracellular D-amino acids which regulate diverse cellular processes such as cell wall biogenesis, biofilm integrity, and spore germination. Non-canonical D-amino acids are mainly produced by broad spectrum racemases (Bsr). Bsr’s promiscuity allows it to generate high concentrations of D-amino acids in environments with variable compositions of L-amino acids. However, it was not clear until recent whether these molecules exhibit divergent functions. Here we review the distinctive biological roles of D-amino acids, their mechanisms of action and their modulatory properties of the biodiversity of complex eco-systems. PMID:29681896

  5. Complex Systems

    Directory of Open Access Journals (Sweden)

    Yi Zhao

    2012-01-01

    Full Text Available Quantum instanton (QI approximation is recently proposed for the evaluations of the chemical reaction rate constants with use of full dimensional potential energy surfaces. Its strategy is to use the instanton mechanism and to approximate time-dependent quantum dynamics to the imaginary time propagation of the quantities of partition function. It thus incorporates the properties of the instanton idea and the quantum effect of partition function and can be applied to chemical reactions of complex systems. In this paper, we present the QI approach and its applications to several complex systems mainly done by us. The concrete systems include, (1 the reaction of H+CH4→H2+CH3, (2 the reaction of H+SiH4→H2+SiH3, (3 H diffusion on Ni(100 surface; and (4 surface-subsurface transport and interior migration for H/Ni. Available experimental and other theoretical data are also presented for the purpose of comparison.

  6. Compositional Modeling of Biological Systems

    OpenAIRE

    Zámborszky, Judit

    2010-01-01

    Molecular interactions are wired in a fascinating way resulting in complex behavior of bio-logical systems. Theoretical modeling provides us a useful framework for understanding the dynamics and the function of such networks. The complexity of the biological systems calls for conceptual tools that manage the combinatorial explosion of the set of possible interac-tions. A suitable conceptual tool to attack complexity is compositionality, already success-fully used in the process algebra field ...

  7. Development trend of radiation biology research-systems radiation biology

    International Nuclear Information System (INIS)

    Min Rui

    2010-01-01

    Radiation biology research has past 80 years. We have known much more about fundamentals, processes and results of biology effects induced by radiation and various factors that influence biology effects wide and deep, however many old and new scientific problems occurring in the field of radiation biology research remain to be illustrated. To explore and figure these scientific problems need systemic concept, methods and multi dimension view on the base of considerations of complexity of biology system, diversity of biology response, temporal and spatial process of biological effects during occurrence, and complex feed back network of biological regulations. (authors)

  8. Informing biological design by integration of systems and synthetic biology.

    Science.gov (United States)

    Smolke, Christina D; Silver, Pamela A

    2011-03-18

    Synthetic biology aims to make the engineering of biology faster and more predictable. In contrast, systems biology focuses on the interaction of myriad components and how these give rise to the dynamic and complex behavior of biological systems. Here, we examine the synergies between these two fields. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. A tree-like Bayesian structure learning algorithm for small-sample datasets from complex biological model systems.

    Science.gov (United States)

    Yin, Weiwei; Garimalla, Swetha; Moreno, Alberto; Galinski, Mary R; Styczynski, Mark P

    2015-08-28

    There are increasing efforts to bring high-throughput systems biology techniques to bear on complex animal model systems, often with a goal of learning about underlying regulatory network structures (e.g., gene regulatory networks). However, complex animal model systems typically have significant limitations on cohort sizes, number of samples, and the ability to perform follow-up and validation experiments. These constraints are particularly problematic for many current network learning approaches, which require large numbers of samples and may predict many more regulatory relationships than actually exist. Here, we test the idea that by leveraging the accuracy and efficiency of classifiers, we can construct high-quality networks that capture important interactions between variables in datasets with few samples. We start from a previously-developed tree-like Bayesian classifier and generalize its network learning approach to allow for arbitrary depth and complexity of tree-like networks. Using four diverse sample networks, we demonstrate that this approach performs consistently better at low sample sizes than the Sparse Candidate Algorithm, a representative approach for comparison because it is known to generate Bayesian networks with high positive predictive value. We develop and demonstrate a resampling-based approach to enable the identification of a viable root for the learned tree-like network, important for cases where the root of a network is not known a priori. We also develop and demonstrate an integrated resampling-based approach to the reduction of variable space for the learning of the network. Finally, we demonstrate the utility of this approach via the analysis of a transcriptional dataset of a malaria challenge in a non-human primate model system, Macaca mulatta, suggesting the potential to capture indicators of the earliest stages of cellular differentiation during leukopoiesis. We demonstrate that by starting from effective and efficient approaches

  10. Introducing Flexibility to Complex, Resilient Socio-Ecological Systems: A Comparative Analysis of Economics, Flexible Manufacturing Systems, Evolutionary Biology, and Supply Chain Management

    Directory of Open Access Journals (Sweden)

    Vivek Anand Asokan

    2017-06-01

    Full Text Available In this paper, a framework incorporating flexibility as a characteristic is proposed for designing complex, resilient socio-ecological systems. In an interconnected complex system, flexibility allows prompt deployment of resources where they are needed and is crucial for both innovation and robustness. A comparative analysis of flexible manufacturing systems, economics, evolutionary biology, and supply chain management is conducted to identify the most important characteristics of flexibility. Evolutionary biology emphasises overlapping functions and multi-functionality, which allow a system with structurally different elements to perform the same function, enhancing resilience. In economics, marginal cost and marginal expected profit are factors that are considered to be important in incorporating flexibility while making changes to the system. In flexible manufacturing systems, the size of choice sets is important in creating flexibility, as initial actions preserve more options for future actions that will enhance resilience. Given the dynamic nature of flexibility, identifying the characteristics that can lead to flexibility will introduce a crucial dimension to designing resilient and sustainable socio-ecological systems with a long-term perspective in mind.

  11. Systems Biology Approach to the Dissection of the Complexity of Regulatory Networks in the S. scrofa Cardiocirculatory System

    Directory of Open Access Journals (Sweden)

    Paolo Martini

    2013-11-01

    Full Text Available Genome-wide experiments are routinely used to increase the understanding of the biological processes involved in the development and maintenance of a variety of pathologies. Although the technical feasibility of this type of experiment has improved in recent years, data analysis remains challenging. In this context, gene set analysis has emerged as a fundamental tool for the interpretation of the results. Here, we review strategies used in the gene set approach, and using datasets for the pig cardiocirculatory system as a case study, we demonstrate how the use of a combination of these strategies can enhance the interpretation of results. Gene set analyses are able to distinguish vessels from the heart and arteries from veins in a manner that is consistent with the different cellular composition of smooth muscle cells. By integrating microRNA elements in the regulatory circuits identified, we find that vessel specificity is maintained through specific miRNAs, such as miR-133a and miR-143, which show anti-correlated expression with their mRNA targets.

  12. Biological conversion system

    Science.gov (United States)

    Scott, C.D.

    A system for bioconversion of organic material comprises a primary bioreactor column wherein a biological active agent (zymomonas mobilis) converts the organic material (sugar) to a product (alcohol), a rejuvenator column wherein the biological activity of said biological active agent is enhanced, and means for circulating said biological active agent between said primary bioreactor column and said rejuvenator column.

  13. Using stereoscopy to teach complex biological concepts.

    Science.gov (United States)

    Ferdig, Richard; Blank, James; Kratcoski, Annette; Clements, Robert

    2015-09-01

    Used effectively, stereoscopic three-dimensional (3D) technologies can engage students with complex disciplinary content as they are presented with informative representations of abstract concepts. In addition, preliminary evidence suggests that stereoscopy may enhance learning and retention in some educational settings. Biological concepts particularly benefit from this type of presentation since complex spatially oriented structures frequently define function within these systems. Viewing biological phenomena in 3D as they are in real life allows the user to relate these spatial relationships and easily grasp concepts making the key connection between structure and function. In addition, viewing these concepts interactively in 3D and in a manner that leads to increased engagement for young prospective scientists can further increase the impact. We conducted two studies evaluating the use of this technology as an instructional tool to teach high school students complex biological concepts. The first study tested the use of stereoscopic materials for teaching brain function and human anatomy to four classes. The second study evaluated stereoscopic images to support the learning of cell structure and DNA in four different high school classes. Most important, students who used stereoscopic 3D had significantly higher test scores than those who did not. In addition, students reported enjoying 3D presentations, and it was among their top choices for learning about these complex concepts. In summary, our evidence adds further support for the benefits of 3D images to students' learning of science concepts. Copyright © 2015 The American Physiological Society.

  14. Interdisciplinary Symposium on Complex Systems

    CERN Document Server

    Rössler, Otto; Zelinka, Ivan

    2015-01-01

    The book you hold in your hands is the outcome of the “2014 Interdisciplinary Symposium on Complex Systems” held in the historical city of Florence. The book consists of 37 chapters from 4 areas of Physical Modeling of Complex Systems, Evolutionary Computations, Complex Biological Systems and Complex Networks. All 4 parts contain contributions that give interesting point of view on complexity in different areas in science and technology. The book starts with a comprehensive overview and classification of complexity problems entitled Physics in the world of ideas: Complexity as Energy”  , followed by chapters about complexity measures and physical principles, its observation, modeling and its applications, to solving various problems including real-life applications. Further chapters contain recent research about evolution, randomness and complexity, as well as complexity in biological systems and complex networks. All selected papers represent innovative ideas, philosophical overviews and state-of-the-...

  15. Complexity: the organizing principle at the interface of biological (dis ...

    Indian Academy of Sciences (India)

    We then introduce a developmental and an evolutionary understanding of what it means for biological systems to be complex.We propose that the complexity of living systems can be understood through two interdependent structural properties: multiscalarity of interconstituent mechanisms and excitability of the biological ...

  16. Improving fundamental abilities of atomic force microscopy for investigating quantitative nanoscale physical properties of complex biological systems

    Science.gov (United States)

    Cartagena-Rivera, Alexander X.

    Measurements of local material properties of complex biological systems (e.g. live cells and viruses) in their respective physiological conditions are extremely important in the fields of biophysics, nanotechnology, material science, and nanomedicine. Yet, little is known about the structure-function-property relationship of live cells and viruses. In the case of live cells, the measurements of progressive variations in viscoelastic properties in vitro can provide insight to the mechanistic processes underpinning morphogenesis, mechano-transduction, motility, metastasis, and many more fundamental cellular processes. In the case of living viruses, the relationship between capsid structural framework and the role of the DNA molecule interaction within viruses influencing their stiffness, damping and electrostatic properties can shed light in virological processes like protein subunits assembly/dissassembly, maturation, and infection. The study of mechanics of live cells and viruses has been limited in part due to the lack of technology capable of acquiring high-resolution (nanoscale, subcellular) images of its heterogeneous material properties which vary widely depending on origin and physical interaction. The capabilities of the atomic force microscope (AFM) for measuring forces and topography with sub-nm precision have greatly contributed to research related to biophysics and biomechanics during the past two decades. AFM based biomechanical studies have the unique advantage of resolving/mapping spatially the local material properties over living cells and viruses. However, conventional AFM techniques such as force-volume and quasi-static force-distance curves are too low resolution and low speed to resolve interesting biophysical processes such as cytoskeletal dynamics for cells or assembly/dissasembly of viruses. To overcome this bottleneck, a novel atomic force microscopy mode is developed, that leads to sub-10-nm resolution and sub-15-minutes mapping of local

  17. Mammalian Synthetic Biology: Engineering Biological Systems.

    Science.gov (United States)

    Black, Joshua B; Perez-Pinera, Pablo; Gersbach, Charles A

    2017-06-21

    The programming of new functions into mammalian cells has tremendous application in research and medicine. Continued improvements in the capacity to sequence and synthesize DNA have rapidly increased our understanding of mechanisms of gene function and regulation on a genome-wide scale and have expanded the set of genetic components available for programming cell biology. The invention of new research tools, including targetable DNA-binding systems such as CRISPR/Cas9 and sensor-actuator devices that can recognize and respond to diverse chemical, mechanical, and optical inputs, has enabled precise control of complex cellular behaviors at unprecedented spatial and temporal resolution. These tools have been critical for the expansion of synthetic biology techniques from prokaryotic and lower eukaryotic hosts to mammalian systems. Recent progress in the development of genome and epigenome editing tools and in the engineering of designer cells with programmable genetic circuits is expanding approaches to prevent, diagnose, and treat disease and to establish personalized theranostic strategies for next-generation medicines. This review summarizes the development of these enabling technologies and their application to transforming mammalian synthetic biology into a distinct field in research and medicine.

  18. The `What is a system' reflection interview as a knowledge integration activity for high school students' understanding of complex systems in human biology

    Science.gov (United States)

    Tripto, Jaklin; Ben-Zvi Assaraf, Orit; Snapir, Zohar; Amit, Miriam

    2016-03-01

    This study examined the reflection interview as a tool for assessing and facilitating the use of 'systems language' amongst 11th grade students who have recently completed their first year of high school biology. Eighty-three students composed two concept maps in the 10th grade-one at the beginning of the school year and one at its end. The first part of the interview is dedicated to guiding the students through comparing their two concept maps and by means of both explicit and non-explicit teaching. Our study showed that the explicit guidance in comparing the two concept maps was more effective than the non-explicit, eliciting a variety of different, more specific, types of interactions and patterns (e.g. 'hierarchy', 'dynamism', 'homeostasis') in the students' descriptions of the human body system. The reflection interview as a knowledge integration activity was found to be an effective tool for assessing the subjects' conceptual models of 'system complexity', and for identifying those aspects of a system that are most commonly misunderstood.

  19. Teaching systems biology.

    Science.gov (United States)

    Alves, R; Vilaprinyo, E; Sorribas, A

    2011-03-01

    Advances in systems biology are increasingly dependent upon the integration of various types of data and different methodologies to reconstruct how cells work at the systemic level. Thus, teams with a varied array of expertise and people with interdisciplinary training are needed. So far this training was thought to be more productive if aimed at the Masters or PhD level. At this level, multiple specialised and in-depth courses on the different subject matters of systems biology are taught to already well-prepared students. This approach is mostly based on the recognition that systems biology requires a wide background that is hard to find in undergraduate students. Nevertheless, and given the importance of the field, the authors argue that exposition of undergraduate students to the methods and paradigms of systems biology would be advantageous. Here they present and discuss a successful experiment in teaching systems biology to third year undergraduate biotechnology students at the University of Lleida in Spain. The authors' experience, together with that from others, argues for the adequateness of teaching systems biology at the undergraduate level. [Includes supplementary material].

  20. Systems biology approach to bioremediation

    Energy Technology Data Exchange (ETDEWEB)

    Chakraborty, Romy; Wu, Cindy H.; Hazen, Terry C.

    2012-06-01

    Bioremediation has historically been approached as a ‘black box’ in terms of our fundamental understanding. Thus it succeeds and fails, seldom without a complete understanding of why. Systems biology is an integrated research approach to study complex biological systems, by investigating interactions and networks at the molecular, cellular, community, and ecosystem level. The knowledge of these interactions within individual components is fundamental to understanding the dynamics of the ecosystem under investigation. Finally, understanding and modeling functional microbial community structure and stress responses in environments at all levels have tremendous implications for our fundamental understanding of hydrobiogeochemical processes and the potential for making bioremediation breakthroughs and illuminating the ‘black box’.

  1. Complex agent networks: An emerging approach for modeling complex systems

    NARCIS (Netherlands)

    Mei, S.; Zarrabi, N.; Lees, M.; Sloot, P.M.A.

    2015-01-01

    Complexity and complex systems are all around us: from molecular and cellular systems in biology up to economics and human societies. There is an urgent need for methods that can capture the multi-scale spatio-temporal characteristics of complex systems. Recent emphasis has centered on two methods

  2. Systems Biology for Smart Crops and Agricultural Innovation: Filling the Gaps between Genotype and Phenotype for Complex Traits Linked with Robust Agricultural Productivity and Sustainability.

    Science.gov (United States)

    Kumar, Anil; Pathak, Rajesh Kumar; Gupta, Sanjay Mohan; Gaur, Vikram Singh; Pandey, Dinesh

    2015-10-01

    In recent years, rapid developments in several omics platforms and next generation sequencing technology have generated a huge amount of biological data about plants. Systems biology aims to develop and use well-organized and efficient algorithms, data structure, visualization, and communication tools for the integration of these biological data with the goal of computational modeling and simulation. It studies crop plant systems by systematically perturbing them, checking the gene, protein, and informational pathway responses; integrating these data; and finally, formulating mathematical models that describe the structure of system and its response to individual perturbations. Consequently, systems biology approaches, such as integrative and predictive ones, hold immense potential in understanding of molecular mechanism of agriculturally important complex traits linked to agricultural productivity. This has led to identification of some key genes and proteins involved in networks of pathways involved in input use efficiency, biotic and abiotic stress resistance, photosynthesis efficiency, root, stem and leaf architecture, and nutrient mobilization. The developments in the above fields have made it possible to design smart crops with superior agronomic traits through genetic manipulation of key candidate genes.

  3. Systems Biology for Smart Crops and Agricultural Innovation: Filling the Gaps between Genotype and Phenotype for Complex Traits Linked with Robust Agricultural Productivity and Sustainability

    Science.gov (United States)

    Pathak, Rajesh Kumar; Gupta, Sanjay Mohan; Gaur, Vikram Singh; Pandey, Dinesh

    2015-01-01

    Abstract In recent years, rapid developments in several omics platforms and next generation sequencing technology have generated a huge amount of biological data about plants. Systems biology aims to develop and use well-organized and efficient algorithms, data structure, visualization, and communication tools for the integration of these biological data with the goal of computational modeling and simulation. It studies crop plant systems by systematically perturbing them, checking the gene, protein, and informational pathway responses; integrating these data; and finally, formulating mathematical models that describe the structure of system and its response to individual perturbations. Consequently, systems biology approaches, such as integrative and predictive ones, hold immense potential in understanding of molecular mechanism of agriculturally important complex traits linked to agricultural productivity. This has led to identification of some key genes and proteins involved in networks of pathways involved in input use efficiency, biotic and abiotic stress resistance, photosynthesis efficiency, root, stem and leaf architecture, and nutrient mobilization. The developments in the above fields have made it possible to design smart crops with superior agronomic traits through genetic manipulation of key candidate genes. PMID:26484978

  4. Nutritional Systems Biology

    DEFF Research Database (Denmark)

    Jensen, Kasper

    and network biology has the potential to increase our understanding of how small molecules affect metabolic pathways and homeostasis, how this perturbation changes at the disease state, and to what extent individual genotypes contribute to this. A fruitful strategy in approaching and exploring the field...... biology research. The paper also shows as a proof-of-concept that a systems biology approach to diet is meaningful and demonstrates some basic principles on how to work with diet systematic. The second chapter of this thesis we developed the resource NutriChem v1.0. A foodchemical database linking...... sites of diet on the disease pathway. We propose a framework for interrogating the critical targets in colon cancer process and identifying plant-based dietary interventions as important modifiers using a systems chemical biology approach. The fifth chapter of the thesis is on discovering of novel anti...

  5. Complex Systems: An Introduction

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 14; Issue 9. Complex Systems: An Introduction - Anthropic Principle, Terrestrial Complexity, Complex Materials. V K Wadhawan. General Article Volume 14 Issue 9 September 2009 pp 894-906 ...

  6. Study of the interaction of multiply charged ions and complex systems of biological interest: effects of the molecular environment

    International Nuclear Information System (INIS)

    Capron, Michael

    2011-01-01

    This PhD thesis describes the experimental study of the interaction between slow multiply charged ions (tens of keV) and molecular systems of biological interest (amino acids and nucleobases). It is the aim to identify and to better understand the effect of a molecular environment on different collision induced phenomena. To do so, the time of flight spectra of cationic products emerging from collisions with isolated molecules as well as clusters are compared. It is shown that the molecular environment protects the molecule as it allows to distribute the transferred energies and charges over the whole system (global decrease of the fragmentation and quenching of some fragmentation channels). Furthermore, in the case of adenine clusters, the molecular environment weakens some intramolecular bonds. Moreover, products of chemical reactions are observed concerning proton transfer processes in hydrated cluster of adenine and the formation of peptides bonds between beta-alanine molecules in a cluster. The latter finding is studied as a function of the cluster size and type of the projectile. Some criteria for peptide bond formation, such as flexibility and geometry of the molecule, are investigated for different amino acids. (author)

  7. Language Networks as Complex Systems

    Science.gov (United States)

    Lee, Max Kueiming; Ou, Sheue-Jen

    2008-01-01

    Starting in the late eighties, with a growing discontent with analytical methods in science and the growing power of computers, researchers began to study complex systems such as living organisms, evolution of genes, biological systems, brain neural networks, epidemics, ecology, economy, social networks, etc. In the early nineties, the research…

  8. Circulating immune complexes – reviewing the biological roles in ...

    African Journals Online (AJOL)

    Circulating immune complexes – reviewing the biological roles in human immune function and exercise. ... studies that have investigated CIC's following exercise and proposes that a comprehensive understanding and interpretation of immune system responses to exercise should take these complexes into consideration.

  9. Plant Systems Biology (editorial)

    Science.gov (United States)

    In June 2003, Plant Physiology published an Arabidopsis special issue devoted to plant systems biology. The intention of Natasha Raikhel and Gloria Coruzzi, the two editors of this first-of-its-kind issue, was ‘‘to help nucleate this new effort within the plant community’’ as they considered that ‘‘...

  10. Systems biology at work

    NARCIS (Netherlands)

    Martins Dos Santos, V.A.P.; Damborsky, J.

    2010-01-01

    In his editorial overview for the 2008 Special Issue on this topic, the late Jaroslav Stark pointedly noted that systems biology is no longer a niche pursuit, but a recognized discipline in its own right “noisily” coming of age [1]. Whilst general underlying principles and basic techniques are now

  11. Promoting Mastery of Complex Biological Mechanisms

    Science.gov (United States)

    Bradshaw, William S.; Groneman, Kathryn J.; Nelson, Jennifer; Bell, John D.

    2018-01-01

    This article describes efforts aimed at improving comprehension and retention of complex molecular mechanisms commonly studied in undergraduate biology and biochemistry courses. The focus is on the design of appropriate assessments, an active classroom emphasizing formative practice, and more effective out-of-class study habits. Assessments that…

  12. Integrative radiation systems biology

    International Nuclear Information System (INIS)

    Unger, Kristian

    2014-01-01

    Maximisation of the ratio of normal tissue preservation and tumour cell reduction is the main concept of radiotherapy alone or combined with chemo-, immuno- or biologically targeted therapy. The foremost parameter influencing this ratio is radiation sensitivity and its modulation towards a more efficient killing of tumour cells and a better preservation of normal tissue at the same time is the overall aim of modern therapy schemas. Nevertheless, this requires a deep understanding of the molecular mechanisms of radiation sensitivity in order to identify its key players as potential therapeutic targets. Moreover, the success of conventional approaches that tried to statistically associate altered radiation sensitivity with any molecular phenotype such as gene expression proofed to be somewhat limited since the number of clinically used targets is rather sparse. However, currently a paradigm shift is taking place from pure frequentistic association analysis to the rather holistic systems biology approach that seeks to mathematically model the system to be investigated and to allow the prediction of an altered phenotype as the function of one single or a signature of biomarkers. Integrative systems biology also considers the data from different molecular levels such as the genome, transcriptome or proteome in order to partially or fully comprehend the causal chain of molecular mechanisms. An example for the application of this concept currently carried out at the Clinical Cooperation Group “Personalized Radiotherapy in Head and Neck Cancer” of the Helmholtz-Zentrum München and the LMU Munich is described. This review article strives for providing a compact overview on the state of the art of systems biology, its actual challenges, potential applications, chances and limitations in radiation oncology research working towards improved personalised therapy concepts using this relatively new methodology

  13. Systems Biology of Industrial Microorganisms

    Science.gov (United States)

    Papini, Marta; Salazar, Margarita; Nielsen, Jens

    The field of industrial biotechnology is expanding rapidly as the chemical industry is looking towards more sustainable production of chemicals that can be used as fuels or building blocks for production of solvents and materials. In connection with the development of sustainable bioprocesses, it is a major challenge to design and develop efficient cell factories that can ensure cost efficient conversion of the raw material into the chemical of interest. This is achieved through metabolic engineering, where the metabolism of the cell factory is engineered such that there is an efficient conversion of sugars, the typical raw materials in the fermentation industry, into the desired product. However, engineering of cellular metabolism is often challenging due to the complex regulation that has evolved in connection with adaptation of the different microorganisms to their ecological niches. In order to map these regulatory structures and further de-regulate them, as well as identify ingenious metabolic engineering strategies that full-fill mass balance constraints, tools from systems biology can be applied. This involves both high-throughput analysis tools like transcriptome, proteome and metabolome analysis, as well as the use of mathematical modeling to simulate the phenotypes resulting from the different metabolic engineering strategies. It is in fact expected that systems biology may substantially improve the process of cell factory development, and we therefore propose the term Industrial Systems Biology for how systems biology will enhance the development of industrial biotechnology for sustainable chemical production.

  14. The "What Is a System" Reflection Interview as a Knowledge Integration Activity for High School Students' Understanding of Complex Systems in Human Biology

    Science.gov (United States)

    Tripto, Jaklin; Ben-Zvi Assaraf, Orit; Snapir, Zohar; Amit, Miriam

    2016-01-01

    This study examined the reflection interview as a tool for assessing and facilitating the use of "systems language" amongst 11th grade students who have recently completed their first year of high school biology. Eighty-three students composed two concept maps in the 10th grade--one at the beginning of the school year and one at its end.…

  15. A systems biology approach to studying Tai Chi, physiological complexity and healthy aging: design and rationale of a pragmatic randomized controlled trial.

    Science.gov (United States)

    Wayne, Peter M; Manor, Brad; Novak, Vera; Costa, Madelena D; Hausdorff, Jeffrey M; Goldberger, Ary L; Ahn, Andrew C; Yeh, Gloria Y; Peng, C-K; Lough, Matthew; Davis, Roger B; Quilty, Mary T; Lipsitz, Lewis A

    2013-01-01

    Aging is typically associated with progressive multi-system impairment that leads to decreased physical and cognitive function and reduced adaptability to stress. Due to its capacity to characterize complex dynamics within and between physiological systems, the emerging field of complex systems biology and its array of quantitative tools show great promise for improving our understanding of aging, monitoring senescence, and providing biomarkers for evaluating novel interventions, including promising mind-body exercises, that treat age-related disease and promote healthy aging. An ongoing, two-arm randomized clinical trial is evaluating the potential of Tai Chi mind-body exercise to attenuate age-related loss of complexity. A total of 60 Tai Chi-naïve healthy older adults (aged 50-79) are being randomized to either six months of Tai Chi training (n=30), or to a waitlist control receiving unaltered usual medical care (n=30). Our primary outcomes are complexity-based measures of heart rate, standing postural sway and gait stride interval dynamics assessed at 3 and 6months. Multiscale entropy and detrended fluctuation analysis are used as entropy- and fractal-based measures of complexity, respectively. Secondary outcomes include measures of physical and psychological function and tests of physiological adaptability also assessed at 3 and 6months. Results of this study may lead to novel biomarkers that help us monitor and understand the physiological processes of aging and explore the potential benefits of Tai Chi and related mind-body exercises for healthy aging. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. Carbon nanomaterials in biological systems

    Energy Technology Data Exchange (ETDEWEB)

    Pu Chun Ke [Laboratory of Single-Molecule Biophysics and Polymer Physics, Department of Physics and Astronomy, Clemson University, Clemson, SC 29634 (United States); Qiao Rui [Department of Mechanical Engineering, Clemson University, Clemson, SC 29634 (United States)

    2007-09-19

    This paper intends to reflect, from the biophysical viewpoint, our current understanding on interfacing nanomaterials, such as carbon nanotubes and fullerenes, with biological systems. Strategies for improving the solubility, and therefore, the bioavailability of nanomaterials in aqueous solutions are summarized. In particular, the underlining mechanisms of attaching biomacromolecules (DNA, RNA, proteins) and lysophospholipids onto carbon nanotubes and gallic acids onto fullerenes are analyzed. The diffusion and the cellular delivery of RNA-coated carbon nanotubes are characterized using fluorescence microscopy. The translocation of fullerenes across cell membranes is simulated using molecular dynamics to offer new insight into the complex issue of nanotoxicity. To assess the fate of nanomaterials in the environment, the biomodification of lipid-coated carbon nanotubes by the aquatic organism Daphnia magna is discussed. The aim of this paper is to illuminate the need for adopting multidisciplinary approaches in the field study of nanomaterials in biological systems and in the environment. (topical review)

  17. Carbon nanomaterials in biological systems

    International Nuclear Information System (INIS)

    Pu Chun Ke; Qiao Rui

    2007-01-01

    This paper intends to reflect, from the biophysical viewpoint, our current understanding on interfacing nanomaterials, such as carbon nanotubes and fullerenes, with biological systems. Strategies for improving the solubility, and therefore, the bioavailability of nanomaterials in aqueous solutions are summarized. In particular, the underlining mechanisms of attaching biomacromolecules (DNA, RNA, proteins) and lysophospholipids onto carbon nanotubes and gallic acids onto fullerenes are analyzed. The diffusion and the cellular delivery of RNA-coated carbon nanotubes are characterized using fluorescence microscopy. The translocation of fullerenes across cell membranes is simulated using molecular dynamics to offer new insight into the complex issue of nanotoxicity. To assess the fate of nanomaterials in the environment, the biomodification of lipid-coated carbon nanotubes by the aquatic organism Daphnia magna is discussed. The aim of this paper is to illuminate the need for adopting multidisciplinary approaches in the field study of nanomaterials in biological systems and in the environment. (topical review)

  18. Spectroscopic investigation on kinetics, thermodynamics and mechanism for electron transfer reaction of iron(III) complex with sulphur centered radical in stimulated biological system.

    Science.gov (United States)

    Deepalakshmi, S; Sivalingam, A; Kannadasan, T; Subramaniam, P; Sivakumar, P; Brahadeesh, S T

    2014-04-24

    Electron transfer reactions of biological organic sulphides with several metal ions to generate sulphide radical cations are a great concern in biochemical process. To understand the mechanism, a stimulated biological system having model compounds, iron(III)-bipyridyl complex with thio-diglycolic acid (TDGA) was investigated. Spectroscopic study reveals the kinetics and thermodynamics of the reaction in aqueous perchloric acid medium. The reaction follows first and fractional order of 0.412 with respect to [Fe(bpy)3](3+) and TDGA, respectively. The oxidation is insensitive to variation in [H(+)] but slightly decreases with increase in ionic strength ([I]). Addition of acrylamide, a radical scavenger has no effect on the rate of the reaction. The high negative value of ΔS(#) (-74.3±1.09 J K(-1) mol(-1)) indicates the complex formed has a definite orientation higher than the reactants. Based on the above results, a suitable reaction mechanism for this reaction is proposed. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Systems biology in animal sciences

    NARCIS (Netherlands)

    Woelders, H.; Pas, te M.F.W.; Bannink, A.; Veerkamp, R.F.; Smits, M.A.

    2011-01-01

    Systems biology is a rapidly expanding field of research and is applied in a number of biological disciplines. In animal sciences, omics approaches are increasingly used, yielding vast amounts of data, but systems biology approaches to extract understanding from these data of biological processes

  20. Logical analysis of biological systems

    DEFF Research Database (Denmark)

    Mardare, Radu Iulian

    2005-01-01

    R. Mardare, Logical analysis of biological systems. Fundamenta Informaticae, N 64:271-285, 2005.......R. Mardare, Logical analysis of biological systems. Fundamenta Informaticae, N 64:271-285, 2005....

  1. Complex Systems and Dependability

    CERN Document Server

    Zamojski, Wojciech; Sugier, Jaroslaw

    2012-01-01

    Typical contemporary complex system is a multifaceted amalgamation of technical, information, organization, software and human (users, administrators and management) resources. Complexity of such a system comes not only from its involved technical and organizational structure but mainly from complexity of information processes that must be implemented in the operational environment (data processing, monitoring, management, etc.). In such case traditional methods of reliability analysis focused mainly on technical level are usually insufficient in performance evaluation and more innovative meth

  2. Promoting mastery of complex biological mechanisms.

    Science.gov (United States)

    Bradshaw, William S; Groneman, Kathryn J; Nelson, Jennifer; Bell, John D

    2018-01-01

    This article describes efforts aimed at improving comprehension and retention of complex molecular mechanisms commonly studied in undergraduate biology and biochemistry courses. The focus is on the design of appropriate assessments, an active classroom emphasizing formative practice, and more effective out-of-class study habits. Assessments that require students to articulate their understanding through writing are the most effective. Frequent formative practice improves performance on problems that require intellectual transfer, the ability to apply conceptual principles in novel settings. We show that success with such problems is a function of mastery of the intrinsic logic of the biology in play, not variations in the way they are written. Survey data demonstrate that many students would prefer a learning style not dominated by memorization of factual details, but how to develop a more effective strategy is rarely intuitive. Matching individual students with specific learning styles has not proven useful. Instead, teachers can strongly promote individual metacognitive appraisal during both classroom activities and other study environments. © 2017 by The International Union of Biochemistry and Molecular Biology, 46(1):7-21, 2018. © 2017 The International Union of Biochemistry and Molecular Biology.

  3. Philosophy of Systems and Synthetic Biology

    DEFF Research Database (Denmark)

    Green, Sara

    2017-01-01

    This entry aims to clarify how systems and synthetic biology contribute to and extend discussions within philosophy of science. Unlike fields such as developmental biology or molecular biology, systems and synthetic biology are not easily demarcated by a focus on a specific subject area or level...... computational approaches, about the relation between living and artificial systems, and about the implications of interdisciplinary research for science and society. The entry can be openly accessed at the webpage of the Stanford Encyclopaedia of Philosophy: https://plato.stanford.edu/entries/systems-synthetic-biology/...... of organization. Rather, they are characterized by the development and application of mathematical, computational, and synthetic modeling strategies in response to complex problems and challenges within the life sciences. Proponents of systems and synthetic biology often stress the necessity of a perspective...

  4. Introducing systems biology for nursing science.

    Science.gov (United States)

    Founds, Sandra A

    2009-07-01

    Systems biology expands on general systems theory as the "omics'' era rapidly progresses. Although systems biology has been institutionalized as an interdisciplinary framework in the biosciences, it is not yet apparent in nursing. This article introduces systems biology for nursing science by presenting an overview of the theory. This framework for the study of organisms from molecular to environmental levels includes iterations of computational modeling, experimentation, and theory building. Synthesis of complex biological processes as whole systems rather than isolated parts is emphasized. Pros and cons of systems biology are discussed, and relevance of systems biology to nursing is described. Nursing research involving molecular, physiological, or biobehavioral questions may be guided by and contribute to the developing science of systems biology. Nurse scientists can proactively incorporate systems biology into their investigations as a framework for advancing the interdisciplinary science of human health care. Systems biology has the potential to advance the research and practice goals of the National Institute for Nursing Research in the National Institutes of Health Roadmap initiative.

  5. The Physics behind Systems Biology

    Directory of Open Access Journals (Sweden)

    Radde Nicole E.

    2016-12-01

    Full Text Available Systems Biology is a young and rapidly evolving research field, which combines experimental techniques and mathematical modeling in order to achieve a mechanistic understanding of processes underlying the regulation and evolution of living systems. Systems Biology is often associated with an Engineering approach: The purpose is to formulate a data-rich, detailed simulation model that allows to perform numerical (‘in silico’ experiments and then draw conclusions about the biological system. While methods from Engineering may be an appropriate approach to extending the scope of biological investigations to experimentally inaccessible realms and to supporting data-rich experimental work, it may not be the best strategy in a search for design principles of biological systems and the fundamental laws underlying Biology. Physics has a long tradition of characterizing and understanding emergent collective behaviors in systems of interacting units and searching for universal laws. Therefore, it is natural that many concepts used in Systems Biology have their roots in Physics. With an emphasis on Theoretical Physics, we will here review the ‘Physics core’ of Systems Biology, show how some success stories in Systems Biology can be traced back to concepts developed in Physics, and discuss how Systems Biology can further benefit from its Theoretical Physics foundation.

  6. Encyclopedia of Complexity and Systems Science

    CERN Document Server

    Meyers, Robert A

    2009-01-01

    Encyclopedia of Complexity and Systems Science provides an authoritative single source for understanding and applying the concepts of complexity theory together with the tools and measures for analyzing complex systems in all fields of science and engineering. The science and tools of complexity and systems science include theories of self-organization, complex systems, synergetics, dynamical systems, turbulence, catastrophes, instabilities, nonlinearity, stochastic processes, chaos, neural networks, cellular automata, adaptive systems, and genetic algorithms. Examples of near-term problems and major unknowns that can be approached through complexity and systems science include: The structure, history and future of the universe; the biological basis of consciousness; the integration of genomics, proteomics and bioinformatics as systems biology; human longevity limits; the limits of computing; sustainability of life on earth; predictability, dynamics and extent of earthquakes, hurricanes, tsunamis, and other n...

  7. Ins and outs of systems biology vis-à-vis molecular biology: continuation or clear cut?

    Science.gov (United States)

    De Backer, Philippe; De Waele, Danny; Van Speybroeck, Linda

    2010-03-01

    The comprehension of living organisms in all their complexity poses a major challenge to the biological sciences. Recently, systems biology has been proposed as a new candidate in the development of such a comprehension. The main objective of this paper is to address what systems biology is and how it is practised. To this end, the basic tools of a systems biological approach are explored and illustrated. In addition, it is questioned whether systems biology 'revolutionizes' molecular biology and 'transcends' its assumed reductionism. The strength of this claim appears to depend on how molecular and systems biology are characterised and on how reductionism is interpreted. Doing credit to molecular biology and to methodological reductionism, it is argued that the distinction between molecular and systems biology is gradual rather than sharp. As such, the classical challenge in biology to manage, interpret and integrate biological data into functional wholes is further intensified by systems biology's use of modelling and bioinformatics, and by its scale enlargement.

  8. Optical Complex Systems 2008

    Science.gov (United States)

    Brun, Guillaume

    The Optical Complex Systems are more and more in the heart of various systems that industrial applications bring to everyday life. From environment up to spatial applications, OCS is also relevant in monitoring, transportation, robotics, life sciences, sub-marine, and even for agricultural purposes.

  9. System-of-Systems Complexity

    Directory of Open Access Journals (Sweden)

    Hermann Kopetz

    2013-11-01

    Full Text Available The global availability of communication services makes it possible to interconnect independently developed systems, called constituent systems, to provide new synergistic services and more efficient economic processes. The characteristics of these new Systems-of-Systems are qualitatively different from the classic monolithic systems. In the first part of this presentation we elaborate on these differences, particularly with respect to the autonomy of the constituent systems, to dependability, continuous evolution, and emergence. In the second part we look at a SoS from the point of view of cognitive complexity. Cognitive complexity is seen as a relation between a model of an SoS and the observer. In order to understand the behavior of a large SoS we have to generate models of adequate simplicity, i.e, of a cognitive complexity that can be handled by the limited capabilities of the human mind. We will discuss the importance of properly specifying and placing the relied-upon message interfaces between the constituent systems that form an open SoS and discuss simplification strategies that help to reduce the cognitive complexity.

  10. Electromagnetic fields in biological systems

    National Research Council Canada - National Science Library

    Lin, James C

    2012-01-01

    "Focusing on exposure, induced fields, and absorbed energy, this volume covers the interaction of electromagnetic fields and waves with biological systems, spanning static fields to terahertz waves...

  11. Metabolic systems biology: a brief primer.

    Science.gov (United States)

    Edwards, Lindsay M

    2017-05-01

    In the early to mid-20th century, reductionism as a concept in biology was challenged by key thinkers, including Ludwig von Bertalanffy. He proposed that living organisms were specific examples of complex systems and, as such, they should display characteristics including hierarchical organisation and emergent behaviour. Yet the true study of complete biological systems (for example, metabolism) was not possible until technological advances that occurred 60 years later. Technology now exists that permits the measurement of complete levels of the biological hierarchy, for example the genome and transcriptome. The complexity and scale of these data require computational models for their interpretation. The combination of these - systems thinking, high-dimensional data and computation - defines systems biology, typically accompanied by some notion of iterative model refinement. Only sequencing-based technologies, however, offer full coverage. Other 'omics' platforms trade coverage for sensitivity, although the densely connected nature of biological networks suggests that full coverage may not be necessary. Systems biology models are often characterised as either 'bottom-up' (mechanistic) or 'top-down' (statistical). This distinction can mislead, as all models rely on data and all are, to some degree, 'middle-out'. Systems biology has matured as a discipline, and its methods are commonplace in many laboratories. However, many challenges remain, especially those related to large-scale data integration. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

  12. Modeling Complex Systems

    CERN Document Server

    Boccara, Nino

    2010-01-01

    Modeling Complex Systems, 2nd Edition, explores the process of modeling complex systems, providing examples from such diverse fields as ecology, epidemiology, sociology, seismology, and economics. It illustrates how models of complex systems are built and provides indispensable mathematical tools for studying their dynamics. This vital introductory text is useful for advanced undergraduate students in various scientific disciplines, and serves as an important reference book for graduate students and young researchers. This enhanced second edition includes: . -recent research results and bibliographic references -extra footnotes which provide biographical information on cited scientists who have made significant contributions to the field -new and improved worked-out examples to aid a student’s comprehension of the content -exercises to challenge the reader and complement the material Nino Boccara is also the author of Essentials of Mathematica: With Applications to Mathematics and Physics (Springer, 2007).

  13. Philosophy of complex systems

    CERN Document Server

    2011-01-01

    The domain of nonlinear dynamical systems and its mathematical underpinnings has been developing exponentially for a century, the last 35 years seeing an outpouring of new ideas and applications and a concomitant confluence with ideas of complex systems and their applications from irreversible thermodynamics. A few examples are in meteorology, ecological dynamics, and social and economic dynamics. These new ideas have profound implications for our understanding and practice in domains involving complexity, predictability and determinism, equilibrium, control, planning, individuality, responsibility and so on. Our intention is to draw together in this volume, we believe for the first time, a comprehensive picture of the manifold philosophically interesting impacts of recent developments in understanding nonlinear systems and the unique aspects of their complexity. The book will focus specifically on the philosophical concepts, principles, judgments and problems distinctly raised by work in the domain of comple...

  14. Systems biology of fungal infection

    Directory of Open Access Journals (Sweden)

    Fabian eHorn

    2012-04-01

    Full Text Available Elucidation of pathogenicity mechanisms of the most important human pathogenic fungi, Aspergillus fumigatus and Candida albicans, has gained great interest in the light of the steadily increasing number of cases of invasive fungal infections.A key feature of these infections is the interaction of the different fungal morphotypes with epithelial and immune effector cells in the human host. Because of the high level of complexity, it is necessary to describe and understand invasive fungal infection by taking a systems biological approach, i.e., by a comprehensive quantitative analysis of the non-linear and selective interactions of a large number of functionally diverse, and frequently multifunctional, sets of elements, e.g., genes, proteins, metabolites, which produce coherent and emergent behaviours in time and space. The recent advances in systems biology will now make it possible to uncover the structure and dynamics of molecular and cellular cause-effect relationships within these pathogenic interactions.We review current efforts to integrate omics and image-based data of host-pathogen interactions into network and spatio-temporal models. The modelling will help to elucidate pathogenicity mechanisms and to identify diagnostic biomarkers and potential drug targets for therapy and could thus pave the way for novel intervention strategies based on novel antifungal drugs and cell therapy.

  15. Mapping biological systems to network systems

    CERN Document Server

    Rathore, Heena

    2016-01-01

    The book presents the challenges inherent in the paradigm shift of network systems from static to highly dynamic distributed systems – it proposes solutions that the symbiotic nature of biological systems can provide into altering networking systems to adapt to these changes. The author discuss how biological systems – which have the inherent capabilities of evolving, self-organizing, self-repairing and flourishing with time – are inspiring researchers to take opportunities from the biology domain and map them with the problems faced in network domain. The book revolves around the central idea of bio-inspired systems -- it begins by exploring why biology and computer network research are such a natural match. This is followed by presenting a broad overview of biologically inspired research in network systems -- it is classified by the biological field that inspired each topic and by the area of networking in which that topic lies. Each case elucidates how biological concepts have been most successfully ...

  16. DNA micelle flares: a study of the basic properties that contribute to enhanced stability and binding affinity in complex biological systems.

    Science.gov (United States)

    Wang, Yanyue; Wu, Cuichen; Chen, Tao; Sun, Hao; Cansiz, Sena; Zhang, Liqin; Cui, Cheng; Hou, Weijia; Wu, Yuan; Wan, Shuo; Cai, Ren; Liu, Yuan; Sumerlin, Brent; Zhang, Xiaobing; Tan, Weihong

    2016-01-01

    DMFs are spherical DNA-diacyllipid nanostructures formed by hydrophobic effects between lipid tails coupled to single-stranded DNAs. Such properties as high cellular permeability, low critical micelle concentration (CMC) and facile fabrication facilitate intracellular imaging and drug delivery. While the basic properties of NFs have been amply described and tested, few studies have characterized the fundamental properties of DMFs with particular respect to aggregation number, dissociation constant and biostability. Therefore, to further explore their conformational features and enhanced stability in complex biological systems, we herein report a series of characterization studies. Static light scattering (SLS) demonstrated that DMFs possess greater DNA loading capacity when compared to other DNA-based nanostructures. Upon binding to complementary DNA (cDNA), DMFs showed excellent dissociation constants (K d ) and increased melting temperatures, as well as constant CMC (10 nM) independent of DNA length. DMFs also present significantly enhanced stability in aqueous solution with nuclease and cell lysate. These properties make DMFs ideal for versatile applications in bioanalysis and theranostics studies.

  17. Systems biology and biomarker discovery

    Energy Technology Data Exchange (ETDEWEB)

    Rodland, Karin D.

    2010-12-01

    Medical practitioners have always relied on surrogate markers of inaccessible biological processes to make their diagnosis, whether it was the pallor of shock, the flush of inflammation, or the jaundice of liver failure. Obviously, the current implementation of biomarkers for disease is far more sophisticated, relying on highly reproducible, quantitative measurements of molecules that are often mechanistically associated with the disease in question, as in glycated hemoglobin for the diagnosis of diabetes [1] or the presence of cardiac troponins in the blood for confirmation of myocardial infarcts [2]. In cancer, where the initial symptoms are often subtle and the consequences of delayed diagnosis often drastic for disease management, the impetus to discover readily accessible, reliable, and accurate biomarkers for early detection is compelling. Yet despite years of intense activity, the stable of clinically validated, cost-effective biomarkers for early detection of cancer is pathetically small and still dominated by a handful of markers (CA-125, CEA, PSA) first discovered decades ago. It is time, one could argue, for a fresh approach to the discovery and validation of disease biomarkers, one that takes full advantage of the revolution in genomic technologies and in the development of computational tools for the analysis of large complex datasets. This issue of Disease Markers is dedicated to one such new approach, loosely termed the 'Systems Biology of Biomarkers'. What sets the Systems Biology approach apart from other, more traditional approaches, is both the types of data used, and the tools used for data analysis - and both reflect the revolution in high throughput analytical methods and high throughput computing that has characterized the start of the twenty first century.

  18. Radical production in biological systems

    International Nuclear Information System (INIS)

    Johnson, J.R.; Akabani, G.

    1994-10-01

    This paper describes our effort to develop a metric for radiation exposure that is more fundamental than adsorbed dose and upon which a metric for exposure to chemicals could be based. This metric is based on the production of radicals by the two agents. Radicals produced by radiation in biological systems commonly assumed to be the same as those produced in water despite the presence of a variety of complex molecules. This may explain why the extensive efforts to describe the relationship between energy deposition (track structure) and molecular damage to DNA, based on the spectrum of radicals produced, have not been successful in explaining simple biological effects such as cell killing. Current models assume that DNA and its basic elements are immersed in water-like media and only model the production and diffusion of water-based radicals and their interaction with DNA structures; these models lack the cross sections associated with each macro-component of DNA and only treat water-based radicals. It has been found that such models are not realistic because DNA is not immersed in pure water. A computer code capable of simulating electron tracks, low-energy electrons, energy deposition in small molecules, and radical production and diffusion in water like media has been developed. This code is still in at a primitive stage and development is continuing. It is being used to study radical production by radiation, and radical diffusion and interactions in simple molecular systems following their production. We are extending the code to radical production by chemicals to complement our PBPK modeling efforts. It therefore has been developed primarily for use with radionuclides that are in biological materials, and not for radiation fields

  19. Telemetry System of Biological Parameters

    Directory of Open Access Journals (Sweden)

    Jan Spisak

    2005-01-01

    Full Text Available The mobile telemetry system of biological parameters serves for reading and wireless data transfer of measured values of selected biological parameters to an outlying computer. It concerns basically long time monitoring of vital function of car pilot.The goal of this projects is to propose mobile telemetry system for reading, wireless transfer and processing of biological parameters of car pilot during physical and psychical stress. It has to be made with respect to minimal consumption, weight and maximal device mobility. This system has to eliminate signal noise, which is created by biological artifacts and disturbances during the data transfer.

  20. Excited states in biological systems

    International Nuclear Information System (INIS)

    Cilento, G.; Zinner, K.; Bechara, E.J.H.; Duran, N.; Baptista, R.C. de; Shimizu, Y.; Augusto, O.; Faljoni-Alario, A.; Vidigal, C.C.C.; Oliveira, O.M.M.F.; Haun, M.

    1979-01-01

    Some aspects of bioluminescence related to bioenergetics are discussed: 1. chemical generation of excited species, by means of two general processes: electron transference and cyclic - and linear peroxide cleavage; 2. biological systems capable of generating excited states and 3. biological functions of these states, specially the non-emissive ones (tripletes). The production and the role of non-emissive excited states in biological systems are analysed, the main purpose of the study being the search for non-emissive states. Experiences carried out in biological systems are described; results and conclusions are given. (M.A.) [pt

  1. Complexity in Dynamical Systems

    Science.gov (United States)

    Moore, Cristopher David

    The study of chaos has shown us that deterministic systems can have a kind of unpredictability, based on a limited knowledge of their initial conditions; after a finite time, the motion appears essentially random. This observation has inspired a general interest in the subject of unpredictability, and more generally, complexity; how can we characterize how "complex" a dynamical system is?. In this thesis, we attempt to answer this question with a paradigm of complexity that comes from computer science, we extract sets of symbol sequences, or languages, from a dynamical system using standard methods of symbolic dynamics; we then ask what kinds of grammars or automata are needed a generate these languages. This places them in the Chomsky heirarchy, which in turn tells us something about how subtle and complex the dynamical system's behavior is. This gives us insight into the question of unpredictability, since these automata can also be thought of as computers attempting to predict the system. In the culmination of the thesis, we find a class of smooth, two-dimensional maps which are equivalent to the highest class in the Chomsky heirarchy, the turning machine; they are capable of universal computation. Therefore, these systems possess a kind of unpredictability qualitatively different from the usual "chaos": even if the initial conditions are known exactly, questions about the system's long-term dynamics are undecidable. No algorithm exists to answer them. Although this kind of unpredictability has been discussed in the context of distributed, many-degree-of -freedom systems (for instance, cellular automata) we believe this is the first example of such phenomena in a smooth, finite-degree-of-freedom system.

  2. Dimensionality reduction of bistable biological systems.

    Science.gov (United States)

    Zakharova, A; Nikoloski, Z; Koseska, A

    2013-03-01

    Time hierarchies, arising as a result of interactions between system's components, represent a ubiquitous property of dynamical biological systems. In addition, biological systems have been attributed switch-like properties modulating the response to various stimuli across different organisms and environmental conditions. Therefore, establishing the interplay between these features of system dynamics renders itself a challenging question of practical interest in biology. Existing methods are suitable for systems with one stable steady state employed as a well-defined reference. In such systems, the characterization of the time hierarchies has already been used for determining the components that contribute to the dynamics of biological systems. However, the application of these methods to bistable nonlinear systems is impeded due to their inherent dependence on the reference state, which in this case is no longer unique. Here, we extend the applicability of the reference-state analysis by proposing, analyzing, and applying a novel method, which allows investigation of the time hierarchies in systems exhibiting bistability. The proposed method is in turn used in identifying the components, other than reactions, which determine the systemic dynamical properties. We demonstrate that in biological systems of varying levels of complexity and spanning different biological levels, the method can be effectively employed for model simplification while ensuring preservation of qualitative dynamical properties (i.e., bistability). Finally, by establishing a connection between techniques from nonlinear dynamics and multivariate statistics, the proposed approach provides the basis for extending reference-based analysis to bistable systems.

  3. Systems Biology and Livestock Science

    NARCIS (Netherlands)

    Pas, te M.F.W.; Woelders, H.; Bannink, A.

    2011-01-01

    Systems Biology is an interdisciplinary approach to the study of life made possible through the explosion of molecular data made available through the genome revolution and the simultaneous development of computational technologies that allow us to interpret these large data sets. Systems Biology

  4. Static Analysis for Systems Biology

    DEFF Research Database (Denmark)

    Nielson, Flemming; Nielson, Hanne Riis; Rosa, D. Schuch da

    2004-01-01

    This paper shows how static analysis techniques can help understanding biological systems. Based on a simple example we illustrate the outcome of performing three different analyses extracting information of increasing precision. We conclude by reporting on the potential impact and exploitation o...... of these techniques in systems biology....

  5. Complex adaptive systems ecology

    DEFF Research Database (Denmark)

    Sommerlund, Julie

    2003-01-01

    In the following, I will analyze two articles called Complex Adaptive Systems EcologyI & II (Molin & Molin, 1997 & 2000). The CASE-articles are some of the more quirkyarticles that have come out of the Molecular Microbial Ecology Group - a groupwhere I am currently making observational studies...

  6. Complex Macromolecular Architectures for Potential Biological Applications

    Science.gov (United States)

    Jung, Hwayoon

    This thesis describes original research aimed at the development of highly efficient synthetic methods towards complex polymer architectures. An explanation of different polymer architectures, their synthesis and applications, in particular as biomaterials, is provided. Dendronized polymers and block copolymers are identified as two classes of polymer architectures that are important for a variety of applications but whose fabrications still pose a challenge. In the macromonomer route for the synthesis of dendronized polymers, the preferred route due to complete and uniform dendron functionalization, high degrees of polymerization are difficult to achieve due to steric crowding. This limitation was overcome by incorporating linkers between the polymerizable group (norbornene) and the poly(amide)-based dendrons. By increasing the length of the linker, the rate of polymerization increased. The synthesis of block copolymers using non-living polymerization methods often requires the copolymerization of monomers by different polymerization mechanisms. This methodology is hampered by non-quantitative conversions of the precursor polymer into the required macroinitiator. This limitation was overcome by using a bifunctional initiator. Poly(norbornene)-block -poly(lactic acid)s were synthesized using a ruthenium initiator for the ring-opening metathesis polymerization (ROMP) and a hydroxy group to initiate the ring-opening polymerization (ROP) of L-lactide. This method opens up new routes for the creation of functional block copolymers that are created by a combination of ROMP and ROP. Finally, potential strategies towards the synthesis of complex polymer architectures for biomaterials using the methodologies developed in this thesis are described. Firstly, the synthesis of orthogonally functionalizable dendronized polymers for targeted drug-delivery is proposed. Second, studies to establish the relationship between architectures and properties for biological applications

  7. Control of complex systems

    CERN Document Server

    Albertos, Pedro; Blanke, Mogens; Isidori, Alberto; Schaufelberger, Walter; Sanz, Ricardo

    2001-01-01

    The world of artificial systems is reaching complexity levels that es­ cape human understanding. Surface traffic, electricity distribution, air­ planes, mobile communications, etc. , are examples that demonstrate that we are running into problems that are beyond classical scientific or engi­ neering knowledge. There is an ongoing world-wide effort to understand these systems and develop models that can capture its behavior. The reason for this work is clear, if our lack of understanding deepens, we will lose our capability to control these systems and make they behave as we want. Researchers from many different fields are trying to understand and develop theories for complex man-made systems. This book presents re­ search from the perspective of control and systems theory. The book has grown out of activities in the research program Control of Complex Systems (COSY). The program has been sponsored by the Eu­ ropean Science Foundation (ESF) which for 25 years has been one of the leading players in stimula...

  8. Noncommutative Biology: Sequential Regulation of Complex Networks.

    Directory of Open Access Journals (Sweden)

    William Letsou

    2016-08-01

    Full Text Available Single-cell variability in gene expression is important for generating distinct cell types, but it is unclear how cells use the same set of regulatory molecules to specifically control similarly regulated genes. While combinatorial binding of transcription factors at promoters has been proposed as a solution for cell-type specific gene expression, we found that such models resulted in substantial information bottlenecks. We sought to understand the consequences of adopting sequential logic wherein the time-ordering of factors informs the final outcome. We showed that with noncommutative control, it is possible to independently control targets that would otherwise be activated simultaneously using combinatorial logic. Consequently, sequential logic overcomes the information bottleneck inherent in complex networks. We derived scaling laws for two noncommutative models of regulation, motivated by phosphorylation/neural networks and chromosome folding, respectively, and showed that they scale super-exponentially in the number of regulators. We also showed that specificity in control is robust to the loss of a regulator. Lastly, we connected these theoretical results to real biological networks that demonstrate specificity in the context of promiscuity. These results show that achieving a desired outcome often necessitates roundabout steps.

  9. Third International Conference on Complex Systems

    CERN Document Server

    Minai, Ali A; Unifying Themes in Complex Systems

    2006-01-01

    In recent years, scientists have applied the principles of complex systems science to increasingly diverse fields. The results have been nothing short of remarkable: their novel approaches have provided answers to long-standing questions in biology, ecology, physics, engineering, computer science, economics, psychology and sociology. The Third International Conference on Complex Systems attracted over 400 researchers from around the world. The conference aimed to encourage cross-fertilization between the many disciplines represented and to deepen our understanding of the properties common to all complex systems. This volume contains over 35 papers selected from those presented at the conference on topics including: self-organization in biology, ecological systems, language, economic modeling, ecological systems, artificial life, robotics, and complexity and art. ALI MINAI is an Affiliate of the New England Complex Systems Institute and an Associate Professor in the Department of Electrical and Computer Engine...

  10. Quantum Effects in Biological Systems

    CERN Document Server

    2016-01-01

    Since the last decade the study of quantum mechanical phenomena in biological systems has become a vibrant field of research. Initially sparked by evidence of quantum effects in energy transport that is instrumental for photosynthesis, quantum biology asks the question of how methods and models from quantum theory can help us to understand fundamental mechanisms in living organisms. This approach entails a paradigm change challenging the related disciplines: The successful framework of quantum theory is taken out of its low-temperature, microscopic regimes and applied to hot and dense macroscopic environments, thereby extending the toolbox of biology and biochemistry at the same time. The Quantum Effects in Biological Systems conference is a platform for researchers from biology, chemistry and physics to present and discuss the latest developments in the field of quantum biology. After meetings in Lisbon (2009), Harvard (2010), Ulm (2011), Berkeley (2012), Vienna (2013), Singapore (2014) and Florence (2015),...

  11. Modeling Complex Systems

    International Nuclear Information System (INIS)

    Schreckenberg, M

    2004-01-01

    This book by Nino Boccara presents a compilation of model systems commonly termed as 'complex'. It starts with a definition of the systems under consideration and how to build up a model to describe the complex dynamics. The subsequent chapters are devoted to various categories of mean-field type models (differential and recurrence equations, chaos) and of agent-based models (cellular automata, networks and power-law distributions). Each chapter is supplemented by a number of exercises and their solutions. The table of contents looks a little arbitrary but the author took the most prominent model systems investigated over the years (and up until now there has been no unified theory covering the various aspects of complex dynamics). The model systems are explained by looking at a number of applications in various fields. The book is written as a textbook for interested students as well as serving as a comprehensive reference for experts. It is an ideal source for topics to be presented in a lecture on dynamics of complex systems. This is the first book on this 'wide' topic and I have long awaited such a book (in fact I planned to write it myself but this is much better than I could ever have written it!). Only section 6 on cellular automata is a little too limited to the author's point of view and one would have expected more about the famous Domany-Kinzel model (and more accurate citation!). In my opinion this is one of the best textbooks published during the last decade and even experts can learn a lot from it. Hopefully there will be an actualization after, say, five years since this field is growing so quickly. The price is too high for students but this, unfortunately, is the normal case today. Nevertheless I think it will be a great success! (book review)

  12. Electromagnetic fields in biological systems

    CERN Document Server

    Lin, James C

    2016-01-01

    As wireless technology becomes more sophisticated and accessible to more users, the interactions of electromagnetic fields with biological systems have captured the interest not only of the scientific community but also the general public. Unintended or deleterious biological effects of electromagnetic fields and radiation may indicate grounds for health and safety precautions in their use. Spanning static fields to terahertz waves, Electromagnetic Fields in Biological Systems explores the range of consequences these fields have on the human body. With contributions by an array of experts, topics discussed include: Essential interactions and field coupling phenomena, highlighting their importance in research on biological effects and in scientific, industrial, and medical applications Electric field interactions in cells, focusing on ultrashort, pulsed high-intensity fields The effect of exposure to naturally occurring and human-made static, low-frequency, and pulsed magnetic fields in biological systems Dosi...

  13. Validation of systems biology models

    NARCIS (Netherlands)

    Hasdemir, D.

    2015-01-01

    The paradigm shift from qualitative to quantitative analysis of biological systems brought a substantial number of modeling approaches to the stage of molecular biology research. These include but certainly are not limited to nonlinear kinetic models, static network models and models obtained by the

  14. Statistical Model Checking for Biological Systems

    DEFF Research Database (Denmark)

    David, Alexandre; Larsen, Kim Guldstrand; Legay, Axel

    2014-01-01

    Statistical Model Checking (SMC) is a highly scalable simulation-based verification approach for testing and estimating the probability that a stochastic system satisfies a given linear temporal property. The technique has been applied to (discrete and continuous time) Markov chains, stochastic...... timed automata and most recently hybrid systems using the tool Uppaal SMC. In this paper we enable the application of SMC to complex biological systems, by combining Uppaal SMC with ANIMO, a plugin of the tool Cytoscape used by biologists, as well as with SimBiology®, a plugin of Matlab to simulate...

  15. Systems biology of human atherosclerosis.

    Science.gov (United States)

    Shalhoub, Joseph; Sikkel, Markus B; Davies, Kerry J; Vorkas, Panagiotis A; Want, Elizabeth J; Davies, Alun H

    2014-01-01

    Systems biology describes a holistic and integrative approach to understand physiology and pathology. The "omic" disciplines include genomics, transcriptomics, proteomics, and metabolic profiling (metabonomics and metabolomics). By adopting a stance, which is opposing (yet complimentary) to conventional research techniques, systems biology offers an overview by assessing the "net" biological effect imposed by a disease or nondisease state. There are a number of different organizational levels to be understood, from DNA to protein, metabolites, cells, organs and organisms, even beyond this to an organism's context. Systems biology relies on the existence of "nodes" and "edges." Nodes are the constituent part of the system being studied (eg, proteins in the proteome), while the edges are the way these constituents interact. In future, it will be increasingly important to collaborate, collating data from multiple studies to improve data sets, making them freely available and undertaking integrative analyses.

  16. Text mining for systems biology.

    Science.gov (United States)

    Fluck, Juliane; Hofmann-Apitius, Martin

    2014-02-01

    Scientific communication in biomedicine is, by and large, still text based. Text mining technologies for the automated extraction of useful biomedical information from unstructured text that can be directly used for systems biology modelling have been substantially improved over the past few years. In this review, we underline the importance of named entity recognition and relationship extraction as fundamental approaches that are relevant to systems biology. Furthermore, we emphasize the role of publicly organized scientific benchmarking challenges that reflect the current status of text-mining technology and are important in moving the entire field forward. Given further interdisciplinary development of systems biology-orientated ontologies and training corpora, we expect a steadily increasing impact of text-mining technology on systems biology in the future. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. European Conference on Complex Systems 2012

    CERN Document Server

    Kirkilionis, Markus; Nicolis, Gregoire

    2013-01-01

    The European Conference on Complex Systems, held under the patronage of the Complex Systems Society, is an annual event that has become the leading European conference devoted to complexity science. ECCS'12, its ninth edition, took place in Brussels, during the first week of September 2012. It gathered about 650 scholars representing a wide range of topics relating to complex systems research, with emphasis on interdisciplinary approaches. More specifically, the following tracks were covered:  1. Foundations of Complex Systems 2. Complexity, Information and Computation 3. Prediction, Policy and Planning, Environment 4. Biological Complexity 5. Interacting Populations, Collective Behavior 6. Social Systems, Economics and Finance This book contains a selection of the contributions presented at the conference and its satellite meetings. Its contents reflect the extent, diversity and richness of research areas in the field, both fundamental and applied.  

  18. Carbon-13 NMR spectroscopy of biological systems

    CERN Document Server

    Beckmann, Nicolau

    1995-01-01

    This book is intended to provide an in-depth understanding of 13C NMR as a tool in biological research. 13C NMR has provided unique information concerning complex biological systems, from proteins and nucleic acids to animals and humans. The subjects addressed include multidimensional heteronuclear techniques for structural studies of molecules in the liquid and solid states, the investigation of interactions in model membranes, the elucidation of metabolic pathwaysin vitro and in vivo on animals, and noninvasive metabolic studies performed on humans. The book is a unique mix of NMR methods and biological applications which makes it a convenient reference for those interested in research in this interdisciplinary area of physics, chemistry, biology, and medicine.Key Features* An interdisciplinary text with emphasis on both 13C NMR methodology and the relevant biological and biomedical issues* State-of-the-art 13C NMR techniques are described; Whenever possible, their advantages over other approaches are empha...

  19. Analytical ultracentrifugation with fluorescence detection system reveals differences in complex formation between recombinant human TNF and different biological TNF antagonists in various environments.

    Science.gov (United States)

    Krayukhina, Elena; Noda, Masanori; Ishii, Kentaro; Maruno, Takahiro; Wakabayashi, Hirotsugu; Tada, Minoru; Suzuki, Takuo; Ishii-Watabe, Akiko; Kato, Masahiko; Uchiyama, Susumu

    A number of studies have attempted to elucidate the binding mechanism between tumor necrosis factor (TNF) and clinically relevant antagonists. None of these studies, however, have been conducted as close as possible to physiologic conditions, and so the relationship between the size distribution of TNF-antagonist complexes and the antagonists' biological activity or adverse effects remains elusive. Here, we characterized the binding stoichiometry and sizes of soluble TNF-antagonist complexes for adalimumab, infliximab, and etanercept that were formed in human serum and in phosphate-buffered saline (PBS). Fluorescence-detected sedimentation velocity analytical ultracentrifugation analyses revealed that adalimumab and infliximab formed a range of complexes with TNF, with the major complexes consisting of 3 molcules of the respective antagonist and one or 2 molcules of TNF. Considerably greater amounts of high-molecular-weight complexes were detected for infliximab in human serum. The emergence of peaks with higher sedimentation coefficients than the adalimumab monomer as a function of added human serum albumin (HSA) concentration in PBS suggested weak reversible interactions between HSA and immunoglobulins. Etanerept exclusively formed 1:1 complexes with TNF in PBS, and a small amount of complexes with higher stoichiometry was detected in human serum. Consistent with these biophysical characterizations, a reporter assay showed that adalimumab and infliximab, but not etanercept, exerted FcγRIIa- and FcγRIIIa-mediated cell signaling in the presence of TNF and that infliximab exhibited higher potency than adalimumab. This study shows that assessing distribution profiles in serum will contribute to a more comprehensive understanding of the in vivo behavior of therapeutic proteins.

  20. Ten questions about systems biology

    DEFF Research Database (Denmark)

    Joyner, Michael J; Pedersen, Bente K

    2011-01-01

    In this paper we raise 'ten questions' broadly related to 'omics', the term systems biology, and why the new biology has failed to deliver major therapeutic advances for many common diseases, especially diabetes and cardiovascular disease. We argue that a fundamentally narrow and reductionist...... to understand how whole animals adapt to the real world. We argue that a lack of fluency in these concepts is a major stumbling block for what has been narrowly defined as 'systems biology' by some of its leading advocates. We also point out that it is a failure of regulation at multiple levels that causes many...

  1. Graphics processing units in bioinformatics, computational biology and systems biology.

    Science.gov (United States)

    Nobile, Marco S; Cazzaniga, Paolo; Tangherloni, Andrea; Besozzi, Daniela

    2017-09-01

    Several studies in Bioinformatics, Computational Biology and Systems Biology rely on the definition of physico-chemical or mathematical models of biological systems at different scales and levels of complexity, ranging from the interaction of atoms in single molecules up to genome-wide interaction networks. Traditional computational methods and software tools developed in these research fields share a common trait: they can be computationally demanding on Central Processing Units (CPUs), therefore limiting their applicability in many circumstances. To overcome this issue, general-purpose Graphics Processing Units (GPUs) are gaining an increasing attention by the scientific community, as they can considerably reduce the running time required by standard CPU-based software, and allow more intensive investigations of biological systems. In this review, we present a collection of GPU tools recently developed to perform computational analyses in life science disciplines, emphasizing the advantages and the drawbacks in the use of these parallel architectures. The complete list of GPU-powered tools here reviewed is available at http://bit.ly/gputools. © The Author 2016. Published by Oxford University Press.

  2. Complex adaptive systems ecology

    DEFF Research Database (Denmark)

    Sommerlund, Julie

    2003-01-01

    In the following, I will analyze two articles called Complex Adaptive Systems EcologyI & II (Molin & Molin, 1997 & 2000). The CASE-articles are some of the more quirkyarticles that have come out of the Molecular Microbial Ecology Group - a groupwhere I am currently making observational studies....... They are the result of acooperation between Søren Molin, professor in the group, and his brother, JanMolin, professor at Department of Organization and Industrial Sociology atCopenhagen Business School. The cooperation arises from the recognition that bothmicrobial ecology and sociology/organization theory works...

  3. Systems Biology and Stem Cell Pluripotency

    DEFF Research Database (Denmark)

    Mashayekhi, Kaveh; Hall, Vanessa Jane; Freude, Kristine

    2016-01-01

    Recent breakthroughs in stem cell biology have accelerated research in the area of regenerative medicine. Over the past years, it has become possible to derive patient-specific stem cells which can be used to generate different cell populations for potential cell therapy. Systems biological...... improve systems biology and its uses in the field. In this chapter, we first give a general background on stem cell biology and regenerative medicine. Stem cell potency is introduced together with the hierarchy of stem cells ranging from pluripotent embryonic stem cells (ESCs) and induced pluripotent stem...... modeling of stem cell pluripotency and differentiation have largely been based on prior knowledge of signaling pathways, gene regulatory networks, and epigenetic factors. However, there is a great need to extend the complexity of the modeling and to integrate different types of data, which would further...

  4. Integrative Systems Biology Visualization with MAYDAY

    Directory of Open Access Journals (Sweden)

    Symonsy Stephan

    2010-12-01

    Full Text Available Visualization is pivotal for gaining insight in systems biology data. As the size and complexity of datasets and supplemental information increases, an efficient, integrated framework for general and specialized views is necessary. MAYDAY is an application for analysis and visualization of general ‘omics’ data. It follows a trifold approach for data visualization, consisting of flexible data preprocessing, highly customizable data perspective plots for general purpose visualization and systems based plots. Here, we introduce two new systems biology visualization tools for MAYDAY. Efficiently implemented genomic viewers allow the display of variables associated with genomic locations. Multiple variables can be viewed using our new track-based ChromeTracks tool. A functional perspective is provided by visualizing metabolic pathways either in KEGG or BioPax format. Multiple options of displaying pathway components are available, including Systems Biology Graphical Notation (SBGN glyphs. Furthermore, pathways can be viewed together with gene expression data either as heatmaps or profiles.

  5. Systems Biology of Metabolism: Annual Review of Biochemistry

    DEFF Research Database (Denmark)

    Nielsen, Jens

    2017-01-01

    Metabolism is highly complex and involves thousands of different connected reactions; it is therefore necessary to use mathematical models for holistic studies. The use of mathematical models in biology is referred to as systems biology. In this review, the principles of systems biology......, the application of systems biology for analyzing global regulatory structures, engineering the metabolism of cell factories, and analyzing human diseases is discussed....

  6. Inverse problems in systems biology

    International Nuclear Information System (INIS)

    Engl, Heinz W; Lu, James; Müller, Stefan; Flamm, Christoph; Schuster, Peter; Kügler, Philipp

    2009-01-01

    Systems biology is a new discipline built upon the premise that an understanding of how cells and organisms carry out their functions cannot be gained by looking at cellular components in isolation. Instead, consideration of the interplay between the parts of systems is indispensable for analyzing, modeling, and predicting systems' behavior. Studying biological processes under this premise, systems biology combines experimental techniques and computational methods in order to construct predictive models. Both in building and utilizing models of biological systems, inverse problems arise at several occasions, for example, (i) when experimental time series and steady state data are used to construct biochemical reaction networks, (ii) when model parameters are identified that capture underlying mechanisms or (iii) when desired qualitative behavior such as bistability or limit cycle oscillations is engineered by proper choices of parameter combinations. In this paper we review principles of the modeling process in systems biology and illustrate the ill-posedness and regularization of parameter identification problems in that context. Furthermore, we discuss the methodology of qualitative inverse problems and demonstrate how sparsity enforcing regularization allows the determination of key reaction mechanisms underlying the qualitative behavior. (topical review)

  7. Modeling Power Systems as Complex Adaptive Systems

    Energy Technology Data Exchange (ETDEWEB)

    Chassin, David P.; Malard, Joel M.; Posse, Christian; Gangopadhyaya, Asim; Lu, Ning; Katipamula, Srinivas; Mallow, J V.

    2004-12-30

    Physical analogs have shown considerable promise for understanding the behavior of complex adaptive systems, including macroeconomics, biological systems, social networks, and electric power markets. Many of today's most challenging technical and policy questions can be reduced to a distributed economic control problem. Indeed, economically based control of large-scale systems is founded on the conjecture that the price-based regulation (e.g., auctions, markets) results in an optimal allocation of resources and emergent optimal system control. This report explores the state-of-the-art physical analogs for understanding the behavior of some econophysical systems and deriving stable and robust control strategies for using them. We review and discuss applications of some analytic methods based on a thermodynamic metaphor, according to which the interplay between system entropy and conservation laws gives rise to intuitive and governing global properties of complex systems that cannot be otherwise understood. We apply these methods to the question of how power markets can be expected to behave under a variety of conditions.

  8. Systems biology: leading the revolution in ecotoxicology.

    Science.gov (United States)

    Garcia-Reyero, Natàlia; Perkins, Edward J

    2011-02-01

    The rapid development of new technologies such as transcriptomics, proteomics, and metabolomics (Omics) are changing the way ecotoxicology is practiced. The data deluge has begun with genomes of over 65 different aquatic species that are currently being sequenced, and many times that number with at least some level of transcriptome sequencing. Integrating these top-down methodologies is an essential task in the field of systems biology. Systems biology is a biology-based interdisciplinary field that focuses on complex interactions in biological systems, with the intent to model and discover emergent properties of the system. Recent studies demonstrate that Omics technologies provide valuable insight into ecotoxicity, both in laboratory exposures with model organisms and with animals exposed in the field. However, these approaches require a context of the whole animal and population to be relevant. Powerful approaches using reverse engineering to determine interacting networks of genes, proteins, or biochemical reactions are uncovering unique responses to toxicants. Modeling efforts in aquatic animals are evolving to interrelate the interacting networks of a system and the flow of information linking these elements. Just as is happening in medicine, systems biology approaches that allow the integration of many different scales of interaction and information are already driving a revolution in understanding the impacts of pollutants on aquatic systems. © 2010 SETAC.

  9. Nanoscale technology in biological systems

    CERN Document Server

    Greco, Ralph S; Smith, R Lane

    2004-01-01

    Reviewing recent accomplishments in the field of nanobiology Nanoscale Technology in Biological Systems introduces the application of nanoscale matrices to human biology. It focuses on the applications of nanotechnology fabrication to biomedical devices and discusses new physical methods for cell isolation and manipulation and intracellular communication at the molecular level. It also explores the application of nanobiology to cardiovascular diseases, oncology, transplantation, and a range of related disciplines. This book build a strong background in nanotechnology and nanobiology ideal for

  10. FY 1997 report on the results of the industrial technology R and D project. Development of technology to use biological resources such as the complex biological system (Development of biological use petroleum substitution fuel production technology); 1997 nendo fukugo seibutsukei nado seibutsu shigen riyo gijutsu kaihatsu seika hokokusho. Seibutsu riyo sekiyu daitai nenryo seizo gijutsu no kaihatsu

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-03-01

    Experimental researches were conducted and the FY 1997 results were reported with the aim of establishing analytical technology for the complex biological system by which the complex biological system can be analyzed in such a state as it is using the molecular biological method. In the study of the molecular genetic analytical technology, PCR primers used for amplification of topoisomerase II genes of the whole eukaryote was designed. As to the histochemical analytical technology, a study was made on the new constitution microorganism detection method by the hybridization method and the antibody specific dyeing method, and the following were conducted: manifestation in quantity of colibacillus and the recovery, refining, and construction of peptide library by fuzzy display method. Concerning the functional analytical technology, technological researches were made such as the environmental adaptation mechanism of high thermophile and the information transfer mechanism among bacteria through cell membranes for elucidation of the special environment detection/response mechanism and the special environment adaptation/resistance mechanism. As to the separation/culture technology, various anaerobic microorganisms were separated from marine sponge for the development of a method of culturing in 3D matrices. (NEDO)

  11. Network biology concepts in complex disease comorbidities

    DEFF Research Database (Denmark)

    Hu, Jessica Xin; Thomas, Cecilia Engel; Brunak, Søren

    2016-01-01

    The co-occurrence of diseases can inform the underlying network biology of shared and multifunctional genes and pathways. In addition, comorbidities help to elucidate the effects of external exposures, such as diet, lifestyle and patient care. With worldwide health transaction data now often being...

  12. Systems biology: the reincarnation of systems theory applied in biology?

    Science.gov (United States)

    Wolkenhauer, O

    2001-09-01

    With the availability of quantitative data on the transcriptome and proteome level, there is an increasing interest in formal mathematical models of gene expression and regulation. International conferences, research institutes and research groups concerned with systems biology have appeared in recent years and systems theory, the study of organisation and behaviour per se, is indeed a natural conceptual framework for such a task. This is, however, not the first time that systems theory has been applied in modelling cellular processes. Notably in the 1960s systems theory and biology enjoyed considerable interest among eminent scientists, mathematicians and engineers. Why did these early attempts vanish from research agendas? Here we shall review the domain of systems theory, its application to biology and the lessons that can be learned from the work of Robert Rosen. Rosen emerged from the early developments in the 1960s as a main critic but also developed a new alternative perspective to living systems, a concept that deserves a fresh look in the post-genome era of bioinformatics.

  13. Biologically relevant heterodinuclear iron-manganese complexes.

    Science.gov (United States)

    Carboni, Michaël; Clémancey, Martin; Molton, Florian; Pécaut, Jacques; Lebrun, Colette; Dubois, Lionel; Blondin, Geneviève; Latour, J-M

    2012-10-01

    The heterodinuclear complexes [Fe(III)Mn(II)(L-Bn)(μ-OAc)(2)](ClO(4))(2) (1) and [Fe(II)Mn(II)(L-Bn)(μ-OAc)(2)](ClO(4)) (2) with the unsymmetrical dinucleating ligand HL-Bn {[2-bis[(2-pyridylmethyl)aminomethyl

  14. Systems biology of cellular rhythms.

    Science.gov (United States)

    Goldbeter, A; Gérard, C; Gonze, D; Leloup, J-C; Dupont, G

    2012-08-31

    Rhythms abound in biological systems, particularly at the cellular level where they originate from the feedback loops present in regulatory networks. Cellular rhythms can be investigated both by experimental and modeling approaches, and thus represent a prototypic field of research for systems biology. They have also become a major topic in synthetic biology. We review advances in the study of cellular rhythms of biochemical rather than electrical origin by considering a variety of oscillatory processes such as Ca++ oscillations, circadian rhythms, the segmentation clock, oscillations in p53 and NF-κB, synthetic oscillators, and the oscillatory dynamics of cyclin-dependent kinases driving the cell cycle. Finally we discuss the coupling between cellular rhythms and their robustness with respect to molecular noise.

  15. Seasonal allergic rhinitis and systems biology-oriented biomarker discovery

    NARCIS (Netherlands)

    Baars, E.W.; Nierop, A.F.M.; Savelkoul, H.F.J.

    2015-01-01

    There is an increasing interest in science and medicine in the systems approach. Instead of the reductionist approach that focuses on the physical and chemical properties of the individual components, systems biology aims to describe, understand, and explain from the complex biological systems

  16. Radiation interactions with biological systems.

    Science.gov (United States)

    Islam, Muhammad Torequl

    2017-05-01

    The use of radiation, especially ionizing radiation (IR), is currently attracting great attention in the field of medical sciences. However, it should be mentioned that IR has both beneficial and harmful effects in biological systems. This review aims to focus on IR-mediated physiological events in a mechanistic way. Evidence from the databases, mainly from PUBMED and SCIENCE DIRECT were considered. IR directly and/or with their lyses products (indirect) causes oxidative stresses to biological systems. These activities may be localized and systematic. Otherwise, IR-induced non-/multi-targeted effects are also evident. IR in diagnosis and cancer radiotherapy is well-known. Reactive species produced by IR are not only beneficial, but also can exert harmful effects in a biological system such as aging, genetic instability and mutagenicity, membrane lysis and cell death, alteration of enzymatic activity and metabolic events, mitochondrial dysfunction, and even cancer. Additionally, DNA adducts formation, after IR-induced DNA breakage, is a cause of blockage of DNA repair capability with an increase in cellular radiosensitivity. These may allow cellular ruin even at low IR levels. Dependent on the dose, duration of action and quality, IR plays diverse roles in biological systems.

  17. Tunable promoters in systems biology

    DEFF Research Database (Denmark)

    Mijakovic, Ivan; Petranovic, Dina; Jensen, Peter Ruhdal

    2005-01-01

    The construction of synthetic promoter libraries has represented a major breakthrough in systems biology, enabling the subtle tuning of enzyme activities. A number of tools are now available that allow the modulation of gene expression and the detection of changes in expression patterns. But, how...

  18. Systems biology solutions for biochemical production challenges

    DEFF Research Database (Denmark)

    Hansen, Anne Sofie Lærke; Lennen, Rebecca M; Sonnenschein, Nikolaus

    2017-01-01

    characterization, genome-scale metabolic modeling, and adaptive laboratory evolution can be readily deployed in metabolic engineering projects. However, high performance strains usually carry tens of genetic modifications and need to operate in challenging environmental conditions. This additional complexity......There is an urgent need to significantly accelerate the development of microbial cell factories to produce fuels and chemicals from renewable feedstocks in order to facilitate the transition to a biobased society. Methods commonly used within the field of systems biology including omics...

  19. Extending Life Concepts to Complex Systems

    Directory of Open Access Journals (Sweden)

    Jean Le Fur

    2013-01-01

    Full Text Available There is still no consensus definition of complex systems. This article explores, as a heuristic approach, the possibility of using notions associated with life as transversal concepts for defining complex systems. This approach is developed within a general classification of systems, with complex systems considered as a general ‘living things’ category and living organisms as a specialised class within this category. Concepts associated with life are first explored in the context of complex systems: birth, death and lifetime, adaptation, ontogeny and growth, reproduction. Thereafter, a refutation approach is used to test the proposed classification against a set of diverse systems, including a reference case, edge cases and immaterial complex systems. The summary of this analysis is then used to generate a definition of complex systems, based on the proposal, and within the background of cybernetics, complex adaptive systems and biology. Using notions such as ‘birth’ or ‘lifespan’ as transversal concepts may be of heuristic value for the generic characterization of complex systems, opening up new lines of research for improving their definition.

  20. Complex systems in metabolic engineering.

    Science.gov (United States)

    Winkler, James D; Erickson, Keesha; Choudhury, Alaksh; Halweg-Edwards, Andrea L; Gill, Ryan T

    2015-12-01

    Metabolic engineers manipulate intricate biological networks to build efficient biological machines. The inherent complexity of this task, derived from the extensive and often unknown interconnectivity between and within these networks, often prevents researchers from achieving desired performance. Other fields have developed methods to tackle the issue of complexity for their unique subset of engineering problems, but to date, there has not been extensive and comprehensive examination of how metabolic engineers use existing tools to ameliorate this effect on their own research projects. In this review, we examine how complexity affects engineering at the protein, pathway, and genome levels within an organism, and the tools for handling these issues to achieve high-performing strain designs. Quantitative complexity metrics and their applications to metabolic engineering versus traditional engineering fields are also discussed. We conclude by predicting how metabolic engineering practices may advance in light of an explicit consideration of design complexity. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Fourth International Conference on Complex Systems

    CERN Document Server

    Minai, Ali A; Unifying Themes in Complex Systems IV

    2008-01-01

    In June of 2002, over 500 professors, students and researchers met in Boston, Massachusetts for the Fourth International Conference on Complex Systems. The attendees represented a remarkably diverse collection of fields: biology, ecology, physics, engineering, computer science, economics, psychology and sociology, The goal of the conference was to encourage cross-fertilization between the many disciplines represented and to deepen understanding of the properties common to all complex systems. This volume contains 43 papers selected from the more than 200 presented at the conference. Topics include: cellular automata, neurology, evolution, computer science, network dynamics, and urban planning. About NECSI: For over 10 years, The New England Complex Systems Institute (NECSI) has been instrumental in the development of complex systems science and its applications. NECSI conducts research, education, knowledge dissemination, and community development around the world for the promotion of the study of complex sys...

  2. Sixth International Conference on Complex Systems

    CERN Document Server

    Minai, Ali; Bar-Yam, Yaneer; Unifying Themes in Complex Systems

    2008-01-01

    The International Conference on Complex Systems (ICCS) creates a unique atmosphere for scientists of all fields, engineers, physicians, executives, and a host of other professionals to explore the common themes and applications of complex systems science. In June 2006, 500 participants convened in Boston for the sixth ICCS, exploring an array of topics, including networks, systems biology, evolution and ecology, nonlinear dynamics and pattern formation, as well as neural, psychological, psycho-social, socio-economic, and global systems. This volume selects 77 papers from over 300 presented at the conference. With this new volume, Unifying Themes in Complex Systems continues to build common ground between the wide-ranging domains of complex systems science.

  3. Systems Biology as an Integrated Platform for Bioinformatics, Systems Synthetic Biology, and Systems Metabolic Engineering

    Science.gov (United States)

    Chen, Bor-Sen; Wu, Chia-Chou

    2013-01-01

    Systems biology aims at achieving a system-level understanding of living organisms and applying this knowledge to various fields such as synthetic biology, metabolic engineering, and medicine. System-level understanding of living organisms can be derived from insight into: (i) system structure and the mechanism of biological networks such as gene regulation, protein interactions, signaling, and metabolic pathways; (ii) system dynamics of biological networks, which provides an understanding of stability, robustness, and transduction ability through system identification, and through system analysis methods; (iii) system control methods at different levels of biological networks, which provide an understanding of systematic mechanisms to robustly control system states, minimize malfunctions, and provide potential therapeutic targets in disease treatment; (iv) systematic design methods for the modification and construction of biological networks with desired behaviors, which provide system design principles and system simulations for synthetic biology designs and systems metabolic engineering. This review describes current developments in systems biology, systems synthetic biology, and systems metabolic engineering for engineering and biology researchers. We also discuss challenges and future prospects for systems biology and the concept of systems biology as an integrated platform for bioinformatics, systems synthetic biology, and systems metabolic engineering. PMID:24709875

  4. Systems Biology as an Integrated Platform for Bioinformatics, Systems Synthetic Biology, and Systems Metabolic Engineering

    Directory of Open Access Journals (Sweden)

    Bor-Sen Chen

    2013-10-01

    Full Text Available Systems biology aims at achieving a system-level understanding of living organisms and applying this knowledge to various fields such as synthetic biology, metabolic engineering, and medicine. System-level understanding of living organisms can be derived from insight into: (i system structure and the mechanism of biological networks such as gene regulation, protein interactions, signaling, and metabolic pathways; (ii system dynamics of biological networks, which provides an understanding of stability, robustness, and transduction ability through system identification, and through system analysis methods; (iii system control methods at different levels of biological networks, which provide an understanding of systematic mechanisms to robustly control system states, minimize malfunctions, and provide potential therapeutic targets in disease treatment; (iv systematic design methods for the modification and construction of biological networks with desired behaviors, which provide system design principles and system simulations for synthetic biology designs and systems metabolic engineering. This review describes current developments in systems biology, systems synthetic biology, and systems metabolic engineering for engineering and biology researchers. We also discuss challenges and future prospects for systems biology and the concept of systems biology as an integrated platform for bioinformatics, systems synthetic biology, and systems metabolic engineering.

  5. Systems biology as an integrated platform for bioinformatics, systems synthetic biology, and systems metabolic engineering.

    Science.gov (United States)

    Chen, Bor-Sen; Wu, Chia-Chou

    2013-10-11

    Systems biology aims at achieving a system-level understanding of living organisms and applying this knowledge to various fields such as synthetic biology, metabolic engineering, and medicine. System-level understanding of living organisms can be derived from insight into: (i) system structure and the mechanism of biological networks such as gene regulation, protein interactions, signaling, and metabolic pathways; (ii) system dynamics of biological networks, which provides an understanding of stability, robustness, and transduction ability through system identification, and through system analysis methods; (iii) system control methods at different levels of biological networks, which provide an understanding of systematic mechanisms to robustly control system states, minimize malfunctions, and provide potential therapeutic targets in disease treatment; (iv) systematic design methods for the modification and construction of biological networks with desired behaviors, which provide system design principles and system simulations for synthetic biology designs and systems metabolic engineering. This review describes current developments in systems biology, systems synthetic biology, and systems metabolic engineering for engineering and biology researchers. We also discuss challenges and future prospects for systems biology and the concept of systems biology as an integrated platform for bioinformatics, systems synthetic biology, and systems metabolic engineering.

  6. Mössbauer study of some biological iron complexes

    Indian Academy of Sciences (India)

    Abstract. Some biological complexes containing iron are investigated experimentally at room temperature using the Mössbauer resonance. The complexes show quadrupole doublet and Kramer's degeneracy is found to exist. The electric field gradient, difference in s-electron densities and quadrupole coupling constant ...

  7. Towards a comprehensive understanding of emerging dynamics and function of pancreatic islets: A complex network approach. Comment on "Network science of biological systems at different scales: A review" by Gosak et al.

    Science.gov (United States)

    Loppini, Alessandro

    2018-03-01

    Complex network theory represents a comprehensive mathematical framework to investigate biological systems, ranging from sub-cellular and cellular scales up to large-scale networks describing species interactions and ecological systems. In their exhaustive and comprehensive work [1], Gosak et al. discuss several scenarios in which the network approach was able to uncover general properties and underlying mechanisms of cells organization and regulation, tissue functions and cell/tissue failure in pathology, by the study of chemical reaction networks, structural networks and functional connectivities.

  8. An ensemble approach to the evolution of complex systems

    Indian Academy of Sciences (India)

    2014-03-15

    Mar 15, 2014 ... pattern formation in biological systems, as well as being ap- plied to specific biological systems, either at the cell and tissue level or at much more macroscopic ecological scales. 3. Null models for the genesis of complex gene regulatory interactions. Let us now turn to some higher-level biological ...

  9. [Circadian rhythms and systems biology].

    Science.gov (United States)

    Goldbeter, Albert; Gérard, Claude; Leloup, Jean-Christophe

    2010-01-01

    Cellular rhythms represent a field of choice for studies in system biology. The examples of circadian rhythms and of the cell cycle show how the experimental and modeling approaches contribute to clarify the conditions in which periodic behavior spontaneously arises in regulatory networks at the cellular level. Circadian rhythms originate from intertwined positive and negative feedback loops controlling the expression of several clock genes. Models can be used to address the dynamical bases of physiological disorders related to dysfunctions of the mammalian circadian clock. The cell cycle is driven by a network of cyclin-dependent kinases (Cdks). Modeled in the form of four modules coupled through multiple regulatory interactions, the Cdk network operates in an oscillatory manner in the presence of sufficient amounts of growth factor. For circadian rhythms and the cell cycle, as for other recently observed cellular rhythms, periodic behavior represents an emergent property of biological systems related to their regulatory structure.

  10. Ten questions about systems biology

    DEFF Research Database (Denmark)

    Joyner, Michael J; Pedersen, Bente K

    2011-01-01

    In this paper we raise 'ten questions' broadly related to 'omics', the term systems biology, and why the new biology has failed to deliver major therapeutic advances for many common diseases, especially diabetes and cardiovascular disease. We argue that a fundamentally narrow and reductionist...... perspective about the contribution of genes and genetic variants to disease is a key reason 'omics' has failed to deliver the anticipated breakthroughs. We then point out the critical utility of key concepts from physiology like homeostasis, regulated systems and redundancy as major intellectual tools...... common diseases. Finally, we attempt to integrate our critique of reductionism into a broader social framework about so-called translational research in specific and the root causes of common diseases in general. Throughout we offer ideas and suggestions that might be incorporated into the current...

  11. Methods of information theory and algorithmic complexity for network biology.

    Science.gov (United States)

    Zenil, Hector; Kiani, Narsis A; Tegnér, Jesper

    2016-03-01

    We survey and introduce concepts and tools located at the intersection of information theory and network biology. We show that Shannon's information entropy, compressibility and algorithmic complexity quantify different local and global aspects of synthetic and biological data. We show examples such as the emergence of giant components in Erdös-Rényi random graphs, and the recovery of topological properties from numerical kinetic properties simulating gene expression data. We provide exact theoretical calculations, numerical approximations and error estimations of entropy, algorithmic probability and Kolmogorov complexity for different types of graphs, characterizing their variant and invariant properties. We introduce formal definitions of complexity for both labeled and unlabeled graphs and prove that the Kolmogorov complexity of a labeled graph is a good approximation of its unlabeled Kolmogorov complexity and thus a robust definition of graph complexity. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Complex engineering systems science meets technology

    CERN Document Server

    Minai, Ali A; Bar-Yam, Yaneer

    2006-01-01

    Every time that we take money out of an ATM, surf the internet or simply turn on a light switch, we enjoy the benefits of complex engineered systems. Systems like power grids and global communication networks are so ubiquitous in our daily lives that we usually take them for granted, only noticing them when they break down. But how do such amazing technologies and infrastructures come to be what they are? How are these systems designed? How do distributed networks work? How are they made to respond rapidly in 'real time'? And as the demands that we place on these systems become increasingly complex, are traditional systems-engineering practices still relevant? This volume examines the difficulties that arise in creating highly complex engineered systems and new approaches that are being adopted. Topics addressed range from the formal representation and classification of distributed networked systems to revolutionary engineering practices inspired by biological evolution. By bringing together the latest resear...

  13. Biological Potential in Serpentinizing Systems

    Science.gov (United States)

    Hoehler, Tori M.

    2016-01-01

    Generation of the microbial substrate hydrogen during serpentinization, the aqueous alteration of ultramafic rocks, has focused interest on the potential of serpentinizing systems to support biological communities or even the origin of life. However the process also generates considerable alkalinity, a challenge to life, and both pH and hydrogen concentrations vary widely across natural systems as a result of different host rock and fluid composition and differing physical and hydrogeologic conditions. Biological potential is expected to vary in concert. We examined the impact of such variability on the bioenergetics of an example metabolism, methanogenesis, using a cell-scale reactive transport model to compare rates of metabolic energy generation as a function of physicochemical environment. Potential rates vary over more than 5 orders of magnitude, including bioenergetically non-viable conditions, across the range of naturally occurring conditions. In parallel, we assayed rates of hydrogen metabolism in wells associated with the actively serpentinizing Coast Range Ophiolite, which includes conditions more alkaline and considerably less reducing than is typical of serpentinizing systems. Hydrogen metabolism is observed at pH approaching 12 but, consistent with the model predictions, biological methanogenesis is not observed.

  14. Dermal tumorigen PAH and complex mixtures for biological research

    International Nuclear Information System (INIS)

    Griest, W.H.; Guerin, M.R.; Ho, C.

    1985-01-01

    Thirteen commercially available, commonly reported four-five ring dermal tumorigen PAHs, were determined in a set of complex mixtures consisting of crude and upgraded coal liquids, and petroleum crude oils and their distillate fractions. Semi-preparative scale, normal phase high performance liquid chromatographic fractionation followed by capillary column gas chromatography or gas chromatography-mass spectroscopy were used for the measurements. Deuterated or carbon-14 labeled PAH served as internal standards or allowed recovery corrections. Approaches for the preparation and measurement of radiolabeled PAH were examined to provide chemical probes for biological study. Synthetic routes for production of 14 C labeled dihydrobenzo[a]pyrene and 14 C- or 3 H 10-azabenzo[a]pyrene are being studied to provide tracers for fundamental studies in tracheal transplant and skin penetration systems. (DT)

  15. Network science of biological systems at different scales: A review

    Science.gov (United States)

    Gosak, Marko; Markovič, Rene; Dolenšek, Jurij; Slak Rupnik, Marjan; Marhl, Marko; Stožer, Andraž; Perc, Matjaž

    2018-03-01

    Network science is today established as a backbone for description of structure and function of various physical, chemical, biological, technological, and social systems. Here we review recent advances in the study of complex biological systems that were inspired and enabled by methods of network science. First, we present

  16. Anion binding in biological systems

    Energy Technology Data Exchange (ETDEWEB)

    Feiters, Martin C [Department of Organic Chemistry, Institute for Molecules and Materials, Faculty of Science, Radboud University Nijmegen, Heyendaalseweg 135, 6525 AJ Nijmegen (Netherlands); Meyer-Klaucke, Wolfram [EMBL Hamburg Outstation at DESY, Notkestrasse 85, D-22607 Hamburg (Germany); Kostenko, Alexander V; Soldatov, Alexander V [Faculty of Physics, Southern Federal University, Sorge 5, Rostov-na-Donu, 344090 (Russian Federation); Leblanc, Catherine; Michel, Gurvan; Potin, Philippe [Centre National de la Recherche Scientifique and Universite Pierre et Marie Curie Paris-VI, Station Biologique de Roscoff, Place Georges Teissier, BP 74, F-29682 Roscoff cedex, Bretagne (France); Kuepper, Frithjof C [Scottish Association for Marine Science, Dunstaffnage Marine Laboratory, Oban, Argyll PA37 1QA, Scotland (United Kingdom); Hollenstein, Kaspar; Locher, Kaspar P [Institute of Molecular Biology and Biophysics, ETH Zuerich, Schafmattstrasse 20, Zuerich, 8093 (Switzerland); Bevers, Loes E; Hagedoorn, Peter-Leon; Hagen, Wilfred R, E-mail: m.feiters@science.ru.n [Department of Biotechnology, Delft University of Technology, Julianalaan 67, 2628 BC Delft (Netherlands)

    2009-11-15

    We compare aspects of biological X-ray absorption spectroscopy (XAS) studies of cations and anions, and report on some examples of anion binding in biological systems. Brown algae such as Laminaria digitata (oarweed) are effective accumulators of I from seawater, with tissue concentrations exceeding 50 mM, and the vanadate-containing enzyme haloperoxidase is implicated in halide accumulation. We have studied the chemical state of iodine and its biological role in Laminaria at the I K edge, and bromoperoxidase from Ascophyllum nodosum (knotted wrack) at the Br K edge. Mo is essential for many forms of life; W only for certain archaea, such as Archaeoglobus fulgidus and the hyperthermophilic archaeon Pyrococcus furiosus, and some bacteria. The metals are bound and transported as their oxo-anions, molybdate and tungstate, which are similar in size. The transport protein WtpA from P. furiosus binds tungstate more strongly than molybdate, and is related in sequence to Archaeoglobus fulgidus ModA, of which a crystal structure is known. We have measured A. fulgidus ModA with tungstate at the W L{sub 3} (2p{sub 3/2}) edge, and compared the results with the refined crystal structure. XAS studies of anion binding are feasible even if only weak interactions are present, are biologically relevant, and give new insights in the spectroscopy.

  17. Anion binding in biological systems

    International Nuclear Information System (INIS)

    Feiters, Martin C; Meyer-Klaucke, Wolfram; Kostenko, Alexander V; Soldatov, Alexander V; Leblanc, Catherine; Michel, Gurvan; Potin, Philippe; Kuepper, Frithjof C; Hollenstein, Kaspar; Locher, Kaspar P; Bevers, Loes E; Hagedoorn, Peter-Leon; Hagen, Wilfred R

    2009-01-01

    We compare aspects of biological X-ray absorption spectroscopy (XAS) studies of cations and anions, and report on some examples of anion binding in biological systems. Brown algae such as Laminaria digitata (oarweed) are effective accumulators of I from seawater, with tissue concentrations exceeding 50 mM, and the vanadate-containing enzyme haloperoxidase is implicated in halide accumulation. We have studied the chemical state of iodine and its biological role in Laminaria at the I K edge, and bromoperoxidase from Ascophyllum nodosum (knotted wrack) at the Br K edge. Mo is essential for many forms of life; W only for certain archaea, such as Archaeoglobus fulgidus and the hyperthermophilic archaeon Pyrococcus furiosus, and some bacteria. The metals are bound and transported as their oxo-anions, molybdate and tungstate, which are similar in size. The transport protein WtpA from P. furiosus binds tungstate more strongly than molybdate, and is related in sequence to Archaeoglobus fulgidus ModA, of which a crystal structure is known. We have measured A. fulgidus ModA with tungstate at the W L 3 (2p 3/2 ) edge, and compared the results with the refined crystal structure. XAS studies of anion binding are feasible even if only weak interactions are present, are biologically relevant, and give new insights in the spectroscopy.

  18. Anion binding in biological systems

    Science.gov (United States)

    Feiters, Martin C.; Meyer-Klaucke, Wolfram; Kostenko, Alexander V.; Soldatov, Alexander V.; Leblanc, Catherine; Michel, Gurvan; Potin, Philippe; Küpper, Frithjof C.; Hollenstein, Kaspar; Locher, Kaspar P.; Bevers, Loes E.; Hagedoorn, Peter-Leon; Hagen, Wilfred R.

    2009-11-01

    We compare aspects of biological X-ray absorption spectroscopy (XAS) studies of cations and anions, and report on some examples of anion binding in biological systems. Brown algae such as Laminaria digitata (oarweed) are effective accumulators of I from seawater, with tissue concentrations exceeding 50 mM, and the vanadate-containing enzyme haloperoxidase is implicated in halide accumulation. We have studied the chemical state of iodine and its biological role in Laminaria at the I K edge, and bromoperoxidase from Ascophyllum nodosum (knotted wrack) at the Br K edge. Mo is essential for many forms of life; W only for certain archaea, such as Archaeoglobus fulgidus and the hyperthermophilic archaeon Pyrococcus furiosus, and some bacteria. The metals are bound and transported as their oxo-anions, molybdate and tungstate, which are similar in size. The transport protein WtpA from P. furiosus binds tungstate more strongly than molybdate, and is related in sequence to Archaeoglobus fulgidus ModA, of which a crystal structure is known. We have measured A. fulgidus ModA with tungstate at the W L3 (2p3/2) edge, and compared the results with the refined crystal structure. XAS studies of anion binding are feasible even if only weak interactions are present, are biologically relevant, and give new insights in the spectroscopy.

  19. Mapping complex traits as a dynamic system

    Science.gov (United States)

    Sun, Lidan; Wu, Rongling

    2015-06-01

    Despite increasing emphasis on the genetic study of quantitative traits, we are still far from being able to chart a clear picture of their genetic architecture, given an inherent complexity involved in trait formation. A competing theory for studying such complex traits has emerged by viewing their phenotypic formation as a "system" in which a high-dimensional group of interconnected components act and interact across different levels of biological organization from molecules through cells to whole organisms. This system is initiated by a machinery of DNA sequences that regulate a cascade of biochemical pathways to synthesize endophenotypes and further assemble these endophenotypes toward the end-point phenotype in virtue of various developmental changes. This review focuses on a conceptual framework for genetic mapping of complex traits by which to delineate the underlying components, interactions and mechanisms that govern the system according to biological principles and understand how these components function synergistically under the control of quantitative trait loci (QTLs) to comprise a unified whole. This framework is built by a system of differential equations that quantifies how alterations of different components lead to the global change of trait development and function, and provides a quantitative and testable platform for assessing the multiscale interplay between QTLs and development. The method will enable geneticists to shed light on the genetic complexity of any biological system and predict, alter or engineer its physiological and pathological states.

  20. Characterization and reactivity of the weakly bound complexes of the [H, N, S]{sup −} anionic system with astrophysical and biological implications

    Energy Technology Data Exchange (ETDEWEB)

    Trabelsi, T.; Ajili, Y.; Ben Yaghlane, S.; Jaidane, N.-E. [Laboratoire de Spectroscopie Atomique, Moléculaire et Applications–LSAMA, Université de Tunis El Manar, Tunis (Tunisia); Mogren Al-Mogren, M. [Chemistry Department, Faculty of Science, King Saud University, P.O. Box 2455, Riyadh 11451 (Saudi Arabia); Francisco, J. S. [Department of Chemistry and Department of Earth and Atmospheric Sciences, Purdue University, West Lafayette, Indiana 47906 (United States); Hochlaf, M., E-mail: hochlaf@univ-mlv.fr [Laboratoire Modélisation et Simulation Multi Echelle, Université Paris-Est, MSME UMR 8208 CNRS, 5 Blvd. Descartes, 77454 Marne-la-Vallée (France)

    2015-07-21

    We investigate the lowest electronic states of doublet and quartet spin multiplicity states of HNS{sup −} and HSN{sup −} together with their parent neutral triatomic molecules. Computations were performed using highly accurate ab initio methods with a large basis set. One-dimensional cuts of the full-dimensional potential energy surfaces (PESs) along the interatomic distances and bending angle are presented for each isomer. Results show that the ground anionic states are stable with respect to the electron detachment process and that the long range parts of the PESs correlating to the SH{sup −} + N, SN{sup −} + H, SN + H{sup −}, NH + S{sup −}, and NH{sup −} + S are bound. In addition, we predict the existence of long-lived weakly bound anionic complexes that can be formed after cold collisions between SN{sup −} and H or SH{sup −} and N. The implications for the reactivity of these species are discussed; specifically, it is shown that the reactions involving SH{sup −}, SN{sup −}, and NH{sup −} lead either to the formation of HNS{sup −} or HSN{sup −} in their electronic ground states or to autodetachment processes. Thus, providing an explanation for why the anions, SH{sup −}, SN{sup −}, and NH{sup −}, have limiting detectability in astrophysical media despite the observation of their corresponding neutral species. In a biological context, we suggest that HSN{sup −} and HNS{sup −} should be incorporated into H{sub 2}S-assisted heme-catalyzed reduction mechanism of nitrites in vivo.

  1. Systems Biology for Organotypic Cell Cultures

    Energy Technology Data Exchange (ETDEWEB)

    Grego, Sonia [RTI International, Research Triangle Park, NC (United States); Dougherty, Edward R. [Texas A & M Univ., College Station, TX (United States); Alexander, Francis J. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Auerbach, Scott S. [National Inst. of Environmental Health Sciences, Research Triangle Park, NC (United States); Berridge, Brian R. [GlaxoSmithKline, Research Triangle Park, NC (United States); Bittner, Michael L. [Translational Genomics Research Inst., Phoenix, AZ (United States); Casey, Warren [National Inst. of Environmental Health Sciences, Research Triangle Park, NC (United States); Cooley, Philip C. [RTI International, Research Triangle Park, NC (United States); Dash, Ajit [HemoShear Therapeutics, Charlottesville, VA (United States); Ferguson, Stephen S. [National Inst. of Environmental Health Sciences, Research Triangle Park, NC (United States); Fennell, Timothy R. [RTI International, Research Triangle Park, NC (United States); Hawkins, Brian T. [RTI International, Research Triangle Park, NC (United States); Hickey, Anthony J. [RTI International, Research Triangle Park, NC (United States); Kleensang, Andre [Johns Hopkins Univ., Baltimore, MD (United States). Center for Alternatives to Animal Testing; Liebman, Michael N. [IPQ Analytics, Kennett Square, PA (United States); Martin, Florian [Phillip Morris International, Neuchatel (Switzerland); Maull, Elizabeth A. [National Inst. of Environmental Health Sciences, Research Triangle Park, NC (United States); Paragas, Jason [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Qiao, Guilin [Defense Threat Reduction Agency, Ft. Belvoir, VA (United States); Ramaiahgari, Sreenivasa [National Inst. of Environmental Health Sciences, Research Triangle Park, NC (United States); Sumner, Susan J. [RTI International, Research Triangle Park, NC (United States); Yoon, Miyoung [The Hamner Inst. for Health Sciences, Research Triangle Park, NC (United States); ScitoVation, Research Triangle Park, NC (United States)

    2016-08-04

    Translating in vitro biological data into actionable information related to human health holds the potential to improve disease treatment and risk assessment of chemical exposures. While genomics has identified regulatory pathways at the cellular level, translation to the organism level requires a multiscale approach accounting for intra-cellular regulation, inter-cellular interaction, and tissue/organ-level effects. Tissue-level effects can now be probed in vitro thanks to recently developed systems of three-dimensional (3D), multicellular, “organotypic” cell cultures, which mimic functional responses of living tissue. However, there remains a knowledge gap regarding interactions across different biological scales, complicating accurate prediction of health outcomes from molecular/genomic data and tissue responses. Systems biology aims at mathematical modeling of complex, non-linear biological systems. We propose to apply a systems biology approach to achieve a computational representation of tissue-level physiological responses by integrating empirical data derived from organotypic culture systems with computational models of intracellular pathways to better predict human responses. Successful implementation of this integrated approach will provide a powerful tool for faster, more accurate and cost-effective screening of potential toxicants and therapeutics. On September 11, 2015, an interdisciplinary group of scientists, engineers, and clinicians gathered for a workshop in Research Triangle Park, North Carolina, to discuss this ambitious goal. Participants represented laboratory-based and computational modeling approaches to pharmacology and toxicology, as well as the pharmaceutical industry, government, non-profits, and academia. Discussions focused on identifying critical system perturbations to model, the computational tools required, and the experimental approaches best suited to generating key data. This consensus report summarizes the discussions held.

  2. Discovery of Chemical Toxicity via Biological Networks and Systems Biology

    Energy Technology Data Exchange (ETDEWEB)

    Perkins, Edward; Habib, Tanwir; Guan, Xin; Escalon, Barbara; Falciani, Francesco; Chipman, J.K.; Antczak, Philipp; Edwards, Stephen; Taylor, Ronald C.; Vulpe, Chris; Loguinov, Alexandre; Van Aggelen, Graham; Villeneuve, Daniel L.; Garcia-Reyero, Natalia

    2010-09-30

    Both soldiers and animals are exposed to many chemicals as the result of military activities. Tools are needed to understand the hazards and risks that chemicals and new materials pose to soldiers and the environment. We have investigated the potential of global gene regulatory networks in understanding the impact of chemicals on reproduction. We characterized effects of chemicals on ovaries of the model animal system, the Fathead minnow (Pimopheles promelas) connecting chemical impacts on gene expression to circulating blood levels of the hormones testosterone and estradiol in addition to the egg yolk protein vitellogenin. We describe the application of reverse engineering complex interaction networks from high dimensional gene expression data to characterize chemicals that disrupt the hypothalamus-pituitary-gonadal endocrine axis that governs reproduction in fathead minnows. The construction of global gene regulatory networks provides deep insights into how drugs and chemicals effect key organs and biological pathways.

  3. Morphogenetic Engineering Toward Programmable Complex Systems

    CERN Document Server

    Sayama, Hiroki; Michel, Olivier

    2012-01-01

    Generally, spontaneous pattern formation phenomena are random and repetitive, whereas elaborate devices are the deterministic product of human design. Yet, biological organisms and collective insect constructions are exceptional examples of complex systems that are both self-organized and architectural.   This book is the first initiative of its kind toward establishing a new field of research, Morphogenetic Engineering, to explore the modeling and implementation of “self-architecturing” systems. Particular emphasis is placed on the programmability and computational abilities of self-organization, properties that are often underappreciated in complex systems science—while, conversely, the benefits of self-organization are often underappreciated in engineering methodologies.   Altogether, the aim of this work is to provide a framework for and examples of a larger class of “self-architecturing” systems, while addressing fundamental questions such as   > How do biological organisms carry out morphog...

  4. Nonlinear dynamics in biological systems

    CERN Document Server

    Carballido-Landeira, Jorge

    2016-01-01

    This book presents recent research results relating to applications of nonlinear dynamics, focusing specifically on four topics of wide interest: heart dynamics, DNA/RNA, cell mobility, and proteins. The book derives from the First BCAM Workshop on Nonlinear Dynamics in Biological Systems, held in June 2014 at the Basque Center of Applied Mathematics (BCAM). At this international meeting, researchers from different but complementary backgrounds, including molecular dynamics, physical chemistry, bio-informatics and biophysics, presented their most recent results and discussed the future direction of their studies using theoretical, mathematical modeling and experimental approaches. Such was the level of interest stimulated that the decision was taken to produce this publication, with the organizers of the event acting as editors. All of the contributing authors are researchers working on diverse biological problems that can be approached using nonlinear dynamics. The book will appeal especially to applied math...

  5. Management of complex dynamical systems

    Science.gov (United States)

    MacKay, R. S.

    2018-02-01

    Complex dynamical systems are systems with many interdependent components which evolve in time. One might wish to control their trajectories, but a more practical alternative is to control just their statistical behaviour. In many contexts this would be both sufficient and a more realistic goal, e.g. climate and socio-economic systems. I refer to it as ‘management’ of complex dynamical systems. In this paper, some mathematics for management of complex dynamical systems is developed in the weakly dependent regime, and questions are posed for the strongly dependent regime.

  6. Distributed redundancy and robustness in complex systems

    KAUST Repository

    Randles, Martin

    2011-03-01

    The uptake and increasing prevalence of Web 2.0 applications, promoting new large-scale and complex systems such as Cloud computing and the emerging Internet of Services/Things, requires tools and techniques to analyse and model methods to ensure the robustness of these new systems. This paper reports on assessing and improving complex system resilience using distributed redundancy, termed degeneracy in biological systems, to endow large-scale complicated computer systems with the same robustness that emerges in complex biological and natural systems. However, in order to promote an evolutionary approach, through emergent self-organisation, it is necessary to specify the systems in an \\'open-ended\\' manner where not all states of the system are prescribed at design-time. In particular an observer system is used to select robust topologies, within system components, based on a measurement of the first non-zero Eigen value in the Laplacian spectrum of the components\\' network graphs; also known as the algebraic connectivity. It is shown, through experimentation on a simulation, that increasing the average algebraic connectivity across the components, in a network, leads to an increase in the variety of individual components termed distributed redundancy; the capacity for structurally distinct components to perform an identical function in a particular context. The results are applied to a specific application where active clustering of like services is used to aid load balancing in a highly distributed network. Using the described procedure is shown to improve performance and distribute redundancy. © 2010 Elsevier Inc.

  7. Tunable promoters in systems biology

    DEFF Research Database (Denmark)

    Mijakovic, Ivan; Petranovic, Dina; Jensen, Peter Ruhdal

    2005-01-01

    The construction of synthetic promoter libraries has represented a major breakthrough in systems biology, enabling the subtle tuning of enzyme activities. A number of tools are now available that allow the modulation of gene expression and the detection of changes in expression patterns. But, how...... does one choose the correct promoter and what are the appropriate methods for reading promoter strength? Furthermore, how fine should the tuning of gene expression be for some specific applications and how can the simultaneous and individual tuning of multiple genes be achieved? Some recent studies...

  8. Decision Making in Biological Systems

    DEFF Research Database (Denmark)

    Tian, Chengzhe

    -dormancy transition is primarily mediated by (p)ppGpp fluctuation. In the second topic, we discuss the transition paths between two stable steady states. We construct a simple model of coupled bistable gene circuits and demonstrate the possibility of bifurcation of transition path in biology. We then construct...... a theory to predict whether a general coupled bistable system exhibits bifurcated path or not and verify the theory through numerical simulation. We also show that a primary function of bifurcated paths is to facilitate transition by lowering the associated action. In the third topic, we discuss...

  9. Systems biology of Microbial Communities

    Energy Technology Data Exchange (ETDEWEB)

    Navid, A; Ghim, C; Fenley, A; Yoon, S; Lee, S; Almaas, E

    2008-04-11

    Microbes exist naturally in a wide range of environments, spanning the extremes of high acidity and high temperature to soil and the ocean, in communities where their interactions are significant. We present a practical discussion of three different approaches for modeling microbial communities: rate equations, individual-based modeling, and population dynamics. We illustrate the approaches with detailed examples. Each approach is best fit to different levels of system representation, and they have different needs for detailed biological input. Thus, this set of approaches is able to address the operation and function of microbial communities on a wide range of organizational levels.

  10. Engineering in complex systems.

    Science.gov (United States)

    Bujara, Matthias; Panke, Sven

    2010-10-01

    The implementation of the engineering design cycle of measure, model, manipulate would drastically enhance the success rate of biotechnological designs. Recent progress for the three elements suggests that the scope of the traditional engineering paradigm in biotechnology is expanding. Substantial advances were made in dynamic in vivo analysis of metabolism, which is essential for the accurate prediction of metabolic pathway behavior. Novel methods that require variable degrees of system knowledge facilitate metabolic system manipulation. The combinatorial testing of pre-characterized parts is particularly promising, because it can profit from automation and limits the search space. Finally, conceptual advances in orthogonalizing cells should enhance the reliability of engineering designs in the future. Coupled to improved in silico models of metabolism, these advances should allow a more rational design of metabolic systems. Copyright © 2010 Elsevier Ltd. All rights reserved.

  11. Dynamical systems in population biology

    CERN Document Server

    Zhao, Xiao-Qiang

    2017-01-01

    This research monograph provides an introduction to the theory of nonautonomous semiflows with applications to population dynamics. It develops dynamical system approaches to various evolutionary equations such as difference, ordinary, functional, and partial differential equations, and pays more attention to periodic and almost periodic phenomena. The presentation includes persistence theory, monotone dynamics, periodic and almost periodic semiflows, basic reproduction ratios, traveling waves, and global analysis of prototypical population models in ecology and epidemiology. Research mathematicians working with nonlinear dynamics, particularly those interested in applications to biology, will find this book useful. It may also be used as a textbook or as supplementary reading for a graduate special topics course on the theory and applications of dynamical systems. Dr. Xiao-Qiang Zhao is a University Research Professor at Memorial University of Newfoundland, Canada. His main research interests involve applied...

  12. Physical and biological determinants of collective behavioural dynamics in complex systems: pulling chain formation in the nest-weaving ant Oecophylla smaragdina.

    Directory of Open Access Journals (Sweden)

    Thomas Bochynek

    Full Text Available The evolution of nest weaving, the inclusion of larval silk in the nest walls, is considered one of the pinnacles of cooperative behaviour in social insects. Within the four ant genera in which this has evolved, Oecophylla are unique in being the only group that precedes the deposition of larval silk by actively manipulating the leaf substrate to form a nest chamber. Here we provide the first descriptions of the manipulation process within a complex-systems framework. Substrate manipulation involves individual ants selecting, grasping and attempting to pull the edge of the substrate. These individuals are then joined by nest mates at the work site, who either select a site beside the first individual or grasp the body of the first or preceding worker to form a chain of pulling ants that together drag and bend the substrate. Site selection by individual workers is not random when confronted with an artificial leaf, with individuals more likely to grasp a substrate at its tip rather than along a more broad edge. The activity of additional individuals is also not random, with their activity being grouped in both space and time. Additional individuals are more likely to join an existing biting individual or pulling group. The positive feedback associated with the early stages of pulling behaviour appears typical for many of the collective actions observed in social insects.

  13. Atomic switch networks as complex adaptive systems

    Science.gov (United States)

    Scharnhorst, Kelsey S.; Carbajal, Juan P.; Aguilera, Renato C.; Sandouk, Eric J.; Aono, Masakazu; Stieg, Adam Z.; Gimzewski, James K.

    2018-03-01

    Complexity is an increasingly crucial aspect of societal, environmental and biological phenomena. Using a dense unorganized network of synthetic synapses it is shown that a complex adaptive system can be physically created on a microchip built especially for complex problems. These neuro-inspired atomic switch networks (ASNs) are a dynamic system with inherent and distributed memory, recurrent pathways, and up to a billion interacting elements. We demonstrate key parameters describing self-organized behavior such as non-linearity, power law dynamics, and multistate switching regimes. Device dynamics are then investigated using a feedback loop which provides control over current and voltage power-law behavior. Wide ranging prospective applications include understanding and eventually predicting future events that display complex emergent behavior in the critical regime.

  14. Interdisciplinary problem-solving: emerging modes in integrative systems biology

    NARCIS (Netherlands)

    MacLeod, Miles Alexander James; Nersessian, Nancy J.

    2016-01-01

    Integrative systems biology is an emerging field that attempts to integrate computation, applied mathematics, engineering concepts and methods, and biological experimentation in order to model large-scale complex biochemical networks. The field is thus an important contemporary instance of an

  15. Biological activities of some Fluoroquinolones-metal complexes ...

    African Journals Online (AJOL)

    Background: Metal ions play a vital role in the design of more biologically active drugs. Aim: The paper reviewed the antimicrobial, toxicological and DNA cleavage studies of some synthesized metal complexes of fluoroquinolone antibiotics. Materials and Methods: Literature searches were done using scientific databases.

  16. European Conference on Complex Systems

    CERN Document Server

    Pellegrini, Francesco; Caldarelli, Guido; Merelli, Emanuela

    2016-01-01

    This work contains a stringent selection of extended contributions presented at the meeting of 2014 and its satellite meetings, reflecting scope, diversity and richness of research areas in the field, both fundamental and applied. The ECCS meeting, held under the patronage of the Complex Systems Society, is an annual event that has become the leading European conference devoted to complexity science. It offers cutting edge research and unique opportunities to study novel scientific approaches in a multitude of application areas. ECCS'14, its eleventh occurrence, took place in Lucca, Italy. It gathered some 650 scholars representing a wide range of topics relating to complex systems research, with emphasis on interdisciplinary approaches. The editors are among the best specialists in the area. The book is of great interest to scientists, researchers and graduate students in complexity, complex systems and networks.

  17. Anomaly Detection for Complex Systems

    Data.gov (United States)

    National Aeronautics and Space Administration — In performance maintenance in large, complex systems, sensor information from sub-components tends to be readily available, and can be used to make predictions about...

  18. Third International Conference on Complex Systems

    CERN Document Server

    Minai, Ali A; Unifying Themes in Complex Systems

    2006-01-01

    In recent years, scientists have applied the principles of complex systems science to increasingly diverse fields. The results have been nothing short of remarkable: their novel approaches have provided answers to long-standing questions in biology, ecology, physics, engineering, computer science, economics, psychology and sociology. The Third International Conference on Complex Systems attracted over 400 researchers from around the world. The conference aimed to encourage cross-fertilization between the many disciplines represented and to deepen our understanding of the properties common to all complex systems. This volume contains selected transcripts from presentations given at the conference. Speakers include: Chris Adami, Kenneth Arrow, Michel Baranger, Dan Braha, Timothy Buchman, Michael Caramanis, Kathleen Carley, Greg Chaitin, David Clark, Jack Cohen, Jim Collins, George Cowan, Clay Easterly, Steven Eppinger, Irving Epstein, Dan Frey, Ary Goldberger, Helen Harte, Leroy Hood, Don Ingber, Atlee Jackson,...

  19. Decentralized control of complex systems

    CERN Document Server

    Siljak, Dragoslav D

    2011-01-01

    Complex systems require fast control action in response to local input, and perturbations dictate the use of decentralized information and control structures. This much-cited reference book explores the approaches to synthesizing control laws under decentralized information structure constraints.Starting with a graph-theoretic framework for structural modeling of complex systems, the text presents results related to robust stabilization via decentralized state feedback. Subsequent chapters explore optimization, output feedback, the manipulative power of graphs, overlapping decompositions and t

  20. Fostering synergy between cell biology and systems biology.

    Science.gov (United States)

    Eddy, James A; Funk, Cory C; Price, Nathan D

    2015-08-01

    In the shared pursuit of elucidating detailed mechanisms of cell function, systems biology presents a natural complement to ongoing efforts in cell biology. Systems biology aims to characterize biological systems through integrated and quantitative modeling of cellular information. The process of model building and analysis provides value through synthesizing and cataloging information about cells and molecules, predicting mechanisms and identifying generalizable themes, generating hypotheses and guiding experimental design, and highlighting knowledge gaps and refining understanding. In turn, incorporating domain expertise and experimental data is crucial for building towards whole cell models. An iterative cycle of interaction between cell and systems biologists advances the goals of both fields and establishes a framework for mechanistic understanding of the genome-to-phenome relationship. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

  1. Stochastic transport processes in discrete biological systems

    CERN Document Server

    Frehland, Eckart

    1982-01-01

    These notes are in part based on a course for advanced students in the applications of stochastic processes held in 1978 at the University of Konstanz. These notes contain the results of re­ cent studies on the stochastic description of ion transport through biological membranes. In particular, they serve as an introduction to an unified theory of fluctuations in complex biological transport systems. We emphasize that the subject of this volume is not to introduce the mathematics of stochastic processes but to present a field of theoretical biophysics in which stochastic methods are important. In the last years the study of membrane noise has become an important method in biophysics. Valuable information on the ion transport mechanisms in membranes can be obtained from noise analysis. A number of different processes such as the opening and closing of ion channels have been shown to be sources of the measured current or voltage fluctuations. Bio­ logical 'transport systems can be complex. For example, the tr...

  2. Editorial overview : Systems biology for biotechnology

    NARCIS (Netherlands)

    Heinemann, Matthias; Pilpel, Yitzhak

    About 15 years ago, systems biology was introduced as a novel approach to biological research. On the one side, its introduction was a result of the recognition that through solely the reductionist approach, we would ulti- mately not be able to understand how biological systems function as a whole.

  3. Morphogenesis and pattern formation in biological systems experiments and models

    CERN Document Server

    Noji, Sumihare; Ueno, Naoto; Maini, Philip

    2003-01-01

    A central goal of current biology is to decode the mechanisms that underlie the processes of morphogenesis and pattern formation. Concerned with the analysis of those phenomena, this book covers a broad range of research fields, including developmental biology, molecular biology, plant morphogenesis, ecology, epidemiology, medicine, paleontology, evolutionary biology, mathematical biology, and computational biology. In Morphogenesis and Pattern Formation in Biological Systems: Experiments and Models, experimental and theoretical aspects of biology are integrated for the construction and investigation of models of complex processes. This collection of articles on the latest advances by leading researchers not only brings together work from a wide spectrum of disciplines, but also provides a stepping-stone to the creation of new areas of discovery.

  4. Development of a General Modeling Framework for Investigating Complex Interactions among Biological and Physical Ecosystem Dynamics

    Science.gov (United States)

    Bennett, C.; Poole, G. C.; Kimball, J. S.; Stanford, J. A.; O'Daniel, S. J.; Mertes, L. A.

    2005-05-01

    Historically, physical scientists have developed models with highly accurate governing equations, while biologists have excelled at abstraction (the strategic simplification of system complexity). These different modeling paradigms yield biological (e.g. food web) and physical (e.g. hydrologic) models that can be difficult to integrate. Complex biological dynamics may be impossible to represent with governing equations. Conversely, physical processes may be oversimplified in biological models. Using agent-based modeling, a technique applied widely in social sciences and economics, we are developing a general modeling system to integrate accurate representations of physical dynamics such as water and heat flux with abstracted biological processes such as nutrient transformations. The modeling system represents an ecosystem as a complex integrated network of intelligent physical and biological "agents" that store, transform, and trade ecosystem resources (e.g., water, heat, nutrients, carbon) using equations that describe either abstracted concepts and/or physical laws. The modular design of the system allows resource submodels to be developed independently and installed into the simulation architecture. The modeling system provides a useful heuristic tool to support integrated physical and biological research topics, such as the influence of hydrologic dynamics and spatio-temporal physical heterogeneity on trophic (food web) dynamics and/or nutrient cycling.

  5. Magnetic Actuation of Biological Systems

    Science.gov (United States)

    Lauback, Stephanie D.

    Central to the advancement of many biomedical and nanotechnology capabilities is the capacity to precisely control the motion of micro and nanostructures. These applications range from single molecule experiments to cell isolation and separation, to drug delivery and nanomachine manipulation. This dissertation focuses on actuation of biological micro- and nano-entities through the use of weak external magnetic fields, superparamagnetic beads, and ferromagnetic thin films. The magnetic platform presents an excellent method for actuation of biological systems due to its ability to directly control the motion of an array of micro and nanostructures in real-time with calibrated picoNewton forces. The energy landscape of two ferromagnetic thin film patterns (disks and zigzag wires) is experimentally explored and compared to corresponding theoretical models to quantify the applied forces and trajectories of superparamagnetic beads due to the magnetic traps. A magnetic method to directly actuate DNA nanomachines in real-time with nanometer resolution and sub-second response times using micromagnetic control was implemented through the use of stiff DNA micro-levers which bridged the large length scale mismatch between the micro-actuator and the nanomachine. Compared to current alternative methods which are limited in the actuation speeds and the number of reconfiguration states of DNA constructs, this magnetic approach enables fast actuation (˜ milliseconds) and reconfigurable conformations achieved through a continuous range of finely tuned steps. The system was initially tested through actuation of the stiff arm tethered to the surface, and two prototype DNA nanomachines (rotor and hinge) were successfully actuated using the stiff mechanical lever. These results open new possibilities in the development of functional robotic systems at the molecular scale. In exploiting the use of DNA stiff levers, a new technique was also developed to investigate the emergence of the

  6. Finding optimal interaction interface alignments between biological complexes

    KAUST Repository

    Cui, Xuefeng

    2015-06-13

    Motivation: Biological molecules perform their functions through interactions with other molecules. Structure alignment of interaction interfaces between biological complexes is an indispensable step in detecting their structural similarities, which are keys to understanding their evolutionary histories and functions. Although various structure alignment methods have been developed to successfully access the similarities of protein structures or certain types of interaction interfaces, existing alignment tools cannot directly align arbitrary types of interfaces formed by protein, DNA or RNA molecules. Specifically, they require a \\'blackbox preprocessing\\' to standardize interface types and chain identifiers. Yet their performance is limited and sometimes unsatisfactory. Results: Here we introduce a novel method, PROSTA-inter, that automatically determines and aligns interaction interfaces between two arbitrary types of complex structures. Our method uses sequentially remote fragments to search for the optimal superimposition. The optimal residue matching problem is then formulated as a maximum weighted bipartite matching problem to detect the optimal sequence order-independent alignment. Benchmark evaluation on all non-redundant protein-DNA complexes in PDB shows significant performance improvement of our method over TM-align and iAlign (with the \\'blackbox preprocessing\\'). Two case studies where our method discovers, for the first time, structural similarities between two pairs of functionally related protein-DNA complexes are presented. We further demonstrate the power of our method on detecting structural similarities between a protein-protein complex and a protein-RNA complex, which is biologically known as a protein-RNA mimicry case. © The Author 2015. Published by Oxford University Press.

  7. Yeast systems biology to unravel the network of life

    DEFF Research Database (Denmark)

    Mustacchi, Roberta; Hohmann, S; Nielsen, Jens

    2006-01-01

    Systems biology focuses on obtaining a quantitative description of complete biological systems, even complete cellular function. In this way, it will be possible to perform computer-guided design of novel drugs, advanced therapies for treatment of complex diseases, and to perform in silico design....... Furthermore, it serves as an industrial workhorse for production of a wide range of chemicals and pharmaceuticals. Systems biology involves the combination of novel experimental techniques from different disciplines as well as functional genomics, bioinformatics and mathematical modelling, and hence no single...... laboratory has access to all the necessary competences. For this reason the Yeast Systems Biology Network (YSBN) has been established. YSBN will coordinate research efforts, in yeast systems biology and, through the recently obtained EU funding for a Coordination Action, it will be possible to set...

  8. SYSTEMIC EFFECTS OF UNIVERSITY COMPLEXES

    Directory of Open Access Journals (Sweden)

    N. O. Vaganova

    2017-01-01

    Full Text Available The aim of the present article is to reveal system effects of the university complexes including the organizations of professional education on different levels.Methodology and research methods. Theoretical methods: receipt of scientific information on systems, collection of data on university complexes; empirical: comparison and correlation of the obtained data.Results and scientific novelty. A university complex is designated as a system. The system effects being the results of integration of the organizations of professional education of different levels are educed: effect of instability of the hierarchical relations when preserving a certain structure of a university complex; effect of a single educational purpose, effect of influence of the external environment. These effects cause emergence of new quality of the integrated pedagogical system which is designated as «ability to self-regulating updating».Practical significance. The materials and results of the study can be used for further development of university complexes as organizations that integrate the establishments of vocational education on different levels.

  9. Cytoscape ESP: simple search of complex biological networks.

    Science.gov (United States)

    Ashkenazi, Maital; Bader, Gary D; Kuchinsky, Allan; Moshelion, Menachem; States, David J

    2008-06-15

    Cytoscape enhanced search plugin (ESP) enables searching complex biological networks on multiple attribute fields using logical operators and wildcards. Queries use an intuitive syntax and simple search line interface. ESP is implemented as a Cytoscape plugin and complements existing search functions in the Cytoscape network visualization and analysis software, allowing users to easily identify nodes, edges and subgraphs of interest, even for very large networks. Availabiity: http://chianti.ucsd.edu/cyto_web/plugins/ ashkenaz@agri.huji.ac.il.

  10. Applicability of Computational Systems Biology in Toxicology

    DEFF Research Database (Denmark)

    Kongsbak, Kristine Grønning; Hadrup, Niels; Audouze, Karine Marie Laure

    2014-01-01

    be used to establish hypotheses on links between the chemical and human diseases. Such information can also be applied for designing more intelligent animal/cell experiments that can test the established hypotheses. Here, we describe how and why to apply an integrative systems biology method......Systems biology as a research field has emerged within the last few decades. Systems biology, often defined as the antithesis of the reductionist approach, integrates information about individual components of a biological system. In integrative systems biology, large data sets from various sources...... and databases are used to model and predict effects of chemicals on, for instance, human health. In toxicology, computational systems biology enables identification of important pathways and molecules from large data sets; tasks that can be extremely laborious when performed by a classical literature search...

  11. 1998 Complex Systems Summer School

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-12-15

    For the past eleven years a group of institutes, centers, and universities throughout the country have sponsored a summer school in Santa Fe, New Mexico as part of an interdisciplinary effort to promote the understanding of complex systems. The goal of these summer schools is to provide graduate students, postdoctoral fellows and active research scientists with an introduction to the study of complex behavior in mathematical, physical, and living systems. The Center for Nonlinear Studies supported the eleventh in this series of highly successful schools in Santa Fe in June, 1998.

  12. PREFACE: Complex Networks: from Biology to Information Technology

    Science.gov (United States)

    Barrat, A.; Boccaletti, S.; Caldarelli, G.; Chessa, A.; Latora, V.; Motter, A. E.

    2008-06-01

    The field of complex networks is one of the most active areas in contemporary statistical physics. Ten years after seminal work initiated the modern study of networks, interest in the field is in fact still growing, as indicated by the ever increasing number of publications in network science. The reason for such a resounding success is most likely the simplicity and broad significance of the approach that, through graph theory, allows researchers to address a variety of different complex systems within a common framework. This special issue comprises a selection of contributions presented at the workshop 'Complex Networks: from Biology to Information Technology' held in July 2007 in Pula (Cagliari), Italy as a satellite of the general conference STATPHYS23. The contributions cover a wide range of problems that are currently among the most important questions in the area of complex networks and that are likely to stimulate future research. The issue is organised into four sections. The first two sections describe 'methods' to study the structure and the dynamics of complex networks, respectively. After this methodological part, the issue proceeds with a section on applications to biological systems. The issue closes with a section concentrating on applications to the study of social and technological networks. The first section, entitled Methods: The Structure, consists of six contributions focused on the characterisation and analysis of structural properties of complex networks: The paper Motif-based communities in complex networks by Arenas et al is a study of the occurrence of characteristic small subgraphs in complex networks. These subgraphs, known as motifs, are used to define general classes of nodes and their communities by extending the mathematical expression of the Newman-Girvan modularity. The same line of research, aimed at characterising network structure through the analysis of particular subgraphs, is explored by Bianconi and Gulbahce in Algorithm

  13. SYSTEMS APPROACH FOR CONTEMPORARY COMPLEX TOURISM SYSTEMS

    Directory of Open Access Journals (Sweden)

    Tadeja Jere Jakulin

    2016-09-01

    Full Text Available Systems approach represents thinking outside the box and is connected to the transformation of common linear approach and thinking. Western society followed rules of classical western science, which form many centuries took analysis as mainstream of thinking and researching. One can find perfect and logical explanation for this. In the past, classical science researched matter and reached optimal results with analysis and analytical thinking. Nowadays more and more scientists research intangible world around matter and cooperate with prevailed, fastest growing service industry such as tourism. Following paper presents systems approach in tourism, which defines wideness, co-dependency among tourism system elements, and "big picture" point of view. In a frame of systems methodology, we will show the importance of systems approach in order to understand complexity in the area of tourism. At once an excellent example of the analytical approach will be shown in so called "the tip of the iceberg" theory, where events represent analytical thinking and structure or base of the iceberg represents systems approach. Complexity of the tourism systems will be explained and a model of a common tourism system developed. We claim that the analysis, in the past, caused technological progress; it caused the development of western science, which we now know it. It led to the discoveries but for dealing with contemporary complex challenges is not sufficient. Today a systems approach is suitable enough for dealing with complex question in the area of tourism and of course in global society.

  14. Adapting to Biology: Maintaining Container-Closure System Compatibility with the Therapeutic Biologic Revolution.

    Science.gov (United States)

    Degrazio, Dominick

    Many pharmaceutical companies are transitioning their research and development drug product pipeline from traditional small-molecule injectables to the dimension of evolving therapeutic biologics. Important concerns associated with this changeover are becoming forefront, as challenges develop of varying complexity uncommon with the synthesis and production of traditional drugs. Therefore, alternative measures must be established that aim to preserve the efficacy and functionality of a biologic that might not be implemented for small molecules. Conserving protein stability is relative to perpetuating a net equilibrium of both intrinsic and extrinsic factors. Key to sustaining this balance is the ability of container-closure systems to maintain their compatibility with the ever-changing dynamics of therapeutic biologics. Failure to recognize and adjust the material properties of packaging components to support compatibility with therapeutic biologics can compromise patient safety, drug productivity, and biological stability. This review will examine the differences between small-molecule drugs and therapeutic biologics, lay a basic foundation for understanding the stability of therapeutic biologics, and demonstrate potential sources of container-closure systems' incompatibilities with therapeutic biologics at a mechanistic level. Many pharmaceutical companies are transitioning their research and development drug product pipeline from traditional small-molecule injectables to recombinantly derived therapeutic biologics. Concerns associated with this transformation are becoming prominent, as therapeutic biologics are uncharacteristic to small-molecule drugs. Maintaining the stability of a therapeutic biologic is a combination of balancing intrinsic factors and external elements within the biologic's microenvironment. An important aspect of this balance is relegated to the overall compatibility of primary, parenteral container-closure systems with therapeutic biologics

  15. Towards Engineering Biological Systems in a Broader Context.

    Science.gov (United States)

    Venturelli, Ophelia S; Egbert, Robert G; Arkin, Adam P

    2016-02-27

    Significant advances have been made in synthetic biology to program information processing capabilities in cells. While these designs can function predictably in controlled laboratory environments, the reliability of these devices in complex, temporally changing environments has not yet been characterized. As human society faces global challenges in agriculture, human health and energy, synthetic biology should develop predictive design principles for biological systems operating in complex environments. Natural biological systems have evolved mechanisms to overcome innumerable and diverse environmental challenges. Evolutionary design rules should be extracted and adapted to engineer stable and predictable ecological function. We highlight examples of natural biological responses spanning the cellular, population and microbial community levels that show promise in synthetic biology contexts. We argue that synthetic circuits embedded in host organisms or designed ecologies informed by suitable measurement of biotic and abiotic environmental parameters could be used as engineering substrates to achieve target functions in complex environments. Successful implementation of these methods will broaden the context in which synthetic biological systems can be applied to solve important problems. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Physical approach to complex systems

    Science.gov (United States)

    Kwapień, Jarosław; Drożdż, Stanisław

    2012-06-01

    Typically, complex systems are natural or social systems which consist of a large number of nonlinearly interacting elements. These systems are open, they interchange information or mass with environment and constantly modify their internal structure and patterns of activity in the process of self-organization. As a result, they are flexible and easily adapt to variable external conditions. However, the most striking property of such systems is the existence of emergent phenomena which cannot be simply derived or predicted solely from the knowledge of the systems’ structure and the interactions among their individual elements. This property points to the holistic approaches which require giving parallel descriptions of the same system on different levels of its organization. There is strong evidence-consolidated also in the present review-that different, even apparently disparate complex systems can have astonishingly similar characteristics both in their structure and in their behaviour. One can thus expect the existence of some common, universal laws that govern their properties. Physics methodology proves helpful in addressing many of the related issues. In this review, we advocate some of the computational methods which in our opinion are especially fruitful in extracting information on selected-but at the same time most representative-complex systems like human brain, financial markets and natural language, from the time series representing the observables associated with these systems. The properties we focus on comprise the collective effects and their coexistence with noise, long-range interactions, the interplay between determinism and flexibility in evolution, scale invariance, criticality, multifractality and hierarchical structure. The methods described either originate from “hard” physics-like the random matrix theory-and then were transmitted to other fields of science via the field of complex systems research, or they originated elsewhere but

  17. Systems Biology and Ecology of Streamlined Bacterioplankton

    Science.gov (United States)

    Giovannoni, S. J.

    2014-12-01

    complex questions hinge on translating gene frequencies into trait based ecological models that reflect the systems biology of cells.

  18. Research Update: Interfacing ultrasmall metal nanoclusters with biological systems

    Science.gov (United States)

    Shang, Li; Nienhaus, G. Ulrich

    2017-05-01

    Metal nanoclusters (NCs), a new type of nanomaterial with unique physicochemical properties, show great potential in many biomedical applications. Understanding their behavior in the complex biological environment is critical not only for designing highly efficient NC-based nanomedicines but also for elucidating the biological impact (e.g., toxicity) of these emerging nanomaterials. In this review, we give an overview of recent progress in exploring interactions of metal NCs with biological systems, including protein adsorption onto NCs, NC interactions with cells, and also the in vivo behavior of NCs. We also discuss the biological responses to the interactions, key parameters defining the interactions, and current challenges in the exploration of NCs in the complex biological environment.

  19. Complexity: the organizing principle at the interface of biological (dis ...

    Indian Academy of Sciences (India)

    RAMRAY BHAT

    2017-07-05

    Jul 5, 2017 ... is used to signify the sheer complicatedness of living systems, especially as a result of the multicomponent aspect of biological form. On the other hand, it has ... one particular process that could give rise to the pattern. Therefore ..... tion, cell division and death, multicellular polarization etc. (Newman and ...

  20. Introduction to Network Analysis in Systems Biology

    OpenAIRE

    Ma’ayan, Avi

    2011-01-01

    This Teaching Resource provides lecture notes, slides, and a problem set for a set of three lectures from a course entitled “Systems Biology: Biomedical Modeling.” The materials are from three separate lectures introducing applications of graph theory and network analysis in systems biology. The first lecture describes different types of intracellular networks, methods for constructing biological networks, and different types of graphs used to represent regulatory intracellular networks. The ...

  1. Drawing inspiration from biological optical systems

    Science.gov (United States)

    Wolpert, H. D.

    2009-08-01

    Bio-Mimicking/Bio-Inspiration: How can we not be inspired by Nature? Life has evolved on earth over the last 3.5 to 4 billion years. Materials formed during this time were not toxic; they were created at low temperatures and low pressures unlike many of the materials developed today. The natural materials formed are self-assembled, multifunctional, nonlinear, complex, adaptive, self-repairing and biodegradable. The designs that failed are fossils. Those that survived are the success stories. Natural materials are mostly formed from organics, inorganic crystals and amorphous phases. The materials make economic sense by optimizing the design of the structures or systems to meet multiple needs. We constantly "see" many similar strategies in approaches, between man and nature, but we seldom look at the details of natures approaches. The power of image processing, in many of natures creatures, is a detail that is often overlooked. Seldon does the engineer interact with the biologist and learn what nature has to teach us. The variety and complexity of biological materials and the optical systems formed should inspire us.

  2. Biological Systems Thinking for Control Engineering Design

    Directory of Open Access Journals (Sweden)

    D. J. Murray-Smith

    2004-01-01

    Full Text Available Artificial neural networks and genetic algorithms are often quoted in discussions about the contribution of biological systems thinking to engineering design. This paper reviews work on the neuromuscular system, a field in which biological systems thinking could make specific contributions to the development and design of automatic control systems for mechatronics and robotics applications. The paper suggests some specific areas in which a better understanding of this biological control system could be expected to contribute to control engineering design methods in the future. Particular emphasis is given to the nonlinear nature of elements within the neuromuscular system and to processes of neural signal processing, sensing and system adaptivity. Aspects of the biological system that are of particular significance for engineering control systems include sensor fusion, sensor redundancy and parallelism, together with advanced forms of signal processing for adaptive and learning control. 

  3. Permutation Complexity in Dynamical Systems

    CERN Document Server

    Amigo, Jose

    2010-01-01

    The study of permutation complexity can be envisioned as a new kind of symbolic dynamics whose basic blocks are ordinal patterns, that is, permutations defined by the order relations among points in the orbits of dynamical systems. Since its inception in 2002 the concept of permutation entropy has sparked a new branch of research in particular regarding the time series analysis of dynamical systems that capitalizes on the order structure of the state space. Indeed, on one hand ordinal patterns and periodic points are closely related, yet ordinal patterns are amenable to numerical methods, while periodicity is not. Another interesting feature is that since it can be shown that random (unconstrained) dynamics has no forbidden patterns with probability one, their existence can be used as a fingerprint to identify any deterministic origin of orbit generation. This book is primarily addressed to researchers working in the field of nonlinear dynamics and complex systems, yet will also be suitable for graduate stude...

  4. Disorder in Complex Human System

    Science.gov (United States)

    Akdeniz, K. Gediz

    2011-11-01

    Since the world of human and whose life becomes more and more complex every day because of the digital technology and under the storm of knowledge (media, internet, governmental and non-governmental organizations, etc...) the simulation is rapidly growing in the social systems and in human behaviors. The formation of the body and mutual interactions are left to digital technological, communication mechanisms and coding the techno genetics of the body. Deconstruction begins everywhere. The linear simulation mechanism with modern realities are replaced by the disorder simulation of human behaviors with awareness realities. In this paper I would like to introduce simulation theory of "Disorder Sensitive Human Behaviors". I recently proposed this theory to critique the role of disorder human behaviors in social systems. In this theory the principle of realty is the chaotic awareness of the complexity of human systems inside of principle of modern thinking in Baudrillard's simulation theory. Proper examples will be also considered to investigate the theory.

  5. Multilayer network modeling of integrated biological systems. Comment on "Network science of biological systems at different scales: A review" by Gosak et al.

    Science.gov (United States)

    De Domenico, Manlio

    2018-03-01

    Biological systems, from a cell to the human brain, are inherently complex. A powerful representation of such systems, described by an intricate web of relationships across multiple scales, is provided by complex networks. Recently, several studies are highlighting how simple networks - obtained by aggregating or neglecting temporal or categorical description of biological data - are not able to account for the richness of information characterizing biological systems. More complex models, namely multilayer networks, are needed to account for interdependencies, often varying across time, of biological interacting units within a cell, a tissue or parts of an organism.

  6. Complexation of oppositely charged polyelectrolytes in gene delivery and biology

    Science.gov (United States)

    Shklovskii, Boris

    2009-03-01

    Charge inversion of a DNA double helix by a positively charged flexible polymer (polyelectrolyte) is widely used to facilitate DNA contact with negative cell membranes for gene delivery. Motivated by this application in the first part of the talk I study the phase diagram a solution of long polyanions (PA) with a shorter polycations (PC) as a function the ratio of total charges of PC and PA in the solution, x, and the concentration of monovalent salt. Each PA attracts many PCs to form a complex. When x= 1, the complexes are neutral and condense in a macroscopic drop. When x is far away from 1, complexes are strongly charged and stable. PA are overcharged by PC at x > 1 and undercharged by PC at x < 1. As x approaches 1, PCs attached to PA disproportionate between complexes. Some complexes become neutral and condensed in a macroscopic drop while others become even stronger charged and stay free. The second part of the talk deals with biological example of PA -PC complexes namely self-assembly of vegetable viruses from long ss-RNA molecule paying role of scaffold and identical capsid proteins with long positive tails. I show that optimization Coulomb energy of the virus leads to the charge of RNA twice larger than the total charge of the capsid, in agreement with the experimental data. Then I discuss kinetics of the Coulomb complexation driven virus self-assembly. Capsid proteins stick to unassembled chain of ss RNA (which we call ``antenna'') and slide on it towards the assembly site. I show that at excess of capsid proteins such one-dimensional diffusion accelerates self-assembly more than ten times. On the other hand at excess of ss-RNA, antenna slows self-assembly down. Several experiments are proposed to verify the role of ss-RNA antenna in self-assembly.

  7. Marine biological data and information management system

    Digital Repository Service at National Institute of Oceanography (India)

    Sarupria, J.S.

    Indian National Oceanographic Data Centre (INODC) is engaged in developing a marine biological data and information management system (BIODIMS). This system will contain the information on zooplankton in the water column, zoobenthic biomass...

  8. Complex Behavior in Simple Models of Biological Coevolution

    Science.gov (United States)

    Rikvold, Per Arne

    We explore the complex dynamical behavior of simple predator-prey models of biological coevolution that account for interspecific and intraspecific competition for resources, as well as adaptive foraging behavior. In long kinetic Monte Carlo simulations of these models we find quite robust 1/f-like noise in species diversity and population sizes, as well as power-law distributions for the lifetimes of individual species and the durations of quiet periods of relative evolutionary stasis. In one model, based on the Holling Type II functional response, adaptive foraging produces a metastable low-diversity phase and a stable high-diversity phase.

  9. Systems biology in critical-care nursing.

    Science.gov (United States)

    Schallom, Lynn; Thimmesch, Amanda R; Pierce, Janet D

    2011-01-01

    Systems biology applies advances in technology and new fields of study including genomics, transcriptomics, proteomics, and metabolomics to the development of new treatments and approaches of care for the critically ill and injured patient. An understanding of systems biology enhances a nurse's ability to implement evidence-based practice and to educate patients and families on novel testing and therapies. Systems biology is an integrated and holistic view of humans in relationship with the environment. Biomarkers are used to measure the presence and severity of disease and are rapidly expanding in systems biology endeavors. A systems biology approach using predictive, preventive, and participatory involvement is being utilized in a plethora of conditions of critical illness and injury including sepsis, cancer, pulmonary disease, and traumatic injuries.

  10. Plant systems biology: insights, advances and challenges.

    Science.gov (United States)

    Sheth, Bhavisha P; Thaker, Vrinda S

    2014-07-01

    Plants dwelling at the base of biological food chain are of fundamental significance in providing solutions to some of the most daunting ecological and environmental problems faced by our planet. The reductionist views of molecular biology provide only a partial understanding to the phenotypic knowledge of plants. Systems biology offers a comprehensive view of plant systems, by employing a holistic approach integrating the molecular data at various hierarchical levels. In this review, we discuss the basics of systems biology including the various 'omics' approaches and their integration, the modeling aspects and the tools needed for the plant systems research. A particular emphasis is given to the recent analytical advances, updated published examples of plant systems biology studies and the future trends.

  11. Complex Biological Systems Analysis of Cell Cycling Models in Carcinogenesis: I. The essential roles of modifications in the c-Myc, TP53/p53, p27 and hTERT modules in Cancer Initiation and Progression

    CERN Document Server

    Prisecaru, V I

    2004-01-01

    A new approach to the integration of results from a modular, complex biological systems analysis of nonlinear dynamics in cell cycling network transformations that are leading to carcinogenesis is proposed. Carcinogenesis is a complex process that involves dynamically inter-connected biomolecules in the intercellular, membrane, cytosolic, nuclear and nucleolar compartments that form numerous inter-related pathways referred to as networks. One such network module contains the cell cyclins whose functions are essential to cell cycling and division. Cyclins are proteins that also link to several critical pro-apoptotic and other cell cycling/division components, such as: c-Myc, p27, the tumor suppressor gene TP53 and its product-- the p53 protein with key roles in controlling DNA repair, inducing apoptosis and activating p21 (which can depress cell cyclins if activated), mdm2(with its biosynthesis activated by p53 and also, in its turn, inhibiting p53), p21, the Thomsen-Friedenreich antigen(T- antigen),Rb,Bax, Ba...

  12. Systematic metabolite annotation and identification in complex biological extracts : combining robust mass spectrometry fragmentation and nuclear magnetic resonance spectroscopy

    NARCIS (Netherlands)

    Hooft, van der J.J.J.

    2012-01-01

    Detailed knowledge of the chemical content of organisms, organs, tissues, and cells is needed to fully characterize complex biological systems. The high chemical variety of compounds present in biological systems is illustrated by the presence of a large variety of compounds, ranging from apolar

  13. Complex Physical, Biophysical and Econophysical Systems

    Science.gov (United States)

    Dewar, Robert L.; Detering, Frank

    1. Introduction to complex and econophysics systems: a navigation map / T. Aste and T. Di Matteo -- 2. An introduction to fractional diffusion / B. I. Henry, T.A.M. Langlands and P. Straka -- 3. Space plasmas and fusion plasmas as complex systems / R. O. Dendy -- 4. Bayesian data analysis / M. S. Wheatland -- 5. Inverse problems and complexity in earth system science / I. G. Enting -- 6. Applied fluid chaos: designing advection with periodically reoriented flows for micro to geophysical mixing and transport enhancement / G. Metcalfe -- 7. Approaches to modelling the dynamical activity of brain function based on the electroencephalogram / D. T. J. Liley and F. Frascoli -- 8. Jaynes' maximum entropy principle, Riemannian metrics and generalised least action bound / R. K. Niven and B. Andresen -- 9. Complexity, post-genomic biology and gene expression programs / R. B. H. Williams and O. J.-H. Luo -- 10. Tutorials on agent-based modelling with NetLogo and network analysis with Pajek / M. J. Berryman and S. D. Angus.

  14. Critical evaluation of the JDO API for the persistence and portability requirements of complex biological databases

    Directory of Open Access Journals (Sweden)

    Schwieger Michael

    2005-01-01

    Full Text Available Abstract Background Complex biological database systems have become key computational tools used daily by scientists and researchers. Many of these systems must be capable of executing on multiple different hardware and software configurations and are also often made available to users via the Internet. We have used the Java Data Object (JDO persistence technology to develop the database layer of such a system known as the SigPath information management system. SigPath is an example of a complex biological database that needs to store various types of information connected by many relationships. Results Using this system as an example, we perform a critical evaluation of current JDO technology; discuss the suitability of the JDO standard to achieve portability, scalability and performance. We show that JDO supports portability of the SigPath system from a relational database backend to an object database backend and achieves acceptable scalability. To answer the performance question, we have created the SigPath JDO application benchmark that we distribute under the Gnu General Public License. This benchmark can be used as an example of using JDO technology to create a complex biological database and makes it possible for vendors and users of the technology to evaluate the performance of other JDO implementations for similar applications. Conclusions The SigPath JDO benchmark and our discussion of JDO technology in the context of biological databases will be useful to bioinformaticians who design new complex biological databases and aim to create systems that can be ported easily to a variety of database backends.

  15. Feedback dynamics and cell function: Why systems biology is called Systems Biology.

    Science.gov (United States)

    Wolkenhauer, Olaf; Mesarovic, Mihajlo

    2005-05-01

    A new paradigm, like Systems Biology, should challenge the way research has been conducted previously. This Opinion article aims to present Systems Biology, not as the application of engineering principles to biology but as a merger of systems- and control theory with molecular- and cell biology. In our view, the central dogma of Systems Biology is that it is system dynamics that gives rise to the functioning and function of cells. The concepts of feedback regulation and control of pathways and the coordination of cell function are emphasized as an important area of Systems Biology research. The hurdles and risks for this area are discussed from the perspective of dynamic pathway modelling. Most of all, the aim of this article is to promote mathematical modelling and simulation as a part of molecular- and cell biology. Systems Biology is a success if it is widely accepted that there is nothing more practical than a good theory.

  16. Genomes, Phylogeny, and Evolutionary Systems Biology

    Energy Technology Data Exchange (ETDEWEB)

    Medina, Monica

    2005-03-25

    With the completion of the human genome and the growing number of diverse genomes being sequenced, a new age of evolutionary research is currently taking shape. The myriad of technological breakthroughs in biology that are leading to the unification of broad scientific fields such as molecular biology, biochemistry, physics, mathematics and computer science are now known as systems biology. Here I present an overview, with an emphasis on eukaryotes, of how the postgenomics era is adopting comparative approaches that go beyond comparisons among model organisms to shape the nascent field of evolutionary systems biology.

  17. Human Error In Complex Systems

    Science.gov (United States)

    Morris, Nancy M.; Rouse, William B.

    1991-01-01

    Report presents results of research aimed at understanding causes of human error in such complex systems as aircraft, nuclear powerplants, and chemical processing plants. Research considered both slips (errors of action) and mistakes (errors of intention), and influence of workload on them. Results indicated that: humans respond to conditions in which errors expected by attempting to reduce incidence of errors; and adaptation to conditions potent influence on human behavior in discretionary situations.

  18. Biocellion: accelerating computer simulation of multicellular biological system models.

    Science.gov (United States)

    Kang, Seunghwa; Kahan, Simon; McDermott, Jason; Flann, Nicholas; Shmulevich, Ilya

    2014-11-01

    Biological system behaviors are often the outcome of complex interactions among a large number of cells and their biotic and abiotic environment. Computational biologists attempt to understand, predict and manipulate biological system behavior through mathematical modeling and computer simulation. Discrete agent-based modeling (in combination with high-resolution grids to model the extracellular environment) is a popular approach for building biological system models. However, the computational complexity of this approach forces computational biologists to resort to coarser resolution approaches to simulate large biological systems. High-performance parallel computers have the potential to address the computing challenge, but writing efficient software for parallel computers is difficult and time-consuming. We have developed Biocellion, a high-performance software framework, to solve this computing challenge using parallel computers. To support a wide range of multicellular biological system models, Biocellion asks users to provide their model specifics by filling the function body of pre-defined model routines. Using Biocellion, modelers without parallel computing expertise can efficiently exploit parallel computers with less effort than writing sequential programs from scratch. We simulate cell sorting, microbial patterning and a bacterial system in soil aggregate as case studies. Biocellion runs on x86 compatible systems with the 64 bit Linux operating system and is freely available for academic use. Visit http://biocellion.com for additional information. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  19. The complexity of DNA damage: relevance to biological consequences

    International Nuclear Information System (INIS)

    Ward, J.F.

    1994-01-01

    Ionizing radiation causes both singly and multiply damaged sites in DNA when the range of radical migration is limited by the presence of hydroxyl radical scavengers (e.g. within cells). Multiply damaged sites are considered to be more biologically relevant because of the challenges they present to cellular repair mechanisms. These sites occur in the form of DNA double-strand breaks (dsb) but also as other multiple damages that can be converted to dsb during attempted repair. The presence of a dsb can lead to loss of base sequence information and/or can permit the two ends of a break to separate and rejoin with the wrong partner. (Multiply damaged sites may also be the biologically relevant type of damage caused by other agents, such as UVA, B and/or C light, and some antitumour antibiotics). The quantitative data available from radiation studies of DNA are shown to support the proposed mechanisms for the production of complex damage in cellular DNA, i.e. via scavengable and non-scavengable mechanisms. The yields of complex damages can in turn be used to support the conclusion that cellular mutations are a consequence of the presence of these damages within a gene. (Author)

  20. Semiotics of constructed complex systems

    Energy Technology Data Exchange (ETDEWEB)

    Landauer, C.; Bellman, K.L.

    1996-12-31

    The scope of this paper is limited to software and other constructed complex systems mediated or integrated by software. Our research program studies foundational issues that we believe will help us develop a theoretically sound approach to constructing complex systems. There have really been only two theoretical approaches that have helped us understand and develop computational systems: mathematics and linguistics. We show how semiotics can also play a role, whether we think of it as part of these other theories or as subsuming one or both of them. We describe our notion of {open_quotes}computational semiotics{close_quotes}, which we define to be the study of computational methods of dealing with symbols, show how such a theory might be formed, and describe what we might get from it in terms of more interesting use of symbols by computing systems. This research was supported in part by the Federal Highway Administration`s Office of Advanced Research and by the Advanced Research Projects Agency`s Software and Intelligent Systems Technology Office.

  1. 5th International Conference on Complex Systems

    CERN Document Server

    Braha, Dan; Bar-Yam, Yaneer

    2011-01-01

    The International Conference on Complex Systems (ICCS) creates a unique atmosphere for scientists of all fields, engineers, physicians, executives, and a host of other professionals to explore common themes and applications of complex system science. With this new volume, Unifying Themes in Complex Systems continues to build common ground between the wide-ranging domains of complex system science.

  2. 7th International Conference on Complex Systems

    CERN Document Server

    Braha, Dan; Bar-Yam, Yaneer

    2012-01-01

    The International Conference on Complex Systems (ICCS) creates a unique atmosphere for scientists of all fields, engineers, physicians, executives, and a host of other professionals to explore common themes and applications of complex system science. With this new volume, Unifying Themes in Complex Systems continues to build common ground between the wide-ranging domains of complex system science.

  3. Proteomics-Based Analysis of Protein Complexes in Pluripotent Stem Cells and Cancer Biology.

    Science.gov (United States)

    Sudhir, Putty-Reddy; Chen, Chung-Hsuan

    2016-03-22

    A protein complex consists of two or more proteins that are linked together through protein-protein interactions. The proteins show stable/transient and direct/indirect interactions within the protein complex or between the protein complexes. Protein complexes are involved in regulation of most of the cellular processes and molecular functions. The delineation of protein complexes is important to expand our knowledge on proteins functional roles in physiological and pathological conditions. The genetic yeast-2-hybrid method has been extensively used to characterize protein-protein interactions. Alternatively, a biochemical-based affinity purification coupled with mass spectrometry (AP-MS) approach has been widely used to characterize the protein complexes. In the AP-MS method, a protein complex of a target protein of interest is purified using a specific antibody or an affinity tag (e.g., DYKDDDDK peptide (FLAG) and polyhistidine (His)) and is subsequently analyzed by means of MS. Tandem affinity purification, a two-step purification system, coupled with MS has been widely used mainly to reduce the contaminants. We review here a general principle for AP-MS-based characterization of protein complexes and we explore several protein complexes identified in pluripotent stem cell biology and cancer biology as examples.

  4. General approach to the biological analysis of complex mixtures.

    Science.gov (United States)

    Thilly, W G; Longwell, J; Andon, B M

    1983-02-01

    The study of potential health effects of combustion effluents involves identifying the substances present and estimating the probable health hazards of each. Unfortunately, this second step cannot be done by using present techniques. Approximations of health hazards by bacterial and human cell assays are being used to set priorities for further biological studies and to suggest needs for modifications of combustion systems. The assumptions underlying this approximation are discussed, and several examples of combustion effluents are reviewed.

  5. Analysis of complex networks from biology to linguistics

    CERN Document Server

    Dehmer, Matthias

    2009-01-01

    Mathematical problems such as graph theory problems are of increasing importance for the analysis of modelling data in biomedical research such as in systems biology, neuronal network modelling etc. This book follows a new approach of including graph theory from a mathematical perspective with specific applications of graph theory in biomedical and computational sciences. The book is written by renowned experts in the field and offers valuable background information for a wide audience.

  6. Decarboxylation mechanisms in biological system.

    Science.gov (United States)

    Li, Tingfeng; Huo, Lu; Pulley, Christopher; Liu, Aimin

    2012-08-01

    This review examines the mechanisms propelling cofactor-independent, organic cofactor-dependent and metal-dependent decarboxylase chemistry. Decarboxylation, the removal of carbon dioxide from organic acids, is a fundamentally important reaction in biology. Numerous decarboxylase enzymes serve as key components of aerobic and anaerobic carbohydrate metabolism and amino acid conversion. In the past decade, our knowledge of the mechanisms enabling these crucial decarboxylase reactions has continued to expand and inspire. This review focuses on the organic cofactors biotin, flavin, NAD, pyridoxal 5'-phosphate, pyruvoyl, and thiamin pyrophosphate as catalytic centers. Significant attention is also placed on the metal-dependent decarboxylase mechanisms. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. Tunable promoters in synthetic and systems biology

    DEFF Research Database (Denmark)

    Dehli, Tore; Solem, Christian; Jensen, Peter Ruhdal

    2012-01-01

    in synthetic biology. A number of tools exist to manipulate the steps in between gene sequence and functional protein in living cells, but out of these the most straight-forward approach is to alter the gene expression level by manipulating the promoter sequence. Some of the promoter tuning tools available......Synthetic and systems biologists need standardized, modular and orthogonal tools yielding predictable functions in vivo. In systems biology such tools are needed to quantitatively analyze the behavior of biological systems while the efficient engineering of artificial gene networks is central...

  8. Computational models of complex systems

    CERN Document Server

    Dabbaghian, Vahid

    2014-01-01

    Computational and mathematical models provide us with the opportunities to investigate the complexities of real world problems. They allow us to apply our best analytical methods to define problems in a clearly mathematical manner and exhaustively test our solutions before committing expensive resources. This is made possible by assuming parameter(s) in a bounded environment, allowing for controllable experimentation, not always possible in live scenarios. For example, simulation of computational models allows the testing of theories in a manner that is both fundamentally deductive and experimental in nature. The main ingredients for such research ideas come from multiple disciplines and the importance of interdisciplinary research is well recognized by the scientific community. This book provides a window to the novel endeavours of the research communities to present their works by highlighting the value of computational modelling as a research tool when investigating complex systems. We hope that the reader...

  9. An engineering design approach to systems biology.

    Science.gov (United States)

    Janes, Kevin A; Chandran, Preethi L; Ford, Roseanne M; Lazzara, Matthew J; Papin, Jason A; Peirce, Shayn M; Saucerman, Jeffrey J; Lauffenburger, Douglas A

    2017-07-17

    Measuring and modeling the integrated behavior of biomolecular-cellular networks is central to systems biology. Over several decades, systems biology has been shaped by quantitative biologists, physicists, mathematicians, and engineers in different ways. However, the basic and applied versions of systems biology are not typically distinguished, which blurs the separate aspirations of the field and its potential for real-world impact. Here, we articulate an engineering approach to systems biology, which applies educational philosophy, engineering design, and predictive models to solve contemporary problems in an age of biomedical Big Data. A concerted effort to train systems bioengineers will provide a versatile workforce capable of tackling the diverse challenges faced by the biotechnological and pharmaceutical sectors in a modern, information-dense economy.

  10. Complexity for Survival of Living Systems

    Science.gov (United States)

    Zak, Michail

    2009-01-01

    A logical connection between the survivability of living systems and the complexity of their behavior (equivalently, mental complexity) has been established. This connection is an important intermediate result of continuing research on mathematical models that could constitute a unified representation of the evolution of both living and non-living systems. Earlier results of this research were reported in several prior NASA Tech Briefs articles, the two most relevant being Characteristics of Dynamics of Intelligent Systems (NPO- 21037), NASA Tech Briefs, Vol. 26, No. 12 (December 2002), page 48; and Self-Supervised Dynamical Systems (NPO- 30634) NASA Tech Briefs, Vol. 27, No. 3 (March 2003), page 72. As used here, living systems is synonymous with active systems and intelligent systems. The quoted terms can signify artificial agents (e.g., suitably programmed computers) or natural biological systems ranging from single-cell organisms at one extreme to the whole of human society at the other extreme. One of the requirements that must be satisfied in mathematical modeling of living systems is reconciliation of evolution of life with the second law of thermodynamics. In the approach followed in this research, this reconciliation is effected by means of a model, inspired partly by quantum mechanics, in which the quantum potential is replaced with an information potential. The model captures the most fundamental property of life - the ability to evolve from disorder to order without any external interference. The model incorporates the equations of classical dynamics, including Newton s equations of motion and equations for random components caused by uncertainties in initial conditions and by Langevin forces. The equations of classical dynamics are coupled with corresponding Liouville or Fokker-Planck equations that describe the evolutions of probability densities that represent the uncertainties. The coupling is effected by fictitious information-based forces that are

  11. Computational Modeling, Formal Analysis, and Tools for Systems Biology.

    Directory of Open Access Journals (Sweden)

    Ezio Bartocci

    2016-01-01

    Full Text Available As the amount of biological data in the public domain grows, so does the range of modeling and analysis techniques employed in systems biology. In recent years, a number of theoretical computer science developments have enabled modeling methodology to keep pace. The growing interest in systems biology in executable models and their analysis has necessitated the borrowing of terms and methods from computer science, such as formal analysis, model checking, static analysis, and runtime verification. Here, we discuss the most important and exciting computational methods and tools currently available to systems biologists. We believe that a deeper understanding of the concepts and theory highlighted in this review will produce better software practice, improved investigation of complex biological processes, and even new ideas and better feedback into computer science.

  12. EURASIP journal on bioinformatics & systems biology

    National Research Council Canada - National Science Library

    2006-01-01

    "The overall aim of "EURASIP Journal on Bioinformatics and Systems Biology" is to publish research results related to signal processing and bioinformatics theories and techniques relevant to a wide...

  13. Sporothrix schenckii complex biology: environment and fungal pathogenicity.

    Science.gov (United States)

    Téllez, M D; Batista-Duharte, A; Portuondo, D; Quinello, C; Bonne-Hernández, R; Carlos, I Z

    2014-11-01

    Sporothrix schenckii is a complex of various species of fungus found in soils, plants, decaying vegetables and other outdoor environments. It is the aetiological agent of sporotrichosis in humans and several animals. Humans and animals can acquire the disease through traumatic inoculation of the fungus into subcutaneous tissue. Despite the importance of sporotrichosis, it being currently regarded as an emergent disease in several countries, the factors driving its increasing medical importance are still largely unknown. There have only been a few studies addressing the influence of the environment on the virulence of these pathogens. However, recent studies have demonstrated that adverse conditions in its natural habitats can trigger the expression of different virulence factors that confer survival advantages both in animal hosts and in the environment. In this review, we provide updates on the important advances in the understanding of the biology of Spor. schenckii and the modification of its virulence linked to demonstrated or putative environmental factors. © 2014 The Authors.

  14. A framework for evolutionary systems biology.

    Science.gov (United States)

    Loewe, Laurence

    2009-02-24

    Many difficult problems in evolutionary genomics are related to mutations that have weak effects on fitness, as the consequences of mutations with large effects are often simple to predict. Current systems biology has accumulated much data on mutations with large effects and can predict the properties of knockout mutants in some systems. However experimental methods are too insensitive to observe small effects. Here I propose a novel framework that brings together evolutionary theory and current systems biology approaches in order to quantify small effects of mutations and their epistatic interactions in silico. Central to this approach is the definition of fitness correlates that can be computed in some current systems biology models employing the rigorous algorithms that are at the core of much work in computational systems biology. The framework exploits synergies between the realism of such models and the need to understand real systems in evolutionary theory. This framework can address many longstanding topics in evolutionary biology by defining various 'levels' of the adaptive landscape. Addressed topics include the distribution of mutational effects on fitness, as well as the nature of advantageous mutations, epistasis and robustness. Combining corresponding parameter estimates with population genetics models raises the possibility of testing evolutionary hypotheses at a new level of realism. EvoSysBio is expected to lead to a more detailed understanding of the fundamental principles of life by combining knowledge about well-known biological systems from several disciplines. This will benefit both evolutionary theory and current systems biology. Understanding robustness by analysing distributions of mutational effects and epistasis is pivotal for drug design, cancer research, responsible genetic engineering in synthetic biology and many other practical applications.

  15. Thermodynamic modeling of complex systems

    DEFF Research Database (Denmark)

    Liang, Xiaodong

    . Contrary to earlier theories, the oil is not only present on the surface, but also in great volumes both in the water column and on the seafloor, which indicates that we do not know enough about how oil behaves in water and interacts with it. Sonar detection is one of the most important and necessary...... after an oil spill. Engineering thermodynamics could be applied in the state-of-the-art sonar products through advanced artificial technology, if the speed of sound, solubility and density of oil-seawater systems could be satisfactorily modelled. The addition of methanol or glycols into unprocessed well...... streams during subsea pipelines is necessary to inhibit gas hydrate formation, and the offshore reservoirs often mean complicated temperature and pressure conditions. Accurate description of the phase behavior and thermalphysical properties of complex systems containing petroleum fluids and polar...

  16. Interdisciplinary Symposium on Complex Systems

    CERN Document Server

    Zelinka, Ivan; Rössler, Otto

    2014-01-01

    The book you hold in your hands is the outcome of the "ISCS 2013: Interdisciplinary Symposium on Complex Systems" held at the historical capital of Bohemia as a continuation of our series of symposia in the science of complex systems. Prague, one of the most beautiful European cities, has its own beautiful genius loci. Here, a great number of important discoveries were made and many important scientists spent fruitful and creative years to leave unforgettable traces. The perhaps most significant period was the time of Rudolf II who was a great supporter of the art and the science and attracted a great number of prominent minds to Prague. This trend would continue. Tycho Brahe, Niels Henrik Abel, Johannes Kepler, Bernard Bolzano, August Cauchy Christian Doppler, Ernst Mach, Albert Einstein and many others followed developing fundamental mathematical and physical theories or expanding them. Thus in the beginning of the 17th century, Kepler formulated here the first two of his three laws of planetary motion on ...

  17. Nonlinear Waves in Complex Systems

    DEFF Research Database (Denmark)

    2007-01-01

    The study of nonlinear waves has exploded due to the combination of analysis and computations, since the discovery of the famous recurrence phenomenon on a chain of nonlinearly coupled oscillators by Fermi-Pasta-Ulam fifty years ago. More than the discovery of new integrable equations, it is the ......The study of nonlinear waves has exploded due to the combination of analysis and computations, since the discovery of the famous recurrence phenomenon on a chain of nonlinearly coupled oscillators by Fermi-Pasta-Ulam fifty years ago. More than the discovery of new integrable equations......, it is the universality and robustness of the main models with respect to perturbations that developped the field. This is true for both continuous and discrete equations. In this volume we keep this broad view and draw new perspectives for nonlinear waves in complex systems. In particular we address energy flow...... in Fourier space and equipartition, the role of inhomogeneities and complex geometry and the importance of coupled systems....

  18. A Philosophical Perspective on Evolutionary Systems Biology.

    Science.gov (United States)

    O'Malley, Maureen A; Soyer, Orkun S; Siegal, Mark L

    2015-03-01

    Evolutionary systems biology (ESB) is an emerging hybrid approach that integrates methods, models, and data from evolutionary and systems biology. Drawing on themes that arose at a cross-disciplinary meeting on ESB in 2013, we discuss in detail some of the explanatory friction that arises in the interaction between evolutionary and systems biology. These tensions appear because of different modeling approaches, diverse explanatory aims and strategies, and divergent views about the scope of the evolutionary synthesis. We locate these discussions in the context of long-running philosophical deliberations on explanation, modeling, and theoretical synthesis. We show how many of the issues central to ESB's progress can be understood as general philosophical problems. The benefits of addressing these philosophical issues feed back into philosophy too, because ESB provides excellent examples of scientific practice for the development of philosophy of science and philosophy of biology.

  19. Complexity, Post-genomic Biology and Gene Expression Programs

    Science.gov (United States)

    Williams, Rohan B. H.; Luo, Oscar Junhong

    Gene expression represents the fundamental phenomenon by which information encoded in a genome is utilised for the overall biological objectives of the organism. Understanding this level of information transfer is therefore essential for dissecting the mechanistic basis of form and function of organisms. We survey recent developments in the methodology of the life sciences that is relevant for understanding the organisation and function of the genome and review our current understanding of the regulation of gene expression, and finally, outline some new approaches that may be useful in understanding the organisation of gene regulatory systems.

  20. Exploitation of complex network topology for link prediction in biological interactomes

    KAUST Repository

    Alanis Lobato, Gregorio

    2014-06-01

    The network representation of the interactions between proteins and genes allows for a holistic perspective of the complex machinery underlying the living cell. However, the large number of interacting entities within the cell makes network construction a daunting and arduous task, prone to errors and missing information. Fortunately, the structure of biological networks is not different from that of other complex systems, such as social networks, the world-wide web or power grids, for which growth models have been proposed to better understand their structure and function. This means that we can design tools based on these models in order to exploit the topology of biological interactomes with the aim to construct more complete and reliable maps of the cell. In this work, we propose three novel and powerful approaches for the prediction of interactions in biological networks and conclude that it is possible to mine the topology of these complex system representations and produce reliable and biologically meaningful information that enriches the datasets to which we have access today.

  1. Compound Synchronization of Four Chaotic Complex Systems

    Directory of Open Access Journals (Sweden)

    Junwei Sun

    2015-01-01

    Full Text Available The chaotic complex system is designed from the start of the chaotic real system. Dynamical properties of a chaotic complex system in complex space are investigated. In this paper, a compound synchronization scheme is achieved for four chaotic complex systems. According to Lyapunov stability theory and the adaptive control method, four chaotic complex systems are considered and the corresponding controllers are designed to realize the compound synchronization scheme. Four novel design chaotic complex systems are given as an example to verify the validity and feasibility of the proposed control scheme.

  2. Effects of abiotic stress on plants: a systems biology perspective.

    Science.gov (United States)

    Cramer, Grant R; Urano, Kaoru; Delrot, Serge; Pezzotti, Mario; Shinozaki, Kazuo

    2011-11-17

    The natural environment for plants is composed of a complex set of abiotic stresses and biotic stresses. Plant responses to these stresses are equally complex. Systems biology approaches facilitate a multi-targeted approach by allowing one to identify regulatory hubs in complex networks. Systems biology takes the molecular parts (transcripts, proteins and metabolites) of an organism and attempts to fit them into functional networks or models designed to describe and predict the dynamic activities of that organism in different environments. In this review, research progress in plant responses to abiotic stresses is summarized from the physiological level to the molecular level. New insights obtained from the integration of omics datasets are highlighted. Gaps in our knowledge are identified, providing additional focus areas for crop improvement research in the future.

  3. Infinite Particle Systems: Complex Systems III

    Directory of Open Access Journals (Sweden)

    Editorial Board

    2008-06-01

    Full Text Available In the years 2002-2005, a group of German and Polish mathematicians worked under a DFG research project No 436 POL 113/98/0-1 entitled "Methods of stochastic analysis in the theory of collective phenomena: Gibbs states and statistical hydrodynamics". The results of their study were summarized at the German-Polish conference, which took place in Poland in October 2005. The venue of the conference was Kazimierz Dolny upon Vistula - a lovely town and a popular place for various cultural, scientific, and even political events of an international significance. The conference was also attended by scientists from France, Italy, Portugal, UK, Ukraine, and USA, which predetermined its international character. Since that time, the conference, entitled "Infinite Particle Systems: Complex Systems" has become an annual international event, attended by leading scientists from Germany, Poland and many other countries. The present volume of the "Condensed Matter Physics" contains proceedings of the conference "Infinite Particle Systems: Complex Systems III", which took place in June 2007.

  4. Modeling of biological intelligence for SCM system optimization.

    Science.gov (United States)

    Chen, Shengyong; Zheng, Yujun; Cattani, Carlo; Wang, Wanliang

    2012-01-01

    This article summarizes some methods from biological intelligence for modeling and optimization of supply chain management (SCM) systems, including genetic algorithms, evolutionary programming, differential evolution, swarm intelligence, artificial immune, and other biological intelligence related methods. An SCM system is adaptive, dynamic, open self-organizing, which is maintained by flows of information, materials, goods, funds, and energy. Traditional methods for modeling and optimizing complex SCM systems require huge amounts of computing resources, and biological intelligence-based solutions can often provide valuable alternatives for efficiently solving problems. The paper summarizes the recent related methods for the design and optimization of SCM systems, which covers the most widely used genetic algorithms and other evolutionary algorithms.

  5. Modeling of Biological Intelligence for SCM System Optimization

    Directory of Open Access Journals (Sweden)

    Shengyong Chen

    2012-01-01

    Full Text Available This article summarizes some methods from biological intelligence for modeling and optimization of supply chain management (SCM systems, including genetic algorithms, evolutionary programming, differential evolution, swarm intelligence, artificial immune, and other biological intelligence related methods. An SCM system is adaptive, dynamic, open self-organizing, which is maintained by flows of information, materials, goods, funds, and energy. Traditional methods for modeling and optimizing complex SCM systems require huge amounts of computing resources, and biological intelligence-based solutions can often provide valuable alternatives for efficiently solving problems. The paper summarizes the recent related methods for the design and optimization of SCM systems, which covers the most widely used genetic algorithms and other evolutionary algorithms.

  6. Modeling of Biological Intelligence for SCM System Optimization

    Science.gov (United States)

    Chen, Shengyong; Zheng, Yujun; Cattani, Carlo; Wang, Wanliang

    2012-01-01

    This article summarizes some methods from biological intelligence for modeling and optimization of supply chain management (SCM) systems, including genetic algorithms, evolutionary programming, differential evolution, swarm intelligence, artificial immune, and other biological intelligence related methods. An SCM system is adaptive, dynamic, open self-organizing, which is maintained by flows of information, materials, goods, funds, and energy. Traditional methods for modeling and optimizing complex SCM systems require huge amounts of computing resources, and biological intelligence-based solutions can often provide valuable alternatives for efficiently solving problems. The paper summarizes the recent related methods for the design and optimization of SCM systems, which covers the most widely used genetic algorithms and other evolutionary algorithms. PMID:22162724

  7. Programming Morphogenesis through Systems and Synthetic Biology.

    Science.gov (United States)

    Velazquez, Jeremy J; Su, Emily; Cahan, Patrick; Ebrahimkhani, Mo R

    2018-04-01

    Mammalian tissue development is an intricate, spatiotemporal process of self-organization that emerges from gene regulatory networks of differentiating stem cells. A major goal in stem cell biology is to gain a sufficient understanding of gene regulatory networks and cell-cell interactions to enable the reliable and robust engineering of morphogenesis. Here, we review advances in synthetic biology, single cell genomics, and multiscale modeling, which, when synthesized, provide a framework to achieve the ambitious goal of programming morphogenesis in complex tissues and organoids. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Systems biology of microbial exopolysaccharides production

    Directory of Open Access Journals (Sweden)

    Ozlem eAtes

    2015-12-01

    Full Text Available Exopolysaccharides (EPS produced by diverse group of microbial systems are rapidly emerging as new and industrially important biomaterials. Due to their unique and complex chemical structures and many interesting physicochemical and rheological properties with novel functionality, the microbial EPSs find wide range of commercial applications in various fields of the economy such as food, feed, packaging, chemical, textile, cosmetics and pharmaceutical industry, agriculture and medicine. EPSs are mainly associated with high-value applications and they have received considerable research attention over recent decades with their biocompatibility, biodegradability, and both environmental and human compatibility. However only a few microbial EPSs have achieved to be used commercially due to their high production costs. The emerging need to overcome economic hurdles and the increasing significance of microbial EPSs in industrial and medical biotechnology call for the elucidation of the interrelations between metabolic pathways and EPS biosynthesis mechanism in order to control and hence enhance its microbial productivity. Moreover a better understanding of biosynthesis mechanism is a significant issue for improvement of product quality and properties and also for the design of novel strains. Therefore a systems-based approach constitutes an important step towards understanding the interplay between metabolism and EPS biosynthesis and further enhances its metabolic performance for industrial application. In this review, primarily the microbial EPSs, their biosynthesis mechanism and important factors for their production will be discussed. After this brief introduction, recent literature on the application of omics technologies and systems biology tools for the improvement of production yields will be critically evaluated. Special focus will be given to EPSs with high market value such as xanthan, levan, pullulan and dextran.

  9. Systems Biology of Microbial Exopolysaccharides Production.

    Science.gov (United States)

    Ates, Ozlem

    2015-01-01

    Exopolysaccharides (EPSs) produced by diverse group of microbial systems are rapidly emerging as new and industrially important biomaterials. Due to their unique and complex chemical structures and many interesting physicochemical and rheological properties with novel functionality, the microbial EPSs find wide range of commercial applications in various fields of the economy such as food, feed, packaging, chemical, textile, cosmetics and pharmaceutical industry, agriculture, and medicine. EPSs are mainly associated with high-value applications, and they have received considerable research attention over recent decades with their biocompatibility, biodegradability, and both environmental and human compatibility. However, only a few microbial EPSs have achieved to be used commercially due to their high production costs. The emerging need to overcome economic hurdles and the increasing significance of microbial EPSs in industrial and medical biotechnology call for the elucidation of the interrelations between metabolic pathways and EPS biosynthesis mechanism in order to control and hence enhance its microbial productivity. Moreover, a better understanding of biosynthesis mechanism is a significant issue for improvement of product quality and properties and also for the design of novel strains. Therefore, a systems-based approach constitutes an important step toward understanding the interplay between metabolism and EPS biosynthesis and further enhances its metabolic performance for industrial application. In this review, primarily the microbial EPSs, their biosynthesis mechanism, and important factors for their production will be discussed. After this brief introduction, recent literature on the application of omics technologies and systems biology tools for the improvement of production yields will be critically evaluated. Special focus will be given to EPSs with high market value such as xanthan, levan, pullulan, and dextran.

  10. Addressing the Complexity of the Earth System

    Energy Technology Data Exchange (ETDEWEB)

    Nobre, Carlos; Brasseur, Guy P.; Shapiro, Melvyn; Lahsen, Myanna; Brunet, Gilbert; Busalacchi, Antonio; Hibbard, Kathleen A.; Seitzinger, Sybil; Noone, Kevin; Ometto, Jean P.

    2010-10-01

    This paper highlights the role of the Earth-system biosphere and illustrates the complex: biosphere-atmosphere interactions in the Amazon Basin, changes in nitrogen cycling, ocean chemistry, and land use. It introduces three important requirements for accelerating the development and use of Earth system information. The first requirement is to develop Earth system analysis and prediction models that account for multi-scale physical, chemical and biological processes, including their interactions in the coupled atmosphere-ocean-land-ice system. The development of these models requires partnerships between academia, national research centers, and operational prediction facilities, and builds upon accomplishments in weather and climate predictions. They will highlight the regional aspects of global change, and include modules for water system, agriculture, forestry, energy, air quality, health, etc. The second requirement is to model the interactions between humans and the weather-climate-biogeochemical system. The third requirement is to introduce novel methodologies to account for societal drivers, impacts and feedbacks. This is a challenging endeavor requiring creative solutions and some compromising because human behavior cannot be fully represented within the framework of present-day physical prediction systems.

  11. Summer School Mathematical Foundations of Complex Networked Information Systems

    CERN Document Server

    Fosson, Sophie; Ravazzi, Chiara

    2015-01-01

    Introducing the reader to the mathematics beyond complex networked systems, these lecture notes investigate graph theory, graphical models, and methods from statistical physics. Complex networked systems play a fundamental role in our society, both in everyday life and in scientific research, with applications ranging from physics and biology to economics and finance. The book is self-contained, and requires only an undergraduate mathematical background.

  12. Multilevel Complex Networks and Systems

    Science.gov (United States)

    Caldarelli, Guido

    2014-03-01

    Network theory has been a powerful tool to model isolated complex systems. However, the classical approach does not take into account the interactions often present among different systems. Hence, the scientific community is nowadays concentrating the efforts on the foundations of new mathematical tools for understanding what happens when multiple networks interact. The case of economic and financial networks represents a paramount example of multilevel networks. In the case of trade, trade among countries the different levels can be described by the different granularity of the trading relations. Indeed, we have now data from the scale of consumers to that of the country level. In the case of financial institutions, we have a variety of levels at the same scale. For example one bank can appear in the interbank networks, ownership network and cds networks in which the same institution can take place. In both cases the systemically important vertices need to be determined by different procedures of centrality definition and community detection. In this talk I will present some specific cases of study related to these topics and present the regularities found. Acknowledged support from EU FET Project ``Multiplex'' 317532.

  13. Synchronizing and controlling hyperchaos in complex Lorentz-Haken systems

    International Nuclear Information System (INIS)

    Fang Jinqing

    1995-03-01

    Synchronizing hyperchaos is realized by the drive-response relationship in the complex Lorentz-Haken system and its higher-order cascading systems for the first time. Controlling hyperchaos is achieved by the intermittent proportional feedback to all of the drive (master) system variables. The complex Lorentz-Haken system describes the detuned single-mode laser and is taken as a typical example of hyperchaotic synchronization to clarify our ideas and results. The ideas and concepts could be extended to some nonlinear dynamical systems and have prospects for potential applications, for example. to laser, electronics, plasma, cryptography, communication, chemical and biological systems and so on. (8 figs., 2 tabs.)

  14. Increase of Organization in Complex Systems

    OpenAIRE

    Georgiev, Georgi Yordanov; Daly, Michael; Gombos, Erin; Vinod, Amrit; Hoonjan, Gajinder

    2013-01-01

    Measures of complexity and entropy have not converged to a single quantitative description of levels of organization of complex systems. The need for such a measure is increasingly necessary in all disciplines studying complex systems. To address this problem, starting from the most fundamental principle in Physics, here a new measure for quantity of organization and rate of self-organization in complex systems based on the principle of least (stationary) action is applied to a model system -...

  15. Complexity and synchronization in stochastic chaotic systems

    Science.gov (United States)

    Son Dang, Thai; Palit, Sanjay Kumar; Mukherjee, Sayan; Hoang, Thang Manh; Banerjee, Santo

    2016-02-01

    We investigate the complexity of a hyperchaotic dynamical system perturbed by noise and various nonlinear speech and music signals. The complexity is measured by the weighted recurrence entropy of the hyperchaotic and stochastic systems. The synchronization phenomenon between two stochastic systems with complex coupling is also investigated. These criteria are tested on chaotic and perturbed systems by mean conditional recurrence and normalized synchronization error. Numerical results including surface plots, normalized synchronization errors, complexity variations etc show the effectiveness of the proposed analysis.

  16. Collaboration in Complex Medical Systems

    Science.gov (United States)

    Xiao, Yan; Mankenzie, Colin F.

    1998-01-01

    Improving our understanding of collaborative work in complex environments has the potential for developing effective supporting technologies, personnel training paradigms, and design principles for multi-crew workplaces. USing a sophisticated audio-video-data acquisition system and a corresponding analysis system, the researchers at University of Maryland have been able to study in detail team performance during real trauma patient resuscitation. The first study reported here was on coordination mechanisms and on characteristics of coordination breakdowns. One of the key findings was that implicit communications were an important coordination mechanism (e.g. through the use of shared workspace and event space). The second study was on the sources of uncertainty during resuscitation. Although incoming trauma patients' status is inherently uncertain, the findings suggest that much of the uncertainty felt by care providers was related to communication and coordination. These two studies demonstrate the value of and need for creating a real-life laboratory for studying team performance with the use of comprehensive and integrated data acquisition and analysis tools.

  17. From structure of the complex to understanding of the biology

    Energy Technology Data Exchange (ETDEWEB)

    Rossmann, Michael G., E-mail: mr@purdue.edu [Department of Biological Sciences, Purdue University, 915 West State Street, West Lafayette, IN 47907-2054 (United States); Arisaka, Fumio [Graduate School and School of Bioscience and Biotechnology, Tokyo Institute of Technology, 5249 Nagatsuta-cho, Yokohama 226-8501-B39 (Japan); Battisti, Anthony J.; Bowman, Valorie D.; Chipman, Paul R.; Fokine, Andrei; Hafenstein, Susan [Department of Biological Sciences, Purdue University, 915 West State Street, West Lafayette, IN 47907-2054 (United States); Kanamaru, Shuji [Department of Biological Sciences, Purdue University, 915 West State Street, West Lafayette, IN 47907-2054 (United States); Graduate School and School of Bioscience and Biotechnology, Tokyo Institute of Technology, 5249 Nagatsuta-cho, Yokohama 226-8501-B39 (Japan); Kostyuchenko, Victor A. [Department of Biological Sciences, Purdue University, 915 West State Street, West Lafayette, IN 47907-2054 (United States); Mesyanzhinov, Vadim V.; Shneider, Mikhail M. [Laboratory of Molecular Bioengineering, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, 16/10 Miklukho-Maklaya Street, Moscow, 117997 (Russian Federation); Morais, Marc C.; Leiman, Petr G. [Department of Biological Sciences, Purdue University, 915 West State Street, West Lafayette, IN 47907-2054 (United States); Palermo, Laura M.; Parrish, Colin R. [James A. Baker Institute, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853 (United States); Xiao, Chuan [Department of Biological Sciences, Purdue University, 915 West State Street, West Lafayette, IN 47907-2054 (United States)

    2007-01-01

    The most extensive structural information on viruses relates to apparently icosahedral virions and is based on X-ray crystallography and on cryo-electron microscopy single-particle reconstructions. This paper concerns itself with the study of the macromolecular complexes that constitute viruses, using structural hybrid techniques. The most extensive structural information on viruses relates to apparently icosahedral virions and is based on X-ray crystallography and on cryo-electron microscopy (cryo-EM) single-particle reconstructions. Both techniques lean heavily on imposing icosahedral symmetry, thereby obscuring any deviation from the assumed symmetry. However, tailed bacteriophages have icosahedral or prolate icosahedral heads that have one obvious unique vertex where the genome can enter for DNA packaging and exit when infecting a host cell. The presence of the tail allows cryo-EM reconstructions in which the special vertex is used to orient the head in a unique manner. Some very large dsDNA icosahedral viruses also develop special vertices thought to be required for infecting host cells. Similarly, preliminary cryo-EM data for the small ssDNA canine parvovirus complexed with receptor suggests that these viruses, previously considered to be accurately icosahedral, might have some asymmetric properties that generate one preferred receptor-binding site on the viral surface. Comparisons are made between rhinoviruses that bind receptor molecules uniformly to all 60 equivalent binding sites, canine parvovirus, which appears to have a preferred receptor-binding site, and bacteriophage T4, which gains major biological advantages on account of its unique vertex and tail organelle.

  18. Engineering Complex Systems: Multiscale Analysis and Evolutionary Engineering

    Science.gov (United States)

    Bar-Yam, Yaneer

    We describe an analytic approach, multiscale analysis, that can demonstrate the fundamental limitations of decomposition based engineering for the development of highly complex systems. The interdependence of components and communication between design teams limits any planning based process. Recognizing this limitation, we found that a new strategy for constructing many highly complex systems should be modeled after biological evolution, or market economies, where multiple design efforts compete in parallel for adoption through testing in actual use. Evolution is the only process that is known to create highly complex systems.

  19. Large-scale computing techniques for complex system simulations

    CERN Document Server

    Dubitzky, Werner; Schott, Bernard

    2012-01-01

    Complex systems modeling and simulation approaches are being adopted in a growing number of sectors, including finance, economics, biology, astronomy, and many more. Technologies ranging from distributed computing to specialized hardware are explored and developed to address the computational requirements arising in complex systems simulations. The aim of this book is to present a representative overview of contemporary large-scale computing technologies in the context of complex systems simulations applications. The intention is to identify new research directions in this field and

  20. Harnessing systems biology approaches to engineer functional microvascular networks.

    Science.gov (United States)

    Sefcik, Lauren S; Wilson, Jennifer L; Papin, Jason A; Botchwey, Edward A

    2010-06-01

    Microvascular remodeling is a complex process that includes many cell types and molecular signals. Despite a continued growth in the understanding of signaling pathways involved in the formation and maturation of new blood vessels, approximately half of all compounds entering clinical trials will fail, resulting in the loss of much time, money, and resources. Most pro-angiogenic clinical trials to date have focused on increasing neovascularization via the delivery of a single growth factor or gene. Alternatively, a focus on the concerted regulation of whole networks of genes may lead to greater insight into the underlying physiology since the coordinated response is greater than the sum of its parts. Systems biology offers a comprehensive network view of the processes of angiogenesis and arteriogenesis that might enable the prediction of drug targets and whether or not activation of the targets elicits the desired outcome. Systems biology integrates complex biological data from a variety of experimental sources (-omics) and analyzes how the interactions of the system components can give rise to the function and behavior of that system. This review focuses on how systems biology approaches have been applied to microvascular growth and remodeling, and how network analysis tools can be utilized to aid novel pro-angiogenic drug discovery.

  1. The semiotics of control and modeling relations in complex systems.

    Science.gov (United States)

    Joslyn, C

    2001-01-01

    We provide a conceptual analysis of ideas and principles from the systems theory discourse which underlie Pattee's semantic or semiotic closure, which is itself foundational for a school of theoretical biology derived from systems theory and cybernetics, and is now being related to biological semiotics and explicated in the relational biological school of Rashevsky and Rosen. Atomic control systems and models are described as the canonical forms of semiotic organization, sharing measurement relations, but differing topologically in that control systems are circularly and models linearly related to their environments. Computation in control systems is introduced, motivating hierarchical decomposition, hybrid modeling and control systems, and anticipatory or model-based control. The semiotic relations in complex control systems are described in terms of relational constraints, and rules and laws are distinguished as contingent and necessary functional entailments, respectively. Finally, selection as a meta-level of constraint is introduced as the necessary condition for semantic relations in control systems and models.

  2. Systems biology: A tool for charting the antiviral landscape.

    Science.gov (United States)

    Bowen, James R; Ferris, Martin T; Suthar, Mehul S

    2016-06-15

    The host antiviral programs that are initiated following viral infection form a dynamic and complex web of responses that we have collectively termed as "the antiviral landscape". Conventional approaches to studying antiviral responses have primarily used reductionist systems to assess the function of a single or a limited subset of molecules. Systems biology is a holistic approach that considers the entire system as a whole, rather than individual components or molecules. Systems biology based approaches facilitate an unbiased and comprehensive analysis of the antiviral landscape, while allowing for the discovery of emergent properties that are missed by conventional approaches. The antiviral landscape can be viewed as a hierarchy of complexity, beginning at the whole organism level and progressing downward to isolated tissues, populations of cells, and single cells. In this review, we will discuss how systems biology has been applied to better understand the antiviral landscape at each of these layers. At the organismal level, the Collaborative Cross is an invaluable genetic resource for assessing how genetic diversity influences the antiviral response. Whole tissue and isolated bulk cell transcriptomics serves as a critical tool for the comprehensive analysis of antiviral responses at both the tissue and cellular levels of complexity. Finally, new techniques in single cell analysis are emerging tools that will revolutionize our understanding of how individual cells within a bulk infected cell population contribute to the overall antiviral landscape. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. A microfluidic dialysis device for complex biological mixture SERS analysis

    KAUST Repository

    Perozziello, Gerardo

    2015-08-01

    In this paper, we present a microfluidic device fabricated with a simple and inexpensive process allowing rapid filtering of peptides from a complex mixture. The polymer microfluidic device can be used for sample preparation in biological applications. The device is fabricated by micromilling and solvent assisted bonding, in which a microdialysis membrane (cut-off of 12-14 kDa) is sandwiched in between an upper and a bottom microfluidic chamber. An external frame connects the microfluidic device to external tubes, microvalves and syringe pumps. Bonding strength and interface sealing are pneumatically tested. Microfluidic protocols are also described by using the presented device to filter a sample composed of specific peptides (MW 1553.73 Da, at a concentration of 1.0 ng/μl) derived from the BRCA1 protein, a tumor-suppressor molecule which plays a pivotal role in the development of breast cancer, and albumin (MW 66.5 kDa, at a concentration of 35 μg/μl), the most represented protein in human plasma. The filtered samples coming out from the microfluidic device were subsequently deposited on a SERS (surface enhanced Raman scattering) substrate for further analysis by Raman spectroscopy. By using this approach, we were able to sort the small peptides from the bigger and highly concentrated protein albumin and to detect them by using a label-free technique at a resolution down to 1.0 ng/μl.

  4. Photosynthetic system as a biological functional element

    International Nuclear Information System (INIS)

    Zakhidov, E.A.; Zakhidova, M.A.; Kasymdzhanov, M.A.; Kurbanov, S.S.; Nematov, Sh.K.; Khabibullaev, P.K.

    2005-01-01

    Photosynthetic apparatus of high plants and photosynthetic bacteria is essentially autonomic system in terms of genetics and structural -functional properties located in specific medium, a bio-membrane. Processes of light absorption and exciton migration in light harvesting antenna, separation and further transfer of charges in reaction centers have specific features, which may be used for application of these objects as key elements in construction of future biological functional elements. Progress in study and genetic modification of photosynthetic membranes achieved during the last decade opens great prospects in development biological functional elements and systems. The main characteristics of photosynthetic system for these purposes are: (i) energy conversion processes in the first light phase of the photosynthesis have very short periods, up to picoseconds, which indicates possibility of creation of ultrafast functional elements on their basis; (ii) characteristics sizes of photosynthetic units, 10-100 nm, and possibility to arrange regularly disposed elements in relevant membranes could be prospective point for creation of nano structures and on their basis relevant biologic functional elements; (iii) elements based on modified photosynthetic apparatus and bio-membranes might be efficiently created by methods of gene engineering and manipulation, that open huge opportunities for development of read biological functional systems. In the paper structural-functional properties and characteristics of high plants and purple photosynthetic bacteria, which may be useful for creation of future biological functional elements are considered. (author)

  5. Biological processing of dinuclear ruthenium complexes in eukaryotic cells.

    Science.gov (United States)

    Li, Xin; Heimann, Kirsten; Dinh, Xuyen Thi; Keene, F Richard; Collins, J Grant

    2016-10-20

    The biological processing - mechanism of cellular uptake, effects on the cytoplasmic and mitochondrial membranes, intracellular sites of localisation and induction of reactive oxygen species - of two dinuclear polypyridylruthenium(ii) complexes has been examined in three eukaryotic cells lines. Flow cytometry was used to determine the uptake of [{Ru(phen)2}2{μ-bb12}](4+) (Rubb12) and [Ru(phen)2(μ-bb7)Ru(tpy)Cl](3+) {Rubb7-Cl, where phen = 1,10-phenanthroline, tpy = 2,2':6',2''-terpyridine and bbn = bis[4(4'-methyl-2,2'-bipyridyl)]-1,n-alkane} in baby hamster kidney (BHK), human embryonic kidney (HEK-293) and liver carcinoma (HepG2) cell lines. The results demonstrated that the major uptake mechanism for Rubb12 and Rubb7-Cl was active transport, although with a significant contribution from carrier-assisted diffusion for Rubb12 and passive diffusion for Rubb7-Cl. Flow cytometry coupled with Annexin V/TO-PRO-3 double-staining was used to compare cell death by membrane damage or apoptosis. Rubb12 induced significant direct membrane damage, particularly with HepG2 cells, while Rubb7-Cl caused considerably less membrane damage but induced greater levels of apoptosis. Confocal microscopy, coupled with JC-1 assays, demonstrated that Rubb12 depolarises the mitochondrial membrane, whereas Rubb7-Cl had a much smaller affect. Cellular localisation experiments indicated that Rubb12 did not accumulate in the mitochondria, whereas significant mitochondrial accumulation was observed for Rubb7-Cl. The effect of Rubb12 and Rubb7-Cl on intracellular superoxide dismutase activity showed that the ruthenium complexes could induce cell death via a reactive oxygen species-mediated pathway. The results of this study demonstrate that Rubb12 predominantly kills eukaryotic cells by damaging the cytoplasmic membrane. As this dinuclear ruthenium complex has been previously shown to exhibit greater toxicity towards bacteria than eukaryotic cells, the results of the present study suggest that

  6. Systems Biology Knowledgebase for a New Era in Biology A Genomics:GTL Report from the May 2008 Workshop

    Energy Technology Data Exchange (ETDEWEB)

    Gregurick, S.; Fredrickson, J. K.; Stevens, R.

    2009-03-01

    Biology has entered a systems-science era with the goal to establish a predictive understanding of the mechanisms of cellular function and the interactions of biological systems with their environment and with each other. Vast amounts of data on the composition, physiology, and function of complex biological systems and their natural environments are emerging from new analytical technologies. Effectively exploiting these data requires developing a new generation of capabilities for analyzing and managing the information. By revealing the core principles and processes conserved in collective genomes across all biology and by enabling insights into the interplay between an organism's genotype and its environment, systems biology will allow scientific breakthroughs in our ability to project behaviors of natural systems and to manipulate and engineer managed systems. These breakthroughs will benefit Department of Energy (DOE) missions in energy security, climate protection, and environmental remediation.

  7. Metasynthetic computing and engineering of complex systems

    CERN Document Server

    Cao, Longbing

    2015-01-01

    Provides a comprehensive overview and introduction to the concepts, methodologies, analysis, design and applications of metasynthetic computing and engineering. The author: Presents an overview of complex systems, especially open complex giant systems such as the Internet, complex behavioural and social problems, and actionable knowledge discovery and delivery in the big data era. Discusses ubiquitous intelligence in complex systems, including human intelligence, domain intelligence, social intelligence, network intelligence, data intelligence and machine intelligence, and their synergy thro

  8. Empirical and theoretical analysis of complex systems

    Science.gov (United States)

    Zhao, Guannan

    This thesis is an interdisciplinary work under the heading of complexity science which focuses on an arguably common "hard" problem across physics, finance and biology [1], to quantify and mimic the macroscopic "emergent phenomenon" in large-scale systems consisting of many interacting "particles" governed by microscopic rules. In contrast to traditional statistical physics, we are interested in systems whose dynamics are subject to feedback, evolution, adaption, openness, etc. Global financial markets, like the stock market and currency market, are ideal candidate systems for such a complexity study: there exists a vast amount of accurate data, which is the aggregate output of many autonomous agents continuously competing with each other. We started by examining the ultrafast "mini flash crash (MFC)" events in the US stock market. An abrupt system-wide composition transition from a mixed human machine phase to a new all-machine phase is uncovered, and a novel theory developed to explain this observation. Then in the study of FX market, we found an unexpected variation in the synchronicity of price changes in different market subsections as a function of the overall trading activity. Several survival models have been tested in analyzing the distribution of waiting times to the next price change. In the region of long waiting-times, the distribution for each currency pair exhibits a power law with exponent in the vicinity of 3.5. By contrast, for short waiting times only, the market activity can be mimicked by the fluctuations emerging from a finite resource competition model containing multiple agents with limited rationality (so called El Farol Model). Switching to the biomedical domain, we present a minimal mathematical model built around a co-evolving resource network and cell population, yielding good agreement with primary tumors in mice experiment and with clinical metastasis data. In the quest to understand contagion phenomena in systems where social group

  9. Heavy ion action on biological systems

    Energy Technology Data Exchange (ETDEWEB)

    Kiefer, J. [Giessen Univ. (Germany). Zentrum fuer Radiologie; Brend`amour, M. [Giessen Univ. (Germany). Zentrum fuer Radiologie; Stoll, U. [Giessen Univ. (Germany). Zentrum fuer Radiologie

    1996-02-01

    Life is governed by molecular processes, particularly involving the expression and conservation of genetic information. Heavy ions deposit large amount of energy at very small scale comparable to the essential molecular structures of biological systems. This paper illustrates the special aspects of heavy ion radiobiology from a fundamental point of view. After a short summary of the structure and function of biological systems, concentrating on the cell and its constituents, the pattern of energy deposition by heavy ions is discussed. Experimental examples are the induction of molecular changes in deoxyribonucleic acid, cell killing and the formation of mutations. It is shown that a close link exists between the physical parameters and the inactivation of biological functions that is not restricted to direct particle traversals but may also be brought about by the action of far-reaching secondary electrons. (orig.).

  10. Reduction of Subjective and Objective System Complexity

    Science.gov (United States)

    Watson, Michael D.

    2015-01-01

    Occam's razor is often used in science to define the minimum criteria to establish a physical or philosophical idea or relationship. Albert Einstein is attributed the saying "everything should be made as simple as possible, but not simpler". These heuristic ideas are based on a belief that there is a minimum state or set of states for a given system or phenomena. In looking at system complexity, these heuristics point us to an idea that complexity can be reduced to a minimum. How then, do we approach a reduction in complexity? Complexity has been described as a subjective concept and an objective measure of a system. Subjective complexity is based on human cognitive comprehension of the functions and inter relationships of a system. Subjective complexity is defined by the ability to fully comprehend the system. Simplifying complexity, in a subjective sense, is thus gaining a deeper understanding of the system. As Apple's Jonathon Ive has stated," It's not just minimalism or the absence of clutter. It involves digging through the depth of complexity. To be truly simple, you have to go really deep". Simplicity is not the absence of complexity but a deeper understanding of complexity. Subjective complexity, based on this human comprehension, cannot then be discerned from the sociological concept of ignorance. The inability to comprehend a system can be either a lack of knowledge, an inability to understand the intricacies of a system, or both. Reduction in this sense is based purely on a cognitive ability to understand the system and no system then may be truly complex. From this view, education and experience seem to be the keys to reduction or eliminating complexity. Objective complexity, is the measure of the systems functions and interrelationships which exist independent of human comprehension. Jonathon Ive's statement does not say that complexity is removed, only that the complexity is understood. From this standpoint, reduction of complexity can be approached

  11. Topological analysis of complexity in multiagent systems

    Science.gov (United States)

    Abaid, Nicole; Bollt, Erik; Porfiri, Maurizio

    2012-04-01

    Social organisms at every level of evolutionary complexity live in groups, such as fish schools, locust swarms, and bird flocks. The complex exchange of multifaceted information across group members may result in a spectrum of salient spatiotemporal patterns characterizing collective behaviors. While instances of collective behavior in animal groups are readily identifiable by trained and untrained observers, a working definition to distinguish these patterns from raw data is not yet established. In this work, we define collective behavior as a manifestation of low-dimensional manifolds in the group motion and we quantify the complexity of such behaviors through the dimensionality of these structures. We demonstrate this definition using the ISOMAP algorithm, a data-driven machine learning algorithm for dimensionality reduction originally formulated in the context of image processing. We apply the ISOMAP algorithm to data from an interacting self-propelled particle model with additive noise, whose parameters are selected to exhibit different behavioral modalities, and from a video of a live fish school. Based on simulations of such model, we find that increasing noise in the system of particles corresponds to increasing the dimensionality of the structures underlying their motion. These low-dimensional structures are absent in simulations where particles do not interact. Applying the ISOMAP algorithm to fish school data, we identify similar low-dimensional structures, which may act as quantitative evidence for order inherent in collective behavior of animal groups. These results offer an unambiguous method for measuring order in data from large-scale biological systems and confirm the emergence of collective behavior in an applicable mathematical model, thus demonstrating that such models are capable of capturing phenomena observed in animal groups.

  12. Radiological/biological/aerosol removal system

    Science.gov (United States)

    Haslam, Jeffery J

    2015-03-17

    An air filter replacement system for existing buildings, vehicles, arenas, and other enclosed airspaces includes a replacement air filter for replacing a standard air filter. The replacement air filter has dimensions and air flow specifications that allow it to replace the standard air filter. The replacement air filter includes a filter material that removes radiological or biological or aerosol particles.

  13. Studies on Semantic Systems Chemical Biology

    Science.gov (United States)

    Chen, Bin

    2012-01-01

    Current "one disease, one target and one drug" drug development paradigm is under question as relatively few drugs have reached the market in the last two decades. Increasingly research focus is being placed on the study of drug action against biological systems as a whole rather than against a single component (called "Systems…

  14. Modular microfluidic system for biological sample preparation

    Science.gov (United States)

    Rose, Klint A.; Mariella, Jr., Raymond P.; Bailey, Christopher G.; Ness, Kevin Dean

    2015-09-29

    A reconfigurable modular microfluidic system for preparation of a biological sample including a series of reconfigurable modules for automated sample preparation adapted to selectively include a) a microfluidic acoustic focusing filter module, b) a dielectrophoresis bacteria filter module, c) a dielectrophoresis virus filter module, d) an isotachophoresis nucleic acid filter module, e) a lyses module, and f) an isotachophoresis-based nucleic acid filter.

  15. Nutritional Systems Biology: Definitions and Approaches

    DEFF Research Database (Denmark)

    Panagiotou, Gianni; Nielsen, Jens

    2009-01-01

    waiting for a predictive knowledge of genetic variation. It is widely recognized that systems and network biology has the potential to increase our understanding of how nutrition influences metabolic pathways and homeostasis, how this regulation is disturbed in a diet-related disease, and to what extent...... individual genotypes contribute to such diseases....

  16. How do biological systems escape 'chaotic' state?

    Indian Academy of Sciences (India)

    B J Rao

    2018-02-13

    Feb 13, 2018 ... triggering 'escape from homeostasis' (Nijhout et al. 2014) where phenotypes begin to become less stable and eventually turn into fully unstable state, the start of 'chaos' in a system. Therefore, the key to biological designs is to stay close to or within the 'homeostatic plateau' and resist drifting into 'chaos'.

  17. Notions of radiation chemistry in biological systems

    International Nuclear Information System (INIS)

    Mastro, N.L. del.

    1989-10-01

    The present paper examines some aspects of the direct and indirect biological radiation effects: pair formation, free radicals, superoxide ion, hydrogen peroxide, hydroxyl radical, oxygen singlet together with the endogen radioprotector mechanisms of organisms and the ways in which an improved radioresistance of biochemical systems can be achieved. (author) [pt

  18. Quantifying electron transfer reactions in biological systems

    DEFF Research Database (Denmark)

    Sjulstok, Emil Sjulstok; Olsen, Jógvan Magnus Haugaard; Solov'yov, Ilia A

    2015-01-01

    to deduce the driving force for the electron transfer reaction and to establish those interactions that play the major role in propelling the electron. The suggested approach is seen as a general recipe to treat electron transfer events in biological systems computationally, and we utilize it to describe...

  19. Micromechanics of engineered and biological systems

    Indian Academy of Sciences (India)

    Microsystems are good examples of integrated engineered systems of small size. Although this .... In develop- mental biology, the application of controlled forces on growing embryos is shown to help in under- standing ..... Optimization is a useful tool for synthesis. Many optimal synthesis methods have been developed for.

  20. Galectin-9: From cell biology to complex disease dynamics

    Indian Academy of Sciences (India)

    Author Affiliations. SEBASTIAN JOHN1 RASHMI MISHRA1. Department of Neurobiology and Genetics, Division of Disease Biology, Rajiv Gandhi Centre for Biotechnology, Poojappura, Thiruvananthapuram 695014, India ...

  1. Visualizing dimensionality reduction of systems biology data

    OpenAIRE

    Lehrmann, Andreas; Huber, Michael; Polatkan, Aydin C.; Pritzkau, Albert; Nieselt, Kay

    2012-01-01

    One of the challenges in analyzing high-dimensional expression data is the detection of important biological signals. A common approach is to apply a dimension reduction method, such as principal component analysis. Typically, after application of such a method the data is projected and visualized in the new coordinate system, using scatter plots or profile plots. These methods provide good results if the data have certain properties which become visible in the new coordinate system and which...

  2. Magnetic biosensor system to detect biological targets

    KAUST Repository

    Li, Fuquan

    2012-09-01

    Magneto-resistive sensors in combination with magnetic beads provide sensing platforms, which are small in size and highly sensitive. These platforms can be fully integrated with microchannels and electronics to enable devices capable of performing complex tasks. Commonly, a sandwich method is used that requires a specific coating of the sensor\\'s surface to immobilize magnetic beads and biological targets on top of the sensor. This paper concerns a micro device to detect biological targets using magnetic concentration, magnetic as well as mechanical trapping and magnetic sensing. Target detection is based on the size difference between bare magnetic beads and magnetic beads with targets attached. This method remedies the need for a coating layer and reduces the number of steps required to run an experiment. © 2012 IEEE.

  3. Systemic Resilience of Complex Urban Systems

    Directory of Open Access Journals (Sweden)

    Serge Salat

    2012-07-01

    Full Text Available Two key paradigms emerge out of the variety of urban forms: certain cities resemble trees, others leaves. The structural difference between a tree and a leaf is huge: one is open, the other closed. Trees are entirely disconnected on a given scale: even if two twigs are spatially close, if they do not belong to the same branch, to go from one to the other implies moving down and then up all the hierarchy of branches.  Leaves on the contrary are entirely connected on intermediary scales. The veins of a leaf are disconnected on the two larger scales but entirely connected on the two or three following intermediary scales before presenting tiny tree-like structures on the finest capillary scales. Deltas are leaves not trees. Neither galaxies nor whirlpools are trees. We will see in this paper that historical cities, like leaves, deltas, galaxies, lungs, brains and vein systems are all fractal structures, multiply connected and complex on all scales. These structures display the same degree of complexity and connectivity, regardless of the magnification scale on which we observe them. We say that these structures are scale free. Mathematical fractal forms are often generated recursively by applying again and again the same generator to an initiator. The iteration creates an arborescence. But scale free structure is not synonymous with a recursive tree-like structure. The fractal structure of the leaf is much more complex than that of the tree by its multiconnectivity on three or more intermediary levels. In contrast, trees in the virgin forest, even when they seem to be entangled, horizontal, and rhizomic, have branches that are not interconnected to form a lattice. As we will see, the history of urban planning has evolved from leaf-like to tree-like patterns, with a consequent loss of efficiency and resilience. Indeed, in a closed foliar path structure, the formation of cycles enables internal complexification and flow fluctuations due to the

  4. Systems biology of vaccination in the elderly.

    Science.gov (United States)

    Duraisingham, Sai S; Rouphael, Nadine; Cavanagh, Mary M; Nakaya, Helder I; Goronzy, Jorg J; Pulendran, Bali

    2013-01-01

    Aging population demographics, combined with suboptimal vaccine responses in the elderly, make the improvement of vaccination strategies in the elderly a developing public health issue. The immune system changes with age, with innate and adaptive cell components becoming increasingly dysfunctional. As such, vaccine responses in the elderly are impaired in ways that differ depending on the type of vaccine (e.g., live attenuated, polysaccharide, conjugate, or subunit) and the mediators of protection (e.g., antibody and/or T cell). The rapidly progressing field of systems biology has been shown to be useful in predicting immunogenicity and offering insights into potential mechanisms of protection in young adults. Future application of systems biology to vaccination in the elderly may help to identify gene signatures that predict suboptimal responses and help to identify more accurate correlates of protection. Moreover, the identification of specific defects may be used to target novel vaccination strategies that improve efficacy in elderly populations.

  5. Measuring cell identity in noisy biological systems

    Science.gov (United States)

    Birnbaum, Kenneth D.; Kussell, Edo

    2011-01-01

    Global gene expression measurements are increasingly obtained as a function of cell type, spatial position within a tissue and other biologically meaningful coordinates. Such data should enable quantitative analysis of the cell-type specificity of gene expression, but such analyses can often be confounded by the presence of noise. We introduce a specificity measure Spec that quantifies the information in a gene's complete expression profile regarding any given cell type, and an uncertainty measure dSpec, which measures the effect of noise on specificity. Using global gene expression data from the mouse brain, plant root and human white blood cells, we show that Spec identifies genes with variable expression levels that are nonetheless highly specific of particular cell types. When samples from different individuals are used, dSpec measures genes’ transcriptional plasticity in each cell type. Our approach is broadly applicable to mapped gene expression measurements in stem cell biology, developmental biology, cancer biology and biomarker identification. As an example of such applications, we show that Spec identifies a new class of biomarkers, which exhibit variable expression without compromising specificity. The approach provides a unifying theoretical framework for quantifying specificity in the presence of noise, which is widely applicable across diverse biological systems. PMID:21803789

  6. Inverse Problems in Systems Biology: A Critical Review.

    Science.gov (United States)

    Guzzi, Rodolfo; Colombo, Teresa; Paci, Paola

    2018-01-01

    Systems Biology may be assimilated to a symbiotic cyclic interplaying between the forward and inverse problems. Computational models need to be continuously refined through experiments and in turn they help us to make limited experimental resources more efficient. Every time one does an experiment we know that there will be some noise that can disrupt our measurements. Despite the noise certainly is a problem, the inverse problems already involve the inference of missing information, even if the data is entirely reliable. So the addition of a certain limited noise does not fundamentally change the situation but can be used to solve the so-called ill-posed problem, as defined by Hadamard. It can be seen as an extra source of information. Recent studies have shown that complex systems, among others the systems biology, are poorly constrained and ill-conditioned because it is difficult to use experimental data to fully estimate their parameters. For these reasons was born the concept of sloppy models, a sequence of models of increasing complexity that become sloppy in the limit of microscopic accuracy. Furthermore the concept of sloppy models contains also the concept of un-identifiability, because the models are characterized by many parameters that are poorly constrained by experimental data. Then a strategy needs to be designed to infer, analyze, and understand biological systems. The aim of this work is to provide a critical review to the inverse problems in systems biology defining a strategy to determine the minimal set of information needed to overcome the problems arising from dynamic biological models that generally may have many unknown, non-measurable parameters.

  7. Catalytic aspects of a copper (II) complex: biological oxidase to ...

    Indian Academy of Sciences (India)

    This copper complex displays excellent catalytic efficiency, kcat /KM (h⁻¹) = 6.17 × 10⁵ towards the oxidative coupling of 2-aminophenol (2-AP) to aminophenoxazin-3-one. Further, upon stoichiometric addition of copper(II) complex to 3,5-DTBC in presence of molecular oxygen in ethanol medium, the copper complex ...

  8. [Systems biology applications to explore secondary metabolites in medicinal plants].

    Science.gov (United States)

    Huang, Luqi; Gao, Wei; Zhou, Jie; Wang, Ruiting

    2010-01-01

    Secondary metabolites are produced during the growth and development of plants along with the adaptation of outer environment, as a rule they are the main active ingredients in medicinal plants and ensure the quality of crude drugs. Since biogenesis is quite complex, the production and accumulation of secondary metabolites are influenced by various biotic and abiotic factors either from gene or environments, the complexity may affect quality control of crude drugs and utilization of the active ingredients. The thought and approach adopted in systems biology is a powerful tool to explore biology fully, along with the development of modern molecular biology and information biology, omics integration like genomics, transcriptomics, proteomics, and metabolomics will bring new opportunities for the study of secondary metabolites of medicinal plant. It has great significance to apply this holistic and systematic method in researches on biosynthetic pathway, signal transduction, ecological environment and metabolic engineering of the formation of the secondary metabolites of medicinal plants, and in building secondary metabolite biosynthesis gene expression and regulation system model, in order to explain the origin of the active ingredients of medicinal plants, formation mechanism of the Chinese herbs, metabolic engineering effecting active ingredients of medicinal plants, and the rational exploitation and utilization of resources of medicinal plants systematically.

  9. Effects of Pesticides on Biological Systems

    Directory of Open Access Journals (Sweden)

    Ergul Belge Kurutas

    2003-06-01

    Full Text Available The use of pesticid both in Turkey and other contries is widespread in order to combat against many pests which cause economical damages. However, pesticides in human pass through skin, respiratory or digestive systems and is metabolized by monooxygenase system dependent upon cytocrome P450 in liver. They also give rise to severe decreases cytochrome P450 and amount of "hem" enzyme activites of glucose-6-phosphatase, pyrophosphatase by stimulating lipid peroxidation on hepatic microsomes. In this study effects of pesticides on biological systems will be presented in genaral terms. [Archives Medical Review Journal 2003; 12(3.000: 215-228

  10. Applying systems biology methods to the study of human physiology in extreme environments

    OpenAIRE

    Edwards, Lindsay M; Thiele, Ines

    2013-01-01

    Systems biology is defined in this review as ‘an iterative process of computational model building and experimental model revision with the aim of understanding or simulating complex biological systems’. We propose that, in practice, systems biology rests on three pillars: computation, the omics disciplines and repeated experimental perturbation of the system of interest. The number of ethical and physiologically relevant perturbations that can be used in experiments on healthy humans is e...

  11. Sandpile model for relaxation in complex systems

    International Nuclear Information System (INIS)

    Vazquez, A.; Sotolongo-Costa, O.; Brouers, F.

    1997-10-01

    The relaxation in complex systems is, in general, nonexponential. After an initial rapid decay the system relaxes slowly following a long time tail. In the present paper a sandpile moderation of the relaxation in complex systems is analysed. Complexity is introduced by a process of avalanches in the Bethe lattice and a feedback mechanism which leads to slower decay with increasing time. In this way, some features of relaxation in complex systems: long time tails relaxation, aging, and fractal distribution of characteristic times, are obtained by simple computer simulations. (author)

  12. Optoelectronic system and apparatus for connection to biological systems

    Energy Technology Data Exchange (ETDEWEB)

    Okandan, Murat; Nielson, Gregory N.

    2018-03-06

    The present invention relates to a biological probe structure, as well as apparatuses, systems, and methods employing this structure. In particular embodiments, the structure includes a hermetically sealed unit configured to receive and transmit one or more optical signals. Furthermore, the structure can be implanted subcutaneously and interrogated externally. In this manner, a minimally invasive method can be employed to detect, treat, and/or assess the biological target. Additional methods and systems are also provided.

  13. Set membership experimental design for biological systems

    Directory of Open Access Journals (Sweden)

    Marvel Skylar W

    2012-03-01

    Full Text Available Abstract Background Experimental design approaches for biological systems are needed to help conserve the limited resources that are allocated for performing experiments. The assumptions used when assigning probability density functions to characterize uncertainty in biological systems are unwarranted when only a small number of measurements can be obtained. In these situations, the uncertainty in biological systems is more appropriately characterized in a bounded-error context. Additionally, effort must be made to improve the connection between modelers and experimentalists by relating design metrics to biologically relevant information. Bounded-error experimental design approaches that can assess the impact of additional measurements on model uncertainty are needed to identify the most appropriate balance between the collection of data and the availability of resources. Results In this work we develop a bounded-error experimental design framework for nonlinear continuous-time systems when few data measurements are available. This approach leverages many of the recent advances in bounded-error parameter and state estimation methods that use interval analysis to generate parameter sets and state bounds consistent with uncertain data measurements. We devise a novel approach using set-based uncertainty propagation to estimate measurement ranges at candidate time points. We then use these estimated measurements at the candidate time points to evaluate which candidate measurements furthest reduce model uncertainty. A method for quickly combining multiple candidate time points is presented and allows for determining the effect of adding multiple measurements. Biologically relevant metrics are developed and used to predict when new data measurements should be acquired, which system components should be measured and how many additional measurements should be obtained. Conclusions The practicability of our approach is illustrated with a case study. This

  14. Large-scale Complex IT Systems

    OpenAIRE

    Sommerville, Ian; Cliff, Dave; Calinescu, Radu; Keen, Justin; Kelly, Tim; Kwiatkowska, Marta; McDermid, John; Paige, Richard

    2011-01-01

    This paper explores the issues around the construction of large-scale complex systems which are built as 'systems of systems' and suggests that there are fundamental reasons, derived from the inherent complexity in these systems, why our current software engineering methods and techniques cannot be scaled up to cope with the engineering challenges of constructing such systems. It then goes on to propose a research and education agenda for software engineering that identifies the major challen...

  15. Large-scale complex IT systems

    OpenAIRE

    Sommerville, Ian; Cliff, Dave; Calinescu, Radu; Keen, Justin; Kelly, Tim; Kwiatkowska, Marta; McDermid, John; Paige, Richard

    2012-01-01

    12 pages, 2 figures This paper explores the issues around the construction of large-scale complex systems which are built as 'systems of systems' and suggests that there are fundamental reasons, derived from the inherent complexity in these systems, why our current software engineering methods and techniques cannot be scaled up to cope with the engineering challenges of constructing such systems. It then goes on to propose a research and education agenda for software engineering that ident...

  16. Natural selection and self-organization in complex adaptive systems.

    Science.gov (United States)

    Di Bernardo, Mirko

    2010-01-01

    The central theme of this work is self-organization "interpreted" both from the point of view of theoretical biology, and from a philosophical point of view. By analysing, on the one hand, those which are now considered--not only in the field of physics--some of the most important discoveries, that is complex systems and deterministic chaos and, on the other hand, the new frontiers of systemic biology, this work highlights how large thermodynamic systems which are open can spontaneously stay in an orderly regime. Such systems can represent the natural source of the order required for a stable self-organization, for homoeostasis and for hereditary variations. The order, emerging in enormous randomly interconnected nets of binary variables, is almost certainly only the precursor of similar orders emerging in all the varieties of complex systems. Hence, this work, by finding new foundations for the order pervading the living world, advances the daring hypothesis according to which Darwinian natural selection is not the only source of order in the biosphere. Thus, the article, by examining the passage from Prigogine's dissipative structures theory to the contemporary theory of biological complexity, highlights the development of a coherent and continuous line of research which is set to individuate the general principles marking the profound reality of that mysterious self-organization characterizing the complexity of life.

  17. Statistical physics of complex systems a concise introduction

    CERN Document Server

    Bertin, Eric

    2016-01-01

    This course-tested primer provides graduate students and non-specialists with a basic understanding of the concepts and methods of statistical physics and demonstrates their wide range of applications to interdisciplinary topics in the field of complex system sciences, including selected aspects of theoretical modeling in biology and the social sciences. Generally speaking, the goals of statistical physics may be summarized as follows: on the one hand to study systems composed of a large number of interacting units, and on the other to predict the macroscopic, collective behavior of the system considered from the perspective of the microscopic laws governing the dynamics of the individual entities. These two goals are essentially also shared by what is now called 'complex systems science', and as such, systems studied in the framework of statistical physics may be considered to be among the simplest examples of complex systems – while also offering a rather well developed mathematical treatment. The second ...

  18. Nonlinear Phenomena in Complex Systems: From Nano to Macro Scale

    CERN Document Server

    Stanley, H

    2014-01-01

    Topics of complex system physics and their interdisciplinary applications to different problems in seismology, biology, economy, sociology,  energy and nanotechnology are covered in this new work from renowned experts in their fields.  In  particular, contributed papers contain original results on network science, earthquake dynamics, econophysics, sociophysics, nanoscience and biological physics. Most of the papers use interdisciplinary approaches based on statistical physics, quantum physics and other topics of complex system physics.  Papers on econophysics and sociophysics are focussed on societal aspects of physics such as, opinion dynamics, public debates and financial and economic stability. This work will be of interest to statistical physicists, economists, biologists, seismologists and all scientists working in interdisciplinary topics of complexity.

  19. The Impact of Systems Biology on Bioprocessing

    DEFF Research Database (Denmark)

    Campbell, Kate; Xia, Jianye; Nielsen, Jens

    2017-01-01

    alongside mathematical modeling to characterize and predict cellular physiology. This approach can drive cycles of design, build, test, and learn implemented by metabolic engineers to optimize the cell factory performance. Streamlining of the design phase requires a clearer understanding of metabolism...... and its regulation, which can be achieved using quantitative and integrated omic characterization, alongside more advanced analytical methods. We discuss here the current impact of systems biology and challenges of closing the gap between bioprocessing and more traditional methods of chemical production....

  20. Nutritional systems biology of type 2 diabetes

    OpenAIRE

    Zhao, Y; Barrere-Cain, RE; Yang, X

    2015-01-01

    © 2015, The Author(s). Type 2 diabetes (T2D) has become an increasingly challenging health burden due to its high morbidity, mortality, and heightened prevalence worldwide. Although dietary and nutritional imbalances have long been recognized as key risk factors for T2D, the underlying mechanisms remain unclear. The advent of nutritional systems biology, a field that aims to elucidate the interactions between dietary nutrients and endogenous molecular entities in disease-related tissues, offe...

  1. Modelling and Inference Strategies for Biological Systems

    OpenAIRE

    Palmisano, Alida

    2010-01-01

    For many years, computers have played an important role in helping scientists to store, manipulate, and analyze data coming from many different disciplines. In recent years, however, new technological capabilities and new ways of thinking about the usefulness of computer science is extending the reach of computers from simple analysis of collected data to hypothesis generation. The aim of this work is to provide a contribution in the Computational Systems Biology field. The main purpose of...

  2. Systems thinking and complexity: considerations for health promoting schools.

    Science.gov (United States)

    Rosas, Scott R

    2017-04-01

    The health promoting schools concept reflects a comprehensive and integrated philosophy to improving student and personnel health and well-being. Conceptualized as a configuration of interacting, interdependent parts connected through a web of relationships that form a whole greater than the sum of its parts, school health promotion initiatives often target several levels (e.g. individual, professional, procedural and policy) simultaneously. Health promoting initiatives, such as those operationalized under the whole school approach, include several interconnected components that are coordinated to improve health outcomes in complex settings. These complex systems interventions are embedded in intricate arrangements of physical, biological, ecological, social, political and organizational relationships. Systems thinking and characteristics of complex adaptive systems are introduced in this article to provide a perspective that emphasizes the patterns of inter-relationships associated with the nonlinear, dynamic and adaptive nature of complex hierarchical systems. Four systems thinking areas: knowledge, networks, models and organizing are explored as a means to further manage the complex nature of the development and sustainability of health promoting schools. Applying systems thinking and insights about complex adaptive systems can illuminate how to address challenges found in settings with both complicated (i.e. multi-level and multisite) and complex aspects (i.e. synergistic processes and emergent outcomes). © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  3. Models of complex attitude systems

    DEFF Research Database (Denmark)

    Sørensen, Bjarne Taulo

    Existing research on public attitudes towards agricultural production systems is largely descriptive, abstracting from the processes through which members of the general public generate their evaluations of such systems. The present paper adopts a systems perspective on such evaluations, understa......Existing research on public attitudes towards agricultural production systems is largely descriptive, abstracting from the processes through which members of the general public generate their evaluations of such systems. The present paper adopts a systems perspective on such evaluations......, understanding them as embedded into a wider attitude system that consists of attitudes towards objects of different abstraction levels, ranging from personal value orientations over general socio-political attitudes to evaluations of specific characteristics of agricultural production systems. It is assumed...... that evaluative affect propagates through the system in such a way that the system becomes evaluatively consistent and operates as a schema for the generation of evaluative judgments. In the empirical part of the paper, the causal structure of an attitude system from which people derive their evaluations of pork...

  4. Reliability of large and complex systems

    CERN Document Server

    Kolowrocki, Krzysztof

    2014-01-01

    Reliability of Large and Complex Systems, previously titled Reliability of Large Systems, is an innovative guide to the current state and reliability of large and complex systems. In addition to revised and updated content on the complexity and safety of large and complex mechanisms, this new edition looks at the reliability of nanosystems, a key research topic in nanotechnology science. The author discusses the importance of safety investigation of critical infrastructures that have aged or have been exposed to varying operational conditions. This reference provides an asympt

  5. Multi-agent and complex systems

    CERN Document Server

    Ren, Fenghui; Fujita, Katsuhide; Zhang, Minjie; Ito, Takayuki

    2017-01-01

    This book provides a description of advanced multi-agent and artificial intelligence technologies for the modeling and simulation of complex systems, as well as an overview of the latest scientific efforts in this field. A complex system features a large number of interacting components, whose aggregate activities are nonlinear and self-organized. A multi-agent system is a group or society of agents which interact with others cooperatively and/or competitively in order to reach their individual or common goals. Multi-agent systems are suitable for modeling and simulation of complex systems, which is difficult to accomplish using traditional computational approaches.

  6. The Promise of Systems Biology for Diabetic Kidney Disease.

    Science.gov (United States)

    Brosius, Frank C; Ju, Wenjun

    2018-03-01

    Diabetic kidney disease (DKD) has a complex and prolonged pathogenesis involving many cell types in the kidney as well as extrarenal factors. It is clinically silent for many years after the onset of diabetes and usually progresses over decades. Given this complexity, a comprehensive and unbiased molecular approach is best suited to help identify the most critical mechanisms responsible for progression of DKD and those most suited for targeted intervention. Systems biological investigations provide such an approach since they examine the entire network of molecular changes that occur in a disease process in a comprehensive way instead of focusing on a single abnormal molecule or pathway. Systems biological studies can also start with analysis of the disease in humans, not in animal or cell culture models that often poorly reproduce the changes in human DKD. Indeed, in the last decade, systems biological approaches have led to the identification of critical molecular abnormalities in DKD and have directly led to development of new biomarkers and potential treatments for DKD. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  7. Systems Biology for Mapping Genotype-Phenotype Relations in Yeast

    KAUST Repository

    Nielsen, Jens

    2016-01-25

    The yeast Saccharomyces cerevisiae is widely used for production of fuels, chemicals, pharmaceuticals and materials. Through metabolic engineering of this yeast a number of novel new industrial processes have been developed over the last 10 years. Besides its wide industrial use, S. cerevisiae serves as an eukaryal model organism, and many systems biology tools have therefore been developed for this organism. Among these genome-scale metabolic models have shown to be most successful as they easy integrate with omics data and at the same time have been shown to have excellent predictive power. Despite our extensive knowledge of yeast metabolism and its regulation we are still facing challenges when we want to engineer complex traits, such as improved tolerance to toxic metabolites like butanol and elevated temperatures or when we want to engineer the highly complex protein secretory pathway. In this presentation it will be demonstrated how we can combine directed evolution with systems biology analysis to identify novel targets for rational design-build-test of yeast strains that have improved phenotypic properties. In this lecture an overview of systems biology of yeast will be presented together with examples of how genome-scale metabolic modeling can be used for prediction of cellular growth at different conditions. Examples will also be given on how adaptive laboratory evolution can be used for identifying targets for improving tolerance towards butanol, increased temperature and low pH and for improving secretion of heterologous proteins.

  8. Integrated Network Analysis and Effective Tools in Plant Systems Biology

    Directory of Open Access Journals (Sweden)

    Atsushi eFukushima

    2014-11-01

    Full Text Available One of the ultimate goals in plant systems biology is to elucidate the genotype-phenotype relationship in plant cellular systems. Integrated network analysis that combines omics data with mathematical models has received particular attention. Here we focus on the latest cutting-edge computational advances that facilitate their combination. We highlight (1 network visualization tools, (2 pathway analyses, (3 genome-scale metabolic reconstruction, and (4 the integration of high-throughput experimental data and mathematical models. Multi-omics data that contain the genome, transcriptome, proteome, and metabolome and mathematical models are expected to integrate and expand our knowledge of complex plant metabolisms.

  9. Monitoring prion protein expression in complex biological samples by SERS for diagnostic applications

    International Nuclear Information System (INIS)

    Manno, D; Filippo, E; Fiore, R; Serra, A; Urso, E; Rizzello, A; Maffia, M

    2010-01-01

    Surface-enhanced Raman spectroscopy (SERS) allows a new insight into the analysis of cell physiology. In this work, the difficulty of producing suitable substrates that, besides permitting the amplification of the Raman signal, do not interact with the biological material causing alteration, has been overcome by a combined method of hydrothermal green synthesis and thermal annealing. The SERS analysis of the cell membrane has been performed with special attention to the cellular prion protein PrP C . In addition, SERS has also been used to reveal the prion protein-Cu(II) interaction in four different cell models (B104, SH-SY5Y, GN11, HeLa), expressing PrP C at different levels. A significant implication of the current work consists of the intriguing possibility of revealing and quantifying prion protein expression in complex biological samples by a cheap SERS-based method, replacing the expensive and time-consuming immuno-assay systems commonly employed.

  10. Mining sensor data from complex systems

    NARCIS (Netherlands)

    Vespier, Ugo

    2015-01-01

    Today, virtually everything, from natural phenomena to complex artificial and physical systems, can be measured and the resulting information collected, stored and analyzed in order to gain new insight. This thesis shows how complex systems often exhibit diverse behavior at different temporal

  11. Biological Complexities in Radiation Carcinogenesis and Cancer Radiotherapy: Impact of New Biological Paradigms

    Directory of Open Access Journals (Sweden)

    Hossein Mozdarani

    2012-01-01

    Full Text Available Although radiation carcinogenesis has been shown both experimentally and epidemiologically, the use of ionizing radiation is also one of the major modalities in cancer treatment. Various known cellular and molecular events are involved in carcinogenesis. Apart from the known phenomena, there could be implications for carcinogenesis and cancer prevention due to other biological processes such as the bystander effect, the abscopal effect, intrinsic radiosensitivity and radioadaptation. Bystander effects have consequences for mutation initiated cancer paradigms of radiation carcinogenesis, which provide the mechanistic justification for low-dose risk estimates. The abscopal effect is potentially important for tumor control and is mediated through cytokines and/or the immune system (mainly cell-mediated immunity. It results from loss of growth and stimulatory and/or immunosuppressive factors from the tumor. Intrinsic radiosensitivity is a feature of some cancer prone chromosomal breakage syndromes such as ataxia telangectiasia. Radiosensitivity is manifested as higher chromosomal aberrations and DNA repair impairment is now known as a good biomarker for breast cancer screening and prediction of prognosis. However, it is not yet known whether this effect is good or bad for those receiving radiation or radiomimetic agents for treatment. Radiation hormesis is another major concern for carcinogenesis. This process which protects cells from higher doses of radiation or radio mimic chemicals, may lead to the escape of cells from mitotic death or apoptosis and put cells with a lower amount of damage into the process of cancer induction. Therefore, any of these biological phenomena could have impact on another process giving rise to genome instability of cells which are not in the field of radiation but still receiving a lower amount of radiation. For prevention of radiation induced carcinogenesis or risk assessment as well as for successful radiation

  12. COMPLEX DESIGN OF INTEGRATED MATERIAL FLOW SYSTEMS

    OpenAIRE

    PÉTER TELEK; TAMÁS BÁNYAI

    2013-01-01

    Material flow systems have in generally very complex structure and relations. During design, building and operation of complex systems there are many different problems. This paper shows some usable solution for the design and selection process of material flow systems. We give a short overview about the theoretical principles of the design process, then describe the base design tasks, the possibilities of the using of heuristic algorithms and the modelling of material flow systems. At the en...

  13. GPSR: A Resource for Genomics Proteomics and Systems Biology

    Indian Academy of Sciences (India)

    GPSR: A Resource for Genomics Proteomics and Systems Biology · Simple Calculation Programs for Biology Immunological Methods · Simple Calculation Programs for Biology Methods in Molecular Biology · Simple Calculation Programs for Biology Other Methods · PowerPoint Presentation · Slide 6 · Slide 7 · Prediction of ...

  14. Electron Transfer Studies of Ruthenium(II) Complexes with Biologically Important Phenolic Acids and Tyrosine.

    Science.gov (United States)

    Rajeswari, Angusamy; Ramdass, Arumugam; Muthu Mareeswaran, Paulpandian; Rajagopal, Seenivasan

    2016-03-01

    The ruthenium(II) complexes having 2,2'-bipyridine and phenanthroline derivatives are synthesized and characterized. The photophysical properties of these complexes at pH 12.5 are studied. The electron transfer reaction of biologically important phenolic acids and tyrosine are studied using absorption, emission and transient absorption spectral techniques. Semiclassical theory is applied to calculate the rate of electron transfer between ruthenium(II) complexes and biologically important phenolic acids.

  15. Change and Identity in Complex Systems

    Directory of Open Access Journals (Sweden)

    Graeme S. Cumming

    2005-06-01

    Full Text Available Complex systems are dynamic and may show high levels of variability in both space and time. It is often difficult to decide on what constitutes a given complex system, i.e., where system boundaries should be set, and what amounts to substantial change within the system. We discuss two central themes: the nature of system definitions and their ability to cope with change, and the importance of system definitions for the mental metamodels that we use to describe and order ideas about system change. Systems can only be considered as single study units if they retain their identity. Previous system definitions have largely ignored the need for both spatial and temporal continuity as essential attributes of identity. After considering the philosophical issues surrounding identity and system definitions, we examine their application to modeling studies. We outline a set of five alternative metamodels that capture a range of the basic dynamics of complex systems. Although Holling's adaptive cycle is a compelling and widely applicable metamodel that fits many complex systems, there are systems that do not necessarily follow the adaptive cycle. We propose that more careful consideration of system definitions and alternative metamodels for complex systems will lead to greater conceptual clarity in the field and, ultimately, to more rigorous research.

  16. Biological activities of some Fluoroquinolones-metal complexes

    African Journals Online (AJOL)

    McRoy

    synthesis of two zinc (II) complexes with ciprofloxacin,. [cfH2]2[ZnCl4].2H2O and. [Zn(cf)2]3H2O[32] and a cobalt complex, compound. [Co(cf)2].3H2O.[33] The complex [cfH2]2[ZnCl4].2H2O was shown to be ionic consisting of a tetrachlorozincate(II) dianion and two protonated monatomic ciprofloxacin molecules, while.

  17. Engineering biological systems toward a sustainable bioeconomy.

    Science.gov (United States)

    Lopes, Mateus Schreiner Garcez

    2015-06-01

    The nature of our major global risks calls for sustainable innovations to decouple economic growth from greenhouse gases emission. The development of sustainable technologies has been negatively impacted by several factors including sugar production costs, production scale, economic crises, hydraulic fracking development and the market inability to capture externality costs. However, advances in engineering of biological systems allow bridging the gap between exponential growth of knowledge about biology and the creation of sustainable value chains for a broad range of economic sectors. Additionally, industrial symbiosis of different biobased technologies can increase competitiveness and sustainability, leading to the development of eco-industrial parks. Reliable policies for carbon pricing and revenue reinvestments in disruptive technologies and in the deployment of eco-industrial parks could boost the welfare while addressing our major global risks toward the transition from a fossil to a biobased economy.

  18. Biological Therapy in Systemic Lupus Erythematosus

    Directory of Open Access Journals (Sweden)

    Mariana Postal

    2012-01-01

    Full Text Available Systemic lupus erythematosus (SLE is a prototypic inflammatory autoimmune disorder characterized by multisystem involvement and fluctuating disease activity. Symptoms range from rather mild manifestations such as rash or arthritis to life-threatening end-organ manifestations. Despite new and improved therapy having positively impacted the prognosis of SLE, a subgroup of patients do not respond to conventional therapy. Moreover, the risk of fatal outcomes and the damaging side effects of immunosuppressive therapies in SLE call for an improvement in the current therapeutic management. New therapeutic approaches are focused on B-cell targets, T-cell downregulation and costimulatory blockade, cytokine inhibition, and the modulation of complement. Several biological agents have been developed, but this encouraging news is associated with several disappointments in trials and provide a timely moment to reflect on biologic therapy in SLE.

  19. Methylene Diphosphonate Chemical and Biological control of MDP complex

    CERN Document Server

    Aungurarat, A

    2000-01-01

    Technetium-9 sup 9 sup m MDP easy prepared from MDP kits which different sources such as OAP (In house), SIGMA. The resulting Tc 9 sup 9 sup m -MDP preparations were controlled in chemical and biological tests to compare the different results in these cases: radiochemical purity, the quantity of starting material and biodistribution result.

  20. Complex System Governance for Acquisition

    Science.gov (United States)

    2016-04-30

    2005; Whitney et al., 2015) and Management Cybernetics ( Beer , 1972, 1979, 1985) and the field has been built upon their philosophical, theoretical, and...et al., 2015), while Management Cybernetics has been identified as the science of effective (system) organization ( Beer , 1972). Following from the...field’s foundations in Systems Theory. It would be easy to dismiss development of the science thrust for acquisition as nonessential or a frivolous waste

  1. Adaptable data management for systems biology investigations

    Directory of Open Access Journals (Sweden)

    Burdick David

    2009-03-01

    Full Text Available Abstract Background Within research each experiment is different, the focus changes and the data is generated from a continually evolving barrage of technologies. There is a continual introduction of new techniques whose usage ranges from in-house protocols through to high-throughput instrumentation. To support these requirements data management systems are needed that can be rapidly built and readily adapted for new usage. Results The adaptable data management system discussed is designed to support the seamless mining and analysis of biological experiment data that is commonly used in systems biology (e.g. ChIP-chip, gene expression, proteomics, imaging, flow cytometry. We use different content graphs to represent different views upon the data. These views are designed for different roles: equipment specific views are used to gather instrumentation information; data processing oriented views are provided to enable the rapid development of analysis applications; and research project specific views are used to organize information for individual research experiments. This management system allows for both the rapid introduction of new types of information and the evolution of the knowledge it represents. Conclusion Data management is an important aspect of any research enterprise. It is the foundation on which most applications are built, and must be easily extended to serve new functionality for new scientific areas. We have found that adopting a three-tier architecture for data management, built around distributed standardized content repositories, allows us to rapidly develop new applications to support a diverse user community.

  2. Adaptable data management for systems biology investigations

    Science.gov (United States)

    Boyle, John; Rovira, Hector; Cavnor, Chris; Burdick, David; Killcoyne, Sarah; Shmulevich, Ilya

    2009-01-01

    Background Within research each experiment is different, the focus changes and the data is generated from a continually evolving barrage of technologies. There is a continual introduction of new techniques whose usage ranges from in-house protocols through to high-throughput instrumentation. To support these requirements data management systems are needed that can be rapidly built and readily adapted for new usage. Results The adaptable data management system discussed is designed to support the seamless mining and analysis of biological experiment data that is commonly used in systems biology (e.g. ChIP-chip, gene expression, proteomics, imaging, flow cytometry). We use different content graphs to represent different views upon the data. These views are designed for different roles: equipment specific views are used to gather instrumentation information; data processing oriented views are provided to enable the rapid development of analysis applications; and research project specific views are used to organize information for individual research experiments. This management system allows for both the rapid introduction of new types of information and the evolution of the knowledge it represents. Conclusion Data management is an important aspect of any research enterprise. It is the foundation on which most applications are built, and must be easily extended to serve new functionality for new scientific areas. We have found that adopting a three-tier architecture for data management, built around distributed standardized content repositories, allows us to rapidly develop new applications to support a diverse user community. PMID:19265554

  3. Genome modularity and synthetic biology: Engineering systems.

    Science.gov (United States)

    Mol, Milsee; Kabra, Ritika; Singh, Shailza

    2018-01-01

    Whole genome sequencing projects running in various laboratories around the world has generated immense data. A systematic phylogenetic analysis of this data shows that genome complexity goes on decreasing as it evolves, due to its modular nature. This modularity can be harnessed to minimize the genome further to reduce it with the bare minimum essential genes. A reduced modular genome, can fuel progress in the area of synthetic biology by providing a ready to use plug and play chassis. Advances in gene editing technology such as the use of tailor made synthetic transcription factors will further enhance the availability of synthetic devices to be applied in the fields of environment, agriculture and health. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Predicting biological system objectives de novo from internal state measurements

    Directory of Open Access Journals (Sweden)

    Maranas Costas D

    2008-01-01

    Full Text Available Abstract Background Optimization theory has been applied to complex biological systems to interrogate network properties and develop and refine metabolic engineering strategies. For example, methods are emerging to engineer cells to optimally produce byproducts of commercial value, such as bioethanol, as well as molecular compounds for disease therapy. Flux balance analysis (FBA is an optimization framework that aids in this interrogation by generating predictions of optimal flux distributions in cellular networks. Critical features of FBA are the definition of a biologically relevant objective function (e.g., maximizing the rate of synthesis of biomass, a unit of measurement of cellular growth and the subsequent application of linear programming (LP to identify fluxes through a reaction network. Despite the success of FBA, a central remaining challenge is the definition of a network objective with biological meaning. Results We present a novel method called Biological Objective Solution Search (BOSS for the inference of an objective function of a biological system from its underlying network stoichiometry as well as experimentally-measured state variables. Specifically, BOSS identifies a system objective by defining a putative stoichiometric "objective reaction," adding this reaction to the existing set of stoichiometric constraints arising from known interactions within a network, and maximizing the putative objective reaction via LP, all the while minimizing the difference between the resultant in silico flux distribution and available experimental (e.g., isotopomer flux data. This new approach allows for discovery of objectives with previously unknown stoichiometry, thus extending the biological relevance from earlier methods. We verify our approach on the well-characterized central metabolic network of Saccharomyces cerevisiae. Conclusion We illustrate how BOSS offers insight into the functional organization of biochemical networks

  5. It's the System, Stupid: How Systems Biology Is Transforming.

    Science.gov (United States)

    2010-01-01

    So far, little is known about systems biology and its potential for changing how we diagnose and treat disease. That will change soon, say the systems experts, who advise payers to begin learning now about how it could make healthcare efficient.

  6. Translating inter-individual genetic variation to biological function in complex phenotypes

    DEFF Research Database (Denmark)

    Yadav, Rachita

    and phosphor-proteome in chemotherapy resistant breast cancer cell lines with high TIMP-1 gene expression. In summary, this thesis work demonstrates applications of various omic variations at different levels of complexity and their integration using systems biology based methodologies to associate them...... artificial neural network (ANN) based methodology of selecting genetic and clinical features with predictive power for childhood asthma. The goal of these studies is to understand the complex genetics of childhood asthma. The third part of this thesis (chapters 5 and 6) focuses on various mechanisms involved...... populations. Next, the second portion of this chapter describes a personalised genome study of an ancient genome which was conducted by calculating the genetic risk scores to unravel phenotypes. Appendix section (Chapter 8) comprises of an integrative functional analysis study of the changing proteome...

  7. Simulation and Analysis of Complex Biological Processes: an Organisation Modelling Perspective

    NARCIS (Netherlands)

    Bosse, T.; Jonker, C.M.; Treur, J.

    2005-01-01

    This paper explores how the dynamics of complex biological processes can be modelled and simulated as an organisation of multiple agents. This modelling perspective identifies organisational structure occurring in complex decentralised processes and handles complexity of the analysis of the dynamics

  8. The systemic dimension of operational decision in complex systems work

    OpenAIRE

    Sampaio, José João

    2009-01-01

    This paper refers to some of my research findings on Decision Making processes in complex systems work. Starting as a complex cognitive process strongly contextualized in the operating environment, it ends up, in complex systems work, as an equally complex network of actors and systems (human and technological) that are confronted, in real time, with uncertainty , a large amount of information and feedback and with multiple standards and operating procedures...

  9. Collaborative Systems Biology Projects for the Military Medical Community.

    Science.gov (United States)

    Zalatoris, Jeffrey J; Scheerer, Julia B; Lebeda, Frank J

    2017-09-01

    This pilot study was conducted to examine, for the first time, the ongoing systems biology research and development projects within the laboratories and centers of the U.S. Army Medical Research and Materiel Command (USAMRMC). The analysis has provided an understanding of the breadth of systems biology activities, resources, and collaborations across all USAMRMC subordinate laboratories. The Systems Biology Collaboration Center at USAMRMC issued a survey regarding systems biology research projects to the eight U.S.-based USAMRMC laboratories and centers in August 2016. This survey included a data call worksheet to gather self-identified project and programmatic information. The general topics focused on the investigators and their projects, on the project's research areas, on omics and other large data types being collected and stored, on the analytical or computational tools being used, and on identifying intramural (i.e., USAMRMC) and extramural collaborations. Among seven of the eight laboratories, 62 unique systems biology studies were funded and active during the final quarter of fiscal year 2016. Of 29 preselected medical Research Task Areas, 20 were associated with these studies, some of which were applicable to two or more Research Task Areas. Overall, studies were categorized among six general types of objectives: biological mechanisms of disease, risk of/susceptibility to injury or disease, innate mechanisms of healing, diagnostic and prognostic biomarkers, and host/patient responses to vaccines, and therapeutic strategies including host responses to therapies. We identified eight types of omics studies and four types of study subjects. Studies were categorized on a scale of increasing complexity from single study subject/single omics technology studies (23/62) to studies integrating results across two study subject types and two or more omics technologies (13/62). Investigators at seven USAMRMC laboratories had collaborations with systems biology experts

  10. Workshop on Nonlinear Phenomena in Complex Systems

    CERN Document Server

    1989-01-01

    This book contains a thorough treatment of neural networks, cellular-automata and synergetics, in an attempt to provide three different approaches to nonlinear phenomena in complex systems. These topics are of major interest to physicists active in the fields of statistical mechanics and dynamical systems. They have been developed with a high degree of sophistication and include the refinements necessary to work with the complexity of real systems as well as the more recent research developments in these areas.

  11. A Concise Introduction to the Statistical Physics of Complex Systems

    CERN Document Server

    Bertin, Eric

    2012-01-01

    This concise primer (based on lectures given at summer schools on complex systems and on a masters degree course in complex systems modeling) will provide graduate students and newcomers to the field with the basic knowledge of the concepts and methods of statistical physics and its potential for application to interdisciplinary topics.  Indeed, in recent years, statistical physics has begun to attract the interest of a broad community of researchers in the field of complex system sciences, ranging from biology to the social sciences, economics and computer science. More generally, a growing number of graduate students and researchers feel the need to learn some basic concepts and questions originating in other disciplines without necessarily having to master all of the corresponding technicalities and jargon. Generally speaking, the goals of statistical physics may be summarized as follows: on the one hand to study systems composed of a large number of interacting ‘entities’, and on the other to predict...

  12. Complex Time-Delay Systems Theory and Applications

    CERN Document Server

    Atay, Fatihcan M

    2010-01-01

    Time delays in dynamical systems arise as an inevitable consequence of finite speeds of information transmission. Realistic models increasingly demand the inclusion of delays in order to properly understand, analyze, design, and control real-life systems. The goal of this book is to present the state-of-the-art in research on time-delay dynamics in the framework of complex systems and networks. While the mathematical theory of delay equations is quite mature, its application to the particular problems of complex systems and complexity is a newly emerging field, and the present volume aims to play a pioneering role in this perspective. The chapters in this volume are authored by renowned experts and cover both theory and applications in a wide range of fields, with examples extending from neuroscience and biology to laser physics and vehicle traffic. Furthermore, all chapters include sufficient introductory material and extensive bibliographies, making the book a self-contained reference for both students and ...

  13. Systems Biology: Impressions from a Newcomer Graduate Student in 2016

    Science.gov (United States)

    Simpson, Melanie Rae

    2016-01-01

    As a newcomer, the philosophical basis of systems biology seems intuitive and appealing, the underlying philosophy being that the whole of a living system cannot be completely understood by the study of its individual parts. Yet answers to the questions "What is systems biology?" and "What constitutes a systems biology approach in…

  14. Complex energy system management using optimization techniques

    Energy Technology Data Exchange (ETDEWEB)

    Bridgeman, Stuart; Hurdowar-Castro, Diana; Allen, Rick; Olason, Tryggvi; Welt, Francois

    2010-09-15

    Modern energy systems are often very complex with respect to the mix of generation sources, energy storage, transmission, and avenues to market. Historically, power was provided by government organizations to load centers, and pricing was provided in a regulatory manner. In recent years, this process has been displaced by the independent system operator (ISO). This complexity makes the operation of these systems very difficult, since the components of the system are interdependent. Consequently, computer-based large-scale simulation and optimization methods like Decision Support Systems are now being used. This paper discusses the application of a DSS to operations and planning systems.

  15. Biological diversity in the patent system.

    Directory of Open Access Journals (Sweden)

    Paul Oldham

    Full Text Available Biological diversity in the patent system is an enduring focus of controversy but empirical analysis of the presence of biodiversity in the patent system has been limited. To address this problem we text mined 11 million patent documents for 6 million Latin species names from the Global Names Index (GNI established by the Global Biodiversity Information Facility (GBIF and Encyclopedia of Life (EOL. We identified 76,274 full Latin species names from 23,882 genera in 767,955 patent documents. 25,595 species appeared in the claims section of 136,880 patent documents. This reveals that human innovative activity involving biodiversity in the patent system focuses on approximately 4% of taxonomically described species and between 0.8-1% of predicted global species. In this article we identify the major features of the patent landscape for biological diversity by focusing on key areas including pharmaceuticals, neglected diseases, traditional medicines, genetic engineering, foods, biocides, marine genetic resources and Antarctica. We conclude that the narrow focus of human innovative activity and ownership of genetic resources is unlikely to be in the long term interest of humanity. We argue that a broader spectrum of biodiversity needs to be opened up to research and development based on the principles of equitable benefit-sharing, respect for the objectives of the Convention on Biological Diversity, human rights and ethics. Finally, we argue that alternative models of innovation, such as open source and commons models, are required to open up biodiversity for research that addresses actual and neglected areas of human need. The research aims to inform the implementation of the 2010 Nagoya Protocol on Access to Genetic Resources and the Equitable Sharing of Benefits Arising from their Utilization and international debates directed to the governance of genetic resources. Our research also aims to inform debates under the Intergovernmental Committee on

  16. Biological Diversity in the Patent System

    Science.gov (United States)

    Oldham, Paul; Hall, Stephen; Forero, Oscar

    2013-01-01

    Biological diversity in the patent system is an enduring focus of controversy but empirical analysis of the presence of biodiversity in the patent system has been limited. To address this problem we text mined 11 million patent documents for 6 million Latin species names from the Global Names Index (GNI) established by the Global Biodiversity Information Facility (GBIF) and Encyclopedia of Life (EOL). We identified 76,274 full Latin species names from 23,882 genera in 767,955 patent documents. 25,595 species appeared in the claims section of 136,880 patent documents. This reveals that human innovative activity involving biodiversity in the patent system focuses on approximately 4% of taxonomically described species and between 0.8–1% of predicted global species. In this article we identify the major features of the patent landscape for biological diversity by focusing on key areas including pharmaceuticals, neglected diseases, traditional medicines, genetic engineering, foods, biocides, marine genetic resources and Antarctica. We conclude that the narrow focus of human innovative activity and ownership of genetic resources is unlikely to be in the long term interest of humanity. We argue that a broader spectrum of biodiversity needs to be opened up to research and development based on the principles of equitable benefit-sharing, respect for the objectives of the Convention on Biological Diversity, human rights and ethics. Finally, we argue that alternative models of innovation, such as open source and commons models, are required to open up biodiversity for research that addresses actual and neglected areas of human need. The research aims to inform the implementation of the 2010 Nagoya Protocol on Access to Genetic Resources and the Equitable Sharing of Benefits Arising from their Utilization and international debates directed to the governance of genetic resources. Our research also aims to inform debates under the Intergovernmental Committee on Intellectual

  17. Proteomics in reproductive biology: beacon for unraveling the molecular complexities.

    Science.gov (United States)

    Upadhyay, Rahul D; Balasinor, N H; Kumar, Anita V; Sachdeva, Geetanjali; Parte, Priyanka; Dumasia, Kushaan

    2013-01-01

    Proteomics, an interface of rapidly evolving advances in physics and biology, is rapidly developing and expanding its potential applications to molecular and cellular biology. Application of proteomics tools has contributed towards identification of relevant protein biomarkers that can potentially change the strategies for early diagnosis and treatment of several diseases. The emergence of powerful mass spectrometry-based proteomics technique has added a new dimension to the field of medical research in liver, heart diseases and certain forms of cancer. Most proteomics tools are also being used to study physiological and pathological events related to reproductive biology. There have been attempts to generate the proteomes of testes, sperm, seminal fluid, epididymis, oocyte, and endometrium from reproductive disease patients. Here, we have reviewed proteomics based investigations in humans over the last decade, which focus on delineating the mechanism underlying various reproductive events such as spermatogenesis, oogenesis, endometriosis, polycystic ovary syndrome, embryo development. The challenge is to harness new technologies like 2-DE, DIGE, MALDI-MS, SELDI-MS, MUDPIT, LC-MS etc., to a greater extent to develop widely applicable clinical tools in understanding molecular aspects of reproduction both in health and disease. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. System for determining sizes of biological macromolecules

    International Nuclear Information System (INIS)

    Nelson, R.M.; Danby, P.C.

    1987-01-01

    An electrophoresis system for determining the sizes of radiolabelled biological macromolecules is described. It comprises a cell containing an electrophoresis gel and having at least one lane, a voltage source connected across the gel for effecting the movement of macromolecules in the lane, a detector fixed relative to the moving molecules for generating electrical pulses responsive to signals emitted by the radiolabelled molecules; a pulse processor for counting the pulse rate, and a computational device for comparing the pulse rate to a predetermined value. (author)

  19. Integrative Systems Biology Applied to Toxicology

    DEFF Research Database (Denmark)

    Kongsbak, Kristine Grønning

    associated with combined exposure to multiple chemicals. Testing all possible combinations of the tens of thousands environmental chemicals is impractical. This PhD project was launched to apply existing computational systems biology methods to toxicological research. In this thesis, I present in three...... projects three different approaches to using computational toxicology to aid classical toxicological investigations. In project I, we predicted human health effects of five pesticides using publicly available data. We obtained a grouping of the chemical according to their potential human health effects...

  20. Characterization and biological activity of Solidago canadensis complex.

    Science.gov (United States)

    Šutovská, M; Capek, P; Kocmálová, M; Fraňová, S; Pawlaczyk, I; Gancarz, R

    2013-01-01

    Polyphenolic-polysaccharide-protein complex has been isolated from flowers of Solidago canadensis L. by hot alkaline extraction procedure. Compositional analyses of S canadensis complex revealed the presence of carbohydrates (43 wt%), protein (27 wt%), phenolics (12 wt%), uronic acids (10 wt%) and inorganic material (8 wt%). The carbohydrate part was rich in neutral sugars (81 wt%) while uronids were determined in lower amount (19 wt%). Monosaccharide analysis of carbohydrate part revealed the presence of five main sugar components, i.e. rhamnose (~23 wt%), arabinose (~20 wt%), uronic acids (~19 wt%), galactose (~17 wt%) and glucose (~14 wt%), and indicated thus the presence of rhamnogalacturonan and arabinogalactan in S. canadensis complex. HPLC analysis of complex showed one single peak of molecule mass at 11.2 kDa. Antitussive activity tests, performed in three doses of Solidago complex, showed the reduction of the number of cough efforts in the dose-dependent manner. Higher doses (50 and 75 mg/kg b.w.) were shown to be by 15 and 20% more effective than that of lower one (25mg/kg b.w.). However, the antitussive effect of the highest dose (75 mg/kg b.w.) was by 10% lower in comparison with that of codeine, the strongest antitussive agent. Besides, the highest dose of the complex (75 mg/kg b.w.) significantly decreased values of specific airways resistance and their effect remained longer as that of salbutamol, a representative of classic antiasthmatic drugs. Copyright © 2012 Elsevier B.V. All rights reserved.

  1. Discrete dynamics of complex systems

    Directory of Open Access Journals (Sweden)

    Hermann Haken

    1997-01-01

    Full Text Available This article extends the slaving principle of synergetics to processes with discrete time steps. Starting point is a set of nonlinear difference equations which contain multiplicative noise and which refer to multidimensional state vectors. The system depends on a control parameter. When its value is changed beyond a critical value, an instability of the solution occurs. The stability analysis allows us to divide the system into stable and unstable modes. The original equations can be transformed to a set of difference equations for the unstable and stable modes. The extension of the slaving principle to the time-discrete case then states that all the stable modes can be explicitly expressed by the unstable modes or so-called order-parameters.

  2. Dynamics of complex quantum systems

    CERN Document Server

    Akulin, Vladimir M

    2014-01-01

    This book gathers together a range of similar problems that can be encountered in different fields of modern quantum physics and that have common features with regard to multilevel quantum systems. The main motivation was to examine from a uniform standpoint various models and approaches that have been developed in atomic, molecular, condensed matter, chemical, laser and nuclear physics in various contexts. The book should help senior-level undergraduate, graduate students and researchers putting particular problems in these fields into a broader scientific context and thereby taking advantage of well-established techniques used in adjacent fields. This second edition has been expanded to include substantial new material (e.g. new sections on Dynamic Localization and on Euclidean Random Matrices and new chapters on Entanglement, Open Quantum Systems, and Coherence Protection). It is based on the author’s lectures at the Moscow Institute of Physics and Technology, at the CNRS Aimé Cotton Laboratory, and on ...

  3. Physicochemical and biological properties of new steroid metal complexes

    International Nuclear Information System (INIS)

    Huber, R.

    1980-04-01

    The aim of this investigation was to prepare stable steroid metal chelates by chemical conversion of the natural steroid hormones testerone, 5α-dihydrotestosterone (5α-DHT) and estradiol and to characterize these by means of their spectroscopic and other physico-chemical properties. In addition, various measuring techniques for the qualitative and quantitative study of complex stabilities and hydrolytic properties were employed. The distribution of some tritiated steroid metal complexes in the tissues of rats was tested using whole animal autoradiography, mainly with a view to identifying whether selective concentration occurs in certain organs. (orig.) [de

  4. Membrane tethering complexes in the endosomal system

    Directory of Open Access Journals (Sweden)

    Anne eSpang

    2016-05-01

    Full Text Available Vesicles that are generated by endocytic events at the plasma membrane are destined to early endosomes. A prerequisite for proper fusion is the tethering of two membrane entities. Tethering of vesicles to early endosomes is mediated by the CORVET complex, while fusion of late endosomes with lysosomes depends on the HOPS complex. Recycling through the TGN and to the plasma membrane is facilitated by the GARP and EARP complexes, respectively. However, there are other tethering functions in the endosomal system as there are multiple pathways through which proteins can be delivered from endosomes to either the TGN or the plasma membrane. Furthermore, complexes that may be part of novel tethering complexes have been recently identified. Thus it is likely that more tethering factors exist. In this review, I will provide an overview of different tethering complexes of the endosomal system and discuss how they may provide specificity in membrane traffic.

  5. Understanding Supply Networks from Complex Adaptive Systems

    Directory of Open Access Journals (Sweden)

    Jamur Johnas Marchi

    2014-10-01

    Full Text Available This theoretical paper is based on complex adaptive systems (CAS that integrate dynamic and holistic elements, aiming to discuss supply networks as complex systems and their dynamic and co-evolutionary processes. The CAS approach can give clues to understand the dynamic nature and co-evolution of supply networks because it consists of an approach that incorporates systems and complexity. This paper’s overall contribution is to reinforce the theoretical discussion of studies that have addressed supply chain issues, such as CAS.

  6. Complex motions and chaos in nonlinear systems

    CERN Document Server

    Machado, José; Zhang, Jiazhong

    2016-01-01

    This book brings together 10 chapters on a new stream of research examining complex phenomena in nonlinear systems—including engineering, physics, and social science. Complex Motions and Chaos in Nonlinear Systems provides readers a particular vantage of the nature and nonlinear phenomena in nonlinear dynamics that can develop the corresponding mathematical theory and apply nonlinear design to practical engineering as well as the study of other complex phenomena including those investigated within social science.

  7. A comprehensive in vitro biological investigation of metal complexes ...

    African Journals Online (AJOL)

    Md. Mahabob Ullah Mazumder

    Objective: The inquisitive objective of the study was to observe the antimicrobial, cytotoxicity, and antioxidant activities of some newly synthesized metal complexes of tolfenamic acid. Methods: While antimicrobial activity was studied by disk diffusion method, cytotoxicity was studied by performing brine shrimp lethality ...

  8. Complexity: the organizing principle at the interface of biological (dis ...

    Indian Academy of Sciences (India)

    RAMRAY BHAT

    2017-07-05

    Jul 5, 2017 ... In the context of evolutionary arguments, complexity has been defined, in a quantifiable fashion, as the amount of .... a breadth of fields such as ecology, economics and sociol- ogy. Given that the three strands of ...... Jeeva J. and Zalik S. E. 1996 Hapten inhibitors of the endogenous galactose binding lectins ...

  9. Synthesis, structural, spectroscopic and biological studies of Schiff base complexes

    Science.gov (United States)

    Diab, M. A.; El-Sonbati, A. Z.; Shoair, A. F.; Eldesoky, A. M.; El-Far, N. M.

    2017-08-01

    Schiff base ligand 4-((pyridin-2- yl)methyleneamino)-1,2-dihydro-2,3-dimethyl-1-phenylpyrazol-5-one (PDMP) and its complexes were prepared and characterized on the basis of elemental analysis, IR, mass spectra and thermogravimetric analysis. All results confirm that the complexes have 1:1 (M: PMDP) stoichiometric formula [M(PMDP)Cl2H2O ] (M = Cu(II), Co(II), Ni(II) and Mn(II)), [Cd(PMDP)Cl2] and the ligand behaves as a bi/tridentate forming five-membered chelating ring towards the metal ions, bonding through azomethine nitrogen/exocyclic carbonyl oxygen, azomethine pyridine nitrogen and exocyclic carbonyl oxygen. The shift in the band positions of the groups involved in coordination has been utilized to estimate the metal-nitrogen and/or oxygen bond lengths. The complexes of Co(II), Ni(II) and Cu(II) are paramagnetic and the magnetic as well as spectral data suggest octahedral geometry, whereas the Cd(II) complex is tetrahedral. The XRD studies show that both the ligand and its metal complexes (1 and 3) show polycrystalline with crystal structure. Molecular docking was used to predict the binding between PMDP ligand and the receptors. The corrosion inhibition of mild steel in 2 M HCl solution by PDMP was explored utilizing potentiodynamic polarization, electrochemical impedance spectroscopy (EIS) and (EFM) electrochemical frequency modulation method. Potentiodynamic polarization demonstrated that PDMP compound is mixed-type inhibitor. EIS spectra exhibit one capacitive loop and confirm the protective ability. The percentage of inhibition efficiency was found to increase with increasing the inhibitor concentration.

  10. Redefining plant systems biology: from cell to ecosystem

    NARCIS (Netherlands)

    Keurentjes, J.J.B.; Angenent, G.C.; Dicke, M.; Martins Dos Santos, V.A.P.; Molenaar, J.; Van der Putten, W.H.; de Ruiter, P.C.; Struik, P.C.; Thomma, B.P.H.J.

    2011-01-01

    Molecular biologists typically restrict systems biology to cellular levels. By contrast, ecologists define biological systems as communities of interacting individuals at different trophic levels that process energy, nutrient and information flows. Modern plant breeding needs to increase

  11. AN INTEGRATED BIOLOGICAL CONTROL SYSTEM AT HANFORD

    Energy Technology Data Exchange (ETDEWEB)

    JOHNSON AR; CAUDILL JG; GIDDINGS RF; RODRIGUEZ JM; ROOS RC; WILDE JW

    2010-02-11

    In 1999 an integrated biological control system was instituted at the U.S. Department of Energy's Hanford Site. Successes and changes to the program needed to be communicated to a large and diverse mix of organizations and individuals. Efforts at communication are directed toward the following: Hanford Contractors (Liquid or Tank Waste, Solid Waste, Environmental Restoration, Science and Technology, Site Infrastructure), General Hanford Employees, and Hanford Advisory Board (Native American Tribes, Environmental Groups, Local Citizens, Washington State and Oregon State regulatory agencies). Communication was done through direct interface meetings, individual communication, where appropriate, and broadly sharing program reports. The objectives of the communication efforts was to have the program well coordinated with Hanford contractors, and to have the program understood well enough that all stakeholders would have confidence in the work performed by the program to reduce or elimated spread of radioactive contamination by biotic vectors. Communication of successes and changes to an integrated biological control system instituted in 1999 at the Department of Energy's Hanford Site have required regular interfaces with not only a diverse group of Hanford contractors (i.e., those responsible for liquid or tank waste, solid wastes, environmental restoration, science and technology, and site infrastructure), and general Hanford employees, but also with a consortium of designated stake holders organized as the Hanford Advisory Board (i.e., Native American tribes, various environmental groups, local citizens, Washington state and Oregon regulatory agencies, etc.). Direct interface meetings, individual communication where appropriate, and transparency of the biological control program were the methods and outcome of this effort.

  12. An Integrated Biological Control System At Hanford

    International Nuclear Information System (INIS)

    Johnson, A.R.; Caudill, J.G.; Giddings, R.F.; Rodriguez, J.M.; Roos, R.C.; Wilde, J.W.

    2010-01-01

    In 1999 an integrated biological control system was instituted at the U.S. Department of Energy's Hanford Site. Successes and changes to the program needed to be communicated to a large and diverse mix of organizations and individuals. Efforts at communication are directed toward the following: Hanford Contractors (Liquid or Tank Waste, Solid Waste, Environmental Restoration, Science and Technology, Site Infrastructure), General Hanford Employees, and Hanford Advisory Board (Native American Tribes, Environmental Groups, Local Citizens, Washington State and Oregon State regulatory agencies). Communication was done through direct interface meetings, individual communication, where appropriate, and broadly sharing program reports. The objectives of the communication efforts was to have the program well coordinated with Hanford contractors, and to have the program understood well enough that all stakeholders would have confidence in the work performed by the program to reduce or elimate spread of radioactive contamination by biotic vectors. Communication of successes and changes to an integrated biological control system instituted in 1999 at the Department of Energy's Hanford Site have required regular interfaces with not only a diverse group of Hanford contractors (i.e., those responsible for liquid or tank waste, solid wastes, environmental restoration, science and technology, and site infrastructure), and general Hanford employees, but also with a consortium of designated stake holders organized as the Hanford Advisory Board (i.e., Native American tribes, various environmental groups, local citizens, Washington state and Oregon regulatory agencies, etc.). Direct interface meetings, individual communication where appropriate, and transparency of the biological control program were the methods and outcome of this effort.

  13. Quantum mechanics in complex systems

    Science.gov (United States)

    Hoehn, Ross Douglas

    This document should be considered in its separation; there are three distinct topics contained within and three distinct chapters within the body of works. In a similar fashion, this abstract should be considered in three parts. Firstly, we explored the existence of multiply-charged atomic ions by having developed a new set of dimensional scaling equations as well as a series of relativistic augmentations to the standard dimensional scaling procedure and to the self-consistent field calculations. Secondly, we propose a novel method of predicting drug efficacy in hopes to facilitate the discovery of new small molecule therapeutics by modeling the agonist-protein system as being similar to the process of Inelastic Electron Tunneling Spectroscopy. Finally, we facilitate the instruction in basic quantum mechanical topics through the use of quantum games; this method of approach allows for the generation of exercises with the intent of conveying the fundamental concepts within a first year quantum mechanics classroom. Furthermore, no to be mentioned within the body of the text, yet presented in appendix form, certain works modeling the proliferation of cells types within the confines of man-made lattices for the purpose of facilitating artificial vascular transplants. In Chapter 2, we present a theoretical framework which describes multiply-charged atomic ions, their stability within super-intense laser fields, also lay corrections to the systems due to relativistic effects. Dimensional scaling calculations with relativistic corrections for systems: H, H-, H 2-, He, He-, He2-, He3- within super-intense laser fields were completed. Also completed were three-dimensional self consistent field calculations to verify the dimensionally scaled quantities. With the aforementioned methods the system's ability to stably bind 'additional' electrons through the development of multiple isolated regions of high potential energy leading to nodes of high electron density is shown

  14. Chaotic systems in complex phase space

    Indian Academy of Sciences (India)

    This paper examines numerically the complex classical trajectories of the kicked rotor and the double pendulum. Both of these systems exhibit a transition to chaos, and this feature is studied in complex phase space. Additionally, it is shown that the short-time and long-time behaviours of these two P T -symmetric dynamical ...

  15. The Self as a Complex Dynamic System

    Science.gov (United States)

    Mercer, Sarah

    2011-01-01

    This article explores the potential offered by complexity theories for understanding language learners' sense of self and attempts to show how the self might usefully be conceived of as a complex dynamic system. Rather than presenting empirical findings, the article discusses existent research on the self and aims at outlining a conceptual…

  16. Systems genetics of complex diseases using RNA-sequencing methods

    DEFF Research Database (Denmark)

    Mazzoni, Gianluca; Kogelman, Lisette; Suravajhala, Prashanth

    2015-01-01

    non-coding RNAs (ncRNAs). The integration of transcriptomics data with genomic data in a systems genetics context represents a valuable possibility to go deep into the causal and regulatory mechanisms that generate complex traits and diseases. However RNA-Seq data have to be treated carefully......Next generation sequencing technologies have enabled the generation of huge quantities of biological data, and nowadays extensive datasets at different ‘omics levels have been generated. Systems genetics is a powerful approach that allows to integrate different ‘omics level and understand...... the biological mechanisms behind complex diseases or traits. In the recent past, transcriptomic studies with microarrays have been replaced with the new powerful RNA-seq technologies. This has led to detection of novel gene transcripts, novel regulatory mechanisms, allele specific gene expression and numerous...

  17. Flow NMR of complex systems

    Energy Technology Data Exchange (ETDEWEB)

    Scheler, U.; Bagusat, F. [Leibniz-Inst. fuer Polymerforschung Dresden e.V., Dresden (Germany)

    2007-07-01

    A combination of NMR imaging and pulsed field gradient (PFG) NMR is applied to investigate flow. NMR longitudinal relaxation is used to generate contrast in a binary system of oil and water. The spatial distribution of each component and its flow pattern are measured separately. As a model a Couette cell with an additional area of high shear is used as model geometry. While a flat smooth interface is found at rest, the interface become bent under rotation, finally emulgation starts because of the velocity differences between the components. Flow from a submillimeter tube into a wide box and out of the box is investigated as well to understand shear-induced mixing and demixing. (orig.)

  18. Modeling a Complex Biological Network with Temporal Heterogeneity: Cardiac Myocyte Plasticity as a Case Study

    Science.gov (United States)

    Mazloom, Amin R.; Basu, Kalyan; Mandal, Subhrangsu S.; Das, Sajal K.

    Complex biological systems often characterize nonlinear dynamics. Employing traditional deterministic or stochastic approaches to quantify these dynamics either fail to capture their existing deviant effects or lead to combinatorial explosion. In this work we devised a novel approach that projects the biological functions within a pathway to a network of stochastic events that are random in time and space. By applying this approach recursively to the object system we build the event network of the entire system. The dynamics of the system evolves through the execution of the event network by a simulation engine which comprised of a time prioritized event queue. As a case study we utilized the current method and conducted an in-silico experiment on the metabolic plasticity of a cardiac myocyete. We aimed to quantify the down stream effects of insulin signaling that predominantly controls the plasticity in myocardium. Intriguingly, our in-silico results on transcription regulatory effect of insulin showed a good agreement with experimental data. Meanwhile we were able to characterize the flux change across major metabolic pathways over 48 hours of the in-silico experiment. Our simulation performed a remarkable efficiency by conducting 48 hours of simulation-time in less that 2 hours of processor time.

  19. Geographical National Condition and Complex System

    Directory of Open Access Journals (Sweden)

    WANG Jiayao

    2016-01-01

    Full Text Available The significance of studying the complex system of geographical national conditions lies in rationally expressing the complex relationships of the “resources-environment-ecology-economy-society” system. Aiming to the problems faced by the statistical analysis of geographical national conditions, including the disunity of research contents, the inconsistency of range, the uncertainty of goals, etc.the present paper conducted a range of discussions from the perspectives of concept, theory and method, and designed some solutions based on the complex system theory and coordination degree analysis methods.By analyzing the concepts of geographical national conditions, geographical national conditions survey and geographical national conditions statistical analysis, as well as investigating the relationships between theirs, the statistical contents and the analytical range of geographical national conditions are clarified and defined. This investigation also clarifies the goals of the statistical analysis by analyzing the basic characteristics of the geographical national conditions and the complex system, and the consistency between the analysis of the degree of coordination and statistical analyses. It outlines their goals, proposes a concept for the complex system of geographical national conditions, and it describes the concept. The complex system theory provides new theoretical guidance for the statistical analysis of geographical national conditions. The degree of coordination offers new approaches on how to undertake the analysis based on the measurement method and decision-making analysis scheme upon which the complex system of geographical national conditions is based. It analyzes the overall trend via the degree of coordination of the complex system on a macro level, and it determines the direction of remediation on a micro level based on the degree of coordination among various subsystems and of single systems. These results establish

  20. Advancing metabolic engineering through systems biology of industrial microorganisms

    DEFF Research Database (Denmark)

    Dai, Zongjie; Nielsen, Jens

    2015-01-01

    resources. The objective of systems biology is to gain a comprehensive and quantitative understanding of living cells and can hereby enhance our ability to characterize and predict cellular behavior. Systems biology of industrial microorganisms is therefore valuable for metabolic engineering. Here we review...... the application of systems biology tools for the identification of metabolic engineering targets which may lead to reduced development time for efficient cell factories. Finally, we present some perspectives of systems biology for advancing metabolic engineering further....

  1. Biological Systems for Hydrogen Photoproduction (Presentation)

    Energy Technology Data Exchange (ETDEWEB)

    Ghirardi, M. L.

    2012-05-01

    This presentation summarizes NREL biological systems for hydrogen photoproduction work for the DOE Hydrogen and Fuel Cells Program Annual Merit Review and Peer Evaluation Meeting, May 14-18, 2012. General goal is develop photobiological systems for large-scale, low cost and efficient H{sub 2} production from water (barriers AH, AI and AJ). Specific tasks are: (1) Address the O{sub 2} sensitivity of hydrogenases that prevent continuity of H{sub 2} photoproduction under aerobic, high solar-to-hydrogen (STH) light conversion efficiency conditions; and (2) Utilize a limited STH H{sub 2}-producing method (sulfur deprivation) as a platform to address or test other factors limiting commercial algal H{sub 2} photoproduction, including low rates due to biochemical and engineering mechanisms.

  2. Language Based Techniques for Systems Biology

    DEFF Research Database (Denmark)

    Pilegaard, Henrik

    Process calculus is the common denominator for a class of compact, idealised, domain-specific formalisms normally associated with the study of reactive concurrent systems within Computer Science. With the rise of the interactioncentred science of Systems Biology a number of bio-inspired process......), is context insensitive, while the other, a poly-variant analysis (2CFA), is context-sensitive. These analyses compute safe approximations to the set of spatial configurations that are reachable according to a given model. This is useful in the qualitative study of cellular self-organisation and, e.......g., the effects of receptor defects or drug delivery mechanisms. The property of sequential realisability. which is closely related to the function of biochemical pathways, is addressed by a variant of traditional Data Flow Analysis (DFA). This so-called ‘Pathway Analysis’ computes safe approximations to the set...

  3. Spatial Structures and Regulation in Biological Systems

    DEFF Research Database (Denmark)

    Yde, Pernille

    , and the other is the spatial regulation of biological systems, here related to different aspects of the inflammatory response. All systems are studied using computational modelling and mathematical analysis. The first part of the thesis explores different protein aggregation scenarios. In Chapter 1, we consider...... a previously studied and very general aggregation model describing frangible linear filaments. This model is especially relevant for the growth of amyloid fibres, that have been related to a number of serious human diseases, and which are known to grow in an accelerated self-enhanced manner.We derive...... model of the tissue and show how coupled cells are able to function as an excitable medium and propagate waves of high cytokine concentration through the tissue. If the internal regulation in the cells is over-productive, the model predicts a continuous amplification of cytokines, which spans the entire...

  4. Microbial stress tolerance for biofuels. Systems biology

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Zonglin Lewis (ed.) [National Center for Agricultural Utilization Research, USDA-ARS, Peoria, IL (United States)

    2012-07-01

    The development of sustainable and renewable biofuels is attracting growing interest. It is vital to develop robust microbial strains for biocatalysts that are able to function under multiple stress conditions. This Microbiology Monograph provides an overview of methods for studying microbial stress tolerance for biofuels applications using a systems biology approach. Topics covered range from mechanisms to methodology for yeast and bacteria, including the genomics of yeast tolerance and detoxification; genetics and regulation of glycogen and trehalose metabolism; programmed cell death; high gravity fermentations; ethanol tolerance; improving biomass sugar utilization by engineered Saccharomyces; the genomics on tolerance of Zymomonas mobilis; microbial solvent tolerance; control of stress tolerance in bacterial host organisms; metabolomics for ethanologenic yeast; automated proteomics work cell systems for strain improvement; and unification of gene expression data for comparable analyses under stress conditions. (orig.)

  5. Complexity of some problems concerning L systems

    DEFF Research Database (Denmark)

    Jones, Neil D.; Skyum, Sven

    1979-01-01

    We determine the computational complexity of membership, emptiness and infiniteness for several types ofL systems. TheL systems we consider are ED0L, E0L, EDT0L, and ET0L, with and without empty productions. For each problem and each type of system we establish both upper and lower bounds...

  6. From System Complexity to Emergent Properties

    CERN Document Server

    Aziz-Alaoui, M. A

    2009-01-01

    Emergence and complexity refer to the appearance of higher-level properties and behaviours of a system that obviously comes from the collective dynamics of that system's components. These properties are not directly deductable from the lower-level motion of that system. Emergent properties are properties of the "whole'' that are not possessed by any of the individual parts making up that whole. Such phenomena exist in various domains and can be described, using complexity concepts and thematic knowledges. This book highlights complexity modelling through dynamical or behavioral systems. The pluridisciplinary purposes, developped along the chapters, are enable to design links between a wide-range of fundamental and applicative Sciences. Developing such links - instead of focusing on specific and narrow researches - is characteristic of the Science of Complexity that we try to promote by this contribution.

  7. Coordination Approaches for Complex Software Systems

    NARCIS (Netherlands)

    Bosse, T.; Hoogendoorn, M.; Treur, J.

    2006-01-01

    This document presents the results of a collaboration between the Vrije Universiteit Amsterdam, Department of Artificial Intelligence and Force Vision to investigate coordination approaches for complex software systems. The project was funded by Force Vision.

  8. Synthesis, Physical Characterization and Biological Activity of Some Schiff Base Complexes

    Directory of Open Access Journals (Sweden)

    R. Rajavel

    2008-01-01

    Full Text Available Structural modification of organic molecule has considerable biological relevance. Further, coordination of a biomolecules to the metal ions significantly alters the effectiveness of the biomolecules. In view of the antimicrobial activity ligand [bis-(2-aminobenzaldehyde] malonoyl dihydrazone], metal complexes with Cu(II, Ni(II, Zn(II and oxovanadium(IV have been synthesized and found to be potential antimicrobial agents. An attempt is also made to correlate the biological activities with geometry of the complexes. The complexes have been characterized by elemental analysis, molar conductance, spectra and cyclicvoltammetric measurements. The structural assessment of the complexes has been carried out based on electronic, infrared and molar conductivity values.

  9. Information and Symmetry: Adumbrating the Abstract Core of Complex Systems

    Directory of Open Access Journals (Sweden)

    Lin Bi

    2017-03-01

    Full Text Available Information and symmetry are essential theoretical concepts that underlie the scientific explanation of a variety of complex systems. In spite of clear-cut developments around both concepts, their intersection is really problematic, either in fields related to mathematics, physics, and chemistry, or even more in those pertaining to biology, neurosciences, and social sciences. The present Special Issue explores recent developments, both theoretical and applied, in most of these disciplines.

  10. Synthesis, characterization and biological assay of Salicylaldehyde Schiff base Cu(II) complexes and their precursors

    Science.gov (United States)

    Iftikhar, Bushra; Javed, Kanwal; Khan, Muhammad Saif Ullah; Akhter, Zareen; Mirza, Bushra; Mckee, Vickie

    2018-03-01

    Three new Schiff base ligands were synthesized by the reaction of Salicylaldehyde with semi-aromatic diamines, prepared by the reduction of corresponding dinitro-compounds, and were further used for the formation of complexes with Cu(II) metal ion. The structural features of the synthesized compounds were confirmed by their physical properties and infrared, electronic and NMR spectroscopic techniques. The studies revealed that the synthesized Schiff bases existed as tetradentate ligands and bonded to the metal ion through the phenolic oxygen and azomethine nitrogen. One of the dinitro precursors was also analyzed by single crystal X-ray crystallography, which showed that it crystallizes in monoclinic system with space group P2/n. The thermal behavior of the Cu(II) complexes was determined by thermogravimetric analysis (TGA) and kinetic parameters were evaluated from the data. Schiff base ligands, their precursors and metal complexes were also screened for antibacterial, antifungal, antitumor, Brine shrimp lethality, DPPH free radical scavenging and DNA damage assays. The results of these analyses indicated the substantial potential of the synthesized Schiff bases, their precursors and Cu(II) complexes in biological field as future drugs.

  11. Optical sensors and their applications for probing biological systems

    DEFF Research Database (Denmark)

    Palanco, Marta Espina

    biological sample to provide a SERS-template where silver nanoparticles can grow, thus providing a new insight into SERS-based sensors for chemically sensing in-situ plant constituents. Optical manipulation techniques have been used to investigate mechanical properties of soft membrane cells, i.e. mammalian......There is a great interest in exploring and developing new optical sensitive methodologies for probing complex biological systems. In this project we developed non-invasive and sensitive biosensor strategies for studying physiologically relevant chemical and physical properties of plant...... parts of the fresh tissues. The location of the nanoparticles inside some of the tissues was examined via SERS images, collected from Raman signatures of the constituents of the tissues as well as from Raman signatures of a specific pH-sensitive reporter molecule attached to the nanoparticles...

  12. Mass balances for a biological life support system simulation model

    Science.gov (United States)

    Volk, Tyler; Rummel, John D.

    1987-01-01

    Design decisions to aid the development of future space based biological life support systems (BLSS) can be made with simulation models. The biochemistry stoichiometry was developed for: (1) protein, carbohydrate, fat, fiber, and lignin production in the edible and inedible parts of plants; (2) food consumption and production of organic solids in urine, feces, and wash water by the humans; and (3) operation of the waste processor. Flux values for all components are derived for a steady state system with wheat as the sole food source. The large scale dynamics of a materially closed (BLSS) computer model is described in a companion paper. An extension of this methodology can explore multifood systems and more complex biochemical dynamics while maintaining whole system closure as a focus.

  13. Mining sensor data from complex systems

    OpenAIRE

    Vespier, Ugo

    2015-01-01

    Today, virtually everything, from natural phenomena to complex artificial and physical systems, can be measured and the resulting information collected, stored and analyzed in order to gain new insight. This thesis shows how complex systems often exhibit diverse behavior at different temporal scales, and that data mining methods should be able to cope with the multiple resolutions (scales) at the same time in order to fully understand the data at hand and extract useful information from it. U...

  14. Project risk management in complex petrochemical system

    Directory of Open Access Journals (Sweden)

    Kirin Snežana

    2012-01-01

    Full Text Available Investigation of risk in complex industrial systems, as well as evaluation of main factors influencing decision making and implementation process using large petrochemical company as an example, has proved the importance of successful project risk management. This is even more emphasized when analyzing systems with complex structure, i.e. with several organizational units. It has been shown that successful risk management requires modern methods, based on adequate application of statistical analysis methods.

  15. Systems biology approaches and pathway tools for investigating cardiovascular disease

    NARCIS (Netherlands)

    Wheelock, C.E.; Wheelock, A.M.; Kawashima, S.; Diez, D.; Kanehisa, M.; Erk, M. van; Kleemann, R.; Haeggström, J.Z.; Goto, S.

    2009-01-01

    Systems biology aims to understand the nonlinear interactions of multiple biomolecular components that characterize a living organism. One important aspect of systems biology approaches is to identify the biological pathways or networks that connect the differing elements of a system, and examine

  16. Application of integrative genomics and systems biology to conventional and in vitro reproductive traits in cattle

    DEFF Research Database (Denmark)

    Mazzoni, Gianluca; Pedersen, Hanne S.; de Oliveira Junior, Gerson A.

    2017-01-01

    by both conventional and ARTs such as OPU-IVP. The integration of systems biology information across different biological layers generates a complete view of the different molecular networks that control complex traits and can provide a strong contribution to the understanding of traits related to ARTs....

  17. Promoting Systems Thinking through Biology Lessons

    Science.gov (United States)

    Riess, Werner; Mischo, Christoph

    2010-04-01

    This study's goal was to analyze various teaching approaches within the context of natural science lessons, especially in biology. The main focus of the paper lies on the effectiveness of different teaching methods in promoting systems thinking in the field of Education for Sustainable Development. The following methods were incorporated into the study: special lessons designed to promote systems thinking, a computer-simulated scenario on the topic "ecosystem forest," and a combination of both special lessons and the computer simulation. These groups were then compared to a control group. A questionnaire was used to assess systems thinking skills of 424 sixth-grade students of secondary schools in Germany. The assessment differentiated between a conceptual understanding (measured as achievement score) and a reflexive justification (measured as justification score) of systems thinking. The following control variables were used: logical thinking, grades in school, memory span, and motivational goal orientation. Based on the pretest-posttest control group design, only those students who received both special instruction and worked with the computer simulation showed a significant increase in their achievement scores. The justification score increased in the computer simulation condition as well as in the combination of computer simulation and lesson condition. The possibilities and limits of promoting various forms of systems thinking by using realistic computer simulations are discussed.

  18. Molecular profiles to biology and pathways: a systems biology approach.

    Science.gov (United States)

    Van Laere, Steven; Dirix, Luc; Vermeulen, Peter

    2016-06-16

    Interpreting molecular profiles in a biological context requires specialized analysis strategies. Initially, lists of relevant genes were screened to identify enriched concepts associated with pathways or specific molecular processes. However, the shortcoming of interpreting gene lists by using predefined sets of genes has resulted in the development of novel methods that heavily rely on network-based concepts. These algorithms have the advantage that they allow a more holistic view of the signaling properties of the condition under study as well as that they are suitable for integrating different data types like gene expression, gene mutation, and even histological parameters.

  19. Modeling life the mathematics of biological systems

    CERN Document Server

    Garfinkel, Alan; Guo, Yina

    2017-01-01

    From predator-prey populations in an ecosystem, to hormone regulation within the body, the natural world abounds in dynamical systems that affect us profoundly. This book develops the mathematical tools essential for students in the life sciences to describe these interacting systems and to understand and predict their behavior. Complex feedback relations and counter-intuitive responses are common in dynamical systems in nature; this book develops the quantitative skills needed to explore these interactions. Differential equations are the natural mathematical tool for quantifying change, and are the driving force throughout this book. The use of Euler’s method makes nonlinear examples tractable and accessible to a broad spectrum of early-stage undergraduates, thus providing a practical alternative to the procedural approach of a traditional Calculus curriculum. Tools are developed within numerous, relevant examples, with an emphasis on the construction, evaluation, and interpretation of mathematical models ...

  20. The complex biology and contribution of Staphylococcus aureus in atopic dermatitis, current and future therapies.

    Science.gov (United States)

    Hepburn, L; Hijnen, D J; Sellman, B R; Mustelin, T; Sleeman, M A; May, R D; Strickland, I

    2017-07-01

    Atopic dermatitis (AD) is a complex, chronic inflammatory skin disorder affecting more than 10% of U.K. children and is a major cause of occupation-related disability. A subset of patients, particularly those with severe AD, are persistently colonized with Staphylococcus aureus and exacerbation of disease is commonly associated with this bacterium by virtue of increased inflammation and allergic sensitization, aggravated by skin barrier defects. Understanding the complex biology of S. aureus is an important factor when developing new drugs to combat infection. Staphylococcus aureus generates exoproteins that enable invasion and dissemination within the host skin but can also damage the skin and activate the host immune system. Antibiotics are often used by dermatologists to aid clearance of S. aureus; however, these are becoming less effective and chronic usage is discouraged with the emergence of multiple antibiotic-resistant strains. New ways to target S. aureus using monoclonal antibodies and vaccines are now being developed. This review will attempt to evaluate the key biology of S. aureus, current treatment of S. aureus infections in AD and recent advances in developing new anti-S. aureus therapies that have potential in severe AD. © 2016 British Association of Dermatologists.

  1. 3S - Systematic, systemic, and systems biology and toxicology.

    Science.gov (United States)

    Smirnova, Lena; Kleinstreuer, Nicole; Corvi, Raffaella; Levchenko, Andre; Fitzpatrick, Suzanne C; Hartung, Thomas

    2018-01-01

    A biological system is more than the sum of its parts - it accomplishes many functions via synergy. Deconstructing the system down to the molecular mechanism level necessitates the complement of reconstructing functions on all levels, i.e., in our conceptualization of biology and its perturbations, our experimental models and computer modelling. Toxicology contains the somewhat arbitrary subclass "systemic toxicities"; however, there is no relevant toxic insult or general disease that is not systemic. At least inflammation and repair are involved that require coordinated signaling mechanisms across the organism. However, the more body components involved, the greater the challenge to reca-pitulate such toxicities using non-animal models. Here, the shortcomings of current systemic testing and the development of alternative approaches are summarized. We argue that we need a systematic approach to integrating existing knowledge as exemplified by systematic reviews and other evidence-based approaches. Such knowledge can guide us in modelling these systems using bioengineering and virtual computer models, i.e., via systems biology or systems toxicology approaches. Experimental multi-organ-on-chip and microphysiological systems (MPS) provide a more physiological view of the organism, facilitating more comprehensive coverage of systemic toxicities, i.e., the perturbation on organism level, without using substitute organisms (animals). The next challenge is to establish disease models, i.e., micropathophysiological systems (MPPS), to expand their utility to encompass biomedicine. Combining computational and experimental systems approaches and the chal-lenges of validating them are discussed. The suggested 3S approach promises to leverage 21st century technology and systematic thinking to achieve a paradigm change in studying systemic effects.

  2. What Is a Complex Innovation System?

    Science.gov (United States)

    Katz, J. Sylvan

    2016-01-01

    Innovation systems are sometimes referred to as complex systems, something that is intuitively understood but poorly defined. A complex system dynamically evolves in non-linear ways giving it unique properties that distinguish it from other systems. In particular, a common signature of complex systems is scale-invariant emergent properties. A scale-invariant property can be identified because it is solely described by a power law function, f(x) = kxα, where the exponent, α, is a measure of scale-invariance. The focus of this paper is to describe and illustrate that innovation systems have properties of a complex adaptive system. In particular scale-invariant emergent properties indicative of their complex nature that can be quantified and used to inform public policy. The global research system is an example of an innovation system. Peer-reviewed publications containing knowledge are a characteristic output. Citations or references to these articles are an indirect measure of the impact the knowledge has on the research community. Peer-reviewed papers indexed in Scopus and in the Web of Science were used as data sources to produce measures of sizes and impact. These measures are used to illustrate how scale-invariant properties can be identified and quantified. It is demonstrated that the distribution of impact has a reasonable likelihood of being scale-invariant with scaling exponents that tended toward a value of less than 3.0 with the passage of time and decreasing group sizes. Scale-invariant correlations are shown between the evolution of impact and size with time and between field impact and sizes at points in time. The recursive or self-similar nature of scale-invariance suggests that any smaller innovation system within the global research system is likely to be complex with scale-invariant properties too. PMID:27258040

  3. What Is a Complex Innovation System?

    Directory of Open Access Journals (Sweden)

    J Sylvan Katz

    Full Text Available Innovation systems are sometimes referred to as complex systems, something that is intuitively understood but poorly defined. A complex system dynamically evolves in non-linear ways giving it unique properties that distinguish it from other systems. In particular, a common signature of complex systems is scale-invariant emergent properties. A scale-invariant property can be identified because it is solely described by a power law function, f(x = kxα, where the exponent, α, is a measure of scale-invariance. The focus of this paper is to describe and illustrate that innovation systems have properties of a complex adaptive system. In particular scale-invariant emergent properties indicative of their complex nature that can be quantified and used to inform public policy. The global research system is an example of an innovation system. Peer-reviewed publications containing knowledge are a characteristic output. Citations or references to these articles are an indirect measure of the impact the knowledge has on the research community. Peer-reviewed papers indexed in Scopus and in the Web of Science were used as data sources to produce measures of sizes and impact. These measures are used to illustrate how scale-invariant properties can be identified and quantified. It is demonstrated that the distribution of impact has a reasonable likelihood of being scale-invariant with scaling exponents that tended toward a value of less than 3.0 with the passage of time and decreasing group sizes. Scale-invariant correlations are shown between the evolution of impact and size with time and between field impact and sizes at points in time. The recursive or self-similar nature of scale-invariance suggests that any smaller innovation system within the global research system is likely to be complex with scale-invariant properties too.

  4. Signs, Systems and Complexity of Transmedia Storytelling

    Directory of Open Access Journals (Sweden)

    Renira Rampazzo Gambarato

    2012-12-01

    Full Text Available This article addresses key concepts such as sign, system and complexity in order to approach transmedia storytelling and better understand its intricate nature. The theoretical framework chosen to investigate transmedia storytelling meanders is Semiotics by Charles Sanders Peirce (1839-1914 and General Systems Theory by Mario Bunge (1919-. The complexity of transmedia storytelling is not simply the one of the signs of the works included in a transmedia franchise. It also includes the complexity of the dispositions of users/consumers/players as interpreters of semiotic elements (e.g. characters, themes, environments, events and outcomes presented by transmedia products. It extends further to the complexity of social, cultural, economical and political constructs. The German transmedia narrative The Ultimate SuperHero-Blog by Stefan Gieren and Sofia’s Diary, a Portuguese multiplatform production by BeActive, are presented as examples of closed and open system transmedia storytelling respectively.

  5. Vibrations and stability of complex beam systems

    CERN Document Server

    Stojanović, Vladimir

    2015-01-01

     This book reports on solved problems concerning vibrations and stability of complex beam systems. The complexity of a system is considered from two points of view: the complexity originating from the nature of the structure, in the case of two or more elastically connected beams; and the complexity derived from the dynamic behavior of the system, in the case of a damaged single beam, resulting from the harm done to its simple structure. Furthermore, the book describes the analytical derivation of equations of two or more elastically connected beams, using four different theories (Euler, Rayleigh, Timoshenko and Reddy-Bickford). It also reports on a new, improved p-version of the finite element method for geometrically nonlinear vibrations. The new method provides more accurate approximations of solutions, while also allowing us to analyze geometrically nonlinear vibrations. The book describes the appearance of longitudinal vibrations of damaged clamped-clamped beams as a result of discontinuity (damage). It...

  6. Hydrogen production from biomass by biological systems

    International Nuclear Information System (INIS)

    Sharifan, H.R.; Qader, S.

    2009-01-01

    Hydrogen gas is seen as a future energy carrier, not involved in 'greenhouse' gas and its released energy in combustion can be converted to electric power. Biological system with low energy can produce hydrogen compared to electrochemical hydrogen production via solar battery-based water splitting which requires the use of solar batteries with high energy requirements. The biological hydrogen production occurs in microalgae and cyanobacteria by photosynthesis. They consume biochemical energy to produce molecular hydrogen. Hydrogen in some algae is an anaerobic production in the absence of light. In cyanobacteria the hydrogen production simultaneously happens with nitrogen fixation, and also catalyzed by nitrogenase as a side reaction. Hydrogen production by photosynthetic bacteria is mediated by nitrogenase activity, although hydrogenases may be active for both hydrogen production and hydrogen uptake under some conditions. Genetic studies on photosynthetic microorganisms have markedly increased in recent times, relatively few genetic engineering studies have focused on altering the characteristics of these microorganisms, particularly with respect to enhancing the hydrogen-producing capabilities of photosynthetic bacteria and cyanobacteria. (author)

  7. Collectives and the design of complex systems

    CERN Document Server

    Wolpert, David

    2004-01-01

    Increasingly powerful computers are making possible distributed systems comprised of many adaptive and self-motivated computational agents. Such systems, when distinguished by system-level performance criteria, are known as "collectives." Collectives and the Design of Complex Systems lays the foundation for a science of collectives and describes how to design them for optimal performance. An introductory survey chapter is followed by descriptions of information-processing problems that can only be solved by the joint actions of large communities of computers, each running its own complex, decentralized machine-learning algorithm. Subsequent chapters analyze the dynamics and structures of collectives, as well as address economic, model-free, and control-theory approaches to designing complex systems. The work assumes a modest understanding of basic statistics and calculus. Topics and Features: Introduces the burgeoning science of collectives and its practical applications in a single useful volume Combines ap...

  8. Complex and Adaptive Dynamical Systems A Primer

    CERN Document Server

    Gros, Claudius

    2011-01-01

    We are living in an ever more complex world, an epoch where human actions can accordingly acquire far-reaching potentialities. Complex and adaptive dynamical systems are ubiquitous in the world surrounding us and require us to adapt to new realities and the way of dealing with them. This primer has been developed with the aim of conveying a wide range of "commons-sense" knowledge in the field of quantitative complex system science at an introductory level, providing an entry point to this both fascinating and vitally important subject. The approach is modular and phenomenology driven. Examples of emerging phenomena of generic importance treated in this book are: -- The small world phenomenon in social and scale-free networks. -- Phase transitions and self-organized criticality in adaptive systems. -- Life at the edge of chaos and coevolutionary avalanches resulting from the unfolding of all living. -- The concept of living dynamical systems and emotional diffusive control within cognitive system theory. Techn...

  9. Complex and adaptive dynamical systems a primer

    CERN Document Server

    Gros, Claudius

    2007-01-01

    We are living in an ever more complex world, an epoch where human actions can accordingly acquire far-reaching potentialities. Complex and adaptive dynamical systems are ubiquitous in the world surrounding us and require us to adapt to new realities and the way of dealing with them. This primer has been developed with the aim of conveying a wide range of "commons-sense" knowledge in the field of quantitative complex system science at an introductory level, providing an entry point to this both fascinating and vitally important subject. The approach is modular and phenomenology driven. Examples of emerging phenomena of generic importance treated in this book are: -- The small world phenomenon in social and scale-free networks. -- Phase transitions and self-organized criticality in adaptive systems. -- Life at the edge of chaos and coevolutionary avalanches resulting from the unfolding of all living. -- The concept of living dynamical systems and emotional diffusive control within cognitive system theory. Techn...

  10. Complex and adaptive dynamical systems a primer

    CERN Document Server

    Gros, Claudius

    2013-01-01

    Complex system theory is rapidly developing and gaining importance, providing tools and concepts central to our modern understanding of emergent phenomena. This primer offers an introduction to this area together with detailed coverage of the mathematics involved. All calculations are presented step by step and are straightforward to follow. This new third edition comes with new material, figures and exercises. Network theory, dynamical systems and information theory, the core of modern complex system sciences, are developed in the first three chapters, covering basic concepts and phenomena like small-world networks, bifurcation theory and information entropy. Further chapters use a modular approach to address the most important concepts in complex system sciences, with the emergence and self-organization playing a central role. Prominent examples are self-organized criticality in adaptive systems, life at the edge of chaos, hypercycles and coevolutionary avalanches, synchronization phenomena, absorbing phase...

  11. Discontinuity and complexity in nonlinear physical systems

    CERN Document Server

    Baleanu, Dumitru; Luo, Albert

    2014-01-01

    This unique book explores recent developments in experimental research in this broad field, organized in four distinct sections. Part I introduces the reader to the fractional dynamics and Lie group analysis for nonlinear partial differential equations. Part II covers chaos and complexity in nonlinear Hamiltonian systems, important to understand the resonance interactions in nonlinear dynamical systems, such as Tsunami waves and wildfire propagations; as well as Lev flights in chaotic trajectories, dynamical system synchronization and DNA information complexity analysis. Part III examines chaos and periodic motions in discontinuous dynamical systems, extensively present in a range of systems, including piecewise linear systems, vibro-impact systems and drilling systems in engineering. And in Part IV, engineering and financial nonlinearity are discussed. The mechanism of shock wave with saddle-node bifurcation and rotating disk stability will be presented, and the financial nonlinear models will be discussed....

  12. Synchronization coupled systems to complex networks

    CERN Document Server

    Boccaletti, Stefano; del Genio, Charo I; Amann, Andreas

    2018-01-01

    A modern introduction to synchronization phenomena, this text presents recent discoveries and the current state of research in the field, from low-dimensional systems to complex networks. The book describes some of the main mechanisms of collective behaviour in dynamical systems, including simple coupled systems, chaotic systems, and systems of infinite-dimension. After introducing the reader to the basic concepts of nonlinear dynamics, the book explores the main synchronized states of coupled systems and describes the influence of noise and the occurrence of synchronous motion in multistable and spatially-extended systems. Finally, the authors discuss the underlying principles of collective dynamics on complex networks, providing an understanding of how networked systems are able to function as a whole in order to process information, perform coordinated tasks, and respond collectively to external perturbations. The demonstrations, numerous illustrations and application examples will help advanced graduate s...

  13. Computational Modeling of Biological Systems From Molecules to Pathways

    CERN Document Server

    2012-01-01

    Computational modeling is emerging as a powerful new approach for studying and manipulating biological systems. Many diverse methods have been developed to model, visualize, and rationally alter these systems at various length scales, from atomic resolution to the level of cellular pathways. Processes taking place at larger time and length scales, such as molecular evolution, have also greatly benefited from new breeds of computational approaches. Computational Modeling of Biological Systems: From Molecules to Pathways provides an overview of established computational methods for the modeling of biologically and medically relevant systems. It is suitable for researchers and professionals working in the fields of biophysics, computational biology, systems biology, and molecular medicine.

  14. A System for Complex Robotic Welding

    DEFF Research Database (Denmark)

    Madsen, Ole; Sørensen, Carsten Bro; Olsen, Birger

    2002-01-01

    This paper presents the architecture of a system for robotic welding of complex tasks. The system integrates off-line programming, control of redundant robots, collision-free motion planning and sensor-based control. An implementation for pipe structure welding made at Odense Steel Shipyard Ltd...

  15. Modeling complex work systems - method meets reality

    NARCIS (Netherlands)

    van der Veer, Gerrit C.; Hoeve, Machteld; Lenting, Bert

    1996-01-01

    Modeling an existing task situation is often a first phase in the (re)design of information systems. For complex systems design, this model should consider both the people and the organization involved, the work, and situational aspects. Groupware Task Analysis (GTA) as part of a method for the

  16. Introducing Complex Systems into the Mathematics Curriculum

    Science.gov (United States)

    English, Lyn D.

    2008-01-01

    Children live in a highly sophisticated world composed of interlocking complex systems. An appreciation and understanding of such systems is critical for making effective decisions about everyone's lives as individuals and as community members. This article addresses one approach to introducing children of all achievement levels to introductory…

  17. Design tools for complex dynamic security systems.

    Energy Technology Data Exchange (ETDEWEB)

    Byrne, Raymond Harry; Rigdon, James Brian; Rohrer, Brandon Robinson; Laguna, Glenn A.; Robinett, Rush D. III (.; ); Groom, Kenneth Neal; Wilson, David Gerald; Bickerstaff, Robert J.; Harrington, John J.

    2007-01-01

    The development of tools for complex dynamic security systems is not a straight forward engineering task but, rather, a scientific task where discovery of new scientific principles and math is necessary. For years, scientists have observed complex behavior but have had difficulty understanding it. Prominent examples include: insect colony organization, the stock market, molecular interactions, fractals, and emergent behavior. Engineering such systems will be an even greater challenge. This report explores four tools for engineered complex dynamic security systems: Partially Observable Markov Decision Process, Percolation Theory, Graph Theory, and Exergy/Entropy Theory. Additionally, enabling hardware technology for next generation security systems are described: a 100 node wireless sensor network, unmanned ground vehicle and unmanned aerial vehicle.

  18. Systems Biology-Driven Hypotheses Tested In Vivo: The Need to Advancing Molecular Imaging Tools.

    Science.gov (United States)

    Verma, Garima; Palombo, Alessandro; Grigioni, Mauro; La Monaca, Morena; D'Avenio, Giuseppe

    2018-01-01

    Processing and interpretation of biological images may provide invaluable insights on complex, living systems because images capture the overall dynamics as a "whole." Therefore, "extraction" of key, quantitative morphological parameters could be, at least in principle, helpful in building a reliable systems biology approach in understanding living objects. Molecular imaging tools for system biology models have attained widespread usage in modern experimental laboratories. Here, we provide an overview on advances in the computational technology and different instrumentations focused on molecular image processing and analysis. Quantitative data analysis through various open source software and algorithmic protocols will provide a novel approach for modeling the experimental research program. Besides this, we also highlight the predictable future trends regarding methods for automatically analyzing biological data. Such tools will be very useful to understand the detailed biological and mathematical expressions under in-silico system biology processes with modeling properties.

  19. Systems biology in practice: concepts, implementation and application

    National Research Council Canada - National Science Library

    Klipp, E

    2005-01-01

    ... approaching systems biology from a different discipline. We see the origin and the methodological foundations for systems biology (1) in the accumulation of detailed biological knowledge with the prospect of utilization in biotechnology and health care, (2) in the emergence of new experimental techniques in genomics and proteomics, (3) in the traditio...

  20. Functionalized diamond nanopowder for phosphopeptides enrichment from complex biological fluids

    Energy Technology Data Exchange (ETDEWEB)

    Hussain, Dilshad [Division of Analytical Chemistry, Institute of Chemical Sciences, Bahauddin Zakariya University, Multan 60800 (Pakistan); Najam-ul-Haq, Muhammad, E-mail: najamulhaq@bzu.edu.pk [Division of Analytical Chemistry, Institute of Chemical Sciences, Bahauddin Zakariya University, Multan 60800 (Pakistan); Institute of Analytical Chemistry and Radiochemistry, Leopold-Franzens University, Innrain 80-82, A-6020 Innsbruck (Austria); Jabeen, Fahmida; Ashiq, Muhammad N.; Athar, Muhammad [Division of Analytical Chemistry, Institute of Chemical Sciences, Bahauddin Zakariya University, Multan 60800 (Pakistan); Rainer, Matthias; Huck, Christian W.; Bonn, Guenther K. [Institute of Analytical Chemistry and Radiochemistry, Leopold-Franzens University, Innrain 80-82, A-6020 Innsbruck (Austria)

    2013-05-02

    Graphical abstract: -- Highlights: •Derivatization of diamond nanopowder as IMAC and RP. •Characterization with SEM, EDX and FT-IR. •Phosphopeptide enrichment from standard as well as real samples. •Desalting and human serum profiling with reproducible results. •MALDI-MS analysis with database identification. -- Abstract: Diamond is known for its high affinity and biocompatibility towards biomolecules and is used exclusively in separation sciences and life science research. In present study, diamond nanopowder is derivatized as Immobilized Metal Ion Affinity Chromatographic (IMAC) material for the phosphopeptides enrichment and as Reversed Phase (C-18) media for the desalting of complex mixtures and human serum profiling through MALDI-TOF-MS. Functionalized diamond nanopowder is characterized by Fourier transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM) and energy dispersive X-ray (EDX) spectroscopy. Diamond-IMAC is applied to the standard protein (β-casein), spiked human serum, egg yolk and non-fat milk for the phosphopeptides enrichment. Results show the selectivity of synthesized IMAC-diamond immobilized with Fe{sup 3+} and La{sup 3+} ions. To comprehend the elaborated use, diamond-IMAC is also applied to the serum samples from gall bladder carcinoma for the potential biomarkers. Database search is carried out by the Mascot program ( (www.matrixscience.com)) for the assignment of phosphorylation sites. Diamond nanopowder is thus a separation media with multifunctional use and can be applied to cancer protein profiling for the diagnosis and biomarker identification.

  1. Major Histocompatibility Complex (MHC) Markers in Conservation Biology

    Science.gov (United States)

    Ujvari, Beata; Belov, Katherine

    2011-01-01

    Human impacts through habitat destruction, introduction of invasive species and climate change are increasing the number of species threatened with extinction. Decreases in population size simultaneously lead to reductions in genetic diversity, ultimately reducing the ability of populations to adapt to a changing environment. In this way, loss of genetic polymorphism is linked with extinction risk. Recent advances in sequencing technologies mean that obtaining measures of genetic diversity at functionally important genes is within reach for conservation programs. A key region of the genome that should be targeted for population genetic studies is the Major Histocompatibility Complex (MHC). MHC genes, found in all jawed vertebrates, are the most polymorphic genes in vertebrate genomes. They play key roles in immune function via immune-recognition and -surveillance and host-parasite interaction. Therefore, measuring levels of polymorphism at these genes can provide indirect measures of the immunological fitness of populations. The MHC has also been linked with mate-choice and pregnancy outcomes and has application for improving mating success in captive breeding programs. The recent discovery that genetic diversity at MHC genes may protect against the spread of contagious cancers provides an added impetus for managing and protecting MHC diversity in wild populations. Here we review the field and focus on the successful applications of MHC-typing for conservation management. We emphasize the importance of using MHC markers when planning and executing wildlife rescue and conservation programs but stress that this should not be done to the detriment of genome-wide diversity. PMID:21954351

  2. The self as a complex dynamic system

    Directory of Open Access Journals (Sweden)

    Sarah Mercer

    2011-04-01

    Full Text Available This article explores the potential offered by complexity theories for understanding language learners’ sense of self and attempts to show how the self might usefully be conceived of as a complex dynamic system. Rather than presenting empirical findings, the article discusses existent research on the self and aims at outlining a conceptual perspective that may inform future studies into the self and possibly other individual learner differences. The article concludes by critically considering the merits of a complexity perspective but also reflecting on the challenges it poses for research.

  3. Fault detection and isolation for complex system

    Science.gov (United States)

    Jing, Chan Shi; Bayuaji, Luhur; Samad, R.; Mustafa, M.; Abdullah, N. R. H.; Zain, Z. M.; Pebrianti, Dwi

    2017-07-01

    Fault Detection and Isolation (FDI) is a method to monitor, identify, and pinpoint the type and location of system fault in a complex multiple input multiple output (MIMO) non-linear system. A two wheel robot is used as a complex system in this study. The aim of the research is to construct and design a Fault Detection and Isolation algorithm. The proposed method for the fault identification is using hybrid technique that combines Kalman filter and Artificial Neural Network (ANN). The Kalman filter is able to recognize the data from the sensors of the system and indicate the fault of the system in the sensor reading. Error prediction is based on the fault magnitude and the time occurrence of fault. Additionally, Artificial Neural Network (ANN) is another algorithm used to determine the type of fault and isolate the fault in the system.

  4. A SYSTEMIC VISION OF BIOLOGY: OVERCOMING LINEARITY

    Directory of Open Access Journals (Sweden)

    M. Mayer

    2005-07-01

    Full Text Available Many  authors have proposed  that contextualization of reality  is necessary  to teach  Biology, empha- sizing students´ social and  economic realities.   However, contextualization means  more than  this;  it is related  to working with  different kinds of phenomena  and/or objects  which enable  the  expression of scientific concepts.  Thus,  contextualization allows the integration of different contents.  Under this perspective,  the  objectives  of this  work were to articulate different  biology concepts  in order  to de- velop a systemic vision of biology; to establish  relationships with other areas of knowledge and to make concrete the  cell molecular  structure and organization as well as their  implications  on living beings´ environment, using  contextualization.  The  methodology  adopted  in this  work  was based  on three aspects:  interdisciplinarity, contextualization and development of competences,  using energy:  its flux and transformations as a thematic axis and  an approach  which allowed the  interconnection between different situations involving  these  concepts.   The  activities developed  were:  1.   dialectic exercise, involving a movement around  micro and macroscopic aspects,  by using questions  and activities,  sup- ported  by the use of alternative material  (as springs, candles on the energy, its forms, transformations and  implications  in the  biological way (microscopic  concepts;  2, Construction of molecular  models, approaching the concepts of atom,  chemical bonds and bond energy in molecules; 3. Observations de- veloped in Manguezal¨(mangrove swamp  ecosystem (Itapissuma, PE  were used to work macroscopic concepts  (as  diversity  and  classification  of plants  and  animals,  concerning  to  energy  flow through food chains and webs. A photograph register of all activities  along the course plus texts

  5. Synthesis, characterization, biological activity and DNA cleavage studies of tridentate Schiff bases and their Co(II complexes

    Directory of Open Access Journals (Sweden)

    P. Kavitha

    2016-01-01

    Full Text Available In the present study a series of Co(II complexes of formyl chromone Schiff bases have been synthesized characterized by analytical, molar conductance, IR, electronic, magnetic susceptibility, thermal, fluorescence and powder XRD measurements and screened for various biological activities (antimicrobial, antioxidant, nematicidal, DNA cleavage and cytotoxicity. In all the Co(II complexes 1:2 metal to ligand molar ratio was obtained from analytical data. The molar conductance data confirm that all complexes are non-electrolytic in nature. Based on the electronic and magnetic data, an octahedral geometry is ascribed for all the Co(II complexes. Thermal behaviour of the synthesized complexes illustrates the general decomposition patterns of the complexes. The X-ray analysis data show that all the Co(II complexes have triclinic crystal system with different unit cell parameters. Metal complexes have greater antimicrobial activity than ligands. Antioxidant and nematicidal activities indicate that the ligands exhibit greater activity when compared to their respective Co(II complexes. All ligands and Co(II complexes of HL1 and HL2 showed considerable anticancer activity against Raw, MCF-7 and COLO 205 cell lines. All ligands and their Co(II complexes showed more pronounced DNA cleavage activity in the presence of H2O2.

  6. Y-12 National Security Complex Biological Monitoring and Abatement Program 2007 Calendar Yeare Report

    Energy Technology Data Exchange (ETDEWEB)

    Peterson, M.J.; Greeley, M. S. Jr.; Morris, G. W.; Roy, W. K.; Ryan, M. G.; Smith, J. G.; Southworth, G. R.

    2008-07-01

    The National Pollutant Discharge Elimination System (NPDES) permit issued for the Oak Ridge Y-12 National Security Complex (Y-12 Complex) which became effective May 1, 2006, continued a requirement for a Biological Monitoring and Abatement Program (BMAP). The BMAP was originally developed in 1985 to demonstrate that the effluent limitations established for the Y-12 Complex protected the classified uses of the receiving stream (East Fork Poplar Creek: EFPC), in particular, the growth and propagation of aquatic life (Loar et al. 1989). The objectives of the current BMAP are similar, specifically to assess stream ecological conditions relative to regulatory limits and criteria, to assess ecological impacts as well as recovery in response to Y-12 operations, and to investigate the causes of continuing impacts. The BMAP consists of three tasks that reflect complementary approaches to evaluating the effects of the Y-12 Complex discharges on the biotic integrity of EFPC. These tasks include: (1) bioaccumulation monitoring, (2) benthic macroinvertebrate community monitoring, and (3) fish community monitoring. As required by the NPDES permit, the BMAP benthic macroinvertebrate community monitoring task includes studies to annually evaluate the receiving stream's biological integrity in comparison to TN Water Quality Criteria. BMAP monitoring is currently being conducted at five primary EFPC sites, although sites may be excluded or added depending upon the specific objectives of the various tasks. Criteria used in selecting the sites include: (1) location of sampling sites used in other studies, (2) known or suspected sources of downstream impacts, (3) proximity to U.S. Department of Energy (DOE) Oak Ridge Reservation (ORR) boundaries, (4) appropriate habitat distribution, and (5) access. The primary sampling sites include upper EFPC at kilometers (EFKs) 24.4 and 23.4 [upstream and downstream of Lake Reality (LR) respectively]; EFK 18.7 (also EFK 18.2 and 19), located

  7. Considerations in starting a patient with advanced frailty on dialysis: complex biology meets challenging ethics.

    Science.gov (United States)

    Swidler, Mark

    2013-08-01

    Nephrologists have focused on the uremic syndrome as an indication for dialysis. The elderly frail renal patient approaching ESRD represents a complex biologic system that is already failing. This patient phenotype exhibits progressive geriatric disabilities and dependence interspersed with shrinking periods of stability regardless of whether dialysis is started. Consequently, the frail renal patient faces challenging treatment choices underpinned by ethical tensions. Identifying the advanced frail renal patient and optimizing the shared decision-making process will enable him or her to make well informed choices based on an understanding of his or her overall condition and personal values and preferences. This approach will also permit nephrologists to fulfill their ethical obligations to respect patient autonomy, promote patient benefit, and minimize patient harm.

  8. Programmable temperature control system for biological materials

    Science.gov (United States)

    Anselmo, V. J.; Harrison, R. G.; Rinfret, A. P.

    1982-01-01

    A system was constructed which allows programmable temperature-time control for a 5 cu cm sample volume of arbitrary biological material. The system also measures the parameters necessary for the determination of the sample volume specific heat and thermal conductivity as a function of temperature, and provides a detailed measurement of the temperature during phase change and a means of calculating the heat of the phase change. Steady-state and dynamic temperature control is obtained by supplying heat to the sample volume through resistive elements constructed as an integral part of the sample container. For cooling purposes, this container is totally immersed into a cold heat sink. Using a mixture of dry ice and alcohol at 79 C, the sample volume can be controlled from +40 to -60 C at rates from steady state to + or - 65 C/min. Steady-state temperature precision is better than 0.2 C, while the dynamic capability depends on the temperature rate of change as well as the mass of both the sample and the container.

  9. Macro to microfluidics system for biological environmental monitoring.

    Science.gov (United States)

    Delattre, Cyril; Allier, Cédric P; Fouillet, Yves; Jary, Dorothée; Bottausci, Frederic; Bouvier, Denis; Delapierre, Guillaume; Quinaud, Manuelle; Rival, Arnaud; Davoust, Laurent; Peponnet, Christine

    2012-01-01

    Biological environmental monitoring (BEM) is a growing field of research which challenges both microfluidics and system automation. The aim is to develop a transportable system with analysis throughput which satisfies the requirements: (i) fully autonomous, (ii) complete protocol integration from sample collection to final analysis, (iii) detection of diluted molecules or biological species in a large real life environmental sample volume, (iv) robustness and (v) flexibility and versatility. This paper discusses all these specifications in order to define an original fluidic architecture based on three connected modules, a sampling module, a sample preparation module and a detection module. The sample preparation module highly concentrates on the pathogens present in a few mL samples of complex and unknown solutions and purifies the pathogens' nucleic acids into a few μL of a controlled buffer. To do so, a two-step concentration protocol based on magnetic beads is automated in a reusable macro-to-micro fluidic system. The detection module is a PCR based miniaturized platform using digital microfluidics, where reactions are performed in 64 nL droplets handled by electrowetting on dielectric (EWOD) actuation. The design and manufacture of the two modules are reported as well as their respective performances. To demonstrate the integration of the complete protocol in the same system, first results of pathogen detection are shown. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. Theory of hybrid dynamical systems and its applications to biological and medical systems.

    Science.gov (United States)

    Aihara, Kazuyuki; Suzuki, Hideyuki

    2010-11-13

    In this introductory article, we survey the contents of this Theme Issue. This Theme Issue deals with a fertile region of hybrid dynamical systems that are characterized by the coexistence of continuous and discrete dynamics. It is now well known that there exist many hybrid dynamical systems with discontinuities such as impact, switching, friction and sliding. The first aim of this Issue is to discuss recent developments in understanding nonlinear dynamics of hybrid dynamical systems in the two main theoretical fields of dynamical systems theory and control systems theory. A combined study of the hybrid systems dynamics in the two theoretical fields might contribute to a more comprehensive understanding of hybrid dynamical systems. In addition, mathematical modelling by hybrid dynamical systems is particularly important for understanding the nonlinear dynamics of biological and medical systems as they have many discontinuities such as threshold-triggered firing in neurons, on-off switching of gene expression by a transcription factor, division in cells and certain types of chronotherapy for prostate cancer. Hence, the second aim is to discuss recent applications of hybrid dynamical systems in biology and medicine. Thus, this Issue is not only general to serve as a survey of recent progress in hybrid systems theory but also specific to introduce interesting and stimulating applications of hybrid systems in biology and medicine. As the introduction to the topics in this Theme Issue, we provide a brief history of nonlinear dynamics and mathematical modelling, different mathematical models of hybrid dynamical systems, the relationship between dynamical systems theory and control systems theory, examples of complex behaviour in a simple neuron model and its variants, applications of hybrid dynamical systems in biology and medicine as a road map of articles in this Theme Issue and future directions of hybrid systems modelling.

  11. Conceptual Modelling of Complex Production Systems

    Directory of Open Access Journals (Sweden)

    Nenad Perši

    2008-12-01

    Full Text Available Complex system dynamics, structure and behaviour performances call for a wide range of methods, algorithms and tools to reach a model capable of finding optimal performing parameters. In the modelling process, it is up to the analyst to select the appropriate combination of methods, algorithms and tools to express significant system performances. Such a methodology for designing complex systems should be based upon conceptual modelling to perform a sensitive analysis of different system levels and views, allowing system representations for developing computer models.Complex systems, such as business systems with a continuous-discrete production process, require a well organised supply chain highly reactive to production assortment changes. Aligning two different production components distinctive in their behaviour is especially delicate at the production parameters transition point. Such system performances require distinctive designing methods that can follow the double nature of the production process behaviour in accordance with their entities dynamics caused by assortment changes. Consequently, such systems need different conceptual presentations for their purpose to be realized from different views and aspects.

  12. Complex systems dynamics in aging: new evidence, continuing questions.

    Science.gov (United States)

    Cohen, Alan A

    2016-02-01

    There have long been suggestions that aging is tightly linked to the complex dynamics of the physiological systems that maintain homeostasis, and in particular to dysregulation of regulatory networks of molecules. This review synthesizes recent work that is starting to provide evidence for the importance of such complex systems dynamics in aging. There is now clear evidence that physiological dysregulation--the gradual breakdown in the capacity of complex regulatory networks to maintain homeostasis--is an emergent property of these regulatory networks, and that it plays an important role in aging. It can be measured simply using small numbers of biomarkers. Additionally, there are indications of the importance during aging of emergent physiological processes, functional processes that cannot be easily understood through clear metabolic pathways, but can nonetheless be precisely quantified and studied. The overall role of such complex systems dynamics in aging remains an important open question, and to understand it future studies will need to distinguish and integrate related aspects of aging research, including multi-factorial theories of aging, systems biology, bioinformatics, network approaches, robustness, and loss of complexity.

  13. Modeling drug- and chemical- induced hepatotoxicity with systems biology approaches

    Directory of Open Access Journals (Sweden)

    Sudin eBhattacharya

    2012-12-01

    Full Text Available We provide an overview of computational systems biology approaches as applied to the study of chemical- and drug-induced toxicity. The concept of ‘toxicity pathways’ is described in the context of the 2007 US National Academies of Science report, Toxicity testing in the 21st Century: A Vision and A Strategy. Pathway mapping and modeling based on network biology concepts are a key component of the vision laid out in this report for a more biologically-based analysis of dose-response behavior and the safety of chemicals and drugs. We focus on toxicity of the liver (hepatotoxicity – a complex phenotypic response with contributions from a number of different cell types and biological processes. We describe three case studies of complementary multi-scale computational modeling approaches to understand perturbation of toxicity pathways in the human liver as a result of exposure to environmental contaminants and specific drugs. One approach involves development of a spatial, multicellular virtual tissue model of the liver lobule that combines molecular circuits in individual hepatocytes with cell-cell interactions and blood-mediated transport of toxicants through hepatic sinusoids, to enable quantitative, mechanistic prediction of hepatic dose-response for activation of the AhR toxicity pathway. Simultaneously, methods are being developing to extract quantitative maps of intracellular signaling and transcriptional regulatory networks perturbed by environmental contaminants, using a combination of gene expression and genome-wide protein-DNA interaction data. A predictive physiological model (DILIsymTM to understand drug-induced liver injury (DILI, the most common adverse event leading to termination of clinical development programs and regulatory actions on drugs, is also described. The model initially focuses on reactive metabolite-induced DILI in response to administration of acetaminophen, and spans multiple biological scales.

  14. Complex Adaptive Systems of Systems (CASOS) engineering environment.

    Energy Technology Data Exchange (ETDEWEB)

    Detry, Richard Joseph; Linebarger, John Michael; Finley, Patrick D.; Maffitt, S. Louise; Glass, Robert John, Jr.; Beyeler, Walter Eugene; Ames, Arlo Leroy

    2012-02-01

    Complex Adaptive Systems of Systems, or CASoS, are vastly complex physical-socio-technical systems which we must understand to design a secure future for the nation. The Phoenix initiative implements CASoS Engineering principles combining the bottom up Complex Systems and Complex Adaptive Systems view with the top down Systems Engineering and System-of-Systems view. CASoS Engineering theory and practice must be conducted together to develop a discipline that is grounded in reality, extends our understanding of how CASoS behave and allows us to better control the outcomes. The pull of applications (real world problems) is critical to this effort, as is the articulation of a CASoS Engineering Framework that grounds an engineering approach in the theory of complex adaptive systems of systems. Successful application of the CASoS Engineering Framework requires modeling, simulation and analysis (MS and A) capabilities and the cultivation of a CASoS Engineering Community of Practice through knowledge sharing and facilitation. The CASoS Engineering Environment, itself a complex adaptive system of systems, constitutes the two platforms that provide these capabilities.

  15. Y-12 National Security Complex Biological Monitoring And Abatement Program 2008 Calendar Year Report

    Energy Technology Data Exchange (ETDEWEB)

    Peterson, M. J.; Greeley Jr., M. S.; Mathews, T. J.; Morris, G. W.; Roy, W. K.; Ryon, M. G.; Smith, J. G.; Southworth, G. R.

    2009-07-01

    The National Pollutant Discharge Elimination System (NPDES) permit issued for the Oak Ridge Y-12 National Security Complex (Y-12 Complex) which became effective May 1, 2006, continued a requirement for a Biological Monitoring and Abatement Program (BMAP). The BMAP was originally developed in 1985 to demonstrate that the effluent limitations established for the Y-12 Complex protected the classified uses of the receiving stream (East Fork Poplar Creek: EFPC), in particular, the growth and propagation of aquatic life (Loar et al. 1989). The objectives of the current BMAP are similar, specifically to assess stream ecological conditions relative to regulatory limits and criteria, to assess ecological impacts as well as recovery in response to Y-12 operations, and to investigate the causes of continuing impacts. The BMAP consists of three tasks that reflect complementary approaches to evaluating the effects of the Y-12 Complex discharges on the biotic integrity of EFPC. These tasks include: (1) bioaccumulation monitoring, (2) benthic macroinvertebrate community monitoring, and (3) fish community monitoring. As required by the NPDES permit, the BMAP benthic macroinvertebrate community monitoring task includes studies to annually evaluate the receiving stream's biological integrity in comparison to TN Water Quality Criteria. BMAP monitoring is currently being conducted at five primary EFPC sites, although sites may be excluded or added depending upon the specific objectives of the various tasks. Criteria used in selecting the sites include: (1) location of sampling sites used in other studies, (2) known or suspected sources of downstream impacts, (3) proximity to U.S. Department of Energy (DOE) Oak Ridge Reservation (ORR) boundaries, (4) appropriate habitat distribution, and (5) access. The primary sampling sites include upper EFPC at kilometers (EFKs) 24.4 and 23.4 [upstream and downstream of Lake Reality (LR) respectively]; EFK 18.7 (also EFK 18.2 and 19), located off

  16. Parametric Linear Hybrid Automata for Complex Environmental Systems Modeling

    Directory of Open Access Journals (Sweden)

    Samar Hayat Khan Tareen

    2015-07-01

    Full Text Available Environmental systems, whether they be weather patterns or predator-prey relationships, are dependent on a number of different variables, each directly or indirectly affecting the system at large. Since not all of these factors are known, these systems take on non-linear dynamics, making it difficult to accurately predict meaningful behavioral trends far into the future. However, such dynamics do not warrant complete ignorance of different efforts to understand and model close approximations of these systems. Towards this end, we have applied a logical modeling approach to model and analyze the behavioral trends and systematic trajectories that these systems exhibit without delving into their quantification. This approach, formalized by René Thomas for discrete logical modeling of Biological Regulatory Networks (BRNs and further extended in our previous studies as parametric biological linear hybrid automata (Bio-LHA, has been previously employed for the analyses of different molecular regulatory interactions occurring across various cells and microbial species. As relationships between different interacting components of a system can be simplified as positive or negative influences, we can employ the Bio-LHA framework to represent different components of the environmental system as positive or negative feedbacks. In the present study, we highlight the benefits of hybrid (discrete/continuous modeling which lead to refinements among the fore-casted behaviors in order to find out which ones are actually possible. We have taken two case studies: an interaction of three microbial species in a freshwater pond, and a more complex atmospheric system, to show the applications of the Bio-LHA methodology for the timed hybrid modeling of environmental systems. Results show that the approach using the Bio-LHA is a viable method for behavioral modeling of complex environmental systems by finding timing constraints while keeping the complexity of the model

  17. Hepatocellular carcinoma: a systems biology perspective

    Directory of Open Access Journals (Sweden)

    Lorenza Alice D'alessandro

    2013-02-01

    Full Text Available Hepatocellular carcinomas (HCC have different etiology and heterogenic genomic alterations lead to high complexity. The molecular features of HCC have largely been studied by gene expression and proteome profiling focusing on the correlations between the expression of specific markers and clinical data. Integration of the increasing amounts of data in databases has facilitated the link of genomic and proteomic profiles of HCC to disease state and clinical outcome. Despite the current knowledge, specific molecular markers remain to be identified and new strategies are required to establish novel targeted therapies. In the last years, mathematical models reconstructing gene and protein networks based on experimental data of HCC have been developed providing powerful tools to predict candidate interactions and potential targets for therapy. Furthermore, the combination of dynamic and logical mathematical models with quantitative data allows detailed mechanistic insights into system properties. To address effects at the organ level, mathematical models reconstructing the three-dimensional organization of liver lobules were developed. In the future, integration of different modeling approaches capturing the effects at the cellular up to the organ level is required to address the complex properties of HCC and to enable the discovery of new targets for HCC prevention or treatment.

  18. Toolsets Maintain Health of Complex Systems

    Science.gov (United States)

    2010-01-01

    First featured in Spinoff 2001, Qualtech Systems Inc. (QSI), of Wethersfield, Connecticut, adapted its Testability, Engineering, and Maintenance System (TEAMS) toolset under Small Business Innovation Research (SBIR) contracts from Ames Research Center to strengthen NASA's systems health management approach for its large, complex, and interconnected systems. Today, six NASA field centers utilize the TEAMS toolset, including TEAMS-Designer, TEAMS-RT, TEAMATE, and TEAMS-RDS. TEAMS is also being used on industrial systems that generate power, carry data, refine chemicals, perform medical functions, and produce semiconductor wafers. QSI finds TEAMS can lower costs by decreasing problems requiring service by 30 to 50 percent.

  19. Network Reconstruction of Dynamic Biological Systems

    OpenAIRE

    Asadi, Behrang

    2013-01-01

    Inference of network topology from experimental data is a central endeavor in biology, since knowledge of the underlying signaling mechanisms a requirement for understanding biological phenomena. As one of the most important tools in bioinformatics area, development of methods to reconstruct biological networks has attracted remarkable attention in the current decade. Integration of different data types can lead to remarkable improvements in our ability to identify the connectivity of differe...

  20. When physics is not "just physics": complexity science invites new measurement frames for exploring the physics of cognitive and biological development.

    Science.gov (United States)

    Kelty-Stephen, Damian; Dixon, James A

    2012-01-01

    The neurobiological sciences have struggled to resolve the physical foundations for biological and cognitive phenomena with a suspicion that biological and cognitive systems, capable of exhibiting and contributing to structure within themselves and through their contexts, are fundamentally distinct or autonomous from purely physical systems. Complexity science offers new physics-based approaches to explaining biological and cognitive phenomena. In response to controversy over whether complexity science might seek to "explain away" biology and cognition as "just physics," we propose that complexity science serves as an application of recent advances in physics to phenomena in biology and cognition without reducing or undermining the integrity of the phenomena to be explained. We highlight that physics is, like the neurobiological sciences, an evolving field and that the threat of reduction is overstated. We propose that distinctions between biological and cognitive systems from physical systems are pretheoretical and thus optional. We review our own work applying insights from post-classical physics regarding turbulence and fractal fluctuations to the problems of developing cognitive structure. Far from hoping to reduce biology and cognition to "nothing but" physics, we present our view that complexity science offers new explanatory frameworks for considering physical foundations of biological and cognitive phenomena.

  1. Modeling and Simulation Tools: From Systems Biology to Systems Medicine.

    Science.gov (United States)

    Olivier, Brett G; Swat, Maciej J; Moné, Martijn J

    2016-01-01

    Modeling is an integral component of modern biology. In this chapter we look into the role of the model, as it pertains to Systems Medicine, and the software that is required to instantiate and run it. We do this by comparing the development, implementation, and characteristics of tools that have been developed to work with two divergent methodologies: Systems Biology and Pharmacometrics. From the Systems Biology perspective we consider the concept of "Software as a Medical Device" and what this may imply for the migration of research-oriented, simulation software into the domain of human health.In our second perspective, we see how in practice hundreds of computational tools already accompany drug discovery and development at every stage of the process. Standardized exchange formats are required to streamline the model exchange between tools, which would minimize translation errors and reduce the required time. With the emergence, almost 15 years ago, of the SBML standard, a large part of the domain of interest is already covered and models can be shared and passed from software to software without recoding them. Until recently the last stage of the process, the pharmacometric analysis used in clinical studies carried out on subject populations, lacked such an exchange medium. We describe a new emerging exchange format in Pharmacometrics which covers the non-linear mixed effects models, the standard statistical model type used in this area. By interfacing these two formats the entire domain can be covered by complementary standards and subsequently the according tools.

  2. Evolution, Complex Systems and the Dialectic

    Directory of Open Access Journals (Sweden)

    Peter Knapp

    2015-08-01

    Full Text Available The status of large scale historical macro-theories is contested both in world-systems theory and in sociology as a whole. I distinguish three types of such dynamic models: evolutionary models, systems models and dialectical models. I define dialectical models as a family of complex systems models characterized by positive feedback (self-reinforcement or auto-catalysis. Such models lead to processes of accumulation and polarization, leading to system crisis. The games of Monopoly and Risk provide popular examples. This paper investigates the dynamic properties of three examples of such models: Myrdal's model of cumulative causation; Collins's models of Marxian transformations and geopolitics; and Chaso-Dunn and Hall's iterative model of world-systems transformations. A combination of evolutionary, complex systems and dialectical analyses has consideralble overlap with chaotic, far-from-equilibrium types of models and with analyses of complex adaptive systems. Such discontinuous, nonlinear dynamic models show great potential for solving problems of dynamic analysis both within world-systems theory and within sociology as a whole.

  3. System crash as dynamics of complex networks.

    Science.gov (United States)

    Yu, Yi; Xiao, Gaoxi; Zhou, Jie; Wang, Yubo; Wang, Zhen; Kurths, Jürgen; Schellnhuber, Hans Joachim

    2016-10-18

    Complex systems, from animal herds to human nations, sometimes crash drastically. Although the growth and evolution of systems have been extensively studied, our understanding of how systems crash is still limited. It remains rather puzzling why some systems, appearing to be doomed to fail, manage to survive for a long time whereas some other systems, which seem to be too big or too strong to fail, crash rapidly. In this contribution, we propose a network-based system dynamics model, where individual actions based on the local information accessible in their respective system structures may lead to the "peculiar" dynamics of system crash mentioned above. Extensive simulations are carried out on synthetic and real-life networks, which further reveal the interesting system evolution leading to the final crash. Applications and possible extensions of the proposed model are discussed.

  4. Complexity in electronic negotiation support systems.

    Science.gov (United States)

    Griessmair, Michele; Strunk, Guido; Vetschera, Rudolf; Koeszegi, Sabine T

    2011-10-01

    It is generally acknowledged that the medium influences the way we communicate and negotiation research directs considerable attention to the impact of different electronic communication modes on the negotiation process and outcomes. Complexity theories offer models and methods that allow the investigation of how pattern and temporal sequences unfold over time in negotiation interactions. By focusing on the dynamic and interactive quality of negotiations as well as the information, choice, and uncertainty contained in the negotiation process, the complexity perspective addresses several issues of central interest in classical negotiation research. In the present study we compare the complexity of the negotiation communication process among synchronous and asynchronous negotiations (IM vs. e-mail) as well as an electronic negotiation support system including a decision support system (DSS). For this purpose, transcripts of 145 negotiations have been coded and analyzed with the Shannon entropy and the grammar complexity. Our results show that negotiating asynchronically via e-mail as well as including a DSS significantly reduces the complexity of the negotiation process. Furthermore, a reduction of the complexity increases the probability of reaching an agreement.

  5. Automatic Emergence Detection in Complex Systems

    Directory of Open Access Journals (Sweden)

    Eugene Santos

    2017-01-01

    Full Text Available Complex systems consist of multiple interacting subsystems, whose nonlinear interactions can result in unanticipated (emergent system events. Extant systems analysis approaches fail to detect such emergent properties, since they analyze each subsystem separately and arrive at decisions typically through linear aggregations of individual analysis results. In this paper, we propose a quantitative definition of emergence for complex systems. We also propose a framework to detect emergent properties given observations of its subsystems. This framework, based on a probabilistic graphical model called Bayesian Knowledge Bases (BKBs, learns individual subsystem dynamics from data, probabilistically and structurally fuses said dynamics into a single complex system dynamics, and detects emergent properties. Fusion is the central element of our approach to account for situations when a common variable may have different probabilistic distributions in different subsystems. We evaluate our detection performance against a baseline approach (Bayesian Network ensemble on synthetic testbeds from UCI datasets. To do so, we also introduce a method to simulate and a metric to measure discrepancies that occur with shared/common variables. Experiments demonstrate that our framework outperforms the baseline. In addition, we demonstrate that this framework has uniform polynomial time complexity across all three learning, fusion, and reasoning procedures.

  6. Biologically inspired collision avoidance system for unmanned vehicles

    Science.gov (United States)

    Ortiz, Fernando E.; Graham, Brett; Spagnoli, Kyle; Kelmelis, Eric J.

    2009-05-01

    In this project, we collaborate with researchers in the neuroscience department at the University of Delaware to develop an Field Programmable Gate Array (FPGA)-based embedded computer, inspired by the brains of small vertebrates (fish). The mechanisms of object detection and avoidance in fish have been extensively studied by our Delaware collaborators. The midbrain optic tectum is a biological multimodal navigation controller capable of processing input from all senses that convey spatial information, including vision, audition, touch, and lateral-line (water current sensing in fish). Unfortunately, computational complexity makes these models too slow for use in real-time applications. These simulations are run offline on state-of-the-art desktop computers, presenting a gap between the application and the target platform: a low-power embedded device. EM Photonics has expertise in developing of high-performance computers based on commodity platforms such as graphic cards (GPUs) and FPGAs. FPGAs offer (1) high computational power, low power consumption and small footprint (in line with typical autonomous vehicle constraints), and (2) the ability to implement massively-parallel computational architectures, which can be leveraged to closely emulate biological systems. Combining UD's brain modeling algorithms and the power of FPGAs, this computer enables autonomous navigation in complex environments, and further types of onboard neural processing in future applications.

  7. Modelling the crop: from system dynamics to systems biology

    NARCIS (Netherlands)

    Yin, X.; Struik, P.C.

    2010-01-01

    There is strong interplant competition in a crop stand for various limiting resources, resulting in complex compensation and regulation mechanisms along the developmental cascade of the whole crop. Despite decades-long use of principles in system dynamics (e.g. feedback control), current crop models

  8. Understanding Complex Construction Systems Through Modularity

    DEFF Research Database (Denmark)

    Jensen, Tor Clarke; Bekdik, Baris; Thuesen, Christian

    2014-01-01

    finds that the main driver of complexity is the fragmentation of the design and production, which causes the production modules to construct and install new product types and variants for each project as the designers are swapped for every project. The many interfaces are characteristics of an integral......This paper develops a framework for understanding complexity in construction projects by combining theories of complexity management and modularization. The framework incorporates three dimensions of product, process, and organizational modularity with the case of gypsum wall elements. The analysis...... system, rather than a modular, although the industry forces modular organizational structures. This creates a high complexity degree caused by the non-alignment of building parts and organizations and the frequent swapping of modules....

  9. Best geoscience approach to complex systems in environment

    Science.gov (United States)

    Mezemate, Yacine; Tchiguirinskaia, Ioulia; Schertzer, Daniel

    2017-04-01

    The environment is a social issue that continues to grow in importance. Its complexity, both cross-disciplinary and multi-scale, has given rise to a large number of scientific and technological locks, that complex systems approaches can solve. Significant challenges must met to achieve the understanding of the environmental complexes systems. There study should proceed in some steps in which the use of data and models is crucial: - Exploration, observation and basic data acquisition - Identification of correlations, patterns, and mechanisms - Modelling - Model validation, implementation and prediction - Construction of a theory Since the e-learning becomes a powerful tool for knowledge and best practice shearing, we use it to teach the environmental complexities and systems. In this presentation we promote the e-learning course dedicated for a large public (undergraduates, graduates, PhD students and young scientists) which gather and puts in coherence different pedagogical materials of complex systems and environmental studies. This course describes a complex processes using numerous illustrations, examples and tests that make it "easy to enjoy" learning process. For the seek of simplicity, the course is divided in different modules and at the end of each module a set of exercises and program codes are proposed for a best practice. The graphical user interface (GUI) which is constructed using an open source Opale Scenari offers a simple navigation through the different module. The course treats the complex systems that can be found in environment and their observables, we particularly highlight the extreme variability of these observables over a wide range of scales. Using the multifractal formalism through different applications (turbulence, precipitation, hydrology) we demonstrate how such extreme variability of the geophysical/biological fields should be used solving everyday (geo-)environmental chalenges.

  10. Systems biology: properties of reconstructed networks

    National Research Council Canada - National Science Library

    Palsson, Bernhard

    2006-01-01

    ... between the mathematical ideas and biological processes are made clear, the book reflects the irreversible trend of increasing mathematical content in biology education. Therefore to assist both teacher and student, Palsson provides problem sets, projects, and PowerPoint slides in an associated web site and keeps the presentation in the book concrete with illustrat...

  11. Stochastic modelling of dynamical systems in biology

    NARCIS (Netherlands)

    Pellin, Danilo

    2017-01-01

    In this thesis two relevant biological problems will be addressed from a statistical modelling perspective. The first regards the study of hematopoiesis, a still not well understood biological process rarely observable in humans due to technical and ethical reasons. Hematopoiesis is responsible for

  12. Isotopic fractionation of tritium in biological systems.

    Science.gov (United States)

    Le Goff, Pierre; Fromm, Michel; Vichot, Laurent; Badot, Pierre-Marie; Guétat, Philippe

    2014-04-01

    Isotopic fractionation of tritium is a highly relevant issue in radiation protection and requires certain radioecological considerations. Sound evaluation of this factor is indeed necessary to determine whether environmental compartments are enriched/depleted in tritium or if tritium is, on the contrary, isotopically well-distributed in a given system. The ubiquity of tritium and the standard analytical methods used to assay it may induce biases in both the measurement and the signification that is accorded to the so-called fractionation: based on an exhaustive review of the literature, we show how, sometimes large deviations may appear. It is shown that when comparing the non-exchangeable fraction of organically bound tritium (neOBT) to another fraction of tritium (e.g. tritiated water) the preparation of samples and the measurement of neOBT reported frequently led to underestimation of the ratio of tritium to hydrogen (T/H) in the non-exchangeable compartment by a factor of 5% to 50%. In the present study, corrections are proposed for most of the biological matrices studied so far. Nevertheless, the values of isotopic fractionation reported in the literature remain difficult to compare with each other, especially since the physical quantities and units often vary between authors. Some improvements are proposed to better define what should encompass the concepts of exchangeable and non-exchangeable fractions. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Cardiovascular Biology of the Incretin System

    Science.gov (United States)

    Ussher, John R.; Drucker, Daniel J.

    2012-01-01

    Glucagon-like peptide-1 (GLP-1) is an incretin hormone that enhances glucose-stimulated insulin secretion and exerts direct and indirect actions on the cardiovascular system. GLP-1 and its related incretin hormone, glucose-dependent insulinotropic polypeptide (GIP), are rapidly inactivated by the enzyme dipeptidyl peptidase 4 (DPP-4), a key determinant of incretin bioactivity. Two classes of medications that enhance incretin action, GLP-1R agonists and DPP-4 inhibitors, are used for the treatment of type 2 diabetes mellitus (T2DM). We review herein the cardiovascular biology of GLP-1R agonists and DPP-4 inhibitors, including direct and indirect effects on cardiomyocytes, blood vessels, adipocytes, the control of blood pressure and postprandial lipoprotein secretion. Both GLP-1R activation and DPP-4 inhibition exert multiple cardioprotective actions in preclinical models of cardiovascular dysfunction, and short term studies in human subjects appear to demonstrate modest yet beneficial actions on cardiac function in subjects with ischemic heart disease. Incretin-based agents control body weight, improve glycemic control with a low risk of hypoglycemia, decrease blood pressure, inhibit the secretion of intestinal chylomicrons, and reduce inflammation in preclinical studies. Nevertheless, there is limited information on the cardiovascular actions of these agents in patients with diabetes and established cardiovascular disease. Hence, a more complete understanding of the cardiovascular risk:benefit ratio of incretin-based therapies will require completion of long term cardiovascular outcome studies currently underway in patients with T2DM. PMID:22323472

  14. Toward mechanical systems biology in bone.

    Science.gov (United States)

    Trüssel, Andreas; Müller, Ralph; Webster, Duncan

    2012-11-01

    Cyclic mechanical loading is perhaps the most important physiological factor regulating bone mass and shape in a way which balances optimal strength with minimal weight. This bone adaptation process spans multiple length and time scales. Forces resulting from physiological exercise at the organ scale are sensed at the cellular scale by osteocytes, which reside inside the bone matrix. Via biochemical pathways, osteocytes orchestrate the local remodeling action of osteoblasts (bone formation) and osteoclasts (bone resorption). Together these local adaptive remodeling activities sum up to strengthen bone globally at the organ scale. To resolve the underlying mechanisms it is required to identify and quantify both cause and effect across the different scales. Progress has been made at the different scales experimentally. Computational models of bone adaptation have been developed to piece together various experimental observations at the different scales into coherent and plausible mechanisms. However additional quantitative experimental validation is still required to build upon the insights which have already been achieved. In this review we discuss emerging as well as state of the art experimental and computational techniques and how they might be used in a mechanical systems biology approach to further our understanding of the mechanisms governing load induced bone adaptation, i.e., ways are outlined in which experimental and computational approaches could be coupled, in a quantitative manner to create more reliable multiscale models of bone.

  15. Extraction of quantifiable information from complex systems

    CERN Document Server

    Dahmen, Wolfgang; Griebel, Michael; Hackbusch, Wolfgang; Ritter, Klaus; Schneider, Reinhold; Schwab, Christoph; Yserentant, Harry

    2014-01-01

    In April 2007, the  Deutsche Forschungsgemeinschaft (DFG) approved the  Priority Program 1324 “Mathematical Methods for Extracting Quantifiable Information from Complex Systems.” This volume presents a comprehensive overview of the most important results obtained over the course of the program.   Mathematical models of complex systems provide the foundation for further technological developments in science, engineering and computational finance.  Motivated by the trend toward steadily increasing computer power, ever more realistic models have been developed in recent years. These models have also become increasingly complex, and their numerical treatment poses serious challenges.   Recent developments in mathematics suggest that, in the long run, much more powerful numerical solution strategies could be derived if the interconnections between the different fields of research were systematically exploited at a conceptual level. Accordingly, a deeper understanding of the mathematical foundations as w...

  16. Complex and adaptive dynamical systems a primer

    CERN Document Server

    Gros, Claudius

    2015-01-01

    This primer offers readers an introduction to the central concepts that form our modern understanding of complex and emergent behavior, together with detailed coverage of accompanying mathematical methods. All calculations are presented step by step and are easy to follow. This new fourth edition has been fully reorganized and includes new chapters, figures and exercises. The core aspects of modern complex system sciences are presented in the first chapters, covering network theory, dynamical systems, bifurcation and catastrophe theory, chaos and adaptive processes, together with the principle of self-organization in reaction-diffusion systems and social animals. Modern information theoretical principles are treated in further chapters, together with the concept of self-organized criticality, gene regulation networks, hypercycles and coevolutionary avalanches, synchronization phenomena, absorbing phase transitions and the cognitive system approach to the brain. Technical course prerequisites are the standard ...

  17. Radionuclide Imaging Technologies for Biological Systems

    Energy Technology Data Exchange (ETDEWEB)

    Howell, Calvin R. [Duke Univ., Durham, NC (United States); Reid, Chantal D. [Duke Univ., Durham, NC (United States); Weisenberger, Andrew G. [Thomas Jefferson National Accelerator Facility (TJNAF), Newport News, VA (United States)

    2014-05-14

    The main objective of this project is to develop technologies and experimental techniques for studying the dynamics of physiological responses of plants to changes in their interface with the local environment and to educate a new generation of scientists in an interdisciplinary environment of biology, physics and engineering. Also an important goal is to perform measurements to demonstrate the new data that can be produced and made available to the plant-biology community using the imaging technologies and experimental techniques developed in this project. The study of the plant-environment interface includes a wide range of topics in plant physiology, e.g., the root-soil interface, resource availability, impact of herbivores, influence of microbes on root surface, and responses to toxins in the air and soil. The initial scientific motivation for our work is to improve understanding of the mechanisms for physiological responses to abrupt changes in the local environment, in particular, the responses that result in short-term adjustments in resource (e.g., sugars, nutrients and water) allocations. Data of time-dependent responses of plants to environmental changes are essential in developing mechanistic models for substance intake and resource allocation. Our approach is to use radioisotope tracing techniques to study whole-plant and plant organ (e.g., leaves, stems, roots) dynamical responses to abrupt changes in environmental conditions such as concentration of CO2 in the atmosphere, nutrient availability and lighting. To this aim we are collaborating with the Radiation Detector and Imaging Group at the Thomas Jefferson National Laboratory Facility (JLab) to develop gamma-ray and beta particle imaging systems optimized for plant studies. The radioisotope tracing measurements are conducted at the Phytotron facility at Duke University. The Phytotron is a controlled environment plant research facility with a variety of plant growth chambers. One chamber

  18. On complex adaptive systems and terrorism

    International Nuclear Information System (INIS)

    Ahmed, E.; Elgazzar, A.S.; Hegazi, A.S.

    2005-01-01

    Complex adaptive systems (CAS) are ubiquitous in nature. They are basic in social sciences. An overview of CAS is given with emphasize on the occurrence of bad side effects to seemingly 'wise' decisions. Hence application to terrorism is given. Some conclusions on how to deal with this phenomena are proposed

  19. Engineering Education as a Complex System

    Science.gov (United States)

    Gattie, David K.; Kellam, Nadia N.; Schramski, John R.; Walther, Joachim

    2011-01-01

    This paper presents a theoretical basis for cultivating engineering education as a complex system that will prepare students to think critically and make decisions with regard to poorly understood, ill-structured issues. Integral to this theoretical basis is a solution space construct developed and presented as a benchmark for evaluating…

  20. Complex systems modeling by cellular automata

    NARCIS (Netherlands)

    Kroc, J.; Sloot, P.M.A.; Rabuñal Dopico, J.R.; Dorado de la Calle, J.; Pazos Sierra, A.

    2009-01-01

    In recent years, the notion of complex systems proved to be a very useful concept to define, describe, and study various natural phenomena observed in a vast number of scientific disciplines. Examples of scientific disciplines that highly benefit from this concept range from physics, mathematics,

  1. Systems Biology Perspectives on Minimal and Simpler Cells

    Science.gov (United States)

    Xavier, Joana C.; Patil, Kiran Raosaheb

    2014-01-01

    SUMMARY The concept of the minimal cell has fascinated scientists for a long time, from both fundamental and applied points of view. This broad concept encompasses extreme reductions of genomes, the last universal common ancestor (LUCA), the creation of semiartificial cells, and the design of protocells and chassis cells. Here we review these different areas of research and identify common and complementary aspects of each one. We focus on systems biology, a discipline that is greatly facilitating the classical top-down and bottom-up approaches toward minimal cells. In addition, we also review the so-called middle-out approach and its contributions to the field with mathematical and computational models. Owing to the advances in genomics technologies, much of the work in this area has been centered on minimal genomes, or rather minimal gene sets, required to sustain life. Nevertheless, a fundamental expansion has been taking place in the last few years wherein the minimal gene set is viewed as a backbone of a more complex system. Complementing genomics, progress is being made in understanding the system-wide properties at the levels of the transcriptome, proteome, and metabolome. Network modeling approaches are enabling the integration of these different omics data sets toward an understanding of the complex molecular pathways connecting genotype to phenotype. We review key concepts central to the mapping and modeling of this complexity, which is at the heart of research on minimal cells. Finally, we discuss the distinction between minimizing the number of cellular components and minimizing cellular complexity, toward an improved understanding and utilization of minimal and simpler cells. PMID:25184563

  2. Applying systems biology methods to the study of human physiology in extreme environments.

    Science.gov (United States)

    Edwards, Lindsay M; Thiele, Ines

    2013-03-22

    Systems biology is defined in this review as 'an iterative process of computational model building and experimental model revision with the aim of understanding or simulating complex biological systems'. We propose that, in practice, systems biology rests on three pillars: computation, the omics disciplines and repeated experimental perturbation of the system of interest. The number of ethical and physiologically relevant perturbations that can be used in experiments on healthy humans is extremely limited and principally comprises exercise, nutrition, infusions (e.g. Intralipid), some drugs and altered environment. Thus, we argue that systems biology and environmental physiology are natural symbionts for those interested in a system-level understanding of human biology. However, despite excellent progress in high-altitude genetics and several proteomics studies, systems biology research into human adaptation to extreme environments is in its infancy. A brief description and overview of systems biology in its current guise is given, followed by a mini review of computational methods used for modelling biological systems. Special attention is given to high-altitude research, metabolic network reconstruction and constraint-based modelling.

  3. Gaia as a complex adaptive system.

    Science.gov (United States)

    Lenton, Timothy M; van Oijen, Marcel

    2002-05-29

    We define the Gaia system of life and its environment on Earth, review the status of the Gaia theory, introduce potentially relevant concepts from complexity theory, then try to apply them to Gaia. We consider whether Gaia is a complex adaptive system (CAS) in terms of its behaviour and suggest that the system is self-organizing but does not reside in a critical state. Gaia has supported abundant life for most of the last 3.8 Gyr. Large perturbations have occasionally suppressed life but the system has always recovered without losing the capacity for large-scale free energy capture and recycling of essential elements. To illustrate how complexity theory can help us understand the emergence of planetary-scale order, we present a simple cellular automata (CA) model of the imaginary planet Daisyworld. This exhibits emergent self-regulation as a consequence of feedback coupling between life and its environment. Local spatial interaction, which was absent from the original model, can destabilize the system by generating bifurcation regimes. Variation and natural selection tend to remove this instability. With mutation in the model system, it exhibits self-organizing adaptive behaviour in its response to forcing. We close by suggesting how artificial life ('Alife') techniques may enable more comprehensive feasibility tests of Gaia.

  4. Dependency visualization for complex system understanding

    Energy Technology Data Exchange (ETDEWEB)

    Smart, J. Allison Cory [Univ. of California, Davis, CA (United States)

    1994-09-01

    With the volume of software in production use dramatically increasing, the importance of software maintenance has become strikingly apparent. Techniques now sought and developed for reverse engineering and design extraction and recovery. At present, numerous commercial products and research tools exist which are capable of visualizing a variety of programming languages and software constructs. The list of new tools and services continues to grow rapidly. Although the scope of the existing commercial and academic product set is quite broad, these tools still share a common underlying problem. The ability of each tool to visually organize object representations is increasingly impaired as the number of components and component dependencies within systems increases. Regardless of how objects are defined, complex ``spaghetti`` networks result in nearly all large system cases. While this problem is immediately apparent in modem systems analysis involving large software implementations, it is not new. As will be discussed in Chapter 2, related problems involving the theory of graphs were identified long ago. This important theoretical foundation provides a useful vehicle for representing and analyzing complex system structures. While the utility of directed graph based concepts in software tool design has been demonstrated in literature, these tools still lack the capabilities necessary for large system comprehension. This foundation must therefore be expanded with new organizational and visualization constructs necessary to meet this challenge. This dissertation addresses this need by constructing a conceptual model and a set of methods for interactively exploring, organizing, and understanding the structure of complex software systems.

  5. A systems biology approach reveals common metastatic pathways in osteosarcoma

    Directory of Open Access Journals (Sweden)

    Flores Ricardo J

    2012-05-01

    Full Text Available Abstract Background Osteosarcoma (OS is the most common malignant bone tumor in children and adolescents. The survival rate of patients with metastatic disease remains very dismal. Nevertheless, metastasis is a complex process and a single-level analysis is not likely to identify its key biological determinants. In this study, we used a systems biology approach to identify common metastatic pathways that are jointly supported by both mRNA and protein expression data in two distinct human metastatic OS models. Results mRNA expression microarray and N-linked glycoproteomic analyses were performed on two commonly used isogenic pairs of human metastatic OS cell lines, namely HOS/143B and SaOS-2/LM7. Pathway analysis of the differentially regulated genes and glycoproteins separately revealed pathways associated to metastasis including cell cycle regulation, immune response, and epithelial-to-mesenchymal-transition. However, no common significant pathway was found at both genomic and proteomic levels between the two metastatic models, suggesting a very different biological nature of the cell lines. To address this issue, we used a topological significance analysis based on a “shortest-path” algorithm to identify topological nodes, which uncovered additional biological information with respect to the genomic and glycoproteomic profiles but remained hidden from the direct analyses. Pathway analysis of the significant topological nodes revealed a striking concordance between the models and identified significant common pathways, including “Cytoskeleton remodeling/TGF/WNT”, “Cytoskeleton remodeling/Cytoskeleton remodeling”, and “Cell adhesion/Chemokines and adhesion”. Of these, the “Cytoskeleton remodeling/TGF/WNT” was the top ranked common pathway from the topological analysis of the genomic and proteomic profiles in the two metastatic models. The up-regulation of proteins in the “Cytoskeleton remodeling/TGF/WNT” pathway in the Sa

  6. Systems Biology Graphical Notation: Entity Relationship language Level 1 Version 2.

    Science.gov (United States)

    Sorokin, Anatoly; Le Novère, Nicolas; Luna, Augustin; Czauderna, Tobias; Demir, Emek; Haw, Robin; Mi, Huaiyu; Moodie, Stuart; Schreiber, Falk; Villéger, Alice

    2015-09-04

    The Systems Biological Graphical Notation (SBGN) is an international community effort for standardized graphical representations of biological pathways and networks. The goal of SBGN is to provide unambiguous pathway and network maps for readers with different scientific backgrounds as well as to support efficient and accurate exchange of biological knowledge between different research communities, industry, and other players in systems biology. Three SBGN languages, Process Description (PD), Entity Relationship (ER) and Activity Flow (AF), allow for the representation of different aspects of biological and biochemical systems at different levels of detail. The SBGN Entity Relationship language (ER) represents biological entities and their interactions and relationships within a network. SBGN ER focuses on all potential relationships between entities without considering temporal aspects. The nodes (elements) describe biological entities, such as proteins and complexes. The edges (connections) provide descriptions of interactions and relationships (or influences), e.g., complex formation, stimulation and inhibition. Among all three languages of SBGN, ER is the closest to protein interaction networks in biological literature and textbooks, but its well-defined semantics offer a superior precision in expressing biological knowledge.

  7. Impact of systems biology on metabolic engineering of Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Nielsen, Jens; Jewett, Michael Christopher

    2008-01-01

    in the industrial application of this yeast. Developments in genomics and high-throughput systems biology tools are enhancing one's ability to rapidly characterize cellular behaviour, which is valuable in the field of metabolic engineering where strain characterization is often the bottleneck in strain development...... programmes. Here, the impact of systems biology on metabolic engineering is reviewed and perspectives on the role of systems biology in the design of cell factories are given....

  8. Interactive analysis of systems biology molecular expression data

    OpenAIRE

    Prabhakar Sunil; Salt David E; Kane Michael D; Stephenson Alan; Ouyang Qi; Zhang Mingwu; Burgner John; Buck Charles; Zhang Xiang

    2008-01-01

    Abstract Background Systems biology aims to understand biological systems on a comprehensive scale, such that the components that make up the whole are connected to one another and work through dependent interactions. Molecular correlations and comparative studies of molecular expression are crucial to establishing interdependent connections in systems biology. The existing software packages provide limited data mining capability. The user must first generate visualization data with a preferr...

  9. Multidimensional approach to complex system resilience analysis

    International Nuclear Information System (INIS)

    Gama Dessavre, Dante; Ramirez-Marquez, Jose E.; Barker, Kash

    2016-01-01

    Recent works have attempted to formally define a general metric for quantifying resilience for complex systems as a relationship of performance of the systems against time. The technical content in the proposed work introduces a new model that allows, for the first time, to compare the system resilience among systems (or different modifications to a system), by introducing a new dimension to system resilience models, called stress, to mimic the definition of resilience in material science. The applicability and usefulness of the model is shown with a new heat map visualization proposed in this work, and it is applied to a simulated network resilience case to exemplify its potential benefits. - Highlights: • We analyzed two of the main current metrics of resilience. • We create a new model that relates events with the effects they have. • We develop a novel heat map visualization to compare system resilience. • We showed the model and visualization usefulness in a simulated case.

  10. Assessing the Possibility of Biological Complexity on Other Worlds, with an Estimate of the Occurrence of Complex Life in the Milky Way Galaxy

    Directory of Open Access Journals (Sweden)

    Louis N. Irwin

    2014-05-01

    Full Text Available Rational speculation about biological evolution on other worlds is one of the outstanding challenges in astrobiology. With the growing confirmation that multiplanetary systems abound in the universe, the prospect that life occurs redundantly throughout the cosmos is gaining widespread support. Given the enormous number of possible abodes for life likely to be discovered on an ongoing basis, the prospect that life could have evolved into complex, macro-organismic communities in at least some cases merits consideration. Toward that end, we here propose a Biological Complexity Index (BCI, designed to provide a quantitative estimate of the relative probability that complex, macro-organismic life forms could have emerged on other worlds. The BCI ranks planets and moons by basic, first-order characteristics detectable with available technology. By our calculation only 11 (~1.7% of the extrasolar planets known to date have a BCI above that of Europa; but by extrapolation, the total of such planets could exceed 100 million in our galaxy alone. This is the first quantitative assessment of the plausibility of complex life throughout the universe based on empirical data. It supports the view that the evolution of complex life on other worlds is rare in frequency but large in absolute number.

  11. Novel metaheuristic for parameter estimation in nonlinear dynamic biological systems

    Directory of Open Access Journals (Sweden)

    Banga Julio R

    2006-11-01

    Full Text Available Abstract Background We consider the problem of parameter estimation (model calibration in nonlinear dynamic models of biological systems. Due to the frequent ill-conditioning and multi-modality of many of these problems, traditional local methods usually fail (unless initialized with very good guesses of the parameter vector. In order to surmount these difficulties, global optimization (GO methods have been suggested as robust alternatives. Currently, deterministic GO methods can not solve problems of realistic size within this class in reasonable computation times. In contrast, certain types of stochastic GO methods have shown promising results, although the computational cost remains large. Rodriguez-Fernandez and coworkers have presented hybrid stochastic-deterministic GO methods which could reduce computation time by one order of magnitude while guaranteeing robustness. Our goal here was to further reduce the computational effort without loosing robustness. Results We have developed a new procedure based on the scatter search methodology for nonlinear optimization of dynamic models of arbitrary (or even unknown structure (i.e. black-box models. In this contribution, we describe and apply this novel metaheuristic, inspired by recent developments in the field of operations research, to a set of complex identification problems and we make a critical comparison with respect to the previous (above mentioned successful methods. Conclusion Robust and efficient methods for parameter estimation are of key importance in systems biology and related areas. The new metaheuristic presented in this paper aims to ensure the proper solution of these problems by adopting a global optimization approach, while keeping the computational effort under reasonable values. This new metaheuristic was applied to a set of three challenging parameter estimation problems of nonlinear dynamic biological systems, outperforming very significantly all the methods previously

  12. Novel metaheuristic for parameter estimation in nonlinear dynamic biological systems.

    Science.gov (United States)

    Rodriguez-Fernandez, Maria; Egea, Jose A; Banga, Julio R

    2006-11-02

    We consider the problem of parameter estimation (model calibration) in nonlinear dynamic models of biological systems. Due to the frequent ill-conditioning and multi-modality of many of these problems, traditional local methods usually fail (unless initialized with very good guesses of the parameter vector). In order to surmount these difficulties, global optimization (GO) methods have been suggested as robust alternatives. Currently, deterministic GO methods can not solve problems of realistic size within this class in reasonable computation times. In contrast, certain types of stochastic GO methods have shown promising results, although the computational cost remains large. Rodriguez-Fernandez and coworkers have presented hybrid stochastic-deterministic GO methods which could reduce computation time by one order of magnitude while guaranteeing robustness. Our goal here was to further reduce the computational effort without loosing robustness. We have developed a new procedure based on the scatter search methodology for nonlinear optimization of dynamic models of arbitrary (or even unknown) structure (i.e. black-box models). In this contribution, we describe and apply this novel metaheuristic, inspired by recent developments in the field of operations research, to a set of complex identification problems and we make a critical comparison with respect to the previous (above mentioned) successful methods. Robust and efficient methods for parameter estimation are of key importance in systems biology and related areas. The new metaheuristic presented in this paper aims to ensure the proper solution of these problems by adopting a global optimization approach, while keeping the computational effort under reasonable values. This new metaheuristic was applied to a set of three challenging parameter estimation problems of nonlinear dynamic biological systems, outperforming very significantly all the methods previously used for these benchmark problems.

  13. Screening the efficient biological prospects of triazole allied mixed ligand metal complexes

    Science.gov (United States)

    Utthra, Ponnukalai Ponya; Kumaravel, Ganesan; Raman, Natarajan

    2017-12-01

    Triazole appended mixed ligand complexes (1-8) of the general formula [ML (bpy/phen)2]Cl2, where M = Cu(II), Co(II), Ni(II) and Zn(II), L = triazole appended Schiff base (E)sbnd N-(4-nitrobenzylidene)-1H-1,2,4-triazol-3-amine and bpy/phen = 2,2‧-bipyridine/1,10-phenanthroline, have been synthesized. The design and synthesis of this elaborate ligand has been performed with the aim of increasing stability and conjugation of 1,2,4 triazole, whose Schiff base derivatives are known as biologically active compounds thereby exploring their DNA binding affinity and other biological applications. The compounds have been comprehensively characterized by elemental analysis, spectroscopic methods (IR, UV-Vis, EPR, 1H and 13C NMR spectroscopy), ESI mass spectrometry and magnetic susceptibility measurements. The complexes were found to exhibit octahedral geometry. The complexes 1-8 were subjected to DNA binding techniques evaluated using UV-Vis absorption, CV, CD, Fluorescence spectroscopy and hydrodynamic measurements. Complex 5 showed a Kb value of 3.9 × 105 M-1. The DNA damaging efficacy for the complexes was observed to be high compared to the ligand. The antimicrobial screening of the compounds against bacterial and fungal strains indicates that the complexes possess excellent antimicrobial activity than the ligand. The overall biological activity of the complexes with phen as a co-ligand possessed superior potential than the ligand.

  14. Energy Flows in Low-Entropy Complex Systems

    Directory of Open Access Journals (Sweden)

    Eric J. Chaisson

    2015-12-01

    Full Text Available Nature’s many complex systems—physical, biological, and cultural—are islands of low-entropy order within increasingly disordered seas of surrounding, high-entropy chaos. Energy is a principal facilitator of the rising complexity of all such systems in the expanding Universe, including galaxies, stars, planets, life, society, and machines. A large amount of empirical evidence—relating neither entropy nor information, rather energy—suggests that an underlying simplicity guides the emergence and growth of complexity among many known, highly varied systems in the 14-billion-year-old Universe, from big bang to humankind. Energy flows are as centrally important to life and society as they are to stars and galaxies. In particular, the quantity energy rate density—the rate of energy flow per unit mass—can be used to explicate in a consistent, uniform, and unifying way a huge collection of diverse complex systems observed throughout Nature. Operationally, those systems able to utilize optimal amounts of energy tend to survive and those that cannot are non-randomly eliminated.

  15. Breeding system and pollination biology of the semidomesticated ...

    African Journals Online (AJOL)

    Breeding system and pollination biology of the semidomesticated fruit tree, Tamarindus indica L. (Leguminosae: Caesalpinioideae ): Implications for fruit production, selective breeding, and conservation of genetic resources.

  16. Complex Dynamical System for Toda Lattice

    Science.gov (United States)

    Konno, Kimiaki

    1988-11-01

    Extending an independent variable into complex and introducing an auxiliary function, we investigate nonlinear interactions between solitons for the Toda lattice by observing behavior of zeros of the function. The Newton’s method calculating them is identified with a complex dynamical system. We present numerical results of the Fatou set on the dynamics. According to motion of solitons, the set changes surprisingly. Since soliton solutions include the exponential function, the Fatou set is different from that of the polynomial and the rational functions.

  17. Unified Computational Intelligence for Complex Systems

    CERN Document Server

    Seiffertt, John

    2010-01-01

    Computational intelligence encompasses a wide variety of techniques that allow computation to learn, to adapt, and to seek. That is, they may be designed to learn information without explicit programming regarding the nature of the content to be retained, they may be imbued with the functionality to adapt to maintain their course within a complex and unpredictably changing environment, and they may help us seek out truths about our own dynamics and lives through their inclusion in complex system modeling. These capabilities place our ability to compute in a category apart from our ability to e

  18. Detection of two isomeric binding configurations in a protein-aptamer complex with a biological nanopore.

    Science.gov (United States)

    Van Meervelt, Veerle; Soskine, Misha; Maglia, Giovanni

    2014-12-23

    Protein-DNA interactions play critical roles in biological systems, and they often involve complex mechanisms and dynamics that are not easily measured by ensemble experiments. Recently, we showed that folded proteins can be internalized inside ClyA nanopores and studied by ionic current recordings at the single-molecule level. Here, we use ClyA nanopores to sample the interaction between the G-quadruplex fold of the thrombin binding aptamer (TBA) and human thrombin (HT). Surprisingly, the internalization of the HT:TBA complex inside the nanopore induced two types of current blockades with distinguished residual current and lifetime. Using single nucleobase substitutions to TBA we showed that these two types of blockades originate from TBA binding to thrombin with two isomeric orientations. Voltage dependencies and the use of ClyA nanopores with two different diameters allowed assessing the effect of the applied potential and confinement and revealed that the two binding configurations of TBA to HT display different lifetimes. These results show that the ClyA nanopores can be used to probe conformational heterogeneity in protein:DNA interactions.

  19. Reduction theories elucidate the origins of complex biological rhythms generated by interacting delay-induced oscillations.

    Directory of Open Access Journals (Sweden)

    Ikuhiro Yamaguchi

    Full Text Available Time delay is known to induce sustained oscillations in many biological systems such as electroencephalogram (EEG activities and gene regulations. Furthermore, interactions among delay-induced oscillations can generate complex collective rhythms, which play important functional roles. However, due to their intrinsic infinite dimensionality, theoretical analysis of interacting delay-induced oscillations has been limited. Here, we show that the two primary methods for finite-dimensional limit cycles, namely, the center manifold reduction in the vicinity of the Hopf bifurcation and the phase reduction for weak interactions, can successfully be applied to interacting infinite-dimensional delay-induced oscillations. We systematically derive the complex Ginzburg-Landau equation and the phase equation without delay for general interaction networks. Based on the reduced low-dimensional equations, we demonstrate that diffusive (linearly attractive coupling between a pair of delay-induced oscillations can exhibit nontrivial amplitude death and multimodal phase locking. Our analysis provides unique insights into experimentally observed EEG activities such as sudden transitions among different phase-locked states and occurrence of epileptic seizures.

  20. A Multifaceted Mathematical Approach for Complex Systems

    Energy Technology Data Exchange (ETDEWEB)

    Alexander, F.; Anitescu, M.; Bell, J.; Brown, D.; Ferris, M.; Luskin, M.; Mehrotra, S.; Moser, B.; Pinar, A.; Tartakovsky, A.; Willcox, K.; Wright, S.; Zavala, V.

    2012-03-07

    Applied mathematics has an important role to play in developing the tools needed for the analysis, simulation, and optimization of complex problems. These efforts require the development of the mathematical foundations for scientific discovery, engineering design, and risk analysis based on a sound integrated approach for the understanding of complex systems. However, maximizing the impact of applied mathematics on these challenges requires a novel perspective on approaching the mathematical enterprise. Previous reports that have surveyed the DOE's research needs in applied mathematics have played a key role in defining research directions with the community. Although these reports have had significant impact, accurately assessing current research needs requires an evaluation of today's challenges against the backdrop of recent advances in applied mathematics and computing. To address these needs, the DOE Applied Mathematics Program sponsored a Workshop for Mathematics for the Analysis, Simulation and Optimization of Complex Systems on September 13-14, 2011. The workshop had approximately 50 participants from both the national labs and academia. The goal of the workshop was to identify new research areas in applied mathematics that will complement and enhance the existing DOE ASCR Applied Mathematics Program efforts that are needed to address problems associated with complex systems. This report describes recommendations from the workshop and subsequent analysis of the workshop findings by the organizing committee.

  1. A guide to numerical modelling in systems biology

    CERN Document Server

    Deuflhard, Peter

    2015-01-01

    This book is intended for students of computational systems biology with only a limited background in mathematics. Typical books on systems biology merely mention algorithmic approaches, but without offering a deeper understanding. On the other hand, mathematical books are typically unreadable for computational biologists. The authors of the present book have worked hard to fill this gap. The result is not a book on systems biology, but on computational methods in systems biology. This book originated from courses taught by the authors at Freie Universität Berlin. The guiding idea of the courses was to convey those mathematical insights that are indispensable for systems biology, teaching the necessary mathematical prerequisites by means of many illustrative examples and without any theorems. The three chapters cover the mathematical modelling of biochemical and physiological processes, numerical simulation of the dynamics of biological networks, and identification of model parameters by means of comparisons...

  2. Applying systems biology methods to the study of human physiology in extreme environments

    Science.gov (United States)

    2013-01-01

    Systems biology is defined in this review as ‘an iterative process of computational model building and experimental model revision with the aim of understanding or simulating complex biological systems’. We propose that, in practice, systems biology rests on three pillars: computation, the omics disciplines and repeated experimental perturbation of the system of interest. The number of ethical and physiologically relevant perturbations that can be used in experiments on healthy humans is extremely limited and principally comprises exercise, nutrition, infusions (e.g. Intralipid), some drugs and altered environment. Thus, we argue that systems biology and environmental physiology are natural symbionts for those interested in a system-level understanding of human biology. However, despite excellent progress in high-altitude genetics and several proteomics studies, systems biology research into human adaptation to extreme environments is in its infancy. A brief description and overview of systems biology in its current guise is given, followed by a mini review of computational methods used for modelling biological systems. Special attention is given to high-altitude research, metabolic network reconstruction and constraint-based modelling. PMID:23849719

  3. Structured analysis and modeling of complex systems

    Science.gov (United States)

    Strome, David R.; Dalrymple, Mathieu A.

    1992-01-01

    The Aircrew Evaluation Sustained Operations Performance (AESOP) facility at Brooks AFB, Texas, combines the realism of an operational environment with the control of a research laboratory. In recent studies we collected extensive data from the Airborne Warning and Control Systems (AWACS) Weapons Directors subjected to high and low workload Defensive Counter Air Scenarios. A critical and complex task in this environment involves committing a friendly fighter against a hostile fighter. Structured Analysis and Design techniques and computer modeling systems were applied to this task as tools for analyzing subject performance and workload. This technology is being transferred to the Man-Systems Division of NASA Johnson Space Center for application to complex mission related tasks, such as manipulating the Shuttle grappler arm.

  4. Analysis of Complex Valve and Feed Systems

    Science.gov (United States)

    Ahuja, Vineet; Hosangadi, Ashvin; Shipman, Jeremy; Cavallo, Peter; Dash, Sanford

    2007-01-01

    A numerical framework for analysis of complex valve systems supports testing of propulsive systems by simulating key valve and control system components in the test loop. In particular, it is designed to enhance the analysis capability in terms of identifying system transients and quantifying the valve response to these transients. This system has analysis capability for simulating valve motion in complex systems operating in diverse flow regimes ranging from compressible gases to cryogenic liquids. A key feature is the hybrid, unstructured framework with sub-models for grid movement and phase change including cryogenic cavitations. The multi-element unstructured framework offers improved predictions of valve performance characteristics under steady conditions for structurally complex valves such as pressure regulator valve. Unsteady simulations of valve motion using this computational approach have been carried out for various valves in operation at Stennis Space Center such as the split-body valve and the 10-in. (approx.25.4-cm) LOX (liquid oxygen) valve and the 4-in. (approx.10 cm) Y-pattern valve (liquid nitrogen). Such simulations make use of variable grid topologies, thereby permitting solution accuracy and resolving important flow physics in the seat region of the moving valve. An advantage to this software includes possible reduction in testing costs incurred due to disruptions relating to unexpected flow transients or functioning of valve/flow control systems. Prediction of the flow anomalies leading to system vibrations, flow resonance, and valve stall can help in valve scheduling and significantly reduce the need for activation tests. This framework has been evaluated for its ability to predict performance metrics like flow coefficient for cavitating venturis and valve coefficient curves, and could be a valuable tool in predicting and understanding anomalous behavior of system components at rocket propulsion testing and design sites.

  5. Driving developmental and evolutionary change: A systems biology view.

    Science.gov (United States)

    Bard, Jonathan

    2013-04-01

    Embryonic development is underpinned by ∼50 core processes that drive morphogenesis, growth, patterning and differentiation, and each is the functional output of a complex molecular network. Processes are thus the natural and parsimonious link between genotype and phenotype and the obvious focus for any discussion of biological change. Here, the implications of this approach are explored. One is that many features of developmental change can be modeled as mathematical graphs, or sets of connected triplets of the general form . In these, the verbs (edges) are the outputs of the processes that drive change and the nouns (nodes) are the time-dependent states of biological entities (from molecules to tissues). Such graphs help unpick the multi-level complexity of developmental phenomena and may help suggest new experiments. Another comes from analyzing the effect of mutation that lead to tinkering with the dynamic properties of these processes and to congenital abnormalities; if these changes are both inherited and advantageous, they become evolutionary modifications. In this context, protein networks often represents what classical evolutionary genetics sees as genes, and the realization that traits reflect the output processes of complex networks, particularly for growth, patterning and pigmentation, rather than anything simpler clarifies some problems that the evolutionary synthesis of the 1950s has found hard to solve. In the wider context, most processes are used many times in development and cooperate to produce tissue modules (bones, branching duct systems, muscles etc.). Their underlying generative networks can thus be thought of as genomic modules or subroutines. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Tensegrity I. Cell structure and hierarchical systems biology

    Science.gov (United States)

    Ingber, Donald E.

    2003-01-01

    In 1993, a Commentary in this journal described how a simple mechanical model of cell structure based on tensegrity architecture can help to explain how cell shape, movement and cytoskeletal mechanics are controlled, as well as how cells sense and respond to mechanical forces (J. Cell Sci. 104, 613-627). The cellular tensegrity model can now be revisited and placed in context of new advances in our understanding of cell structure, biological networks and mechanoregulation that have been made over the past decade. Recent work provides strong evidence to support the use of tensegrity by cells, and mathematical formulations of the model predict many aspects of cell behavior. In addition, development of the tensegrity theory and its translation into mathematical terms are beginning to allow us to define the relationship between mechanics and biochemistry at the molecular level and to attack the larger problem of biological complexity. Part I of this two-part article covers the evidence for cellular tensegrity at the molecular level and describes how this building system may provide a structural basis for the hierarchical organization of living systems--from molecule to organism. Part II, which focuses on how these structural networks influence information processing networks, appears in the next issue.

  7. Dependability problems of complex information systems

    CERN Document Server

    Zamojski, Wojciech

    2014-01-01

    This monograph presents original research results on selected problems of dependability in contemporary Complex Information Systems (CIS). The ten chapters are concentrated around the following three aspects: methods for modelling of the system and its components, tasks ? or in more generic and more adequate interpretation, functionalities ? accomplished by the system and conditions for their correct realization in the dynamic operational environment. While the main focus is on theoretical advances and roadmaps for implementations of new technologies, a?much needed forum for sharing of the bes

  8. Systems Biology and P4 Medicine: Past, Present, and Future

    Directory of Open Access Journals (Sweden)

    Leroy Hood

    2013-04-01

    Full Text Available Studying complex biological systems in a holistic rather than a “one gene or one protein” at a time approach requires the concerted effort of scientists from a wide variety of disciplines. The Institute for Systems Biology (ISB has seamlessly integrated these disparate fields to create a cross-disciplinary platform and culture in which “biology drives technology drives computation.” To achieve this platform/culture, it has been necessary for cross-disciplinary ISB scientists to learn one another’s languages and work together effectively in teams. The focus of this “systems” approach on disease has led to a discipline denoted systems medicine. The advent of technological breakthroughs in the fields of genomics, proteomics, and, indeed, the other “omics” is catalyzing striking advances in systems medicine that have and are transforming diagnostic and therapeutic strategies. Systems medicine has united genomics and genetics through family genomics to more readily identify disease genes. It has made blood a window into health and disease. It is leading to the stratification of diseases (division into discrete subtypes for proper impedance match against drugs and the stratification of patients into subgroups that respond to environmental challenges in a similar manner (e.g. response to drugs, response to toxins, etc.. The convergence of patient-activated social networks, big data and their analytics, and systems medicine has led to a P4 medicine that is predictive, preventive, personalized, and participatory. Medicine will focus on each individual. It will become proactive in nature. It will increasingly focus on wellness rather than disease. For example, in 10 years each patient will be surrounded by a virtual cloud of billions of data points, and we will have the tools to reduce this enormous data dimensionality into simple hypotheses about how to optimize wellness and avoid disease for each individual. P4 medicine will be able to

  9. Complex Systems Design & Management : Proceedings of the Second International Conference on Complex Systems Design & Management

    CERN Document Server

    Krob, Daniel; Voirin, Jean-Luc

    2012-01-01

    This book contains all refereed papers that were accepted to the second edition of the « Complex Systems Design & Management » (CSDM 2011) international conference that took place in Paris (France) from December 7 to December 9, 2011. (Website: http://www.csdm2011.csdm.fr/). These proceedings cover the most recent trends in the emerging field of complex systems sciences & practices from an industrial and academic perspective, including the main industrial domains (transport, defense & security, electronics, energy & environment, e-services), scientific & technical topics (systems fundamentals, systems architecture& engineering, systems metrics & quality, systemic  tools) and system types (transportation systems, embedded systems, software & information systems, systems of systems, artificial ecosystems). The CSDM 2011 conference is organized under the guidance of the CESAMES non-profit organization (http://www.cesames.net/).

  10. Complex Systems Design & Management : Proceedings of the Third International Conference on Complex Systems Design & Management

    CERN Document Server

    Caseau, Yves; Krob, Daniel; Rauzy, Antoine

    2013-01-01

    This book contains all refereed papers that were accepted to the third edition of the « Complex Systems Design & Management » (CSD&M 2012) international conference that took place in Paris (France) from December 12-14, 2012. (Website: http://www.csdm2012.csdm.fr)  These proceedings cover the most recent trends in the emerging field of complex systems sciences & practices from an industrial and academic perspective, including the main industrial domains (transport, defense & security, electronics, energy & environment, e-services), scientific & technical topics (systems fundamentals, systems architecture& engineering, systems metrics & quality, systemic  tools) and system types (transportation systems, embedded systems, software & information systems, systems of systems, artificial ecosystems). The CSD&M 2012 conference is organized under the guidance of the CESAMES non-profit organization (http://www.cesames.net).

  11. Automated design of complex dynamic systems.

    Directory of Open Access Journals (Sweden)

    Michiel Hermans

    Full Text Available Several fields of study are concerned with uniting the concept of computation with that of the design of physical systems. For example, a recent trend in robotics is to design robots in such a way that they require a minimal control effort. Another example is found in the domain of photonics, where recent efforts try to benefit directly from the complex nonlinear dynamics to achieve more efficient signal processing. The underlying goal of these and similar research efforts is to internalize a large part of the necessary computations within the physical system itself by exploiting its inherent non-linear dynamics. This, however, often requires the optimization of large numbers of system parameters, related to both the system's structure as well as its material properties. In addition, many of these parameters are subject to fabrication variability or to variations through time. In this paper we apply a machine learning algorithm to optimize physical dynamic systems. We show that such algorithms, which are normally applied on abstract computational entities, can be extended to the field of differential equations and used to optimize an associated set of parameters which determine their behavior. We show that machine learning training methodologies are highly useful in designing robust systems, and we provide a set of both simple and complex examples using models of physical dynamical systems. Interestingly, the derived optimization method is intimately related to direct collocation a method known in the field of optimal control. Our work suggests that the application domains of both machine learning and optimal control have a largely unexplored overlapping area which envelopes a novel design methodology of smart and highly complex physical systems.

  12. Synthesis, Crystal Structure, Spectroscopic Properties and Potential Biological Activities of Salicylate‒Neocuproine Ternary Copper(II Complexes

    Directory of Open Access Journals (Sweden)

    Lenka Kucková

    2015-01-01

    Full Text Available Mixed ligand copper(II complexes containing derivatives of salicylic acid and heterocyclic ligands with nitrogen donor atoms have been the subject of various studies and reviews. In this paper, synthesis and characterization of the ternary copper(II complexes of neocuproine (2,9-dimethyl-1,10-phenanthroline, Neo and salicylate ligands (Sal are reported. In addition, the crystal structures of ([Cu(H2O(5-Cl-Sal(Neo] (1, [Cu(μ-Sal(Neo]2 (2, Cu2(μ-5-Cl-Sal(5-Cl-HSal2(Neo2]·EtOH (3 were determined. In order to compare structural and biological properties of the prepared complexes, spectroscopic and biological studies were performed. Results of X-ray diffraction show that prepared complexes form three types of crystal structures in a given system: monomeric, dimeric and dinuclear complex. The preliminary study on the DNA cleavage activity has shown that the complexes under study behave as the chemical nucleases in the presence of added hydrogen peroxide with slight differences in the activity (1 > 2 > 3. The complexes 1 and 2 exhibited nuclease activity itself indicating the interaction of complexes with the DNA. It has been proposed that the enhanced destructive effect of the complexes 1 and 2 on the DNA is a result of two possible mechanisms of action: (i the conversion of closed circular DNA (form I to the nicked DNA (form II caused by the copper complex itself and (ii damage of DNA by Reactive Oxygen Species (ROS—products of the interaction of copper with hydrogen peroxide by means of Fenton reaction (hydroxyl radicals. Thus the biological activity of the prepared Cu(II complexes containing derivatives of salicylic acid and phenanthroline molecules is substantiated by two independent mechanisms. While derivatives of salicylic acids in the coordination sphere of copper complexes are responsible for radical-scavenging activity (predominantly towards superoxide radical anion, the presence of chelating ligand 2,9-dimethyl-1,10-phenanthroline

  13. A Magnetic Sensor System for Biological Detection

    KAUST Repository

    Li, Fuquan

    2015-05-01

    Magnetic biosensors detect biological targets through sensing the stray field of magnetic beads which label the targets. Commonly, magnetic biosensors employ the “sandwich” method to immobilize biological targets, i.e., the targets are sandwiched between a bio-functionalized sensor surface and bio-functionalized magnetic beads. This method has been used very successfully in different application, but its execution requires a rather elaborate procedure including several washing and incubation steps. This dissertation investigates a new magnetic biosensor concept, which enables a simple and effective detection of biological targets. The biosensor takes advantage of the size difference between bare magnetic beads and compounds of magnetic beads and biological targets. First, the detection of super-paramagnetic beads via magnetic tunnel junction (MTJ) sensors is implemented. Frequency modulation is used to enhance the signal-to-noise ratio, enabling the detection of a single magnetic bead. Second, the concept of the magnetic biosensor is investigated theoretically. The biosensor consists of an MTJ sensor, which detects the stray field of magnetic beads inside of a trap on top of the MTJ. A microwire between the trap and the MTJ is used to attract magnetic beads to the trapping well by applying a current to it. The MTJ sensor’s output depends on the number of beads inside the trap. If biological targets are in the sample solution, the beads will form bead compounds consisting of beads linked to the biological targets. Since bead compounds are larger than bare beads, the number of beads inside the trapping well will depend on the presence of biological targets. Hence, the output of the MTJ sensor will depend on the biological targets. The dependences of sensor signals on the sizes of the MTJ sensor, magnetic beads and biological targets are studied to find the optimum constellations for the detection of specific biological targets. The optimization is demonstrated

  14. Linking Microbiota to Human Diseases: A Systems Biology Perspective.

    Science.gov (United States)

    Wu, Hao; Tremaroli, Valentina; Bäckhed, Fredrik

    2015-12-01

    The human gut microbiota encompasses a densely populated ecosystem that provides essential functions for host development, immune maturation, and metabolism. Alterations to the gut microbiota have been observed in numerous diseases, including human metabolic diseases such as obesity, type 2 diabetes (T2D), and irritable bowel syndrome, and some animal experiments have suggested causality. However, few studies have validated causality in humans and the underlying mechanisms remain largely to be elucidated. We discuss how systems biology approaches combined with new experimental technologies may disentangle some of the mechanistic details in the complex interactions of diet, microbiota, and host metabolism and may provide testable hypotheses for advancing our current understanding of human-microbiota interaction. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. A conceptual review on systems biology in health and diseases: from biological networks to modern therapeutics

    OpenAIRE

    Somvanshi, Pramod Rajaram; Venkatesh, K. V.

    2013-01-01

    Human physiology is an ensemble of various biological processes spanning from intracellular molecular interactions to the whole body phenotypic response. Systems biology endures to decipher these multi-scale biological networks and bridge the link between genotype to phenotype. The structure and dynamic properties of these networks are responsible for controlling and deciding the phenotypic state of a cell. Several cells and various tissues coordinate together to generate an organ level respo...

  16. Systems biology applied to vaccine and immunotherapy development

    Directory of Open Access Journals (Sweden)

    Marincola Francesco M

    2011-09-01

    Full Text Available Abstract Immunotherapies, including vaccines, represent a potent tool to prevent or contain disease with high morbidity or mortality such as infections and cancer. However, despite their widespread use, we still have a limited understanding of the mechanisms underlying the induction of protective immune responses. Immunity is made of a multifaceted set of integrated responses involving a dynamic interaction of thousands of molecules; among those is a growing appreciation for the role the innate immunity (i.e. pathogen recognition receptors - PRRs plays in determining the nature and duration (immune memory of adaptive T and B cell immunity. The complex network of interactions between immune manipulation of the host (immunotherapy on one side and innate and adaptive responses on the other might be fully understood only employing the global level of investigation provided by systems biology. In this framework, the advancement of high-throughput technologies, together with the extensive identification of new genes, proteins and other biomolecules in the "omics" era, facilitate large-scale biological measurements. Moreover, recent development of new computational tools enables the comprehensive and quantitative analysis of the interactions between all of the components of immunity over time. Here, we review recent progress in using systems biology to study and evaluate immunotherapy and vaccine strategies for infectious and neoplastic diseases. Multi-parametric data provide novel and often unsuspected mechanistic insights while enabling the identification of common immune signatures relevant to human investigation such as the prediction of immune responsiveness that could lead to the improvement of the design of future immunotherapy trials. Thus, the paradigm switch from "empirical" to "knowledge-based" conduct of medicine and immunotherapy in particular, leading to patient-tailored treatment.

  17. A review of imaging techniques for systems biology

    Directory of Open Access Journals (Sweden)

    Po Ming J

    2008-08-01

    Full Text Available Abstract This paper presents a review of imaging techniques and of their utility in system biology. During the last decade systems biology has matured into a distinct field and imaging has been increasingly used to enable the interplay of experimental and theoretical biology. In this review, we describe and compare the roles of microscopy, ultrasound, CT (Computed Tomography, MRI (Magnetic Resonance Imaging, PET (Positron Emission Tomography, and molecular probes such as quantum dots and nanoshells in systems biology. As a unified application area among these different imaging techniques, examples in cancer targeting are highlighted.

  18. Topics in Complexity: From Physical to Life Science Systems

    Science.gov (United States)

    Charry, Pedro David Manrique

    Complexity seeks to unwrap the mechanisms responsible for collective phenomena across the physical, biological, chemical, economic and social sciences. This thesis investigates real-world complex dynamical systems ranging from the quantum/natural domain to the social domain. The following novel understandings are developed concerning these systems' out-of-equilibrium and nonlinear behavior. Standard quantum techniques show divergent outcomes when a quantum system comprising more than one subunit is far from thermodynamic equilibrium. Abnormal photon inter-arrival times help fulfill the metabolic needs of a terrestrial photosynthetic bacterium. Spatial correlations within incident light can act as a driving mechanism for an organism's adaptation toward more ordered structures. The group dynamics of non-identical objects, whose assembly rules depend on mutual heterogeneity, yield rich transition dynamics between isolation and cohesion, with the cohesion regime reproducing a particular universal pattern commonly found in many real-world systems. Analyses of covert networks reveal collective gender superiority in the connectivity that provides benefits for system robustness and survival. Nodal migration in a network generates complex contagion profiles that lie beyond traditional approaches and yet resemble many modern-day outbreaks.

  19. Sender-receiver systems and applying information theory for quantitative synthetic biology.

    Science.gov (United States)

    Barcena Menendez, Diego; Senthivel, Vivek Raj; Isalan, Mark

    2015-02-01

    Sender-receiver (S-R) systems abound in biology, with communication systems sending information in various forms. Information theory provides a quantitative basis for analysing these processes and is being applied to study natural genetic, enzymatic and neural networks. Recent advances in synthetic biology are providing us with a wealth of artificial S-R systems, giving us quantitative control over networks with a finite number of well-characterised components. Combining the two approaches can help to predict how to maximise signalling robustness, and will allow us to make increasingly complex biological computers. Ultimately, pushing the boundaries of synthetic biology will require moving beyond engineering the flow of information and towards building more sophisticated circuits that interpret biological meaning. Copyright © 2014. Published by Elsevier Ltd.

  20. Analysis of complex systems using neural networks

    International Nuclear Information System (INIS)

    Uhrig, R.E.

    1992-01-01

    The application of neural networks, alone or in conjunction with other advanced technologies (expert systems, fuzzy logic, and/or genetic algorithms), to some of the problems of complex engineering systems has the potential to enhance the safety, reliability, and operability of these systems. Typically, the measured variables from the systems are analog variables that must be sampled and normalized to expected peak values before they are introduced into neural networks. Often data must be processed to put it into a form more acceptable to the neural network (e.g., a fast Fourier transformation of the time-series data to produce a spectral plot of the data). Specific applications described include: (1) Diagnostics: State of the Plant (2) Hybrid System for Transient Identification, (3) Sensor Validation, (4) Plant-Wide Monitoring, (5) Monitoring of Performance and Efficiency, and (6) Analysis of Vibrations. Although specific examples described deal with nuclear power plants or their subsystems, the techniques described can be applied to a wide variety of complex engineering systems

  1. Verification and Examination Management of Complex Systems

    Directory of Open Access Journals (Sweden)

    Stian Ruud

    2014-10-01

    Full Text Available As ship systems become more complex, with an increasing number of safety-critical functions, many interconnected subsystems, tight integration to other systems, and a large amount of potential failure modes, several industry parties have identified the need for improved methods for managing the verification and examination efforts of such complex systems. Such needs are even more prominent now that the marine and offshore industries are targeting more activities and operations in the Arctic environment. In this paper, a set of requirements and a method for verification and examination management are proposed for allocating examination efforts to selected subsystems. The method is based on a definition of a verification risk function for a given system topology and given requirements. The marginal verification risks for the subsystems may then be evaluated, so that examination efforts for the subsystem can be allocated. Two cases of requirements and systems are used to demonstrate the proposed method. The method establishes a systematic relationship between the verification loss, the logic system topology, verification method performance, examination stop criterion, the required examination effort, and a proposed sequence of examinations to reach the examination stop criterion.

  2. Complex Binary Number System Algorithms and Circuits

    CERN Document Server

    Jamil, Tariq

    2013-01-01

    This book is a compilation of the entire research work on the topic of Complex Binary Number System (CBNS) carried out by the author as the principal investigator and members of his research groups at various universities during the years 1992-2012. Pursuant to these efforts spanning several years, the realization of CBNS as a viable alternative to represent complex numbers in an 'all-in-one' binary number format has become possible and efforts are underway to build computer hardware based on this unique number system. It is hoped that this work will be of interest to anyone involved in computer arithmetic and digital logic design and kindle renewed enthusiasm among the engineers working in the areas of digital signal and image processing for developing newer and efficient algorithms and techniques incorporating CBNS.

  3. Relaxation and Diffusion in Complex Systems

    CERN Document Server

    Ngai, K L

    2011-01-01

    Relaxation and Diffusion in Complex Systems comprehensively presents a variety of experimental evidences of universal relaxation and diffusion properties in complex materials and systems. The materials discussed include liquids, glasses, colloids, polymers, rubbers, plastic crystals and aqueous mixtures, as well as carbohydrates, biomolecules, bioprotectants and pharmaceuticals. Due to the abundance of experimental data, emphasis is placed on glass-formers and the glass transition problem, a still unsolved problem in condensed matter physics and chemistry. The evidence for universal properties of relaxation and diffusion dynamics suggests that a fundamental physical law is at work. The origin of the universal properties is traced to the many-body effects of the interaction, rigorous theory of which does not exist at the present time. However, using solutions of simplified models as guides, key quantities have been identified and predictions of the universal properties generated. These predictions from Ngai’...

  4. Simulation of biological flow and transport in complex geometries using embedded boundary/volume-of-fluid methods

    International Nuclear Information System (INIS)

    Trebotich, David

    2007-01-01

    We have developed a simulation capability to model multiscale flow and transport in complex biological systems based on algorithms and software infrastructure developed under the SciDAC APDEC CET. The foundation of this work is a new hybrid fluid-particle method for modeling polymer fluids in irregular microscale geometries that enables long-time simulation of validation experiments. Both continuum viscoelastic and discrete particle representations have been used to model the constitutive behavior of polymer fluids. Complex flow environment geometries are represented on Cartesian grids using an implicit function. Direct simulation of flow in the irregular geometry is then possible using embedded boundary/volume-of-fluid methods without loss of geometric detail. This capability has been used to simulate biological flows in a variety of application geometries including biomedical microdevices, anatomical structures and porous media

  5. Biological oceanography of the red oceanic system

    Science.gov (United States)

    Theil, Hjalmar; Weikert, Horst

    1. In 1977, 1979 and 1980-81, investigations were carried out which aimed at evaluating the potential risks from mining metalliferous muds precipating in the Atlantis II Deep of the central Red Sea. This environmental research was initiated by the Saudi Sudanese Red Sea Joint Commission in order to avoid any danger for the Red Sea ecosystem. The broad environmental research programme coherent studies in physical, chemical, biological, and geological oceanography as well as toxicological investigations in the oceanic and in reef zones. We summarise the results from our biological fiels studies in the open sea. 2. The biological investigations were concentrated on the area of the Atlantis II Deep. Benthos was sampled between 700-2000m. For comparison a few samples were also taken further north in the central Red Sea, and to east and west along the flanking deep terraces (500-1000m). Plankton studies covered the total water column above the Deep, and were extended along the axial through to north and south. 3. Benthos sampling was carried out using a heavy closing trawl, a large box grab (box size 50 × 50 cm), Van Veen grabs and traps; photographic surveys were made a phototrap and a photosled. Community respiration was measured with a ship-board method using grab subsamples. Nutrient concentrations, seston and phytoplankton standing stocks as well as in situ primary production were determined from hydrocast samples. Data on zooplankton and micronekton composition and standing stock were obtained from samples collected using different multiple opening-and-closing nets equipped with 100 μm, 300 μm, and 1000 μm mesh sizes. Daily and ontogenetical vertical migration patterns were studied by comparisons of data from midday and midnight tows. 4. Throughout the whole area the sediment is a pteropod ooze containing low contentrations of organic matter; measured organic carbon and nitrogen contents were 0.5 and 0.05% respectively, and chloroplastic pigment equivalents

  6. Study of complex matrix effect on solid phase microextraction for biological sample analysis.

    Science.gov (United States)

    Jiang, Ruifen; Xu, Jianqiao; Zhu, Fang; Luan, Tiangang; Zeng, Feng; Shen, Yong; Ouyang, Gangfeng

    2015-09-11

    Solid phase microextraction (SPME) has become a useful tool for in vivo monitoring the behavior of environmental organic pollutants in biological species due to its simplicity, relatively non-invasive, and cost-effective manner. However, the complex matrices in biological samples could significantly influence the extraction kinetic, and bias the quantification result. In this study, we investigated the effect of complex matrix on the extraction kinetic of SPME for biological sample analysis. Two sample matrices, phosphate-buffered saline (PBS) with bovine serum albumin (BSA) and agarose gel with BSA were used to simulate the biological fluid and tissue. Results showed that the addition of BSA significantly enhanced the mass transfer of organic compounds onto SPME fiber in both PBS buffer and gel sample. Enhancement factors ranging from 1.3 to 27, and 2.0 to 80 were found for all selected polyaromatic hydrocarbons (PAHs) in PBS buffer and agarose gel with BSA concentration of 0.1-5%, respectively. Then, an improved theoretical model was applied to quantify the observed enhancement effect, and the result showed that the predicted sampling time constant agreed well with the experimental one in complex matrix. Furthermore, a simplified equation was proposed for the real biological sample analysis. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Complex Systems and Self-organization Modelling

    CERN Document Server

    Bertelle, Cyrille; Kadri-Dahmani, Hakima

    2009-01-01

    The concern of this book is the use of emergent computing and self-organization modelling within various applications of complex systems. The authors focus their attention both on the innovative concepts and implementations in order to model self-organizations, but also on the relevant applicative domains in which they can be used efficiently. This book is the outcome of a workshop meeting within ESM 2006 (Eurosis), held in Toulouse, France in October 2006.

  8. FRAM Modelling Complex Socio-technical Systems

    CERN Document Server

    Hollnagel, Erik

    2012-01-01

    There has not yet been a comprehensive method that goes behind 'human error' and beyond the failure concept, and various complicated accidents have accentuated the need for it. The Functional Resonance Analysis Method (FRAM) fulfils that need. This book presents a detailed and tested method that can be used to model how complex and dynamic socio-technical systems work, and understand both why things sometimes go wrong but also why they normally succeed.

  9. A study of ruthenium complexes of some biologically relevant a-N ...

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Chemical Sciences; Volume 112; Issue 3. A study of ruthenium complexes of some biologically relevant ∙ -N-heterocyclic carboxylic acids. P Sengupta S Ghosh. Volume 112 Issue 3 June 2000 pp 355-355. Fulltext. Click here to view fulltext PDF. Permanent link:

  10. Technical equipment in medico-biological complex of Kiev U-120 cyclotron

    International Nuclear Information System (INIS)

    Grantsev, V.I.; Gul'ko, G.M.; Isaenko, V.I.; Koval', G.N.; Linev, A.F.; Nikishin, B.K.; Produvalov, Yu.S.; Svarichevskaya, E.V.

    1988-01-01

    Medico-biological complex on the basis of the U-120 cyclotron designed for radiobiological researches and neutron therapy is described. Beryllium target ensuring complete absorption of incident deuterons with the energy of 13.6 MeV is used as a neutron source. The flowsheet of charged particle transport in the U-120 accelerators is given

  11. AN INTEGRATED NETWORK APPROACH TO IDENTIFYING BIOLOGICAL PATHWAYS AND ENVIRONMENTAL EXPOSURE INTERACTIONS IN COMPLEX DISEASES.

    Science.gov (United States)

    Darabos, Christian; Qiu, Jingya; Moore, Jason H

    2016-01-01

    Complex diseases are the result of intricate interactions between genetic, epigenetic and environmental factors. In previous studies, we used epidemiological and genetic data linking environmental exposure or genetic variants to phenotypic disease to construct Human Phenotype Networks and separately analyze the effects of both environment and genetic factors on disease interactions. To better capture the intricacies of the interactions between environmental exposure and the biological pathways in complex disorders, we integrate both aspects into a single "tripartite" network. Despite extensive research, the mechanisms by which chemical agents disrupt biological pathways are still poorly understood. In this study, we use our integrated network model to identify specific biological pathway candidates possibly disrupted by environmental agents. We conjecture that a higher number of co-occurrences between an environmental substance and biological pathway pair can be associated with a higher likelihood that the substance is involved in disrupting that pathway. We validate our model by demonstrating its ability to detect known arsenic and signal transduction pathway interactions and speculate on candidate cell-cell junction organization pathways disrupted by cadmium. The validation was supported by distinct publications of cell biology and genetic studies that associated environmental exposure to pathway disruption. The integrated network approach is a novel method for detecting the biological effects of environmental exposures. A better understanding of the molecular processes associated with specific environmental exposures will help in developing targeted molecular therapies for patients who have been exposed to the toxicity of environmental chemicals.

  12. Present and future of NMR for RNA-protein complexes: A perspective of integrated structural biology

    Science.gov (United States)

    Carlomagno, Teresa

    2014-04-01

    Nucleic acids are gaining enormous importance as key molecules in almost all biological processes. Most nucleic acids do not act in isolation but are generally associated with proteins to form high-molecular-weight nucleoprotein complexes. In this perspective article I focus on the structural studies of supra-molecular ribonucleoprotein (RNP) assemblies in solution by a combination of state-of-the-art TROSY-based NMR experiments and other structural biology techniques. I discuss ways how to combine sparse NMR data with low-resolution structural information from small-angle scattering, fluorescence and electron paramagnetic resonance spectroscopy to obtain the structure of large RNP particles by an integrated structural biology approach. In the last section I give a perspective for the study of RNP complexes by solid-state NMR.

  13. Chaos from simple models to complex systems

    CERN Document Server

    Cencini, Massimo; Vulpiani, Angelo

    2010-01-01

    Chaos: from simple models to complex systems aims to guide science and engineering students through chaos and nonlinear dynamics from classical examples to the most recent fields of research. The first part, intended for undergraduate and graduate students, is a gentle and self-contained introduction to the concepts and main tools for the characterization of deterministic chaotic systems, with emphasis to statistical approaches. The second part can be used as a reference by researchers as it focuses on more advanced topics including the characterization of chaos with tools of information theor

  14. Small-Angle Neutron Scattering for Structural Biology of Protein-RNA Complexes.

    Science.gov (United States)

    Gabel, Frank

    2015-01-01

    This chapter deals with the applications of small-angle neutron scattering (SANS) for the structural study of protein-RNA complexes in solution. After a brief historical introduction, the basic theory and practical requirements (e.g., sample state) for SANS experiments will be treated. Next, model-free parameters, such as the molecular mass and the radius of gyration, which can be obtained without a priori structural information, will be introduced. A more detailed section on the specific properties of SANS (with respect to its sister technique, small-angle X-ray scattering), and their implications on possibilities and limits of model building and interpretation will be discussed with a focus on protein-RNA systems. A practical illustration of the information content of SANS data will be given by applying ab initio modeling to a tRNA-synthetase system of known high-resolution structure. Finally, two present state-of-the-art examples that combine SANS data with complementary structural biology techniques (NMR and crystallography) will be presented and possible future developments and applications will be discussed. © 2015 Elsevier Inc. All rights reserved.

  15. Complex Engineered Systems: A New Paradigm

    Science.gov (United States)

    Mina, Ali A.; Braha, Dan; Bar-Yam, Yaneer

    Human history is often seen as an inexorable march towards greater complexity — in ideas, artifacts, social, political and economic systems, technology, and in the structure of life itself. While we do not have detailed knowledge of ancient times, it is reasonable to conclude that the average resident of New York City today faces a world of much greater complexity than the average denizen of Carthage or Tikal. A careful consideration of this change, however, suggests that most of it has occurred recently, and has been driven primarily by the emergence of technology as a force in human life. In the 4000 years separating the Indus Valley Civilization from 18th century Europe, human transportation evolved from the bullock cart to the hansom, and the methods of communication used by George Washington did not differ significantly from those used by Alexander or Rameses. The world has moved radically towards greater complexity in the last two centuries. We have moved from buggies and letter couriers to airplanes and the Internet — an increase in capacity, and through its diversity also in complexity, orders of magnitude greater than that accumulated through the rest of human history. In addition to creating iconic artifacts — the airplane, the car, the computer, the television, etc. — this change has had a profound effect on the scope of experience by creating massive, connected and multiultra- level systems — traffic networks, power grids, markets, multinational corporations — that defy analytical understanding and seem to have a life of their own. This is where complexity truly enters our lives.

  16. Hybrid deterministic/stochastic simulation of complex biochemical systems.

    Science.gov (United States)

    Lecca, Paola; Bagagiolo, Fabio; Scarpa, Marina

    2017-11-21

    In a biological cell, cellular functions and the genetic regulatory apparatus are implemented and controlled by complex networks of chemical reactions involving genes, proteins, and enzymes. Accurate computational models are indispensable means for understanding the mechanisms behind the evolution of a complex system, not always explored with wet lab experiments. To serve their purpose, computational models, however, should be able to describe and simulate the complexity of a biological system in many of its aspects. Moreover, it should be implemented by efficient algorithms requiring the shortest possible execution time, to avoid enlarging excessively the time elapsing between data analysis and any subsequent experiment. Besides the features of their topological structure, the complexity of biological networks also refers to their dynamics, that is often non-linear and stiff. The stiffness is due to the presence of molecular species whose abundance fluctuates by many orders of magnitude. A fully stochastic simulation of a stiff system is computationally time-expensive. On the other hand, continuous models are less costly, but they fail to capture the stochastic behaviour of small populations of molecular species. We introduce a new efficient hybrid stochastic-deterministic computational model and the software tool MoBioS (MOlecular Biology Simulator) implementing it. The mathematical model of MoBioS uses continuous differential equations to describe the deterministic reactions and a Gillespie-like algorithm to describe the stochastic ones. Unlike the majority of current hybrid methods, the MoBioS algorithm divides the reactions' set into fast reactions, moderate reactions, and slow reactions and implements a hysteresis switching between the stochastic model and the deterministic model. Fast reactions are approximated as continuous-deterministic processes and modelled by deterministic rate equations. Moderate reactions are those whose reaction waiting time is

  17. Optical Biosensors to Explore Biological Systems

    DEFF Research Database (Denmark)

    Palanco, Marta Espina; Mogensen, Klaus Bo; Andersen, Nils H. Skovgaard

    2016-01-01

    protein may be used as an efficient sensor in an organic environment via a biomimetic membrane model. The combination of both biomimetic membranes and protein membranes as a signal transduction medium has interesting applications in biology and medicine. It is crucial that the matrix where a protein...

  18. A Systems Approach to Biology (SAB).

    Science.gov (United States)

    Bush, Kenneth H.; And Others

    This pupil's study guide is intended to be used with audio-taped biology modules. Each of the units (on laboratory techniques, plant and animal diversity, chemistry, cells, energy, microbiology, genetics, and development) contains an abstract providing an overview of the unit, the rationale and performance objectives for each module, questions to…

  19. Tracing organizing principles: Learning from the history of systems biology

    DEFF Research Database (Denmark)

    Green, Sara; Wolkenhauer, Olaf

    2014-01-01

    With the emergence of systems biology, the identification of organizing principles is being highlighted as a key research aim. Researchers attempt to “reverse engineer” the functional organization of biological systems using methodologies from mathematics, engineering and computer science while...... taking advantage of data produced by new experimental techniques. While systems biology is a relatively new approach, the quest for general principles of biological organization dates back to systems theoretic approaches in early and mid-twentieth century. The aim of this paper is to draw...... on this historical background in order to increase the understanding of the motivation behind the search for general principles and to clarify different epistemic aims within systems biology. We pinpoint key aspects of earlier approaches that also underlie the current practice. These are i) the focus on relational...

  20. Chemometric and Statistical Analyses of ToF-SIMS Spectra of Increasingly Complex Biological Samples

    Energy Technology Data Exchange (ETDEWEB)

    Berman, E S; Wu, L; Fortson, S L; Nelson, D O; Kulp, K S; Wu, K J

    2007-10-24

    Characterizing and classifying molecular variation within biological samples is critical for determining fundamental mechanisms of biological processes that will lead to new insights including improved disease understanding. Towards these ends, time-of-flight secondary ion mass spectrometry (ToF-SIMS) was used to examine increasingly complex samples of biological relevance, including monosaccharide isomers, pure proteins, complex protein mixtures, and mouse embryo tissues. The complex mass spectral data sets produced were analyzed using five common statistical and chemometric multivariate analysis techniques: principal component analysis (PCA), linear discriminant analysis (LDA), partial least squares discriminant analysis (PLSDA), soft independent modeling of class analogy (SIMCA), and decision tree analysis by recursive partitioning. PCA was found to be a valuable first step in multivariate analysis, providing insight both into the relative groupings of samples and into the molecular basis for those groupings. For the monosaccharides, pure proteins and protein mixture samples, all of LDA, PLSDA, and SIMCA were found to produce excellent classification given a sufficient number of compound variables calculated. For the mouse embryo tissues, however, SIMCA did not produce as accurate a classification. The decision tree analysis was found to be the least successful for all the data sets, providing neither as accurate a classification nor chemical insight for any of the tested samples. Based on these results we conclude that as the complexity of the sample increases, so must the sophistication of the multivariate technique used to classify the samples. PCA is a preferred first step for understanding ToF-SIMS data that can be followed by either LDA or PLSDA for effective classification analysis. This study demonstrates the strength of ToF-SIMS combined with multivariate statistical and chemometric techniques to classify increasingly complex biological samples