WorldWideScience

Sample records for biological complex system

  1. Stochastic Physics, Complex Systems and Biology

    CERN Document Server

    Qian, Hong

    2012-01-01

    In complex systems, the interplay between nonlinear and stochastic dynamics gives rise to an evolution process in Darwinian sense with punctuated equilibrium, random "mutations" and "adaptations". The emergent discrete states in such a system, i.e., attractors, have natural robustness against both internal and external perturbations. Epigenetic states of a biological cell, a mesoscopic nonlinear stochastic open biochemical system, could be understood through such a framework.

  2. 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.

  3. 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

  4. Stochastic Physics, Complex Systems and Biology

    OpenAIRE

    Qian, Hong

    2012-01-01

    In complex systems, the interplay between nonlinear and stochastic dynamics, e.g., J. Monod's necessity and chance, gives rise to an evolutionary process in Darwinian sense, in terms of discrete jumps among attractors, with punctuated equilibrium, spontaneous random "mutations" and "adaptations". On an evlutionary time scale it produces sustainable diversity among individuals in a homogeneous population rather than convergence as usually predicted by a deterministic dynamics. The emergent dis...

  5. 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 ...

  6. Integrative Systems Biology: Elucidating Complex Traits

    DEFF Research Database (Denmark)

    Pers, Tune Hannes

    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...... that body-mass index associated gene products coalesce onto distinct protein complexes, and show that these putative risk modules incriminate novel candidate obesitysusceptibility genes. e last overall line of research presented here, provides examples on how networks of human metabolism may serve...... for weight maintenance upon dietary-induced weight loss. e approaches presented in this PhD esis provide integrative methodologies for the aggregation of multiple, functionally relevant data types. Together they represent a novel bioinformatics-based toolbox for analyses of genetic variation in human...

  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. Systems Biology Approaches to Epidemiological Studies of Complex Diseases

    OpenAIRE

    Li, Hongzhe

    2013-01-01

    Systems biology approaches to epidemiological studies of complex diseases include collection of genetic, genomic, epigenomic and metagenomic data in large-scale epidemiological studies of complex phenotypes. Designs and analyses of such studies raise many statistical challenges. This paper reviews some issues related to integrative analysis of such high dimensional and inter-related data sets and outline some possible solutions. I focus my review on integrative approaches for genome-wide gene...

  9. 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.

  10. From globally coupled maps to complex-systems biology

    Science.gov (United States)

    Kaneko, Kunihiko

    2015-09-01

    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.

  11. Biological Computation as the Revolution of Complex Engineered Systems

    CERN Document Server

    Gómez-Cruz, Nelson Alfonso

    2011-01-01

    Provided that there is no theoretical frame for complex engineered systems (CES) as yet, this paper claims that bio-inspired engineering can help provide such a frame. Within CES bio-inspired systems play a key role. The disclosure from bio-inspired systems and biological computation has not been sufficiently worked out, however. Biological computation is to be taken as the processing of information by living systems that is carried out in polynomial time, i.e., efficiently; such processing however is grasped by current science and research as an intractable problem (for instance, the protein folding problem). A remark is needed here: P versus NP problems should be well defined and delimited but biological computation problems are not. The shift from conventional engineering to bio-inspired engineering needs bring the subject (or problem) of computability to a new level. Within the frame of computation, so far, the prevailing paradigm is still the Turing-Church thesis. In other words, conventional engineering...

  12. 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.

  13. Complex systems of biological interest stability under ionising radiations

    International Nuclear Information System (INIS)

    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)

  14. Bridging Mechanistic and Phenomenological Models of Complex Biological Systems

    Science.gov (United States)

    Transtrum, Mark K.; Qiu, Peng

    2016-01-01

    The inherent complexity of biological systems gives rise to complicated mechanistic models with a large number of parameters. On the other hand, the collective behavior of these systems can often be characterized by a relatively small number of phenomenological parameters. We use the Manifold Boundary Approximation Method (MBAM) as a tool for deriving simple phenomenological models from complicated mechanistic models. The resulting models are not black boxes, but remain expressed in terms of the microscopic parameters. In this way, we explicitly connect the macroscopic and microscopic descriptions, characterize the equivalence class of distinct systems exhibiting the same range of collective behavior, and identify the combinations of components that function as tunable control knobs for the behavior. We demonstrate the procedure for adaptation behavior exhibited by the EGFR pathway. From a 48 parameter mechanistic model, the system can be effectively described by a single adaptation parameter τ characterizing the ratio of time scales for the initial response and recovery time of the system which can in turn be expressed as a combination of microscopic reaction rates, Michaelis-Menten constants, and biochemical concentrations. The situation is not unlike modeling in physics in which microscopically complex processes can often be renormalized into simple phenomenological models with only a few effective parameters. The proposed method additionally provides a mechanistic explanation for non-universal features of the behavior. PMID:27187545

  15. Bridging Mechanistic and Phenomenological Models of Complex Biological Systems.

    Directory of Open Access Journals (Sweden)

    Mark K Transtrum

    2016-05-01

    Full Text Available The inherent complexity of biological systems gives rise to complicated mechanistic models with a large number of parameters. On the other hand, the collective behavior of these systems can often be characterized by a relatively small number of phenomenological parameters. We use the Manifold Boundary Approximation Method (MBAM as a tool for deriving simple phenomenological models from complicated mechanistic models. The resulting models are not black boxes, but remain expressed in terms of the microscopic parameters. In this way, we explicitly connect the macroscopic and microscopic descriptions, characterize the equivalence class of distinct systems exhibiting the same range of collective behavior, and identify the combinations of components that function as tunable control knobs for the behavior. We demonstrate the procedure for adaptation behavior exhibited by the EGFR pathway. From a 48 parameter mechanistic model, the system can be effectively described by a single adaptation parameter τ characterizing the ratio of time scales for the initial response and recovery time of the system which can in turn be expressed as a combination of microscopic reaction rates, Michaelis-Menten constants, and biochemical concentrations. The situation is not unlike modeling in physics in which microscopically complex processes can often be renormalized into simple phenomenological models with only a few effective parameters. The proposed method additionally provides a mechanistic explanation for non-universal features of the behavior.

  16. Multimode lasers as analogs of complex biological systems (a survey)

    Science.gov (United States)

    Danilov, O. B.; Rosanov, N. N.; Solov'ev, N. A.; Soms, L. N.

    2016-04-01

    Simulating the activity of complex biological systems, in particular, the human brain, is a topical problem the solution of which is necessary both for understanding their functioning and for developing new classes of computational system based on operating principles of the brain. Some features and analogies that can be found in the operation of laser systems and brain and used for developing new generation computational systems are discussed. The appropriateness of such analogies is justified by the fact that both laser systems and the brain are open (interacting with the environment) dissipative spatially distributed nonlinear systems. Therefore, laser optical systems and, in particular, systems with dissipative optical solitons offer an opportunity to experimentally and theoretically model some important cognitive brain functions. One of particularities of the brain operation is the ability to manipulate images. Proceeding from this, in this work, problems related to generation and amplification with laser of spatial structures (images), as well as to amplification of signals coming to it from outside are discussed.

  17. 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).

  18. 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.

  19. Decisions, dopamine, and degeneracy in complex biological systems

    Directory of Open Access Journals (Sweden)

    Regan CM

    2014-01-01

    Full Text Available Ciaran M Regan School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Belfield, Dublin, Ireland Abstract: The neurobiological and computational analysis of value-based decision-making rests within the domain of neuroeconomics which has the goal of providing a biological account of human behavior relevant to both natural and social sciences. This review proposes a framework to investigate different aspects of the theoretical and molecular neurobiology of decision-making. In order to learn how to make good decisions, the brain needs to compute a separate value signal that measures the desirability of the outcomes that were generated by its previous decisions. The framework presented here combines aspects of current ideas relating to information processing by the hippocampal formation and how these relate to the phasic midbrain dopaminergic firing that occurs in response to the spatial and motivational aspects of rewarding events in the environment. The activities of hippocampal ensembles are considered to reflect a continuous updating process for attended experiences, defining both regular and irregular stimuli, environments, and actions, that are rapidly encoded as schemas into pre-existing knowledge bases. Keywords: hippocampus, schemas, synapse assemblies, cell assemblies, synapse plasticity

  20. Inference, simulation, modeling, and analysis of complex networks, with special emphasis on complex networks in systems biology

    Science.gov (United States)

    Christensen, Claire Petra

    Across diverse fields ranging from physics to biology, sociology, and economics, the technological advances of the past decade have engendered an unprecedented explosion of data on highly complex systems with thousands, if not millions of interacting components. These systems exist at many scales of size and complexity, and it is becoming ever-more apparent that they are, in fact, universal, arising in every field of study. Moreover, they share fundamental properties---chief among these, that the individual interactions of their constituent parts may be well-understood, but the characteristic behaviour produced by the confluence of these interactions---by these complex networks---is unpredictable; in a nutshell, the whole is more than the sum of its parts. There is, perhaps, no better illustration of this concept than the discoveries being made regarding complex networks in the biological sciences. In particular, though the sequencing of the human genome in 2003 was a remarkable feat, scientists understand that the "cellular-level blueprints" for the human being are cellular-level parts lists, but they say nothing (explicitly) about cellular-level processes. The challenge of modern molecular biology is to understand these processes in terms of the networks of parts---in terms of the interactions among proteins, enzymes, genes, and metabolites---as it is these processes that ultimately differentiate animate from inanimate, giving rise to life! It is the goal of systems biology---an umbrella field encapsulating everything from molecular biology to epidemiology in social systems---to understand processes in terms of fundamental networks of core biological parts, be they proteins or people. By virtue of the fact that there are literally countless complex systems, not to mention tools and techniques used to infer, simulate, analyze, and model these systems, it is impossible to give a truly comprehensive account of the history and study of complex systems. The author

  1. Systems Biology as a Comparative Approach to Understand Complex Gene Expression in Neurological Diseases

    Directory of Open Access Journals (Sweden)

    Francisco J. Esteban

    2013-05-01

    Full Text Available Systems biology interdisciplinary approaches have become an essential analytical tool that may yield novel and powerful insights about the nature of human health and disease. Complex disorders are known to be caused by the combination of genetic, environmental, immunological or neurological factors. Thus, to understand such disorders, it becomes necessary to address the study of this complexity from a novel perspective. Here, we present a review of integrative approaches that help to understand the underlying biological processes involved in the etiopathogenesis of neurological diseases, for example, those related to autism and autism spectrum disorders (ASD endophenotypes. Furthermore, we highlight the role of systems biology in the discovery of new biomarkers or therapeutic targets in complex disorders, a key step in the development of personalized medicine, and we demonstrate the role of systems approaches in the design of classifiers that can shorten the time for behavioral diagnosis of autism.

  2. Inference, simulation, modeling, and analysis of complex networks, with special emphasis on complex networks in systems biology

    Science.gov (United States)

    Christensen, Claire Petra

    Across diverse fields ranging from physics to biology, sociology, and economics, the technological advances of the past decade have engendered an unprecedented explosion of data on highly complex systems with thousands, if not millions of interacting components. These systems exist at many scales of size and complexity, and it is becoming ever-more apparent that they are, in fact, universal, arising in every field of study. Moreover, they share fundamental properties---chief among these, that the individual interactions of their constituent parts may be well-understood, but the characteristic behaviour produced by the confluence of these interactions---by these complex networks---is unpredictable; in a nutshell, the whole is more than the sum of its parts. There is, perhaps, no better illustration of this concept than the discoveries being made regarding complex networks in the biological sciences. In particular, though the sequencing of the human genome in 2003 was a remarkable feat, scientists understand that the "cellular-level blueprints" for the human being are cellular-level parts lists, but they say nothing (explicitly) about cellular-level processes. The challenge of modern molecular biology is to understand these processes in terms of the networks of parts---in terms of the interactions among proteins, enzymes, genes, and metabolites---as it is these processes that ultimately differentiate animate from inanimate, giving rise to life! It is the goal of systems biology---an umbrella field encapsulating everything from molecular biology to epidemiology in social systems---to understand processes in terms of fundamental networks of core biological parts, be they proteins or people. By virtue of the fact that there are literally countless complex systems, not to mention tools and techniques used to infer, simulate, analyze, and model these systems, it is impossible to give a truly comprehensive account of the history and study of complex systems. The author

  3. Complex dynamics in biological systems arising from multiple limit cycle bifurcation.

    Science.gov (United States)

    Yu, P; Lin, W

    2016-12-01

    In this paper, we study complex dynamical behaviour in biological systems due to multiple limit cycles bifurcation. We use simple epidemic and predator-prey models to show exact routes to new types of bistability, that is, bistability between equilibrium and periodic oscillation, and bistability between two oscillations, which may more realistically describe the real situations. Bifurcation theory and normal form theory are applied to investigate the multiple limit cycles bifurcating from Hopf critical point. PMID:27042877

  4. Complexity, Information and Biological Organisation

    Directory of Open Access Journals (Sweden)

    Attila Grandpierre

    2005-12-01

    Full Text Available Regarding the widespread confusion about the concept and nature of complexity, information and biological organization, we look for some coordinated conceptual considerations corresponding to quantitative measures suitable to grasp the main characteristics of biological complexity. Quantitative measures of algorithmic complexity of supercomputers like Blue Gene/L are compared with the complexity of the brain. We show that both the computer and the brain have a more fundamental, dynamic complexity measure corresponding to the number of operations per second. Recent insights suggest that the origin of complexity may go back to simplicity at a deeper level, corresponding to algorithmic complexity. We point out that for physical systems Ashby’s Law, Kahre’s Law and causal closure of the physical exclude the generation of information, and since genetic information corresponds to instructions, we are faced with a controversy telling that the algorithmic complexity of physics is much lower than the instructions’ complexity of the human DNA: I_algorithmic(physics ~ 10^3 bit << I_instructions(DNA ~ 10^9 bit. Analyzing the genetic complexity we obtain that actually the genetic information corresponds to a deeper than algorithmic level of complexity, putting an even greater emphasis to the information paradox. We show that the resolution of the fundamental information paradox may lie either in the chemical evolution of inheritance in abiogenesis, or in the existence of an autonomous biological principle allowing the production of information beyond physics.

  5. Systems interface biology

    OpenAIRE

    Francis J Doyle; Stelling, Jörg

    2006-01-01

    The field of systems biology has attracted the attention of biologists, engineers, mathematicians, physicists, chemists and others in an endeavour to create systems-level understanding of complex biological networks. In particular, systems engineering methods are finding unique opportunities in characterizing the rich behaviour exhibited by biological systems. In the same manner, these new classes of biological problems are motivating novel developments in theoretical systems approaches. Henc...

  6. Recovery Management in All Optical Networks Using Biologically-Inspired Complex Adaptive System

    Directory of Open Access Journals (Sweden)

    Inadyuti Dutt

    2013-01-01

    Full Text Available All-Optical Networks have the ability to display varied advantages like performance efficiency, throughput etc but their efficiency depends on their survivability as they are attack prone. These attacks can be categorised as active or passive because they try to access information within the network or alter the information in the network. The attack once detected has to be recovered by formulating back-up or alternative paths. The proposed heuristic uses biologically inspired Complex Adaptive System, inspired by Natural Immune System. The study shows that natural immune system exhibit unique behaviour of detecting foreign bodies in our body and removing them on their first occurrences. This phenomenon is being utilised in the proposed heuristic for recovery management in All-optical Network

  7. Dissecting Complex and Multifactorial Nature of Alzheimer's Disease Pathogenesis: a Clinical, Genomic, and Systems Biology Perspective.

    Science.gov (United States)

    Talwar, Puneet; Sinha, Juhi; Grover, Sandeep; Rawat, Chitra; Kushwaha, Suman; Agarwal, Rachna; Taneja, Vibha; Kukreti, Ritushree

    2016-09-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by loss of memory and other cognitive functions. AD can be classified into familial AD (FAD) and sporadic AD (SAD) based on heritability and into early onset AD (EOAD) and late onset AD (LOAD) based on age of onset. LOAD cases are more prevalent with genetically complex architecture. In spite of significant research focused on understanding the etiological mechanisms, search for diagnostic biomarker(s) and disease-modifying therapy is still on. In this article, we aim to comprehensively review AD literature on established etiological mechanisms including role of beta-amyloid and apolipoprotein E (APOE) along with promising newer etiological factors such as epigenetic modifications that have been associated with AD suggesting its multifactorial nature. As genomic studies have recently played a significant role in elucidating AD pathophysiology, a systematic review of findings from genome-wide linkage (GWL), genome-wide association (GWA), genome-wide expression (GWE), and epigenome-wide association studies (EWAS) was conducted. The availability of multi-dimensional genomic data has further coincided with the advent of computational and network biology approaches in recent years. Our review highlights the importance of integrative approaches involving genomics and systems biology perspective in elucidating AD pathophysiology. The promising newer approaches may provide reliable means of early and more specific diagnosis and help identify therapeutic interventions for LOAD. PMID:26351077

  8. Degeneracy: a link between evolvability, robustness and complexity in biological systems

    CERN Document Server

    Whitacre, James

    2010-01-01

    A full accounting of biological robustness remains elusive; both in terms of the mechanisms by which robustness is achieved and the forces that have caused robustness to grow over evolutionary time. Although its importance to topics such as ecosystem services and resilience is well recognized, the broader relationship between robustness and evolution is only starting to be fully appreciated. A renewed interest in this relationship has been prompted by evidence that mutational robustness can play a positive role in the discovery of future adaptive innovations (evolvability) and evidence of an intimate relationship between robustness and complexity in biology. This paper offers a new perspective on the mechanics of evolution and the origins of complexity, robustness, and evolvability. Here we explore the hypothesis that degeneracy, a partial overlap in the functioning of multi-functional components, plays a central role in the evolution and robustness of complex forms. In support of this hypothesis, we present ...

  9. Engineering and control of biological systems: A new way to tackle complex diseases.

    Science.gov (United States)

    Menolascina, Filippo; Siciliano, Velia; di Bernardo, Diego

    2012-07-16

    The ongoing merge between engineering and biology has contributed to the emerging field of synthetic biology. The defining features of this new discipline are abstraction and standardisation of biological parts, decoupling between parts to prevent undesired cross-talking, and the application of quantitative modelling of synthetic genetic circuits in order to guide their design. Most of the efforts in the field of synthetic biology in the last decade have been devoted to the design and development of functional gene circuits in prokaryotes and unicellular eukaryotes. Researchers have used synthetic biology not only to engineer new functions in the cell, but also to build simpler models of endogenous gene regulatory networks to gain knowledge of the "rules" governing their wiring diagram. However, the need for innovative approaches to study and modify complex signalling and regulatory networks in mammalian cells and multicellular organisms has prompted advances of synthetic biology also in these species, thus contributing to develop innovative ways to tackle human diseases. In this work, we will review the latest progress in synthetic biology and the most significant developments achieved so far, both in unicellular and multicellular organisms, with emphasis on human health. PMID:22580058

  10. The biological networks in studying cell signal transduction complexity: The examples of sperm capacitation and of endocannabinoid system

    OpenAIRE

    Nicola Bernabò; Barbara Barboni; Mauro Maccarrone

    2014-01-01

    Cellular signal transduction is a complex phenomenon, which plays a central role in cell surviving and adaptation. The great amount of molecular data to date present in literature, together with the adoption of high throughput technologies, on the one hand, made available to scientists an enormous quantity of information, on the other hand, failed to provide a parallel increase in the understanding of biological events. In this context, a new discipline arose, the systems biology, aimed to ma...

  11. Complex monitoring system for analytical detection and biological evaluation of soil micropollutants for a sustainable environment

    International Nuclear Information System (INIS)

    Complete text of publication follows. In the development of a complex soil contamination monitoring system including the detection of agriculture-related micropollutants, heavy metal contamination and ecotoxicity, a survey has been carried out in Bekes county (Hungary) using different techniques for the characterisation of soil and surface water status. Besides the representativity-optimisation of the sampling technique, in situ sensoric methods, instrumental analysis, biological tests (soil biology, ecotoxicity and mutagenicity) were also applied, and results obtained were presented in a spatial informatics system. The target group, indicators and methodology is in compliance with recommendations of the EEA monitoring working group. Contamination in arable lands and industrial areas has been investigated in 13 plots with 5 replications. Sampling has been carried out by using drilling machine and contaminant concentrations of soil profiles have been characterised down to ground water table. Pesticide residues were monitored by using GC-MS. Target analytes included triazine, phenoxyacetic acid, acetanilide and dinitroaniline herbicides, chlorinated hydrocarbon (CHC), organophosphate and carbamate insecticides, an insect hormonal agonist and a triazole fungicide. Besides banned persistent CHC insecticides (DDT, HCH, etc.), atrazine and acetochlor herbicides are common contaminants in Hungary, reaching 200 ng/g and 300 ng/ml concentration in the soil and surface water samples studied, and trifluralin and metolachlor were also detected in some cases. Heavy metal contamination was detected by ICP AES, and within-plot heterogeneities were studied throughout soil profiles. Nickel has been fund as a relatively common contaminant in arable lands in the area; however relation to fertilisers could not be confirmed. Even in small spatial scale (50x50 meters) a very high variability has been demonstrated in half of the experimental plots. The effects of pesticide residues in

  12. Analysis of undergraduate students' conceptual models of a complex biological system across a diverse body of learners

    Science.gov (United States)

    Dirnbeck, Matthew R.

    Biological systems pose a challenge both for learners and teachers because they are complex systems mediated by feedback loops; networks of cause-effect relationships; and non-linear, hierarchical, and emergent properties. Teachers and scientists routinely use models to communicate ideas about complex systems. Model-based pedagogies engage students in model construction as a means of practicing higher-order reasoning skills. One such modeling paradigm describes systems in terms of their structures, behaviors, and functions (SBF). The SBF framework is a simple modeling language that has been used to teach about complex biological systems. Here, we used student-generated SBF models to assess students' causal reasoning in the context of a novel biological problem on an exam. We compared students' performance on the modeling problem, their performance on a set of knowledge/comprehension questions, and their performance on a set of scientific reasoning questions. We found that students who performed well on knowledge and understanding questions also constructed more networked, higher quality models. Previous studies have shown that learners' mental maps increase in complexity with increased expertise. We wanted to investigate if biology students with varying levels of training in biology showed a similar pattern when constructing system models. In a pilot study, we administered the same modeling problem to two additional groups of students: 1) an animal physiology course for students pursuing a major in biology (n=37) and 2) an exercise physiology course for non-majors (n=27). We found that there was no significant difference in model organization across the three student populations, but there was a significant difference in the ability to represent function between the three populations. Between the three groups the non-majors had the lowest function scores, the introductory majors had the middle function scores, and the upper division majors had the highest function

  13. ECO-BIOLOGICAL SYSTEM MODELING

    Directory of Open Access Journals (Sweden)

    T. I. Burak

    2015-01-01

    Full Text Available The methodology for computer modeling of complex eco-biological models is presented in this paper. It is based on system approach of J. Forrester. Developed methodology is universal for complex ecological and biological systems. Modeling algorithm considers specialties of eco-biological systems and shows adequate and accurate results in practice. 

  14. Solid state structures of cadmium complexes with relevance for biological systems.

    Science.gov (United States)

    Carballo, Rosa; Castiñeiras, Alfonso; Domínguez-Martín, Alicia; García-Santos, Isabel; Niclós-Gutiérrez, Juan

    2013-01-01

    This chapter provides a review of the literature on structural information from crystal structures determined by X-ray diffractometry of cadmium(II) complexes containing ligands of potential biological interest. These ligands fall into three broad classes, (i) those containing N-donors such as purine or pyrimidine bases and derivatives of adenine, guanine or cytosine, (ii) those containing carboxylate groups such as α-amino acids, in particular the twenty essential ones, the water soluble vitamins (B-complex) or the polycarboxylates of EDTA type ligands, and (iii) S-donors such as thiols/thiolates or dithiocarbamates. A crystal and molecular structural analysis has been carried out for some representative complexes of these ligands, specifically addressing the coordination mode of ligands, the coordination environment of cadmium and, in some significant cases, the intermolecular interactions. PMID:23430774

  15. 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."

  16. Modelling biological complexity: a physical scientist's perspective

    OpenAIRE

    Coveney, Peter V.; Fowler, Philip W.

    2005-01-01

    We discuss the modern approaches of complexity and self-organization to understanding dynamical systems and how these concepts can inform current interest in systems biology. From the perspective of a physical scientist, it is especially interesting to examine how the differing weights given to philosophies of science in the physical and biological sciences impact the application of the study of complexity. We briefly describe how the dynamics of the heart and circadian rhythms, canonical exa...

  17. Studies of Complex Biological Systems with Applications to Molecular Medicine: The Need to Integrate Transcriptomic and Proteomic Approaches

    Directory of Open Access Journals (Sweden)

    Elena Silvestri

    2011-01-01

    Full Text Available Omics approaches to the study of complex biological systems with potential applications to molecular medicine are attracting great interest in clinical as well as in basic biological research. Genomics, transcriptomics and proteomics are characterized by the lack of an a priori definition of scope, and this gives sufficient leeway for investigators (a to discern all at once a globally altered pattern of gene/protein expression and (b to examine the complex interactions that regulate entire biological processes. Two popular platforms in “omics” are DNA microarrays, which measure messenger RNA transcript levels, and proteomic analyses, which identify and quantify proteins. Because of their intrinsic strengths and weaknesses, no single approach can fully unravel the complexities of fundamental biological events. However, an appropriate combination of different tools could lead to integrative analyses that would furnish new insights not accessible through one-dimensional datasets. In this review, we will outline some of the challenges associated with integrative analyses relating to the changes in metabolic pathways that occur in complex pathophysiological conditions (viz. ageing and altered thyroid state in relevant metabolically active tissues. In addition, we discuss several new applications of proteomic analysis to the investigation of mitochondrial activity.

  18. The biological networks in studying cell signal transduction complexity: The examples of sperm capacitation and of endocannabinoid system

    Science.gov (United States)

    Bernabò, Nicola; Barboni, Barbara; Maccarrone, Mauro

    2014-01-01

    Cellular signal transduction is a complex phenomenon, which plays a central role in cell surviving and adaptation. The great amount of molecular data to date present in literature, together with the adoption of high throughput technologies, on the one hand, made available to scientists an enormous quantity of information, on the other hand, failed to provide a parallel increase in the understanding of biological events. In this context, a new discipline arose, the systems biology, aimed to manage the information with a computational modeling-based approach. In particular, the use of biological networks has allowed the making of huge progress in this field. Here we discuss two possible application of the use of biological networks to explore cell signaling: the study of the architecture of signaling systems that cooperate in determining the acquisition of a complex cellular function (as it is the case of the process of activation of spermatozoa) and the organization of a single specific signaling systems expressed by different cells in different tissues (i.e. the endocannabinoid system). In both the cases we have found that the networks follow a scale free and small world topology, likely due to the evolutionary advantage of robustness against random damages, fastness and specific of information processing, and easy navigability. PMID:25379139

  19. Attraction basins as gauges of robustness against boundary conditions in biological complex systems.

    Directory of Open Access Journals (Sweden)

    Jacques Demongeot

    Full Text Available One fundamental concept in the context of biological systems on which researches have flourished in the past decade is that of the apparent robustness of these systems, i.e., their ability to resist to perturbations or constraints induced by external or boundary elements such as electromagnetic fields acting on neural networks, micro-RNAs acting on genetic networks and even hormone flows acting both on neural and genetic networks. Recent studies have shown the importance of addressing the question of the environmental robustness of biological networks such as neural and genetic networks. In some cases, external regulatory elements can be given a relevant formal representation by assimilating them to or modeling them by boundary conditions. This article presents a generic mathematical approach to understand the influence of boundary elements on the dynamics of regulation networks, considering their attraction basins as gauges of their robustness. The application of this method on a real genetic regulation network will point out a mathematical explanation of a biological phenomenon which has only been observed experimentally until now, namely the necessity of the presence of gibberellin for the flower of the plant Arabidopsis thaliana to develop normally.

  20. Modeling Complex Biological Flows in Multi-Scale Systems using the APDEC Framework

    Energy Technology Data Exchange (ETDEWEB)

    Trebotich, D

    2006-06-24

    We have developed advanced numerical algorithms to model biological fluids in multiscale flow environments using the software framework developed under the SciDAC APDEC ISIC. The foundation of our computational effort is an approach for modeling DNA-laden fluids as ''bead-rod'' polymers whose dynamics are fully coupled to an incompressible viscous solvent. The method is capable of modeling short range forces and interactions between particles using soft potentials and rigid constraints. Our methods are based on higher-order finite difference methods in complex geometry with adaptivity, leveraging algorithms and solvers in the APDEC Framework. Our Cartesian grid embedded boundary approach to incompressible viscous flow in irregular geometries has also been interfaced to a fast and accurate level-sets method within the APDEC Framework for extracting surfaces from volume renderings of medical image data and used to simulate cardio-vascular and pulmonary flows in critical anatomies.

  1. [Systems biology of cancer].

    Science.gov (United States)

    Barillot, Emmanuel; Calzone, Laurence; Zinovyev, Andrei

    2009-01-01

    Cancer Systems Biology is now accepted and recognized as a promising field both in biological and clinical research. It relies on a rigorous formalization of regulation networks into precise and unambiguous languages. It provides both detailed and modular views of the complex biological system of interest (which in cancer research is typically an interaction network governing essential cellular events such as proliferation, differentiation, cell death...) in order to facilitate the interpretation of molecular profiles of tumors. The translation of these networks into mathematical models allows prediction of the evolution of the system in time and under certain perturbations. As a result, it can not only propose specific target points for pharmaceutical purposes, but also anticipate the evolution of tumors as well as their classifications. These characteristics emphasize the important role of Systems Biology of Cancer in the future of biomedical research.

  2. The Role of Model Integration in Complex Systems Modelling An Example from Cancer Biology

    CERN Document Server

    Patel, Manish

    2010-01-01

    Model integration – the process by which different modelling efforts can be brought together to simulate the target system – is a core technology in the field of Systems Biology. In the work presented here model integration was addressed directly taking cancer systems as an example. An in-depth literature review was carried out to survey the model forms and types currently being utilised. This was used to formalise the main challenges that model integration poses, namely that of paradigm (the formalism on which a model is based), focus (the real-world system the model represents) and scale. A two-tier model integration strategy, including a knowledge-driven approach to address model semantics, was developed to tackle these challenges. In the first step a novel description of models at the level of behaviour, rather than the precise mathematical or computational basis of the model, is developed by distilling a set of abstract classes and properties. These can accurately describe model behaviour and hence d...

  3. 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....

  4. Protein microarrays for systems biology

    Institute of Scientific and Technical Information of China (English)

    Lina Yang; Shujuan Guo; Yang Li; Shumin Zhou; Shengce Tao

    2011-01-01

    Systems biology holds the key for understanding biological systems on a system level. It eventually holds the key for the treatment and cure of complex diseases such as cancer,diabetes, obesity, mental disorders, and many others. The '-omics' technologies, such as genomics, transcriptomics,proteomics, and metabonomics, are among the major driving forces of systems biology. Featured as highthroughput, miniaturized, and capable of parallel analysis,protein microarrays have already become an important technology platform for systems biology, In this review, we will focus on the system level or global analysis of biological systems using protein microarrays. Four major types of protein microarrays will be discussed: proteome microarrays, antibody microarrays, reverse-phase protein arrays,and lectin microarrays. We will also discuss the challenges and future directions of protein microarray technologies and their applications for systems biology. We strongly believe that protein microarrays will soon become an indispensable and invaluable tool for systems biology.

  5. Reduction enhances yields of nitric oxide trapping by iron-diethyldithiocarbamate complex in biological systems.

    NARCIS (Netherlands)

    Vanin, A.F.; Bevers, L.M.; Mikoyan, V.D.; Poltorakov, A.P.; Kubrina, L.N.; Faassen, E. van

    2007-01-01

    The mechanism of NO trapping by iron-diethylthiocarbamate complexes was investigated in cultured cells and animal and plant tissues. Contrary to common belief, the NO radicals are trapped by iron-diethylthiocarbamates not only in ferrous but in ferric state also in the biosystems. When DETC was exce

  6. Informing Biological Design by Integration of Systems and Synthetic Biology

    OpenAIRE

    Smolke, Christina D.; Silver, Pamela A.

    2011-01-01

    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.

  7. Unraveling human complexity and disease with systems biology and personalized medicine

    OpenAIRE

    Naylor, Stephen; Jake Y Chen

    2010-01-01

    We are all perplexed that current medical practice often appears maladroit in curing our individual illnesses or disease. However, as is often the case, a lack of understanding, tools and technologies are the root cause of such situations. Human individuality is an often-quoted term but, in the context of human biology, it is poorly understood. This is compounded when there is a need to consider the variability of human populations. In the case of the former, it is possible to quantify human ...

  8. 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.

  9. Computational Systems Chemical Biology

    OpenAIRE

    Oprea, Tudor I.; May, Elebeoba E.; Leitão, Andrei; Tropsha, Alexander

    2011-01-01

    There is a critical need for improving the level of chemistry awareness in systems biology. The data and information related to modulation of genes and proteins by small molecules continue to accumulate at the same time as simulation tools in systems biology and whole body physiologically-based pharmacokinetics (PBPK) continue to evolve. We called this emerging area at the interface between chemical biology and systems biology systems chemical biology, SCB (Oprea et al., 2007).

  10. New and improved proteomics technologies for understanding complex biological systems: addressing a grand challenge in the life sciences.

    Science.gov (United States)

    Hood, Leroy E; Omenn, Gilbert S; Moritz, Robert L; Aebersold, Ruedi; Yamamoto, Keith R; Amos, Michael; Hunter-Cevera, Jennie; Locascio, Laurie

    2012-09-01

    This White Paper sets out a Life Sciences Grand Challenge for Proteomics Technologies to enhance our understanding of complex biological systems, link genomes with phenotypes, and bring broad benefits to the biosciences and the US economy. The paper is based on a workshop hosted by the National Institute of Standards and Technology (NIST) in Gaithersburg, MD, 14-15 February 2011, with participants from many federal R&D agencies and research communities, under the aegis of the US National Science and Technology Council (NSTC). Opportunities are identified for a coordinated R&D effort to achieve major technology-based goals and address societal challenges in health, agriculture, nutrition, energy, environment, national security, and economic development.

  11. Building phenomenological models of complex biological processes

    Science.gov (United States)

    Daniels, Bryan; Nemenman, Ilya

    2009-11-01

    A central goal of any modeling effort is to make predictions regarding experimental conditions that have not yet been observed. Overly simple models will not be able to fit the original data well, but overly complex models are likely to overfit the data and thus produce bad predictions. Modern quantitative biology modeling efforts often err on the complexity side of this balance, using myriads of microscopic biochemical reaction processes with a priori unknown kinetic parameters to model relatively simple biological phenomena. In this work, we show how Bayesian model selection (which is mathematically similar to low temperature expansion in statistical physics) can be used to build coarse-grained, phenomenological models of complex dynamical biological processes, which have better predictive powers than microscopically correct, but poorely constrained mechanistic molecular models. We illustrate this on the example of a multiply-modifiable protein molecule, which is a simplified description of multiple biological systems, such as an immune receptors and an RNA polymerase complex. Our approach is similar in spirit to the phenomenological Landau expansion for the free energy in the theory of critical phenomena.

  12. Towards targeting anticancer drugs: ruthenium(ii)-arene complexes with biologically active naphthoquinone-derived ligand systems.

    Science.gov (United States)

    Kubanik, Mario; Kandioller, Wolfgang; Kim, Kunwoo; Anderson, Robert F; Klapproth, Erik; Jakupec, Michael A; Roller, Alexander; Söhnel, Tilo; Keppler, Bernhard K; Hartinger, Christian G

    2016-08-16

    Anticancer active metal complexes with biologically active ligands have the potential to interact with more than one biological target, which could help to overcome acquired and/or intrinsic resistance of tumors to small molecule drugs. In this paper we present the preparation of 2-hydroxy-[1,4]-naphthoquinone-derived ligands and their coordination to a Ru(II)(η(6)-p-cymene)Cl moiety. The synthesis of oxime derivatives resulted in the surprising formation of nitroso-naphthalene complexes, as confirmed by X-ray diffraction analysis. The compounds were shown to be stable in aqueous solution but reacted with glutathione and ascorbic acid rather than undergoing reduction. One-electron reduction with pulse radiolysis revealed different behavior for the naphthoquinone and nitroso-naphthalene complexes, which was also observed in in vitro anticancer assays. PMID:27214822

  13. Bridging the gap between systems biology and synthetic biology

    OpenAIRE

    Liu, Di; Hoynes-O’Connor, Allison; Zhang, Fuzhong

    2013-01-01

    Systems biology is an inter-disciplinary science that studies the complex interactions and the collective behavior of a cell or an organism. Synthetic biology, as a technological subject, combines biological science and engineering, allowing the design and manipulation of a system for certain applications. Both systems and synthetic biology have played important roles in the recent development of microbial platforms for energy, materials, and environmental applications. More importantly, syst...

  14. Computational systems chemical biology.

    Science.gov (United States)

    Oprea, Tudor I; May, Elebeoba E; Leitão, Andrei; Tropsha, Alexander

    2011-01-01

    There is a critical need for improving the level of chemistry awareness in systems biology. The data and information related to modulation of genes and proteins by small molecules continue to accumulate at the same time as simulation tools in systems biology and whole body physiologically based pharmacokinetics (PBPK) continue to evolve. We called this emerging area at the interface between chemical biology and systems biology systems chemical biology (SCB) (Nat Chem Biol 3: 447-450, 2007).The overarching goal of computational SCB is to develop tools for integrated chemical-biological data acquisition, filtering and processing, by taking into account relevant information related to interactions between proteins and small molecules, possible metabolic transformations of small molecules, as well as associated information related to genes, networks, small molecules, and, where applicable, mutants and variants of those proteins. There is yet an unmet need to develop an integrated in silico pharmacology/systems biology continuum that embeds drug-target-clinical outcome (DTCO) triplets, a capability that is vital to the future of chemical biology, pharmacology, and systems biology. Through the development of the SCB approach, scientists will be able to start addressing, in an integrated simulation environment, questions that make the best use of our ever-growing chemical and biological data repositories at the system-wide level. This chapter reviews some of the major research concepts and describes key components that constitute the emerging area of computational systems chemical biology.

  15. Can biological complexity be reverse engineered?

    Science.gov (United States)

    Green, Sara

    2015-10-01

    Concerns with the use of engineering approaches in biology have recently been raised. I examine two related challenges to biological research that I call the synchronic and diachronic underdetermination problem. The former refers to challenges associated with the inference of design principles underlying system capacities when the synchronic relations between lower-level processes and higher-level systems capacities are degenerate (many-to-many). The diachronic underdetermination problem regards the problem of reverse engineering a system where the non-linear relations between system capacities and lower-level mechanisms are changing over time. Braun and Marom argue that recent insights to biological complexity leave the aim of reverse engineering hopeless - in principle as well as in practice. While I support their call for systemic approaches to capture the dynamic nature of living systems, I take issue with the conflation of reverse engineering with naïve reductionism. I clarify how the notion of design principles can be more broadly conceived and argue that reverse engineering is compatible with a dynamic view of organisms. It may even help to facilitate an integrated account that bridges the gap between mechanistic and systems approaches.

  16. 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-...

  17. Engineering scalable biological systems

    OpenAIRE

    Lu, Timothy K.

    2010-01-01

    Synthetic biology is focused on engineering biological organisms to study natural systems and to provide new solutions for pressing medical, industrial, and environmental problems. At the core of engineered organisms are synthetic biological circuits that execute the tasks of sensing inputs, processing logic, and performing output functions. In the last decade, significant progress has been made in developing basic designs for a wide range of biological circuits in bacteria, yeast, and mammal...

  18. 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

  19. [From the mechanical complexity in biology].

    Science.gov (United States)

    Uribe, Libia Herrero

    2008-03-01

    From the mechanical complexity in biology. Through history, each century has brought new discoveries and beliefs that have resulted in different perspectives to study life organisms. In this essay, 1 define three periods: in the first, organisms were studied in the context of their environment, in the second, on the basis of physical and chemical laws, and on the third, systemically. My analysis starts with primitive humans, continues to Aristoteles and Newton, Lamarck and Darwin, the DNA doble helix discovery, and the beginnings of reduccionism in science. I propose that life is paradigmatical, that it obeys physical and chemical laws but cannot be explained by them I review the systemic theory, autopoiesis, discipative structures and non- linear dynamics. 1 propose that the deterministic, lineal and quantitative paradigm of nature are not the only way to study nature and invite the reader to explore the complexity paradigm. PMID:18624253

  20. [From the mechanical complexity in biology].

    Science.gov (United States)

    Uribe, Libia Herrero

    2008-03-01

    From the mechanical complexity in biology. Through history, each century has brought new discoveries and beliefs that have resulted in different perspectives to study life organisms. In this essay, 1 define three periods: in the first, organisms were studied in the context of their environment, in the second, on the basis of physical and chemical laws, and on the third, systemically. My analysis starts with primitive humans, continues to Aristoteles and Newton, Lamarck and Darwin, the DNA doble helix discovery, and the beginnings of reduccionism in science. I propose that life is paradigmatical, that it obeys physical and chemical laws but cannot be explained by them I review the systemic theory, autopoiesis, discipative structures and non- linear dynamics. 1 propose that the deterministic, lineal and quantitative paradigm of nature are not the only way to study nature and invite the reader to explore the complexity paradigm.

  1. Systems biology and cancer, [Editorial

    OpenAIRE

    Soto, A M; Sonnenschein, C; Maini, P.K.

    2011-01-01

    The systems approach to complex biological problems has rapidly gained ground during the first decade of this century. There are several reasons for this development. An important one is that while the achievement of sequencing the complete human genome, and those of other species, has been of great benefit to fundamental science, for example in comparative genomics and evolutionary biology, it has not led to the expected quick and simple solutions to multifactorial diseases (2010). On the co...

  2. Aging and computational systems biology.

    Science.gov (United States)

    Mooney, Kathleen M; Morgan, Amy E; Mc Auley, Mark T

    2016-01-01

    Aging research is undergoing a paradigm shift, which has led to new and innovative methods of exploring this complex phenomenon. The systems biology approach endeavors to understand biological systems in a holistic manner, by taking account of intrinsic interactions, while also attempting to account for the impact of external inputs, such as diet. A key technique employed in systems biology is computational modeling, which involves mathematically describing and simulating the dynamics of biological systems. Although a large number of computational models have been developed in recent years, these models have focused on various discrete components of the aging process, and to date no model has succeeded in completely representing the full scope of aging. Combining existing models or developing new models may help to address this need and in so doing could help achieve an improved understanding of the intrinsic mechanisms which underpin aging.

  3. Robust Design of Biological Circuits: Evolutionary Systems Biology Approach

    OpenAIRE

    Bor-Sen Chen; Chih-Yuan Hsu; Jing-Jia Liou

    2011-01-01

    Artificial gene circuits have been proposed to be embedded into microbial cells that function as switches, timers, oscillators, and the Boolean logic gates. Building more complex systems from these basic gene circuit components is one key advance for biologic circuit design and synthetic biology. However, the behavior of bioengineered gene circuits remains unstable and uncertain. In this study, a nonlinear stochastic system is proposed to model the biological systems with intrinsic parameter ...

  4. The GLOBE 3D Genome Platform - towards a novel system-biological paper tool to integrate the huge complexity of genome organization and function.

    Science.gov (United States)

    Knoch, Tobias A; Lesnussa, Michael; Kepper, Nick; Eussen, Hubert B; Grosveld, Frank G

    2009-01-01

    Genomes are tremendous co-evolutionary holistic systems for molecular storage, processing and fabrication of information. Their system-biological complexity remains, however, still largely mysterious, despite immense sequencing achievements and huge advances in the understanding of the general sequential, three-dimensional and regulatory organization. Here, we present the GLOBE 3D Genome Platform a completely novel grid based virtual "paper" tool and in fact the first system-biological genome browser integrating the holistic complexity of genomes in a single easy comprehensible platform: Based on a detailed study of biophysical and IT requirements, every architectural level from sequence to morphology of one or several genomes can be approached in a real and in a symbolic representation simultaneously and navigated by continuous scale-free zooming within a unique three-dimensional OpenGL and grid driven environment. In principle an unlimited number of multi-dimensional data sets can be visualized, customized in terms of arrangement, shape, colour, and texture etc. as well as accessed and annotated individually or in groups using internal or external data bases/facilities. Any information can be searched and correlated by importing or calculating simple relations in real-time using grid resources. A general correlation and application platform for more complex correlative analysis and a front-end for system-biological simulations both using again the huge capabilities of grid infrastructures is currently under development. Hence, the GLOBE 3D Genome Platform is an example of a grid based approach towards a virtual desktop for genomic work combining the three fundamental distributed resources: i) visual data representation, ii) data access and management, and iii) data analysis and creation. Thus, the GLOBE 3D Genome Platform is the novel system-biology oriented information system urgently needed to access, present, annotate, and to simulate the holistic genome

  5. 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.

  6. 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’.

  7. Modeling biological systems with Answer Set Programming

    OpenAIRE

    Thiele, Sven

    2012-01-01

    Biology has made great progress in identifying and measuring the building blocks of life. The availability of high-throughput methods in molecular biology has dramatically accelerated the growth of biological knowledge for various organisms. The advancements in genomic, proteomic and metabolomic technologies allow for constructing complex models of biological systems. An increasing number of biological repositories is available on the web, incorporating thousands of biochemical reactions and ...

  8. Systems cell biology.

    Science.gov (United States)

    Mast, Fred D; Ratushny, Alexander V; Aitchison, John D

    2014-09-15

    Systems cell biology melds high-throughput experimentation with quantitative analysis and modeling to understand many critical processes that contribute to cellular organization and dynamics. Recently, there have been several advances in technology and in the application of modeling approaches that enable the exploration of the dynamic properties of cells. Merging technology and computation offers an opportunity to objectively address unsolved cellular mechanisms, and has revealed emergent properties and helped to gain a more comprehensive and fundamental understanding of cell biology.

  9. Circadian systems biology in Metazoa.

    Science.gov (United States)

    Lin, Li-Ling; Huang, Hsuan-Cheng; Juan, Hsueh-Fen

    2015-11-01

    Systems biology, which can be defined as integrative biology, comprises multistage processes that can be used to understand components of complex biological systems of living organisms and provides hierarchical information to decoding life. Using systems biology approaches such as genomics, transcriptomics and proteomics, it is now possible to delineate more complicated interactions between circadian control systems and diseases. The circadian rhythm is a multiscale phenomenon existing within the body that influences numerous physiological activities such as changes in gene expression, protein turnover, metabolism and human behavior. In this review, we describe the relationships between the circadian control system and its related genes or proteins, and circadian rhythm disorders in systems biology studies. To maintain and modulate circadian oscillation, cells possess elaborative feedback loops composed of circadian core proteins that regulate the expression of other genes through their transcriptional activities. The disruption of these rhythms has been reported to be associated with diseases such as arrhythmia, obesity, insulin resistance, carcinogenesis and disruptions in natural oscillations in the control of cell growth. This review demonstrates that lifestyle is considered as a fundamental factor that modifies circadian rhythm, and the development of dysfunctions and diseases could be regulated by an underlying expression network with multiple circadian-associated signals.

  10. Complex Networks: from Graph Theory to Biology

    Science.gov (United States)

    Lesne, Annick

    2006-12-01

    The aim of this text is to show the central role played by networks in complex system science. A remarkable feature of network studies is to lie at the crossroads of different disciplines, from mathematics (graph theory, combinatorics, probability theory) to physics (statistical physics of networks) to computer science (network generating algorithms, combinatorial optimization) to biological issues (regulatory networks). New paradigms recently appeared, like that of ‘scale-free networks’ providing an alternative to the random graph model introduced long ago by Erdös and Renyi. With the notion of statistical ensemble and methods originally introduced for percolation networks, statistical physics is of high relevance to get a deep account of topological and statistical properties of a network. Then their consequences on the dynamics taking place in the network should be investigated. Impact of network theory is huge in all natural sciences, especially in biology with gene networks, metabolic networks, neural networks or food webs. I illustrate this brief overview with a recent work on the influence of network topology on the dynamics of coupled excitable units, and the insights it provides about network emerging features, robustness of network behaviors, and the notion of static or dynamic motif.

  11. Systems Biology of the Fluxome

    Directory of Open Access Journals (Sweden)

    Miguel A. Aon

    2015-07-01

    Full Text Available The advent of high throughput -omics has made the accumulation of comprehensive data sets possible, consisting of changes in genes, transcripts, proteins and metabolites. Systems biology-inspired computational methods for translating metabolomics data into fluxomics provide a direct functional, dynamic readout of metabolic networks. When combined with appropriate experimental design, these methods deliver insightful knowledge about cellular function under diverse conditions. The use of computational models accounting for detailed kinetics and regulatory mechanisms allow us to unravel the control and regulatory properties of the fluxome under steady and time-dependent behaviors. This approach extends the analysis of complex systems from description to prediction, including control of complex dynamic behavior ranging from biological rhythms to catastrophic lethal arrhythmias. The powerful quantitative metabolomics-fluxomics approach will help our ability to engineer unicellular and multicellular organisms evolve from trial-and-error to a more predictable process, and from cells to organ and organisms.

  12. 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 ‘‘...

  13. 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…

  14. 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.

  15. Integrative radiation systems biology.

    Science.gov (United States)

    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. PMID:24411063

  16. Integrative radiation systems biology

    International Nuclear Information System (INIS)

    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

  17. Systems biology, emergence and antireductionism.

    Science.gov (United States)

    Kesić, Srdjan

    2016-09-01

    This study explores the conceptual history of systems biology and its impact on philosophical and scientific conceptions of reductionism, antireductionism and emergence. Development of systems biology at the beginning of 21st century transformed biological science. Systems biology is a new holistic approach or strategy how to research biological organisms, developed through three phases. The first phase was completed when molecular biology transformed into systems molecular biology. Prior to the second phase, convergence between applied general systems theory and nonlinear dynamics took place, hence allowing the formation of systems mathematical biology. The second phase happened when systems molecular biology and systems mathematical biology, together, were applied for analysis of biological data. Finally, after successful application in science, medicine and biotechnology, the process of the formation of modern systems biology was completed. Systems and molecular reductionist views on organisms were completely opposed to each other. Implications of systems and molecular biology on reductionist-antireductionist debate were quite different. The analysis of reductionism, antireductionism and emergence issues, in the era of systems biology, revealed the hierarchy between methodological, epistemological and ontological antireductionism. Primarily, methodological antireductionism followed from the systems biology. Only after, epistemological and ontological antireductionism could be supported.

  18. Real-Time Agent-Based Modeling Simulation with in-situ Visualization of Complex Biological Systems

    Science.gov (United States)

    Seekhao, Nuttiiya; Shung, Caroline; JaJa, Joseph; Mongeau, Luc; Li-Jessen, Nicole Y. K.

    2016-01-01

    We present an efficient and scalable scheme for implementing agent-based modeling (ABM) simulation with In Situ visualization of large complex systems on heterogeneous computing platforms. The scheme is designed to make optimal use of the resources available on a heterogeneous platform consisting of a multicore CPU and a GPU, resulting in minimal to no resource idle time. Furthermore, the scheme was implemented under a client-server paradigm that enables remote users to visualize and analyze simulation data as it is being generated at each time step of the model. Performance of a simulation case study of vocal fold inflammation and wound healing with 3.8 million agents shows 35× and 7× speedup in execution time over single-core and multi-core CPU respectively. Each iteration of the model took less than 200 ms to simulate, visualize and send the results to the client. This enables users to monitor the simulation in real-time and modify its course as needed. PMID:27547508

  19. Network systems biology for targeted cancer therapies

    Institute of Scientific and Technical Information of China (English)

    Ting-Ting Zhou

    2012-01-01

    The era of targeted cancer therapies has arrived.However,due to the complexity of biological systems,the current progress is far from enough.From biological network modeling to structural/dynamic network analysis,network systems biology provides unique insight into the potential mechanisms underlying the growth and progression of cancer cells.It has also introduced great changes into the research paradigm of cancer-associated drug discovery and drug resistance.

  20. Integrating systems biology models and biomedical ontologies

    Directory of Open Access Journals (Sweden)

    de Bono Bernard

    2011-08-01

    Full Text Available Abstract Background Systems biology is an approach to biology that emphasizes the structure and dynamic behavior of biological systems and the interactions that occur within them. To succeed, systems biology crucially depends on the accessibility and integration of data across domains and levels of granularity. Biomedical ontologies were developed to facilitate such an integration of data and are often used to annotate biosimulation models in systems biology. Results We provide a framework to integrate representations of in silico systems biology with those of in vivo biology as described by biomedical ontologies and demonstrate this framework using the Systems Biology Markup Language. We developed the SBML Harvester software that automatically converts annotated SBML models into OWL and we apply our software to those biosimulation models that are contained in the BioModels Database. We utilize the resulting knowledge base for complex biological queries that can bridge levels of granularity, verify models based on the biological phenomenon they represent and provide a means to establish a basic qualitative layer on which to express the semantics of biosimulation models. Conclusions We establish an information flow between biomedical ontologies and biosimulation models and we demonstrate that the integration of annotated biosimulation models and biomedical ontologies enables the verification of models as well as expressive queries. Establishing a bi-directional information flow between systems biology and biomedical ontologies has the potential to enable large-scale analyses of biological systems that span levels of granularity from molecules to organisms.

  1. 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 an

  2. Complex systems: physics beyond physics

    CERN Document Server

    Holovatch, Yurij; Thurner, Stefan

    2016-01-01

    Complex systems are characterized by specific time-dependent interactions among their many constituents. As a consequence they often manifest rich, non-trivial and unexpected behavior. Examples arise both in the physical and non-physical world. The study of complex systems forms a new interdisciplinary research area that cuts across physics, biology, ecology, economics, sociology, and the humanities. In this paper we review the essence of complex systems from a physicist's point of view, and try to clarify what makes them conceptually different from systems that are traditionally studied in physics. Our goal is to demonstrate how the dynamics of such systems may be conceptualized in quantitative and predictive terms by extending notions from statistical physics and how they can often be captured in a framework of co-evolving multiplex network structures. We mention three areas of complex-systems science that are currently studied extensively, the science of cities, dynamics of societies, and the representatio...

  3. Mechanistic modeling confronts the complexity of molecular cell biology

    OpenAIRE

    Phair, Robert D.

    2014-01-01

    Mechanistic modeling has the potential to transform how cell biologists contend with the inescapable complexity of modern biology. I am a physiologist–electrical engineer–systems biologist who has been working at the level of cell biology for the past 24 years. This perspective aims 1) to convey why we build models, 2) to enumerate the major approaches to modeling and their philosophical differences, 3) to address some recurrent concerns raised by experimentalists, and then 4) to imagine a fu...

  4. SYSTEMS WITH COMPLEXITY

    Institute of Scientific and Technical Information of China (English)

    WANG Chenghong; ZHANG Lijun

    2004-01-01

    Science of Complexity is a newly emerging branch of natural scienceAlthoughwe still haven't a precise definition, there are some principles for justifying whether a systemis a complex systemThe purpose of this article is to reveal some of such principlesOnthe basis of them, the concept of a system with complexity is proposedThey may helpus to distinguish a real complex system from complicated objects in common senseThenwe propose some fundamental problems faced by the study of systems with complexity.

  5. 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....

  6. System biology of gene regulation.

    Science.gov (United States)

    Baitaluk, Michael

    2009-01-01

    ) questions of biological relevance. Thus systems biology could be treated as such a socioscientific phenomenon and a new approach to both experiments and theory that is defined by the strategy of pursuing integration of complex data about the interactions in biological systems from diverse experimental sources using interdisciplinary tools and personnel. PMID:19623486

  7. 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

  8. Assessment of crosstalks between the Snf1 kinase complex and sphingolipid metabolism in S. cerevisiae via systems biology approaches.

    Science.gov (United States)

    Borklu Yucel, Esra; Ulgen, Kutlu O

    2013-11-01

    Sphingolipids are essential building blocks of the plasma membranes and are highly bioactive in the regulation of diverse cellular functions and pathological processes, a fact which renders the sphingolipid metabolism an important research area. In this study, a computational framework was recruited for the reconstruction of a functional interaction network for sphingolipid metabolism in Baker's yeast, SSN. Gene Ontology (GO) annotations were integrated with functional interaction data of the BIOGRID database and the reconstructed protein interaction network was subjected to topological and descriptive analyses. SSN was of a scale-free nature, following a power law model with γ=1.41. Prominent processes of SSN revealed that the reconstructed network encapsulated the involvement of sphingolipid metabolism in vital cellular processes such as energy homeostasis, cell growth and/or death and synthesis of building blocks. To investigate the potential of SSN for predicting signal transduction pathways regulating and/or being regulated by sphingolipid biosynthesis in yeast, a case study involving the S. cerevisiae counterpart of AMP-activated protein kinase, the Snf1 kinase complex, was conducted. The mutant strain lacking the catalytic α subunit, snf1Δ/snf1Δ, had elevated inositol phosphorylceramide and mannosyl-inositol phosphorylceramide levels, and decreased mannosyl-diinositol phosphorylceramide levels compared to the wild type strain, revealing that Snf1p has a regulatory role in the sphingolipid metabolism. Transcriptome data belonging to that strain available in the literature were mapped onto SSN and the correlated SSN was further investigated to evaluate the possible crosstalk machineries where sphingolipids and Snf1p function in coordination, in other words the crosstalk points between sphingolipid-mediated and Snf1 kinase signalling. The subsequent investigation of the discovered candidate crosstalk processes by performing sensitivity experiments imply a

  9. Mechanistic modeling confronts the complexity of molecular cell biology.

    Science.gov (United States)

    Phair, Robert D

    2014-11-01

    Mechanistic modeling has the potential to transform how cell biologists contend with the inescapable complexity of modern biology. I am a physiologist-electrical engineer-systems biologist who has been working at the level of cell biology for the past 24 years. This perspective aims 1) to convey why we build models, 2) to enumerate the major approaches to modeling and their philosophical differences, 3) to address some recurrent concerns raised by experimentalists, and then 4) to imagine a future in which teams of experimentalists and modelers build-and subject to exhaustive experimental tests-models covering the entire spectrum from molecular cell biology to human pathophysiology. There is, in my view, no technical obstacle to this future, but it will require some plasticity in the biological research mind-set.

  10. 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...

  11. 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.

  12. 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 ...

  13. 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.

  14. Telemetry System of Biological Parameters

    OpenAIRE

    2005-01-01

    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 consum...

  15. 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....

  16. 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.

  17. 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),...

  18. Noncommutative Biology: Sequential Regulation of Complex Networks

    Science.gov (United States)

    Letsou, William; Cai, Long

    2016-01-01

    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. PMID:27560383

  19. Topics in complex systems

    OpenAIRE

    Yap, Yee Jiun

    2006-01-01

    This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University. Fundamental laws of physics, although successful in explaining many phenomena observed in nature and society, cannot account for the behaviour of complex, non-Hamiltonian systems. Much effort has been devoted to better understanding the topological properties of these systems. Neither ordered nor disordered, these systems of high variability are found in many areas of science. Studies on sand...

  20. 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...

  1. 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).

  2. 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...... of nutritional research is, therefore, to borrow methods that are well established in medical and pharmacological research. In this thesis, we use advanced data-mining tools for the construction of a database with available, state-of-the-art information concerning the interaction of food and its molecular...

  3. 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...

  4. Complexity of Economical Systems

    Directory of Open Access Journals (Sweden)

    G. P. Pavlos

    2015-01-01

    Full Text Available In this study new theoretical concepts are described concerning the interpretation of economical complex dynamics. In addition a summary of an extended algorithm of nonlinear time series analysis is provided which is applied not only in economical time series but also in other physical complex systems (e.g. [22, 24]. In general, Economy is a vast and complicated set of arrangements and actions wherein agents—consumers, firms, banks, investors, government agencies—buy and sell, speculate, trade, oversee, bring products into being, offer services, invest in companies, strategize, explore, forecast, compete, learn, innovate, and adapt. As a result the economic and financial variables such as foreign exchange rates, gross domestic product, interest rates, production, stock market prices and unemployment exhibit large-amplitude and aperiodic fluctuations evident in complex systems. Thus, the Economics can be considered as spatially distributed non-equilibrium complex system, for which new theoretical concepts, such as Tsallis non extensive statistical mechanics and strange dynamics, percolation, nonGaussian, multifractal and multiscale dynamics related to fractional Langevin equations can be used for modeling and understanding of the economical complexity locally or globally.

  5. 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.

  6. 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...

  7. Systems Biology — the Broader Perspective

    Directory of Open Access Journals (Sweden)

    Jonathan Bard

    2013-06-01

    Full Text Available Systems biology has two general aims: a narrow one, which is to discover how complex networks of proteins work, and a broader one, which is to integrate the molecular and network data with the generation and function of organism phenotypes. Doing all this involves complex methodologies, but underpinning the subject are more general conceptual problems about upwards and downwards causality, complexity and information storage, and their solutions provide the constraints within which these methodologies can be used. This essay considers these general aspects and the particular role of protein networks; their functional outputs are often the processes driving phenotypic change and physiological function—networks are, in a sense, the units of systems biology much as proteins are for molecular biology. It goes on to argue that the natural language for systems-biological descriptions of biological phenomena is the mathematical graph (a set of connected facts of the general form [process] (e.g., [activates] . Such graphs not only integrate events at different levels but emphasize the distributed nature of control as well as displaying a great deal of data. The implications and successes of these ideas for physiology, pharmacology, development and evolution are briefly considered. The paper concludes with some challenges for the future.

  8. 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...

  9. 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...

  10. 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...

  11. Modelling coordination in biological systems

    OpenAIRE

    Clarke, David; Oliveira Costa, de, David; Arbab, Farhad

    2004-01-01

    We present an application of the Reo coordination paradigm to provide a compositional formal model for describing and reasoning about the behaviour of biological systems, such as regulatory gene networks. Reo governs the interaction and flow of data between components by allowing the construction of connector circuits which have a precise formal semantics. When applied to systems biology, the result is a graphical model, which is comprehensible, mathematically precise, and flexible

  12. Optimization in computational systems biology

    OpenAIRE

    Banga Julio R

    2008-01-01

    Abstract Optimization aims to make a system or design as effective or functional as possible. Mathematical optimization methods are widely used in engineering, economics and science. This commentary is focused on applications of mathematical optimization in computational systems biology. Examples are given where optimization methods are used for topics ranging from model building and optimal experimental design to metabolic engineering and synthetic biology. Finally, several perspectives for ...

  13. 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...

  14. Integrated Design of Antibodies for Systems Biology Using Ab Designer

    OpenAIRE

    Pisitkun, Trairak; Dummer, Patrick; Somparn, Poorichaya; Hirankarn, Nattiya; Kopp, Jeffrey B.; Knepper, Mark A.

    2014-01-01

    In the current era of large-scale biology, systems biology has evolved as a powerful approach to identify complex interactions within biological systems. In addition to high throughput identification and quantification techniques, methods based on high-quality mono-specific antibodies remain an essential element of the approach. To assist the large-scale design and production of peptide-directed antibodies for systems biology studies, we developed a fully integrated online application, AbDesi...

  15. Computational systems biology in cancer brain metastasis.

    Science.gov (United States)

    Peng, Huiming; Tan, Hua; Zhao, Weiling; Jin, Guangxu; Sharma, Sambad; Xing, Fei; Watabe, Kounosuke; Zhou, Xiaobo

    2016-01-01

    Brain metastases occur in 20-40% of patients with advanced malignancies. A better understanding of the mechanism of this disease will help us to identify novel therapeutic strategies. In this review, we will discuss the systems biology approaches used in this area, including bioinformatics and mathematical modeling. Bioinformatics has been used for identifying the molecular mechanisms driving brain metastasis and mathematical modeling methods for analyzing dynamics of a system and predicting optimal therapeutic strategies. We will illustrate the strategies, procedures, and computational techniques used for studying systems biology in cancer brain metastases. We will give examples on how to use a systems biology approach to analyze a complex disease. Some of the approaches used to identify relevant networks, pathways, and possibly biomarkers in metastasis will be reviewed into details. Finally, certain challenges and possible future directions in this area will also be discussed.

  16. Data driven computing for Biological Systems

    Energy Technology Data Exchange (ETDEWEB)

    Samatova, Nagiza F.; Gorin, Andrey; Uberbacher, Edward; Karpinets, Tatiana V.; Park, Byung H.; Pan, Chongle; Straatsma, TP; Cannon, William R.; Resat, Haluk; Lins, Roberto D.; Oehmen, Christopher S.

    2007-11-01

    Biological breakthroughs that can lead to improved diagnosis and treatment of diseases, generation of clean energy, and solutions to other critical societal problems require high performance, data-intensive computational tools that have the ability to process, analyze and cohesively integrate massive amounts of data and information in real time. Biological computing problems are typically data-intensive and must share very large sets of data effectively across many processors. However, the various components of biological systems, composed of complex networks and pathways, must be integrated to gain a coherent understanding of the system. The more different types of data that can be integrated, the deeper the insights into the biology of the system being studied. Conventional analysis software, however, hasn’t been able to efficiently deal with such massive data set. The goal of the Data-Intensive Computing for Complex Biological Systems (BioPilot) project, a multiyear project funded by the U.S. Department of Energy’s Office of Advanced Scientific Computing Research (ASCR), is to create an integrated suite of highly flexible, highly adaptable pipelines of computational tools for analyzing large-scale data sets that will be used to address specific challenges facing the U.S. Department of Energy (DOE) and our society.

  17. Kinetic Modeling of Biological Systems

    Energy Technology Data Exchange (ETDEWEB)

    Resat, Haluk; Petzold, Linda; Pettigrew, Michel F.

    2009-04-21

    The dynamics of how its constituent components interact define the spatio-temporal response of a natural system to stimuli. Modeling the kinetics of the processes that represent a biophysical system has long been pursued with the aim of improving our understanding of the studied system. Due to the unique properties of biological systems, in addition to the usual difficulties faced in modeling the dynamics of physical or chemical systems, biological simulations encounter difficulties that result from intrinsic multiscale and stochastic nature of the biological processes. This chapter discusses the implications for simulation of models involving interacting species with very low copy numbers, which often occur in biological systems and give rise to significant relative fluctuations. The conditions necessitating the use of stochastic kinetic simulation methods and the mathematical foundations of the stochastic simulation algorithms are presented. How the well-organized structural hierarchies often seen in biological systems can lead to multiscale problems, and possible ways to address the encountered computational difficulties are discussed. We present the details of the existing kinetic simulation methods, and discuss their strengths and shortcomings. A list of the publicly available kinetic simulation tools and our reflections for future prospects are also provided.

  18. 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.  

  19. 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.

  20. STUDYING COMPLEX ADAPTIVE SYSTEMS

    Institute of Scientific and Technical Information of China (English)

    John H. Holland

    2006-01-01

    Complex adaptive systems (cas) - systems that involve many components that adapt or learn as they interact - are at the heart of important contemporary problems. The study of cas poses unique challenges: Some of our most powerful mathematical tools, particularly methods involving fixed points, attractors, and the like, are of limited help in understanding the development of cas. This paper suggests ways to modify research methods and tools, with an emphasis on the role of computer-based models, to increase our understanding of cas.

  1. 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

  2. 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)

  3. 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...... 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...

  4. 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 bein...

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

    OpenAIRE

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

    2011-01-01

    Abstract 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 dynam...

  6. Directed evolution and synthetic biology applications to microbial systems.

    Science.gov (United States)

    Bassalo, Marcelo C; Liu, Rongming; Gill, Ryan T

    2016-06-01

    Biotechnology applications require engineering complex multi-genic traits. The lack of knowledge on the genetic basis of complex phenotypes restricts our ability to rationally engineer them. However, complex phenotypes can be engineered at the systems level, utilizing directed evolution strategies that drive whole biological systems toward desired phenotypes without requiring prior knowledge of the genetic basis of the targeted trait. Recent developments in the synthetic biology field accelerates the directed evolution cycle, facilitating engineering of increasingly complex traits in biological systems. In this review, we summarize some of the most recent advances in directed evolution and synthetic biology that allows engineering of complex traits in microbial systems. Then, we discuss applications that can be achieved through engineering at the systems level. PMID:27054950

  7. Forecasting in Complex Systems

    Science.gov (United States)

    Rundle, J. B.; Holliday, J. R.; Graves, W. R.; Turcotte, D. L.; Donnellan, A.

    2014-12-01

    Complex nonlinear systems are typically characterized by many degrees of freedom, as well as interactions between the elements. Interesting examples can be found in the areas of earthquakes and finance. In these two systems, fat tails play an important role in the statistical dynamics. For earthquake systems, the Gutenberg-Richter magnitude-frequency is applicable, whereas for daily returns for the securities in the financial markets are known to be characterized by leptokurtotic statistics in which the tails are power law. Very large fluctuations are present in both systems. In earthquake systems, one has the example of great earthquakes such as the M9.1, March 11, 2011 Tohoku event. In financial systems, one has the example of the market crash of October 19, 1987. Both were largely unexpected events that severely impacted the earth and financial systems systemically. Other examples include the M9.3 Andaman earthquake of December 26, 2004, and the Great Recession which began with the fall of Lehman Brothers investment bank on September 12, 2013. Forecasting the occurrence of these damaging events has great societal importance. In recent years, national funding agencies in a variety of countries have emphasized the importance of societal relevance in research, and in particular, the goal of improved forecasting technology. Previous work has shown that both earthquakes and financial crashes can be described by a common Landau-Ginzburg-type free energy model. These metastable systems are characterized by fat tail statistics near the classical spinodal. Correlations in these systems can grow and recede, but do not imply causation, a common source of misunderstanding. In both systems, a common set of techniques can be used to compute the probabilities of future earthquakes or crashes. In this talk, we describe the basic phenomenology of these systems and emphasize their similarities and differences. We also consider the problem of forecast validation and verification

  8. 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.

  9. Modelling coordination in biological systems

    NARCIS (Netherlands)

    Clarke, D.G.; Oliveira Costa, D.F. de; Arbab, F.

    2004-01-01

    We present an application of the Reo coordination paradigm to provide a compositional formal model for describing and reasoning about the behaviour of biological systems, such as regulatory gene networks. Reo governs the interaction and flow of data between components by allowing the construction of

  10. 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...

  11. Trends in modeling Biomedical Complex Systems

    OpenAIRE

    Remondini Daniel; Castellani Gastone; Romano Paolo; Milanesi Luciano; Liò Petro

    2009-01-01

    Abstract In this paper we provide an introduction to the techniques for multi-scale complex biological systems, from the single bio-molecule to the cell, combining theoretical modeling, experiments, informatics tools and technologies suitable for biological and biomedical research, which are becoming increasingly multidisciplinary, multidimensional and information-driven. The most important concepts on mathematical modeling methodologies and statistical inference, bioinformatics and standards...

  12. Chapter 5: Network biology approach to complex diseases.

    Directory of Open Access Journals (Sweden)

    Dong-Yeon Cho

    Full Text Available Complex diseases are caused by a combination of genetic and environmental factors. Uncovering the molecular pathways through which genetic factors affect a phenotype is always difficult, but in the case of complex diseases this is further complicated since genetic factors in affected individuals might be different. In recent years, systems biology approaches and, more specifically, network based approaches emerged as powerful tools for studying complex diseases. These approaches are often built on the knowledge of physical or functional interactions between molecules which are usually represented as an interaction network. An interaction network not only reports the binary relationships between individual nodes but also encodes hidden higher level organization of cellular communication. Computational biologists were challenged with the task of uncovering this organization and utilizing it for the understanding of disease complexity, which prompted rich and diverse algorithmic approaches to be proposed. We start this chapter with a description of the general characteristics of complex diseases followed by a brief introduction to physical and functional networks. Next we will show how these networks are used to leverage genotype, gene expression, and other types of data to identify dysregulated pathways, infer the relationships between genotype and phenotype, and explain disease heterogeneity. We group the methods by common underlying principles and first provide a high level description of the principles followed by more specific examples. We hope that this chapter will give readers an appreciation for the wealth of algorithmic techniques that have been developed for the purpose of studying complex diseases as well as insight into their strengths and limitations.

  13. ON COMPLEX DYNAMIC CONTROL SYSTEMS

    Institute of Scientific and Technical Information of China (English)

    CHENG Daizhan

    2003-01-01

    This paper presents some recent works on the control of dynamic systems, which have certain complex properties caused by singularity of the nonlinear structures, structure-varyings, or evolution process etc. First, we consider the structure singularity of nonlinear control systems. It was revealed that the focus of researches on nonlinear control theory is shifting from regular systems to singular systems. The singularity of nonlinear systems causes certain complexity. Secondly, the switched systems are considered. For such systems the complexity is caused by the structure varying. We show that the switched systems have significant characteristics of complex systems. Finally, we investigate the evolution systems. The evolution structure makes complexity, and itself is a proper model for complex systems.

  14. Computational systems biology for aging research.

    Science.gov (United States)

    Mc Auley, Mark T; Mooney, Kathleen M

    2015-01-01

    Computational modelling is a key component of systems biology and integrates with the other techniques discussed thus far in this book by utilizing a myriad of data that are being generated to quantitatively represent and simulate biological systems. This chapter will describe what computational modelling involves; the rationale for using it, and the appropriateness of modelling for investigating the aging process. How a model is assembled and the different theoretical frameworks that can be used to build a model are also discussed. In addition, the chapter will describe several models which demonstrate the effectiveness of each computational approach for investigating the constituents of a healthy aging trajectory. Specifically, a number of models will be showcased which focus on the complex age-related disorders associated with unhealthy aging. To conclude, we discuss the future applications of computational systems modelling to aging research.

  15. 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.

  16. The Fallacy of Univariate Solutions to Complex Systems Problems.

    Science.gov (United States)

    Lessov-Schlaggar, Christina N; Rubin, Joshua B; Schlaggar, Bradley L

    2016-01-01

    Complex biological systems, by definition, are composed of multiple components that interact non-linearly. The human brain constitutes, arguably, the most complex biological system known. Yet most investigation of the brain and its function is carried out using assumptions appropriate for simple systems-univariate design and linear statistical approaches. This heuristic must change before we can hope to discover and test interventions to improve the lives of individuals with complex disorders of brain development and function. Indeed, a movement away from simplistic models of biological systems will benefit essentially all domains of biology and medicine. The present brief essay lays the foundation for this argument. PMID:27375425

  17. Mössbauer study of some biological iron complexes

    Indian Academy of Sciences (India)

    Sikander Ali; Alimuddin; V R Reddy

    2005-12-01

    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 -electron densities and quadrupole coupling constant have been calculated in each case. These parameters are used to obtain information on the surroundings of the Mössbauer atom.

  18. 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...

  19. 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. PMID:26319897

  20. 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.

  1. Bridging the gaps in systems biology

    OpenAIRE

    Marija Cvijovic; Joachim Almquist; Jonas Hagmar; Stefan Hohmann; Hans\\u2011Michael Kaltenbach; Edda Klipp; Marcus Krantz; Pedro Mendes; Sven Nelander; Jens Nielsen; Andrea Pagnani; Natasa Przulj; Andreas Raue; J\\xf6rg Stelling; Szymon Stoma

    2014-01-01

    International audience Systems biology aims at creating mathematical models, i.e., computational reconstructions of biological systems and processes that will result in a new level of understanding-the elucidation of the basic and presumably conserved "design" and "engineering" principles of biomolecular systems. Thus, systems biology will move biology from a phenomenological to a predictive science. Mathematical modeling of biological networks and processes has already greatly improved ou...

  2. 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.

  3. 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.

  4. 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.

  5. [Systems theory in medicine and biology].

    Science.gov (United States)

    Feigl, W; Bonet, E M

    1989-03-15

    We try to determinate, that systems theory has to be introduced into modern medicine. The biological roots as well as the cybernetic ones are outlined. Among various concepts about systems theory the evaluation by Riedl seems to be the most efficient to explain medical procedures. His basic informations refer to von Bertalanffy, the additional introduction of a 4-cause-principle, Aristoteles, permits the explanation of complex relations. The examples of tumor and inflammation are used to demonstrate the basic idea of the formal cause as well as the final cause. The latter should also become an important fact in the solution of other medical problems.

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

    OpenAIRE

    Bor-Sen Chen; Chia-Chou Wu

    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...

  7. Dermal tumorigen PAH and complex mixtures for biological research

    International Nuclear Information System (INIS)

    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 14C labeled dihydrobenzo[a]pyrene and 14C- or 3H 10-azabenzo[a]pyrene are being studied to provide tracers for fundamental studies in tracheal transplant and skin penetration systems. (DT)

  8. 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.

  9. 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.

  10. Industrial systems biology and its impact on synthetic biology of yeast cell factories.

    Science.gov (United States)

    Fletcher, Eugene; Krivoruchko, Anastasia; Nielsen, Jens

    2016-06-01

    Engineering industrial cell factories to effectively yield a desired product while dealing with industrially relevant stresses is usually the most challenging step in the development of industrial production of chemicals using microbial fermentation processes. Using synthetic biology tools, microbial cell factories such as Saccharomyces cerevisiae can be engineered to express synthetic pathways for the production of fuels, biopharmaceuticals, fragrances, and food flavors. However, directing fluxes through these synthetic pathways towards the desired product can be demanding due to complex regulation or poor gene expression. Systems biology, which applies computational tools and mathematical modeling to understand complex biological networks, can be used to guide synthetic biology design. Here, we present our perspective on how systems biology can impact synthetic biology towards the goal of developing improved yeast cell factories. Biotechnol. Bioeng. 2016;113: 1164-1170. © 2015 Wiley Periodicals, Inc.

  11. Peroxisystem: harnessing systems cell biology to study peroxisomes.

    Science.gov (United States)

    Schuldiner, Maya; Zalckvar, Einat

    2015-04-01

    In recent years, high-throughput experimentation with quantitative analysis and modelling of cells, recently dubbed systems cell biology, has been harnessed to study the organisation and dynamics of simple biological systems. Here, we suggest that the peroxisome, a fascinating dynamic organelle, can be used as a good candidate for studying a complete biological system. We discuss several aspects of peroxisomes that can be studied using high-throughput systematic approaches and be integrated into a predictive model. Such approaches can be used in the future to study and understand how a more complex biological system, like a cell and maybe even ultimately a whole organism, works.

  12. 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...

  13. Apparatus and Methods for Manipulation and Optimization of Biological Systems

    Science.gov (United States)

    Ho, Chih-Ming (Inventor); Wong, Pak Kin (Inventor); Sun, Ren (Inventor); Yu, Fuqu (Inventor)

    2014-01-01

    The invention provides systems and methods for manipulating biological systems, for example to elicit a more desired biological response from a biological sample, such as a tissue, organ, and/or a cell. In one aspect, the invention operates by efficiently searching through a large parametric space of stimuli and system parameters to manipulate, control, and optimize the response of biological samples sustained in the system. In one aspect, the systems and methods of the invention use at least one optimization algorithm to modify the actuator's control inputs for stimulation, responsive to the sensor's output of response signals. The invention can be used, e.g., to optimize any biological system, e.g., bioreactors for proteins, and the like, small molecules, polysaccharides, lipids, and the like. Another use of the apparatus and methods includes is for the discovery of key parameters in complex biological systems.

  14. 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...

  15. 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.

  16. Complex network problems in physics, computer science and biology

    Science.gov (United States)

    Cojocaru, Radu Ionut

    There is a close relation between physics and mathematics and the exchange of ideas between these two sciences are well established. However until few years ago there was no such a close relation between physics and computer science. Even more, only recently biologists started to use methods and tools from statistical physics in order to study the behavior of complex system. In this thesis we concentrate on applying and analyzing several methods borrowed from computer science to biology and also we use methods from statistical physics in solving hard problems from computer science. In recent years physicists have been interested in studying the behavior of complex networks. Physics is an experimental science in which theoretical predictions are compared to experiments. In this definition, the term prediction plays a very important role: although the system is complex, it is still possible to get predictions for its behavior, but these predictions are of a probabilistic nature. Spin glasses, lattice gases or the Potts model are a few examples of complex systems in physics. Spin glasses and many frustrated antiferromagnets map exactly to computer science problems in the NP-hard class defined in Chapter 1. In Chapter 1 we discuss a common result from artificial intelligence (AI) which shows that there are some problems which are NP-complete, with the implication that these problems are difficult to solve. We introduce a few well known hard problems from computer science (Satisfiability, Coloring, Vertex Cover together with Maximum Independent Set and Number Partitioning) and then discuss their mapping to problems from physics. In Chapter 2 we provide a short review of combinatorial optimization algorithms and their applications to ground state problems in disordered systems. We discuss the cavity method initially developed for studying the Sherrington-Kirkpatrick model of spin glasses. We extend this model to the study of a specific case of spin glass on the Bethe

  17. [Network structures in biological systems].

    Science.gov (United States)

    Oleskin, A V

    2013-01-01

    Network structures (networks) that have been extensively studied in the humanities are characterized by cohesion, a lack of a central control unit, and predominantly fractal properties. They are contrasted with structures that contain a single centre (hierarchies) as well as with those whose elements predominantly compete with one another (market-type structures). As far as biological systems are concerned, their network structures can be subdivided into a number of types involving different organizational mechanisms. Network organization is characteristic of various structural levels of biological systems ranging from single cells to integrated societies. These networks can be classified into two main subgroups: (i) flat (leaderless) network structures typical of systems that are composed of uniform elements and represent modular organisms or at least possess manifest integral properties and (ii) three-dimensional, partly hierarchical structures characterized by significant individual and/or intergroup (intercaste) differences between their elements. All network structures include an element that performs structural, protective, and communication-promoting functions. By analogy to cell structures, this element is denoted as the matrix of a network structure. The matrix includes a material and an immaterial component. The material component comprises various structures that belong to the whole structure and not to any of its elements per se. The immaterial (ideal) component of the matrix includes social norms and rules regulating network elements' behavior. These behavioral rules can be described in terms of algorithms. Algorithmization enables modeling the behavior of various network structures, particularly of neuron networks and their artificial analogs.

  18. 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.

  19. Managing complexity of aerospace systems

    Science.gov (United States)

    Tamaskar, Shashank

    Growing complexity of modern aerospace systems has exposed the limits of conventional systems engineering tools and challenged our ability to design them in a timely and cost effective manner. According to the US Government Accountability Office (GAO), in 2009 nearly half of the defense acquisition programs are expecting 25% or more increase in unit acquisition cost. Increase in technical complexity has been identified as one of the primary drivers behind cost-schedule overruns. Thus to assure the affordability of future aerospace systems, it is increasingly important to develop tools and capabilities for managing their complexity. We propose an approach for managing the complexity of aerospace systems to address this pertinent problem. To this end, we develop a measure that improves upon the state-of-the-art metrics and incorporates key aspects of system complexity. We address the problem of system decomposition by presenting an algorithm for module identification that generates modules to minimize integration complexity. We demonstrate the framework on diverse spacecraft and show the impact of design decisions on integration cost. The measure and the algorithm together help the designer track and manage complexity in different phases of system design. We next investigate how complexity can be used as a decision metric in the model-based design (MBD) paradigm. We propose a framework for complexity enabled design space exploration that introduces the idea of using complexity as a non-traditional design objective. We also incorporate complexity with the component based design paradigm (a sub-field of MBD) and demonstrate it on several case studies. The approach for managing complexity is a small but significant contribution to the vast field of complexity management. We envision our approach being used in concert with a suite of complexity metrics to provide an ability to measure and track complexity through different stages of design and development. This will not

  20. 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...

  1. Statistically validated networks in bipartite complex systems.

    Directory of Open Access Journals (Sweden)

    Michele Tumminello

    Full Text Available Many complex systems present an intrinsic bipartite structure where elements of one set link to elements of the second set. In these complex systems, such as the system of actors and movies, elements of one set are qualitatively different than elements of the other set. The properties of these complex systems are typically investigated by constructing and analyzing a projected network on one of the two sets (for example the actor network or the movie network. Complex systems are often very heterogeneous in the number of relationships that the elements of one set establish with the elements of the other set, and this heterogeneity makes it very difficult to discriminate links of the projected network that are just reflecting system's heterogeneity from links relevant to unveil the properties of the system. Here we introduce an unsupervised method to statistically validate each link of a projected network against a null hypothesis that takes into account system heterogeneity. We apply the method to a biological, an economic and a social complex system. The method we propose is able to detect network structures which are very informative about the organization and specialization of the investigated systems, and identifies those relationships between elements of the projected network that cannot be explained simply by system heterogeneity. We also show that our method applies to bipartite systems in which different relationships might have different qualitative nature, generating statistically validated networks in which such difference is preserved.

  2. Integrating phosphoproteomics in systems biology

    Directory of Open Access Journals (Sweden)

    Yu Liu

    2014-07-01

    Full Text Available Phosphorylation of serine, threonine and tyrosine plays significant roles in cellular signal transduction and in modifying multiple protein functions. Phosphoproteins are coordinated and regulated by a network of kinases, phosphatases and phospho-binding proteins, which modify the phosphorylation states, recognize unique phosphopeptides, or target proteins for degradation. Detailed and complete information on the structure and dynamics of these networks is required to better understand fundamental mechanisms of cellular processes and diseases. High-throughput technologies have been developed to investigate phosphoproteomes in model organisms and human diseases. Among them, mass spectrometry (MS-based technologies are the major platforms and have been widely applied, which has led to explosive growth of phosphoproteomic data in recent years. New bioinformatics tools are needed to analyze and make sense of these data. Moreover, most research has focused on individual phosphoproteins and kinases. To gain a more complete knowledge of cellular processes, systems biology approaches, including pathways and networks modeling, have to be applied to integrate all components of the phosphorylation machinery, including kinases, phosphatases, their substrates, and phospho-binding proteins. This review presents the latest developments of bioinformatics methods and attempts to apply systems biology to analyze phosphoproteomics data generated by MS-based technologies. Challenges and future directions in this field will be also discussed.

  3. Complex Digital Visual Systems

    Science.gov (United States)

    Sweeny, Robert W.

    2013-01-01

    This article identifies possibilities for data visualization as art educational research practice. The author presents an analysis of the relationship between works of art and digital visual culture, employing aspects of network analysis drawn from the work of Barabási, Newman, and Watts (2006) and Castells (1994). Describing complex network…

  4. 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.

  5. ON COMPLEXITY OF POWER SYSTEMS

    Institute of Scientific and Technical Information of China (English)

    MA Jin; CHENG Daizhan; HONG Yiguang; SUN Yuanzhang

    2003-01-01

    The power system is a classical example of complex systems. In this paper it is shown that the power industry in China is facing a tremendous challenge. The complexity in power systems is investigated as follows. First, the cascade failure in power systems is analyzed, and compared with sand-pile model. Next, we show that the agent-based modelling is a proper way for power network. Mathematically, the geometric dynamics and differential inclusion are useful tools for the stability analysis of large scale power systems. As for power market, the game theory and generalized control system model are proposed. For a complex power system, an evolutive model may be more accurate in description and analysis. Finally, certain newly developed numerical methods in the power system computation are introduced. Overall, we are convinced that the theorem of complexity, combined with modern control theory, may be the right way to answer the challenges faced by the power industry in China.

  6. Analyzing the Biology on the System Level

    Institute of Scientific and Technical Information of China (English)

    Wei Tong

    2004-01-01

    Although various genome projects have provided us enormous static sequence information, understanding of the sophisticated biology continues to require integrating the computational modeling, system analysis, technology development for experiments, and quantitative experiments all together to analyze the biology architecture on various levels, which is just the origin of systems biology subject. This review discusses the object, its characteristics, and research attentions in systems biology, and summarizes the analysis methods, experimental technologies, research developments, and so on in the four key fields of systems biology-systemic structures, dynamics, control methods, and design principles.

  7. 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.

  8. 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.

  9. 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.

  10. 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...

  11. Principles of Systems Biology, No. 8.

    Science.gov (United States)

    2016-08-01

    Advances in biological engineering headline this month's Cell Systems call (Cell Systems 1, 307), alongside intriguing applications of modeling from the Elf, Goentoro, and Wolf groups. Check out our recent blogpost: http://crosstalk.cell.com/blog/a-call-for-papers-on-biological-engineering-and-synthetic-biology. PMID:27559920

  12. 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.

  13. The Current State and Perspectives of Systems Biology

    Institute of Scientific and Technical Information of China (English)

    Tielui Shi; Yixue Li

    2006-01-01

    Emerging as a new field in biology recently, Systems Biology provides a branch new way to study the biological activities in organisms. In order to decode the complexity of life systematically,systems biology integrates the "-omics" and uses the high throughput methods from transcriptomics,protomics and metabonomics to detect the dynamic activities in cell; and then, it incorporates bioinformatics methods to integrate and analyze those data, and simulate the biological processes based on the model built from those integrated data. In this paper, the current state, the research field and the methods for the Systems Biology are introduced briefly, and then, several ideas about future development in this field are also proposed.

  14. Challenges in Complex Systems Science

    CERN Document Server

    Miguel, Maxi San; Kertesz, Janos; Kaski, Kimmo; Díaz-Guilera, Albert; MacKay, Robert S; Loreto, Vittorio; Erdi, Peter; Helbing, Dirk

    2012-01-01

    FuturICT foundations are social science, complex systems science, and ICT. The main concerns and challenges in the science of complex systems in the context of FuturICT are laid out in this paper with special emphasis on the Complex Systems route to Social Sciences. This include complex systems having: many heterogeneous interacting parts; multiple scales; complicated transition laws; unexpected or unpredicted emergence; sensitive dependence on initial conditions; path-dependent dynamics; networked hierarchical connectivities; interaction of autonomous agents; self-organisation; non-equilibrium dynamics; combinatorial explosion; adaptivity to changing environments; co-evolving subsystems; ill-defined boundaries; and multilevel dynamics. In this context, science is seen as the process of abstracting the dynamics of systems from data. This presents many challenges including: data gathering by large-scale experiment, participatory sensing and social computation, managing huge distributed dynamic and heterogeneou...

  15. Search for organising principles: understanding in systems biology.

    Science.gov (United States)

    Mesarovic, M D; Sreenath, S N; Keene, J D

    2004-06-01

    Due in large measure to the explosive progress in molecular biology, biology has become arguably the most exciting scientific field. The first half of the 21st century is sometimes referred to as the 'era of biology', analogous to the first half of the 20th century, which was considered to be the 'era of physics'. Yet, biology is facing a crisis--or is it an opportunity--reminiscent of the state of biology in pre-double-helix time. The principal challenge facing systems biology is complexity. According to Hood, 'Systems biology defines and analyses the interrelationships of all of the elements in a functioning system in order to understand how the system works.' With 30000+ genes in the human genome the study of all relationships simultaneously becomes a formidably complex problem. Hanahan and Weinberg raised the question as to whether progress will consist of 'adding further layers of complexity to a scientific literature that is already complex almost beyond measure' or whether the progress will lead to a 'science with a conceptual structure and logical coherence that rivals that of chemistry or physics.' At the core of the challenge is the need for a new approach, a shift from reductionism to a holistic perspective. However, more than just a pronouncement of a new approach is needed. We suggest that what is needed is to provide a conceptual framework for systems biology research. We propose that the concept of a complex system, i.e. a system of systems as defined in mathematical general systems theory (MGST), is central to provide such a framework. We further argue that for a deeper understanding in systems biology investigations should go beyond building numerical mathematical or computer models--important as they are. Biological phenomena cannot be predicted with the level of numerical precision as in classical physics. Explanations in terms of how the categories of systems are organised to function in ever changing conditions are more revealing. Non

  16. Search for organising principles: understanding in systems biology.

    Science.gov (United States)

    Mesarovic, M D; Sreenath, S N; Keene, J D

    2004-06-01

    Due in large measure to the explosive progress in molecular biology, biology has become arguably the most exciting scientific field. The first half of the 21st century is sometimes referred to as the 'era of biology', analogous to the first half of the 20th century, which was considered to be the 'era of physics'. Yet, biology is facing a crisis--or is it an opportunity--reminiscent of the state of biology in pre-double-helix time. The principal challenge facing systems biology is complexity. According to Hood, 'Systems biology defines and analyses the interrelationships of all of the elements in a functioning system in order to understand how the system works.' With 30000+ genes in the human genome the study of all relationships simultaneously becomes a formidably complex problem. Hanahan and Weinberg raised the question as to whether progress will consist of 'adding further layers of complexity to a scientific literature that is already complex almost beyond measure' or whether the progress will lead to a 'science with a conceptual structure and logical coherence that rivals that of chemistry or physics.' At the core of the challenge is the need for a new approach, a shift from reductionism to a holistic perspective. However, more than just a pronouncement of a new approach is needed. We suggest that what is needed is to provide a conceptual framework for systems biology research. We propose that the concept of a complex system, i.e. a system of systems as defined in mathematical general systems theory (MGST), is central to provide such a framework. We further argue that for a deeper understanding in systems biology investigations should go beyond building numerical mathematical or computer models--important as they are. Biological phenomena cannot be predicted with the level of numerical precision as in classical physics. Explanations in terms of how the categories of systems are organised to function in ever changing conditions are more revealing. Non

  17. 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.

  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. 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.

  20. 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...

  1. HEALTHCARE: A COMPLEX SERVICE SYSTEM

    Institute of Scientific and Technical Information of China (English)

    James M. TIEN; Pascal J. GOLDSCHMIDT-CLERMONT

    2009-01-01

    Healthcare is indeed a complex service system, one requiring the technobiology approach of systems engineering to underpin its development as an integrated and adaptive system. In general, healthcare services are carried out with knowledge-intensive agents or components which work together as providers and consumers to create or co-produce value. Indeed, the engineering design of a healthcare system must recognize the fact that it is actually a complex integration of human-centered activities that is increasingly dependent on information technology and knowledge. Like any service system, healthcare can be considered to be a combination or recombination of three essential components-people (characterized by behaviors, values, knowledge, etc.), processes (characterized by collaboration, customization, etc.) and products (characterized by software, hardware, infrastructures, etc.). Thus, a healthcare system is an integrated and adaptive set of people, processes and products. It is, in essence, a system of systems which objectives are to enhance its efficiency (leading to greater interdependency) and effectiveness (leading to improved health). Integration occurs over the physical, temporal, organizational and functional dimensions, while adaptation occurs over the monitoring, feedback, cybernetic and learning dimensions. In sum, such service systems as healthcare are indeed complex, especially due to the uncertainties associated with the human-centered aspects of these systems. Moreover, the system complexities can only be dealt with methods that enhance system integration and adaptation.

  2. Spatial Aspects in Biological System Simulations

    Energy Technology Data Exchange (ETDEWEB)

    Resat, Haluk; Costa, Michelle N.; Shankaran, Harish

    2011-01-30

    Mathematical models of the dynamical properties of biological systems aim to improve our understanding of the studied system with the ultimate goal of being able to predict system responses in the absence of experimentation. Despite the enormous advances that have been made in biological modeling and simulation, the inherently multiscale character of biological systems and the stochasticity of biological processes continue to present significant computational and conceptual challenges. Biological systems often consist of well-organized structural hierarchies, which inevitably lead to multiscale problems. This chapter introduces and discusses the advantages and shortcomings of several simulation methods that are being used by the scientific community to investigate the spatio-temporal properties of model biological systems. We first describe the foundations of the methods and then describe their relevance and possible application areas with illustrative examples from our own research. Possible ways to address the encountered computational difficulties are also discussed.

  3. 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...

  4. Systems biology of lignin biosynthesis in Populus trichocarpa: heteromeric 4-coumaric acid:coenzyme A ligase protein complex formation, regulation, and numerical modeling.

    Science.gov (United States)

    Chen, Hsi-Chuan; Song, Jina; Wang, Jack P; Lin, Ying-Chung; Ducoste, Joel; Shuford, Christopher M; Liu, Jie; Li, Quanzi; Shi, Rui; Nepomuceno, Angelito; Isik, Fikret; Muddiman, David C; Williams, Cranos; Sederoff, Ronald R; Chiang, Vincent L

    2014-03-01

    As a step toward predictive modeling of flux through the pathway of monolignol biosynthesis in stem differentiating xylem of Populus trichocarpa, we discovered that the two 4-coumaric acid:CoA ligase (4CL) isoforms, 4CL3 and 4CL5, interact in vivo and in vitro to form a heterotetrameric protein complex. This conclusion is based on laser microdissection, coimmunoprecipitation, chemical cross-linking, bimolecular fluorescence complementation, and mass spectrometry. The tetramer is composed of three subunits of 4CL3 and one of 4CL5. 4CL5 appears to have a regulatory role. This protein-protein interaction affects the direction and rate of metabolic flux for monolignol biosynthesis in P. trichocarpa. A mathematical model was developed for the behavior of 4CL3 and 4CL5 individually and in mixtures that form the enzyme complex. The model incorporates effects of mixtures of multiple hydroxycinnamic acid substrates, competitive inhibition, uncompetitive inhibition, and self-inhibition, along with characteristic of the substrates, the enzyme isoforms, and the tetrameric complex. Kinetic analysis of different ratios of the enzyme isoforms shows both inhibition and activation components, which are explained by the mathematical model and provide insight into the regulation of metabolic flux for monolignol biosynthesis by protein complex formation.

  5. Integrative systems biology for data-driven knowledge discovery.

    Science.gov (United States)

    Greene, Casey S; Troyanskaya, Olga G

    2010-09-01

    Integrative systems biology is an approach that brings together diverse high-throughput experiments and databases to gain new insights into biological processes or systems at molecular through physiological levels. These approaches rely on diverse high-throughput experimental techniques that generate heterogeneous data by assaying varying aspects of complex biological processes. Computational approaches are necessary to provide an integrative view of these experimental results and enable data-driven knowledge discovery. Hypotheses generated from these approaches can direct definitive molecular experiments in a cost-effective manner. By using integrative systems biology approaches, we can leverage existing biological knowledge and large-scale data to improve our understanding of as yet unknown components of a system of interest and how its malfunction leads to disease.

  6. Challenges in complex systems science

    Science.gov (United States)

    San Miguel, M.; Johnson, J. H.; Kertesz, J.; Kaski, K.; Díaz-Guilera, A.; MacKay, R. S.; Loreto, V.; Érdi, P.; Helbing, D.

    2012-11-01

    FuturICT foundations are social science, complex systems science, and ICT. The main concerns and challenges in the science of complex systems in the context of FuturICT are laid out in this paper with special emphasis on the Complex Systems route to Social Sciences. This include complex systems having: many heterogeneous interacting parts; multiple scales; complicated transition laws; unexpected or unpredicted emergence; sensitive dependence on initial conditions; path-dependent dynamics; networked hierarchical connectivities; interaction of autonomous agents; self-organisation; non-equilibrium dynamics; combinatorial explosion; adaptivity to changing environments; co-evolving subsystems; ill-defined boundaries; and multilevel dynamics. In this context, science is seen as the process of abstracting the dynamics of systems from data. This presents many challenges including: data gathering by large-scale experiment, participatory sensing and social computation, managing huge distributed dynamic and heterogeneous databases; moving from data to dynamical models, going beyond correlations to cause-effect relationships, understanding the relationship between simple and comprehensive models with appropriate choices of variables, ensemble modeling and data assimilation, modeling systems of systems of systems with many levels between micro and macro; and formulating new approaches to prediction, forecasting, and risk, especially in systems that can reflect on and change their behaviour in response to predictions, and systems whose apparently predictable behaviour is disrupted by apparently unpredictable rare or extreme events. These challenges are part of the FuturICT agenda.

  7. Constructing minimal models for complex system dynamics

    Science.gov (United States)

    Barzel, Baruch; Liu, Yang-Yu; Barabási, Albert-László

    2015-05-01

    One of the strengths of statistical physics is the ability to reduce macroscopic observations into microscopic models, offering a mechanistic description of a system's dynamics. This paradigm, rooted in Boltzmann's gas theory, has found applications from magnetic phenomena to subcellular processes and epidemic spreading. Yet, each of these advances were the result of decades of meticulous model building and validation, which are impossible to replicate in most complex biological, social or technological systems that lack accurate microscopic models. Here we develop a method to infer the microscopic dynamics of a complex system from observations of its response to external perturbations, allowing us to construct the most general class of nonlinear pairwise dynamics that are guaranteed to recover the observed behaviour. The result, which we test against both numerical and empirical data, is an effective dynamic model that can predict the system's behaviour and provide crucial insights into its inner workings.

  8. 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.

  9. 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. PMID:26546279

  10. A unified biological modeling and simulation system for analyzing biological reaction networks

    Science.gov (United States)

    Yu, Seok Jong; Tung, Thai Quang; Park, Junho; Lim, Jongtae; Yoo, Jaesoo

    2013-12-01

    In order to understand the biological response in a cell, a researcher has to create a biological network and design an experiment to prove it. Although biological knowledge has been accumulated, we still don't have enough biological models to explain complex biological phenomena. If a new biological network is to be created, integrated modeling software supporting various biological models is required. In this research, we design and implement a unified biological modeling and simulation system, called ezBioNet, for analyzing biological reaction networks. ezBioNet designs kinetic and Boolean network models and simulates the biological networks using a server-side simulation system with Object Oriented Parallel Accelerator Library framework. The main advantage of ezBioNet is that a user can create a biological network by using unified modeling canvas of kinetic and Boolean models and perform massive simulations, including Ordinary Differential Equation analyses, sensitivity analyses, parameter estimates and Boolean network analysis. ezBioNet integrates useful biological databases, including the BioModels database, by connecting European Bioinformatics Institute servers through Web services Application Programming Interfaces. In addition, we employ Eclipse Rich Client Platform, which is a powerful modularity framework to allow various functional expansions. ezBioNet is intended to be an easy-to-use modeling tool and a simulation system for understanding the control mechanism by monitoring the change of each component in a biological network. The simulation result can be managed and visualized on ezBioNet, which is available free of charge at http://ezbionet.sourceforge.net or http://ezbionet.cbnu.ac.kr.

  11. Tritium Exchange in Biological Systems

    International Nuclear Information System (INIS)

    Whenever tritium-labelled water is employed as a test solute or tracer in biological systems, an appreciable exchange between tritium and labile hydrogen atoms occurs that frequently affects the nature and interpretation of experimental results. The studies reported here are concerned with the magnitude of the effect that tritium exchange introduces into measurements of total body water and water metabolism in animals and humans. Direct measurements of exchange were made in rats, guinea pigs, pigeons, and rabbits. Tritium-labelled water was administered intravenously or by mouth, and tritium space and turnover determined from the concentration of tritium in blood. The animals were then desiccated to constant weight in vacuo. The specific activity of water collected periodically during desiccation increased by 50% as a result of isotope effects. Water from combustion of dried rabbit tissues contained about 2% of the tritium originally given to the animal. Adipose tissue alone contained little or no exchange tritium. The dried tissues of the other animals were rehydrated with inactive water and the appearance of tritium in the water observed. The specific activity of the water increased in exponential fashion, i.e., 1-exp. (kt), with about 90% of exchange occurring with a half-time of 1 h, and the remaining 10% with a half-time of 10 h. The total tritium extracted accounted for 1.5 to 3.5% of the dose given to the animal, which agrees with the difference between the tritium space and total body water determined by desiccation. An indirect estimate of exchange in humans was derived from concurrent measurements of tritium and antipyrene spaces. The average difference of about 2% in water volume agrees with the direct estimates of exchanges in animals. It is evident that tritium space should be reduced by about 2% to identify it with total body water. The magnitude and relatively slow rate of exchange may also influence the interpretation of metabolic studies with

  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. Correlation of mRNA and protein in complex biological samples.

    Science.gov (United States)

    Maier, Tobias; Güell, Marc; Serrano, Luis

    2009-12-17

    The correlation between mRNA and protein abundances in the cell has been reported to be notoriously poor. Recent technological advances in the quantitative analysis of mRNA and protein species in complex samples allow the detailed analysis of this pathway at the center of biological systems. We give an overview of available methods for the identification and quantification of free and ribosome-bound mRNA, protein abundances and individual protein turnover rates. We review available literature on the correlation of mRNA and protein abundances and discuss biological and technical parameters influencing the correlation of these central biological molecules.

  14. Control principles of complex systems

    Science.gov (United States)

    Liu, Yang-Yu; Barabási, Albert-László

    2016-07-01

    A reflection of our ultimate understanding of a complex system is our ability to control its behavior. Typically, control has multiple prerequisites: it requires an accurate map of the network that governs the interactions between the system's components, a quantitative description of the dynamical laws that govern the temporal behavior of each component, and an ability to influence the state and temporal behavior of a selected subset of the components. With deep roots in dynamical systems and control theory, notions of control and controllability have taken a new life recently in the study of complex networks, inspiring several fundamental questions: What are the control principles of complex systems? How do networks organize themselves to balance control with functionality? To address these questions here recent advances on the controllability and the control of complex networks are reviewed, exploring the intricate interplay between the network topology and dynamical laws. The pertinent mathematical results are matched with empirical findings and applications. Uncovering the control principles of complex systems can help us explore and ultimately understand the fundamental laws that govern their behavior.

  15. Detection of Two Isomeric Binding Configurations in a Protein-Aptamer Complex with a Biological Nanopore

    NARCIS (Netherlands)

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

    2014-01-01

    ProteinDNA 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 a

  16. Life as Complex Systems Viewpoint from Intra-Inter Dynamics

    CERN Document Server

    Kaneko, K

    1998-01-01

    Basic problems in complex systems are surveyed in connection with Life. As a key issue for complex systems, complementarity between syntax/rule/parts and semantics/behavior/whole is stressed. To address the issue, a constructive approach for a biological system is proposed. As a construction in a computer, intra-inter dynamics is presented for cell biology, where the following five general features are drawn from our model experiments; intrinsic diversification, recursive type formation, rule generation, formation of internal representation, and macroscopic robustness. Significance of the constructed logic to the biology of existing organisms is also discussed.

  17. 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...

  18. 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 lip

  19. 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.

  20. Pluralistic Modeling of Complex Systems

    CERN Document Server

    Helbing, Dirk

    2010-01-01

    The modeling of complex systems such as ecological or socio-economic systems can be very challenging. Although various modeling approaches exist, they are generally not compatible and mutually consistent, and empirical data often do not allow one to decide what model is the right one, the best one, or most appropriate one. Moreover, as the recent financial and economic crisis shows, relying on a single, idealized model can be very costly. This contribution tries to shed new light on problems that arise when complex systems are modeled. While the arguments can be transferred to many different systems, the related scientific challenges are illustrated for social, economic, and traffic systems. The contribution discusses issues that are sometimes overlooked and tries to overcome some frequent misunderstandings and controversies of the past. At the same time, it is highlighted how some long-standing scientific puzzles may be solved by considering non-linear models of heterogeneous agents with spatio-temporal inte...

  1. 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.

  2. Computational Proteomics: High-throughput Analysis for Systems Biology

    Energy Technology Data Exchange (ETDEWEB)

    Cannon, William R.; Webb-Robertson, Bobbie-Jo M.

    2007-01-03

    High-throughput (HTP) proteomics is a rapidly developing field that offers the global profiling of proteins from a biological system. The HTP technological advances are fueling a revolution in biology, enabling analyses at the scales of entire systems (e.g., whole cells, tumors, or environmental communities). However, simply identifying the proteins in a cell is insufficient for understanding the underlying complexity and operating mechanisms of the overall system. Systems level investigations are relying more and more on computational analyses, especially in the field of proteomics generating large-scale global data.

  3. 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.

  4. The Complex System in Babel

    Directory of Open Access Journals (Sweden)

    Dwi Setiawan

    2008-01-01

    Full Text Available This article discusses how the plot of Babel reflects the principles of the quantum-physic theory of complex system such as complexity, indeterminacy and non-linearity. In terms of complexity, the movie exposes more than two distinct subplots with their subcomponents. Yet, every subplot is only meaningful when it is mentally put in relation to the others. Due to its complexity, it is highly difficult for the audience and the characters of Babel to determine the meaning or the significance of a component in the story. Finally, Babel also displays the phenomena of non-linearity and chaos. Babel's non-linearity expresses both positive and negative feedback loops, with the first being dominant. This is largely responsible for the chaotic development of the plot.

  5. 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...

  6. Systems Medicine: Evolution of Systems Biology From Bench To Bedside

    OpenAIRE

    Wang, Rui-Sheng; Maron, Bradley A.; Loscalzo, Joseph

    2015-01-01

    High-throughput experimental techniques for generating genomes, transcriptomes, proteomes, metabolomes, and interactomes have provided unprecedented opportunities to interrogate biological systems and human diseases on a global level. Systems biology integrates the mass of heterogeneous high-throughput data and predictive computational modeling to understand biological functions as system-level properties. Most human diseases are biological states caused by multiple components of perturbed pa...

  7. Biological control in greenhouse systems.

    Science.gov (United States)

    Paulitz, T C; Bélanger, R R

    2001-01-01

    The controlled environment of greenhouses, the high value of the crops, and the limited number of registered fungicides offer a unique niche for the biological control of plant diseases. During the past ten years, over 80 biocontrol products have been marketed worldwide. A large percentage of these have been developed for greenhouse crops. Products to control soilborne pathogens such as Sclerotinia, Pythium, Rhizoctonia and Fusarium include Coniothyrium minitans, species of Gliocladium, Trichoderma, Streptomyces, and Bacillus, and nonpathogenic Fusarium. Products containing Trichoderma, Ampelomyces quisqualis, Bacillus, and Ulocladium are being developed to control the primary foliar diseases, Botrytis and powdery mildew. The development of Pseudomonas for the control of Pythium diseases in hydroponics and Pseudozyma flocculosa for the control of powdery mildew by two Canadian research programs is presented. In the future, biological control of diseases in greenhouses could predominate over chemical pesticides, in the same way that biological control of greenhouse insects predominates in the United Kingdom. The limitations in formulation, registration, and commercialization are discussed, along with suggested future research priorities. PMID:11701861

  8. Genomes, phylogeny, and evolutionary systems biology

    OpenAIRE

    Medina, Monica

    2005-01-01

    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 c...

  9. Bilinear effect in complex systems

    CERN Document Server

    Lam, Lui; Han, Xiao-Pu; Liu, Chih-Hui Alston; Shu, Chang-Qing; Wei, Zhengjin; Zhou, Tao; Zhu, Jichen

    2010-01-01

    A new, generic type of Zipf-plot behavior in complex systems has been discovered. This Zipf plot does not obey the power law or stretched-exponent distribution but appears as two monotonically decreasing straight lines intersecting each other. This is called the Bilinear Effect. Examples from real systems (including lifetime distributions of Chinese dynasties) are presented. A 3-layer network model that leads to the bilinear effect is given.

  10. COOPERATIVE BEHAVIOUR IN COMPLEX SYSTEMS

    OpenAIRE

    Karsai Márton

    2009-01-01

    In my PhD thesis I studied cooperative phenomena arise in complex systems using the methods of statistical and computational physics. The aim of my work was also to study the critical behaviour of interacting many-body systems during their phase transitions and describe their universal features analytically and by means of numerical calculations. In order to do so I completed studies in four different subjects. My first investigated subject was a study of non-equilibrium phase transitions in ...

  11. Developmental systems biology flourishing on new technologies

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Organism development is a systems level process. It has benefited greatly from the recent technological advances in the field of systems biology. DNA microarray, phenome, interactome and transcriptome mapping, the new generation of deep sequencing technologies,and faster and better computational and modeling approaches have opened new frontiers for both systems biologists and developmental biologists to reexamine the old developmental biology questions, such as pattern formation, and to tackle new problems, such as stem cell reprogramming. As showcased in the International Developmental Systems Biology Symposium organized by Chinese Academy of Sciences, developmental systems biology is flourishing in many perspectives, from the evolution of developmental systems, to the underlying genetic and molecular pathways and networks, to the genomic, epigenomic and noncoding levels, to the computational analysis and modeling. We believe that the field will continue to reap rewards into the future with these new approaches.

  12. Developmental systems biology flourishing on new technologies.

    Science.gov (United States)

    Han, Jing-Dong J; Liu, Yi; Xue, Huiling; Xia, Kai; Yu, Hong; Zhu, Shanshan; Chen, Zhang; Zhang, Wei; Huang, Zheng; Jin, Chunyu; Xian, Bo; Li, Jing; Hou, Lei; Han, Yixing; Niu, Chaoqun; Alcon, Timothy C

    2008-10-01

    Organism development is a systems level process. It has benefited greatly from the recent technological advances in the field of systems biology. DNA microarray, phenome, interactome and transcriptome mapping, the new generation of deep sequencing technologies, and faster and better computational and modeling approaches have opened new frontiers for both systems biologists and developmental biologists to reexamine the old developmental biology questions, such as pattern formation, and to tackle new problems, such as stem cell reprogramming. As showcased in the International Developmental Systems Biology Symposium organized by Chinese Academy of Sciences, developmental systems biology is flourishing in many perspectives, from the evolution of developmental systems, to the underlying genetic and molecular pathways and networks, to the genomic, epigenomic and noncoding levels, to the computational analysis and modeling. We believe that the field will continue to reap rewards into the future with these new approaches. PMID:18937914

  13. 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

  14. Applicability of computational systems biology in toxicology.

    Science.gov (United States)

    Kongsbak, Kristine; Hadrup, Niels; Audouze, Karine; Vinggaard, Anne Marie

    2014-07-01

    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. However, computational systems biology offers more advantages than providing a high-throughput literature search; it may form the basis for establishment of hypotheses on potential links between environmental chemicals and human diseases, which would be very difficult to establish experimentally. This is possible due to the existence of comprehensive databases containing information on networks of human protein-protein interactions and protein-disease associations. Experimentally determined targets of the specific chemical of interest can be fed into these networks to obtain additional information that can 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 in the hypothesis-generating phase of toxicological research.

  15. Biological robustness: paradigms, mechanisms, and systems principles.

    Science.gov (United States)

    Whitacre, James Michael

    2012-01-01

    Robustness has been studied through the analysis of data sets, simulations, and a variety of experimental techniques that each have their own limitations but together confirm the ubiquity of biological robustness. Recent trends suggest that different types of perturbation (e.g., mutational, environmental) are commonly stabilized by similar mechanisms, and system sensitivities often display a long-tailed distribution with relatively few perturbations representing the majority of sensitivities. Conceptual paradigms from network theory, control theory, complexity science, and natural selection have been used to understand robustness, however each paradigm has a limited scope of applicability and there has been little discussion of the conditions that determine this scope or the relationships between paradigms. Systems properties such as modularity, bow-tie architectures, degeneracy, and other topological features are often positively associated with robust traits, however common underlying mechanisms are rarely mentioned. For instance, many system properties support robustness through functional redundancy or through response diversity with responses regulated by competitive exclusion and cooperative facilitation. Moreover, few studies compare and contrast alternative strategies for achieving robustness such as homeostasis, adaptive plasticity, environment shaping, and environment tracking. These strategies share similarities in their utilization of adaptive and self-organization processes that are not well appreciated yet might be suggestive of reusable building blocks for generating robust behavior. PMID:22593762

  16. Biological Robustness: Paradigms, Mechanisms, and Systems Principles

    Directory of Open Access Journals (Sweden)

    James Michael Whitacre

    2012-05-01

    Full Text Available Robustness has been studied through the analysis of data sets, simulations, and a variety of experimental techniques that each have their own limitations but together confirm the ubiquity of biological robustness. Recent trends suggest that different types of perturbation (e.g. mutational, environmental are commonly stabilized by similar mechanisms, and system sensitivities often display a long-tailed distribution with relatively few perturbations representing the majority of sensitivities. Conceptual paradigms from network theory, control theory, complexity science, and natural selection have been used to understand robustness, however each paradigm has a limited scope of applicability and there has been little discussion of the conditions that determine this scope or the relationships between paradigms. Systems properties such as modularity, bow-tie architectures, degeneracy, and other topological features are often positively associated with robust traits, however common underlying mechanisms are rarely mentioned. For instance, many system properties support robustness through functional redundancy or through response diversity with responses regulated by competitive exclusion and cooperative facilitation. Moreover, few studies compare and contrast alternative strategies for achieving robustness such as homeostasis, adaptive plasticity, environment shaping, and environment tracking. These strategies share similarities in their utilization of adaptive and self-organization processes that are not well appreciated yet might be suggestive of reusable building blocks for generating robust behavior.

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

    Science.gov (United States)

    Sudhir, Putty-Reddy; Chen, Chung-Hsuan

    2016-01-01

    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. PMID:27011181

  18. Integration of proteomics into systems biology of cancer

    OpenAIRE

    Hanash, S; Schliekelman, M.; Q. Zhang; Taguchi, A

    2012-01-01

    Deciphering the complexity and heterogeneity of cancer benefits from integration of proteomic level data into systems biology efforts. The opportunities available as a result of advances in proteomic technologies, the successes to date and the challenges involved in integrating diverse datasets are addressed in this review.

  19. Integration of proteomics into systems biology of cancer.

    Science.gov (United States)

    Hanash, S; Schliekelman, M; Zhang, Q; Taguchi, A

    2012-01-01

    Deciphering the complexity and heterogeneity of cancer, benefits from integration of proteomic level data into systems biology efforts. The opportunities available as a result of advances in proteomic technologies, the successes to date, and the challenges involved in integrating diverse datasets are addressed in this review.

  20. Systems Biology Analysis of Heterocellular Signaling.

    Science.gov (United States)

    Tape, Christopher J

    2016-08-01

    Tissues comprise multiple heterotypic cell types (e.g., epithelial, mesenchymal, and immune cells). Communication between heterotypic cell types is essential for biological cohesion and is frequently dysregulated in disease. Despite the importance of heterocellular communication, most systems biology techniques do not report cell-specific signaling data from mixtures of cells. As a result, our existing perspective of cellular behavior under-represents the influence of heterocellular signaling. Recent technical advances now permit the resolution of systems-level cell-specific signaling data. This review discusses how new physical, spatial, and isotopic resolving methods are facilitating unique systems biology studies of heterocellular communication. PMID:27087613

  1. 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.

  2. 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.

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

    Science.gov (United States)

    Bartocci, Ezio; Lió, Pietro

    2016-01-01

    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.

  4. 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...

  5. The Evolution of Biological Complexity in Digital Organisms

    Science.gov (United States)

    Ofria, Charles

    2013-03-01

    When Darwin first proposed his theory of evolution by natural selection, he realized that it had a problem explaining the origins of traits of ``extreme perfection and complication'' such as the vertebrate eye. Critics of Darwin's theory have latched onto this perceived flaw as a proof that Darwinian evolution is impossible. In anticipation of this issue, Darwin described the perfect data needed to understand this process, but lamented that such data are ``scarcely ever possible'' to obtain. In this talk, I will discuss research where we use populations of digital organisms (self-replicating and evolving computer programs) to elucidate the genetic and evolutionary processes by which new, highly-complex traits arise, drawing inspiration directly from Darwin's wistful thinking and hypotheses. During the process of evolution in these fully-transparent computational environments we can measure the incorporation of new information into the genome, a process akin to a natural Maxwell's Demon, and identify the original source of any such information. We show that, as Darwin predicted, much of the information used to encode a complex trait was already in the genome as part of simpler evolved traits, and that many routes must be possible for a new complex trait to have a high probability of successfully evolving. In even more extreme examples of the evolution of complexity, we are now using these same principles to examine the evolutionary dynamics the drive major transitions in evolution; that is transitions to higher-levels of organization, which are some of the most complex evolutionary events to occur in nature. Finally, I will explore some of the implications of this research to other aspects of evolutionary biology and as well as ways that these evolutionary principles can be applied toward solving computational and engineering problems.

  6. Systems Biology of Fungal Infection

    OpenAIRE

    FabianHorn; ThorstenHeinekamp; JohannesPollmächer; AxelABrakhage

    2012-01-01

    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 i...

  7. Biologic Therapy in Inflammatory Immunomediated Systemic Diseases: Safety Profile.

    Science.gov (United States)

    Moroncini, Gianluca; Albani, Lisa; Nobili, Lorenzo; Gabrielli, Armando

    2016-01-01

    The discovery of some key molecular mechanisms underlying the dysregulation of the immune system responsible for inflammatory systemic diseases as severe as Systemic Lupus Erythematosus (SLE), Systemic Sclerosis (SSc), and Systemic Vasculitides, led to the development and subsequent introduction into clinical practice of biological drugs which are significantly improving the management of such complex disorders. This novel molecular targeted therapeutics represents in fact a valid alternative or complementary treatment to conventional immunosuppressive strategies, characterized by broad, unspecific actions and severe adverse effects. Main advantages of the use of biologic drugs reside in their steroid-sparing effect and in the ability of inducing remission of refractory disease states or curing specific organ involvements. Aim of this article is to review and briefly discuss the scientific evidence supporting the use of biologics in these diseases, with a particular emphasis on their efficacy and safety profile compared to the canonical drugs.

  8. Simulation of complex molecular systems

    International Nuclear Information System (INIS)

    The combined evolution of the electronic structure softwares and computational capabilities makes quantum molecular dynamics simulations available for increasingly complex systems, up to several hundred atoms. Among the various ab initio techniques, Density Functional Theory (DFT) is very successful due to its important computational efficiency with respect to Hartree-Fock type approaches. Its combination with empirical treatments of the weak van der Waals interactions allows the simulation of equilibrium or dynamics properties of numerous systems of interest for the nuclear and defense industry. We present 3 direct applications of quantum molecular dynamics: the determination of the structure of the complex Pu(DTPA) ion where DTPA means diethylen-triamine-penta-acid, the calculation of the equation of state and the Hugoniot curve of TATB monocrystal. (authors)

  9. Bioferroelectricity and optical properties of biological systems

    Science.gov (United States)

    Bystrov, Vladimir; Bystrova, Natalia

    2003-08-01

    A bioferroelectric approach to analysis of ferroelectric behavior of biological systems is presented. The optical properties of nerve fibers, biomembrane ion channels, and purple membrane films containing bacteriorhodopsin are analyzed. The features, influence of the proton subsystem and proton transfer on the hydrogen-bonded biomolecular structures are analyzed within the ferroelectric liquid-crystal model and possible biomedical applications discussed. The ferroelectric behavior of biological systems and the set of various bioferroelectric effects are considered within the limits of phenomenological theory of ferroelectrics. The nonlinear response to weak actions under conditions critical to human organism is one of specific features characterizing biological objects on molecular, cell and organism levels.

  10. Description complexity of lindenmayer systems

    OpenAIRE

    SELAMAT, H.; Mavlankulov, G.; Othman, M.; S. Turaev

    2012-01-01

    In this paper we study the nonterminal complexity of Lindenmayer systems withrespect to tree controlled grammars. We show that all 0L, D0Land E0L languages can begenerated by tree controlled grammars with at most five nonterminals. The results based onthe idea of using a tree controlled grammar in the t-normal form, which has the one activenonterminal, and a coding homomorphism

  11. Description complexity of lindenmayer systems

    Directory of Open Access Journals (Sweden)

    H. Selamat

    2012-12-01

    Full Text Available In this paper we study the nonterminal complexity of Lindenmayer systems withrespect to tree controlled grammars. We show that all 0L, D0Land E0L languages can begenerated by tree controlled grammars with at most five nonterminals. The results based onthe idea of using a tree controlled grammar in the t-normal form, which has the one activenonterminal, and a coding homomorphism

  12. Systems biology analysis merging phenotype, metabolomic and genomic data identifies Non-SMC Condensin I Complex, Subunit G (NCAPG) and cellular maintenance processes as major contributors to genetic variability in bovine feed efficiency.

    Science.gov (United States)

    Widmann, Philipp; Reverter, Antonio; Weikard, Rosemarie; Suhre, Karsten; Hammon, Harald M; Albrecht, Elke; Kuehn, Christa

    2015-01-01

    Feed efficiency is a paramount factor for livestock economy. Previous studies had indicated a substantial heritability of several feed efficiency traits. In our study, we investigated the genetic background of residual feed intake, a commonly used parameter of feed efficiency, in a cattle resource population generated from crossing dairy and beef cattle. Starting from a whole genome association analysis, we subsequently performed combined phenotype-metabolome-genome analysis taking a systems biology approach by inferring gene networks based on partial correlation and information theory approaches. Our data about biological processes enriched with genes from the feed efficiency network suggest that genetic variation in feed efficiency is driven by genetic modulation of basic processes relevant to general cellular functions. When looking at the predicted upstream regulators from the feed efficiency network, the Tumor Protein P53 (TP53) and Transforming Growth Factor beta 1 (TGFB1) genes stood out regarding significance of overlap and number of target molecules in the data set. These results further support the hypothesis that TP53 is a major upstream regulator for genetic variation of feed efficiency. Furthermore, our data revealed a significant effect of both, the Non-SMC Condensin I Complex, Subunit G (NCAPG) I442M (rs109570900) and the Growth /differentiation factor 8 (GDF8) Q204X (rs110344317) loci, on residual feed intake and feed conversion. For both loci, the growth promoting allele at the onset of puberty was associated with a negative, but favorable effect on residual feed intake. The elevated energy demand for increased growth triggered by the NCAPG 442M allele is obviously not fully compensated for by an increased efficiency in converting feed into body tissue. As a consequence, the individuals carrying the NCAPG 442M allele had an additional demand for energy uptake that is reflected by the association of the allele with increased daily energy intake as

  13. 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.

  14. 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.

  15. Testing Complex and Embedded Systems

    CERN Document Server

    Pries, Kim H

    2010-01-01

    Many enterprises regard system-level testing as the final piece of the development effort, rather than as a tool that should be integrated throughout the development process. As a consequence, test teams often execute critical test plans just before product launch, resulting in much of the corrective work being performed in a rush and at the last minute. Presenting combinatorial approaches for improving test coverage, Testing Complex and Embedded Systems details techniques to help you streamline testing and identify problems before they occur--including turbocharged testing using Six Sigma and

  16. 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.

  17. The biology of aging and lymphoma: a complex interplay.

    Science.gov (United States)

    Sarkozy, Clémentine; Salles, Gilles; Falandry, Claire

    2015-07-01

    The probability to develop non-Hodgkin lymphoma grows with age. The biological links between aging and lymphoma are not well described in the literature, and different hypothesis may be raised to explain this complex relationship. First, the impact of chronological age favoring the accumulation of genetic alterations can contribute to the multisteps proces of lymphomagenesis. Then, the age-related defects in cancer protection and the age-related clonal restriction in hematopoietic stem cell may also promote lymphoma development. Finally, the senescent and immunosenescence phenotype might represent a key process explaining this link. In this review, we will explore the current available clinical data and their ability to apply to age-related regulation pathways. PMID:26003736

  18. 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.

  19. Problem Solving and Complex Systems

    CERN Document Server

    Guinand, Frédéric

    2008-01-01

    The observation and modeling of natural Complex Systems (CSs) like the human nervous system, the evolution or the weather, allows the definition of special abilities and models reusable to solve other problems. For instance, Genetic Algorithms or Ant Colony Optimizations are inspired from natural CSs to solve optimization problems. This paper proposes the use of ant-based systems to solve various problems with a non assessing approach. This means that solutions to some problem are not evaluated. They appear as resultant structures from the activity of the system. Problems are modeled with graphs and such structures are observed directly on these graphs. Problems of Multiple Sequences Alignment and Natural Language Processing are addressed with this approach.

  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. Molecular biology of the renin-angiotensin system

    Energy Technology Data Exchange (ETDEWEB)

    Dzau, V.J.; Burt, D.W.; Pratt, R.E. (Harvard Medical School, Boston, MA (USA))

    1988-10-01

    This paper reviews the molecular biology of the renin-angiotensin system. The renin gene structure is analyzed in detail, including an examination of the putative regulatory regions. The combined action of these regulatory sequences would result in the complex, tissue-specific expression and regulation observed in vivo. The expression of the tissue renin-angiotensin systems, which may have important physiological functions, is also described. In addition, the pathway of renin biosynthesis and secretion is reviewed. This includes speculation on the fate of circulating prorenin and the physiological role of multiple renin forms and secretory pathways. The molecular approaches described in this paper have greatly advanced our knowledge of the biology of the renin-angiotensin system. Future studies using these and other approaches should provide further insight into this complex system.

  2. 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

  3. 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.

  4. 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.

  5. Deciphering The Complex Biological Interactions Of Nitric Oxide In Cancer

    Directory of Open Access Journals (Sweden)

    S. Perwez Hussain

    2015-08-01

    Full Text Available NO• is a free radical and is involved in a number of critical physiological processes including vasodilation, neurotransmission, immune regulation and inflammation. There are convincing evidence suggesting a role of NO• in the development and progression of different cancer types. However, the role of NO• in tumorigenesis is highly complex and both pro- and anti-neoplastic functions have been reported, which largely depends on the amount of NO•, cell types, cellular microenvironment, its interaction with other reactive species and presence of metals. An interesting interaction occurs between NO• and p53 tumor suppressor, in which NO•-induced DNA damage causes the stabilization and accumulation of p53, which in turn, transrepresses inducible nitric oxide synthase (NOS2 in a negative feedback loop. In chronic inflammatory diseases, for example ulcerative colitis, NO• induces p53 stabilization and the initiation of DNA-damage response pathway, and also generation of p53 mutation and subsequent clonal selection of p53 mutant cells. Genetic deletion of NOS2 in p53-deficient mice can either suppress or enhance lymphomagenesis depending on the inflammatory microenvironment. These findings highlight the importance of understanding the complex biological interaction of NO• in the context of the molecular makeup of each individual cancer to design NO•-targeted treatment strategies.

  6. 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...

  7. 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.

  8. COMPLEX ECO-ECONOMY SYSTEM

    Institute of Scientific and Technical Information of China (English)

    Pawel Bartoszczuk; Yoshiteru Nakamori

    2003-01-01

    In the past there were a lot of researches on the topic of economic growth. Nevertheless, the environment has been a bit abstracted by standard economics. Scarce natural resources and our choices to protect them or exploit them jointly determine the economic and environmental systems. In this paper we describe a model with a particular focus on the relationship among income, pollution, and non-renewable resources. We want to combine both economic and environmental sectors. The system dynamics approach is used in analyzing these complex relationships. This paper gives an insight into the possibilities for replacing non-renewable resources with more renewable ones. Next, we present the simulation runs of the model that are conducted with the help of existing system dynamics modeling tools. Only the relationships simulated so far between the variables ought to be put under yet more cautious examination.

  9. Functional Genomics Assistant (FUGA: a toolbox for the analysis of complex biological networks

    Directory of Open Access Journals (Sweden)

    Ouzounis Christos A

    2011-10-01

    Full Text Available Abstract Background Cellular constituents such as proteins, DNA, and RNA form a complex web of interactions that regulate biochemical homeostasis and determine the dynamic cellular response to external stimuli. It follows that detailed understanding of these patterns is critical for the assessment of fundamental processes in cell biology and pathology. Representation and analysis of cellular constituents through network principles is a promising and popular analytical avenue towards a deeper understanding of molecular mechanisms in a system-wide context. Findings We present Functional Genomics Assistant (FUGA - an extensible and portable MATLAB toolbox for the inference of biological relationships, graph topology analysis, random network simulation, network clustering, and functional enrichment statistics. In contrast to conventional differential expression analysis of individual genes, FUGA offers a framework for the study of system-wide properties of biological networks and highlights putative molecular targets using concepts of systems biology. Conclusion FUGA offers a simple and customizable framework for network analysis in a variety of systems biology applications. It is freely available for individual or academic use at http://code.google.com/p/fuga.

  10. Revealing complex function, process and pathway interactions with high-throughput expression and biological annotation data.

    Science.gov (United States)

    Singh, Nitesh Kumar; Ernst, Mathias; Liebscher, Volkmar; Fuellen, Georg; Taher, Leila

    2016-10-20

    The biological relationships both between and within the functions, processes and pathways that operate within complex biological systems are only poorly characterized, making the interpretation of large scale gene expression datasets extremely challenging. Here, we present an approach that integrates gene expression and biological annotation data to identify and describe the interactions between biological functions, processes and pathways that govern a phenotype of interest. The product is a global, interconnected network, not of genes but of functions, processes and pathways, that represents the biological relationships within the system. We validated our approach on two high-throughput expression datasets describing organismal and organ development. Our findings are well supported by the available literature, confirming that developmental processes and apoptosis play key roles in cell differentiation. Furthermore, our results suggest that processes related to pluripotency and lineage commitment, which are known to be critical for development, interact mainly indirectly, through genes implicated in more general biological processes. Moreover, we provide evidence that supports the relevance of cell spatial organization in the developing liver for proper liver function. Our strategy can be viewed as an abstraction that is useful to interpret high-throughput data and devise further experiments.

  11. 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...... for accomplishing such altered gene expression levels are discussed here along with examples of their use, and ideas for new tools are described. The road ahead looks very promising for synthetic and systems biologists as tools to achieve just about anything in terms of tuning and timing multiple gene expression...

  12. 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...

  13. 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.

  14. 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.

  15. 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 ...

  16. Photosynthetic system as a biological functional element

    International Nuclear Information System (INIS)

    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)

  17. 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.

  18. Overcoming Problems in the Measurement of Biological Complexity

    CERN Document Server

    Cebrian, Manuel; Ortega, Alfonso

    2010-01-01

    In a genetic algorithm, fluctuations of the entropy of a genome over time are interpreted as fluctuations of the information that the genome's organism is storing about its environment, being this reflected in more complex organisms. The computation of this entropy presents technical problems due to the small population sizes used in practice. In this work we propose and test an alternative way of measuring the entropy variation in a population by means of algorithmic information theory, where the entropy variation between two generational steps is the Kolmogorov complexity of the first step conditioned to the second one. As an example application of this technique, we report experimental differences in entropy evolution between systems in which sexual reproduction is present or absent.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. The complex jujube genome provides insights into fruit tree biology.

    Science.gov (United States)

    Liu, Meng-Jun; Zhao, Jin; Cai, Qing-Le; Liu, Guo-Cheng; Wang, Jiu-Rui; Zhao, Zhi-Hui; Liu, Ping; Dai, Li; Yan, Guijun; Wang, Wen-Jiang; Li, Xian-Song; Chen, Yan; Sun, Yu-Dong; Liu, Zhi-Guo; Lin, Min-Juan; Xiao, Jing; Chen, Ying-Ying; Li, Xiao-Feng; Wu, Bin; Ma, Yong; Jian, Jian-Bo; Yang, Wei; Yuan, Zan; Sun, Xue-Chao; Wei, Yan-Li; Yu, Li-Li; Zhang, Chi; Liao, Sheng-Guang; He, Rong-Jun; Guang, Xuan-Min; Wang, Zhuo; Zhang, Yue-Yang; Luo, Long-Hai

    2014-10-28

    The jujube (Ziziphus jujuba Mill.), a member of family Rhamnaceae, is a major dry fruit and a traditional herbal medicine for more than one billion people. Here we present a high-quality sequence for the complex jujube genome, the first genome sequence of Rhamnaceae, using an integrated strategy. The final assembly spans 437.65 Mb (98.6% of the estimated) with 321.45 Mb anchored to the 12 pseudo-chromosomes and contains 32,808 genes. The jujube genome has undergone frequent inter-chromosome fusions and segmental duplications, but no recent whole-genome duplication. Further analyses of the jujube-specific genes and transcriptome data from 15 tissues reveal the molecular mechanisms underlying some specific properties of the jujube. Its high vitamin C content can be attributed to a unique high level expression of genes involved in both biosynthesis and regeneration. Our study provides insights into jujube-specific biology and valuable genomic resources for the improvement of Rhamnaceae plants and other fruit trees.

  4. Synthetic biology: advancing biological frontiers by building synthetic systems

    OpenAIRE

    Chen, Yvonne Yu-Hsuan; Galloway, Kate E.; Smolke, Christina D.

    2012-01-01

    Advances in synthetic biology are contributing to diverse research areas, from basic biology to biomanufacturing and disease therapy. We discuss the theoretical foundation, applications, and potential of this emerging field.

  5. Semantic annotation for biological information retrieval system.

    Science.gov (United States)

    Oshaiba, Mohamed Marouf Z; El Houby, Enas M F; Salah, Akram

    2015-01-01

    Online literatures are increasing in a tremendous rate. Biological domain is one of the fast growing domains. Biological researchers face a problem finding what they are searching for effectively and efficiently. The aim of this research is to find documents that contain any combination of biological process and/or molecular function and/or cellular component. This research proposes a framework that helps researchers to retrieve meaningful documents related to their asserted terms based on gene ontology (GO). The system utilizes GO by semantically decomposing it into three subontologies (cellular component, biological process, and molecular function). Researcher has the flexibility to choose searching terms from any combination of the three subontologies. Document annotation is taking a place in this research to create an index of biological terms in documents to speed the searching process. Query expansion is used to infer semantically related terms to asserted terms. It increases the search meaningful results using the term synonyms and term relationships. The system uses a ranking method to order the retrieved documents based on the ranking weights. The proposed system achieves researchers' needs to find documents that fit the asserted terms semantically.

  6. Ruthenium(ii) complexes with dppz: from molecular photoswitch to biological applications.

    Science.gov (United States)

    Li, Guanying; Sun, Lingli; Ji, Liangnian; Chao, Hui

    2016-09-14

    The DNA photoswitch [Ru(bpy)2dppz](2+) (bpy = 2,2'-bipyridine, dppz = dipyrido[3,2-a:2',3'-c]phenazine) has attracted much attention and become a powerful tool for studying the interaction of metal polypyridyl complexes with DNA. A large number of Ru-dppz complexes have been designed for a wide range of uses in many fields. In this perspective, we first introduce the latest results of Ru-dppz complexes that bind with DNA. The mechanisms of the light-switch effect and the structural modifications of Ru-dppz systems are also briefly introduced. We also review the recent advances in biological applications of the Ru-dppz system in DNA binders, cellular imaging, anticancer drugs, protein aggregation detection and chemosensors. PMID:27426487

  7. 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.

  8. Systems biology of IL-6, IL-12 family cytokines.

    Science.gov (United States)

    Dittrich, Anna; Hessenkemper, Wiebke; Schaper, Fred

    2015-10-01

    Interleukin-6-type cytokines play important roles in the communication between cells of multicellular organisms. They are involved in the regulation of complex cellular processes such as proliferation and differentiation and act as key player during inflammation and immune response. A major challenge is to understand how these complex non-linear processes are connected and regulated. Systems biology approaches are used to tackle this challenge in an iterative process of quantitative experimental and mathematical analyses. Here we review quantitative experimental studies and systems biology approaches dealing with the function of Interleukin-6-type cytokines in physiological and pathophysiological conditions. These approaches cover the analyses of signal transduction on a cellular level up to pharmacokinetic and pharmacodynamic studies on a whole organism level.

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. 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 -...

  14. Extending Life Concepts to Complex Systems

    OpenAIRE

    Jean Le Fur

    2013-01-01

    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 ...

  15. Philosophical Basis and Some Historical Aspects of Systems Biology: From Hegel to Noble - Applications for Bioenergetic Research

    OpenAIRE

    Valdur Saks; Rita Guzun; Claire Monge

    2009-01-01

    International audience We live in times of paradigmatic changes for the biological sciences. Reductionism, that for the last six decades has been the philosophical basis of biochemistry and molecular biology, is being displaced by Systems Biology, which favors the study of integrated systems. Historically, Systems Biology - defined as the higher level analysis of complex biological systems - was pioneered by Claude Bernard in physiology, Norbert Wiener with the development of cybernetics, ...

  16. Modular microfluidic system for biological sample preparation

    Energy Technology Data Exchange (ETDEWEB)

    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.

  17. Language Based Techniques for Systems Biology

    DEFF Research Database (Denmark)

    Pilegaard, Henrik

    calculi have similarly been used for the study of bio-chemical reactive systems. In this dissertation it is argued that techniques rooted in the theory and practice of programming languages, language based techniques if you will, constitute a strong basis for the investigation of models of biological......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...... systems as formalised in a process calculus. In particular it is argued that Static Program Analysis provides a useful approach to the study of qualitative properties of such models. In support of this claim a number of static program analyses are developed for Regev’s BioAmbients – a bio-inspired variant...

  18. 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.

  19. Cooperative behaviour in complex systems

    Science.gov (United States)

    Karsai, Márton

    2009-07-01

    In my PhD thesis I studied cooperative phenomena arise in complex systems using the methods of statistical and computational physics. The aim of my work was also to study the critical behaviour of interacting many-body systems during their phase transitions and describe their universal features analytically and by means of numerical calculations. In order to do so I completed studies in four different subjects. My first investigated subject was a study of non-equilibrium phase transitions in weighted scale-free networks. The second problem I examined was the ferromagnetic random bond Potts model with large values of q on evolving scale-free networks which problem is equivalent to an optimal cooperation problem. The third examined problem was related to the large-q sate random bond Potts model also and I examined the critical density of clusters which touched a certain border of a perpendicular strip like geometry and expected to hold analytical forms deduced from conformal invariance. The last investigated problem was a study of the non-equilibrium dynamical behaviour of the antiferromagnetic Ising model on two-dimensional triangular lattice at zero temperature in the absence of external field and at the Kosterlitz-Thouless phase transition point.

  20. Synthesis, characterization and biological activity of uranyl thiosemicarbazone complexes

    International Nuclear Information System (INIS)

    A new thiosemicarbazone namely phenacyl thioacetic acid thiosemicarbazone was synthesized and its UO22+ complexes were prepared. The synthesized ligand and complexes were characterized by elemental analyses, spectral (IR, 1H NMR and Mass) studies. In all complexes the ligand coordinates through carboxylic oxygen, azomethine nitrogen and thiolate sulfur. Antimicrobial screening of the free ligand and its complexes showed that, the free ligand and metal complexes possess antimicrobial activities towards two types of bacteria and two types of fungi. (author)

  1. 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

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

    OpenAIRE

    Edwards, Lindsay; 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 extr...

  3. 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

  4. Dynamics and kinetics of model biological systems

    Science.gov (United States)

    Mirigian, Stephen

    In this work we study three systems of biological interest: the translocation of a heterogeneously charged polymer through an infinitely thin pore, the wrapped of a rigid particle by a soft vesicle and the modification of the dynamical properties of a gel due to the presence of rigid inclusions. We study the kinetics of translocation for a heterogeneously charged polyelectrolyte through an infinitely narrow pore using the Fokker-Planck formalism to compute mean first passage times, the probability of successful translocation, and the mean successful translocation time for a diblock copolymer. We find, in contrast to the homopolymer result, that details of the boundary conditions lead to qualitatively different behavior. Under experimentally relevant conditions for a diblock copolymer we find that there is a threshold length of the charged block, beyond which the probability of successful translocation is independent of charge fraction. Additionally, we find that mean successful translocation time exhibits non-monotonic behavior with increasing length of the charged fraction; there is an optimum length of the charged block where the mean successful translocation time is slowest and there can be a substantial range of charge fraction where it is slower than a minimally charged chain. For a fixed total charge on the chain, we find that finer distributions of the charge along the chain leads to a significant reduction in mean translocation time compared to the diblock distribution. Endocytosis is modeled using a simple geometrical model from the literature. We map the process of wrapping a rigid spherical bead onto a one-dimensional stochastic process described by the Fokker-Planck equation to compute uptake rates as a function of membrane properties and system geometry. We find that simple geometrical considerations pick an optimal particle size for uptake and a corresponding maximal uptake rate, which can be controlled by altering the material properties of the

  5. Hierarchical Self-organization of Complex Systems

    Institute of Scientific and Technical Information of China (English)

    CHAI Li-he; WEN Dong-sheng

    2004-01-01

    Researches on organization and structure in complex systems are academic and industrial fronts in modern sciences. Though many theories are tentatively proposed to analyze complex systems, we still lack a rigorous theory on them. Complex systems possess various degrees of freedom, which means that they should exhibit all kinds of structures. However, complex systems often show similar patterns and structures. Then the question arises why such similar structures appear in all kinds of complex systems. The paper outlines a theory on freedom degree compression and the existence of hierarchical self-organization for all complex systems is found. It is freedom degree compression and hierarchical self-organization that are responsible for the existence of these similar patterns or structures observed in the complex systems.

  6. An ensemble approach to the evolution of complex systems

    Indian Academy of Sciences (India)

    Göker Arpağ; Ayşe Erzan

    2014-04-01

    Adaptive systems frequently incorporate complex structures which can arise spontaneously and which may be non-adaptive in the evolutionary sense. We give examples from phase transition and fractal growth to develop the themes of cooperative phenomena and pattern formation. We discuss RNA interference and transcriptional gene regulation networks, where a major part of the topological properties can be accounted for by mere combinatorics. A discussion of ensemble approaches to biological systems and measures of complexity is presented, and a connection is established between complexity and fitness.

  7. An ensemble approach to the evolution of complex systems.

    Science.gov (United States)

    Arpağ, Göker; Erzan, Ayşe

    2014-04-01

    Adaptive systems frequently incorporate complex structures which can arise spontaneously and which may be nonadaptive in the evolutionary sense. We give examples from phase transition and fractal growth to develop the themes of cooperative phenomena and pattern formation. We discuss RNA interference and transcriptional gene regulation networks, where a major part of the topological properties can be accounted for by mere combinatorics. A discussion of ensemble approaches to biological systems and measures of complexity is presented, and a connection is established between complexity and fitness.

  8. An ensemble approach to the evolution of complex systems.

    Science.gov (United States)

    Arpağ, Göker; Erzan, Ayşe

    2014-04-01

    Adaptive systems frequently incorporate complex structures which can arise spontaneously and which may be nonadaptive in the evolutionary sense. We give examples from phase transition and fractal growth to develop the themes of cooperative phenomena and pattern formation. We discuss RNA interference and transcriptional gene regulation networks, where a major part of the topological properties can be accounted for by mere combinatorics. A discussion of ensemble approaches to biological systems and measures of complexity is presented, and a connection is established between complexity and fitness. PMID:24736159

  9. Solid-State Synthesis, Characterization, and Biological Activity of the Bioinorganic Complex of Aspartic Acid and Arsenic Triiodide

    Directory of Open Access Journals (Sweden)

    Guo-Qing Zhong

    2013-01-01

    Full Text Available The bioinorganic complex of aspartic acid and arsenic triiodide was synthesized by a solid-state reaction at room temperature. The formula of the complex is AsI3[HOOCCH2CH(NH2COOH]2.5. The crystal structure of the complex belongs to monoclinic system with lattice parameters: a=1.0019 nm, b=1.5118 nm, c=2.1971 nm, and β=100.28°. The infrared spectra can demonstrate the complex formation between the arsenic ion and aspartic acid, and the complex may be a dimer with bridge structure. The result of primary biological test indicates that the complex possesses better biological activity for the HL-60 cells of the leukemia than arsenic triiodide.

  10. 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.

  11. 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

  12. Controlled biological and biomimetic systems for landmine detection.

    Science.gov (United States)

    Habib, Maki K

    2007-08-30

    Humanitarian demining requires to accurately detect, locate and deactivate every single landmine and other buried mine-like objects as safely and as quickly as possible, and in the most non-invasive manner. The quality of landmine detection affects directly the efficiency and safety of this process. Most of the available methods to detect explosives and landmines are limited by their sensitivity and/or operational complexities. All landmines leak with time small amounts of their explosives that can be found on surrounding ground and plant life. Hence, explosive signatures represent the robust primary indicator of landmines. Accordingly, developing innovative technologies and efficient techniques to identify in real-time explosives residue in mined areas represents an attractive and promising approach. Biological and biologically inspired detection technology has the potential to compete with or be used in conjunction with other artificial technology to complement performance strengths. Biological systems are sensitive to many different scents concurrently, a property that has proven difficult to replicate artificially. Understanding biological systems presents unique opportunities for developing new capabilities through direct use of trained bio-systems, integration of living and non-living components, or inspiring new design by mimicking biological capabilities. It is expected that controlled bio-systems, biotechnology and microbial techniques will contribute to the advancement of mine detection and other application domains. This paper provides directions, evaluation and analysis on the progress of controlled biological and biomimetic systems for landmine detection. It introduces and discusses different approaches developed, underlining their relative advantages and limitations, and highlighting trends, safety and ecology concern, and possible future directions. PMID:17662594

  13. A Converter from the Systems Biology Markup Language to the Synthetic Biology Open Language.

    Science.gov (United States)

    Nguyen, Tramy; Roehner, Nicholas; Zundel, Zach; Myers, Chris J

    2016-06-17

    Standards are important to synthetic biology because they enable exchange and reproducibility of genetic designs. This paper describes a procedure for converting between two standards: the Systems Biology Markup Language (SBML) and the Synthetic Biology Open Language (SBOL). SBML is a standard for behavioral models of biological systems at the molecular level. SBOL describes structural and basic qualitative behavioral aspects of a biological design. Converting SBML to SBOL enables a consistent connection between behavioral and structural information for a biological design. The conversion process described in this paper leverages Systems Biology Ontology (SBO) annotations to enable inference of a designs qualitative function. PMID:26696234

  14. Computer structures perspective on switching dynamics of simple biological systems

    OpenAIRE

    Moškon, Miha

    2012-01-01

    Synthetic biology is a rapidly evolving discipline that copes with the modifications of existent and with the construction of new biological systems with novel functionalities. Its interdisciplinarity arises from combining of engineering and biological sciences. Biological computing is a relatively new research field that is analyzing the possibilities of constructing a biological computer. Synthetic biology approaches can also be used in order to build biological computer. Certain levels of ...

  15. Graphical Modelling in Genetics and Systems Biology

    OpenAIRE

    Scutari, Marco

    2012-01-01

    Graphical modelling has a long history in statistics as a tool for the analysis of multivariate data, starting from Wright's path analysis and Gibbs' applications to statistical physics at the beginning of the last century. In its modern form, it was pioneered by Lauritzen and Wermuth and Pearl in the 1980s, and has since found applications in fields as diverse as bioinformatics, customer satisfaction surveys and weather forecasts. Genetics and systems biology are unique among these fields in...

  16. Systems Biology from a Yeast Omics Perspective

    OpenAIRE

    Snyder, Michael; Gallagher, Jennifer E.G.

    2009-01-01

    Systems biology represents a paradigm shift from the study of individual genes, proteins or other components to that of the analysis of entire pathways, cellular, developmental, or organismal processes. Large scale studies, primarily initiated in S. cerevisiae, have allowed the identification and characterization of components on an unprecedented level. Large scale interaction, transcription factor binding and phosphorylation data have enabled the elucidation of global regulatory networks. Th...

  17. Phylogenetic and biological species diversity within the Neurospora tetrasperma complex

    NARCIS (Netherlands)

    Menkis, A.; Bastiaans, E.; Jacobson, D.J.; Johannesson, H.

    2009-01-01

    The objective of this study was to explore the evolutionary history of the morphologically recognized filamentous ascomycete Neurospora tetrasperma, and to reveal the genetic and reproductive relationships among its individuals and populations. We applied both phylogenetic and biological species rec

  18. Systems biology of cancer biomarker detection.

    Science.gov (United States)

    Mitra, Sanga; Das, Smarajit; Chakrabarti, Jayprokas

    2013-01-01

    Cancer systems-biology is an ever-growing area of research due to explosion of data; how to mine these data and extract useful information is the problem. To have an insight on carcinogenesis one need to systematically mine several resources, such as databases, microarray and next-generation sequences. This review encompasses management and analysis of cancer data, databases construction and data deposition, whole transcriptome and genome comparison, analysing results from high throughput experiments to uncover cellular pathways and molecular interactions, and the design of effective algorithms to identify potential biomarkers. Recent technical advances such as ChIP-on-chip, ChIP-seq and RNA-seq can be applied to get epigenetic information transformed into a high-throughput endeavour to which systems biology and bioinformatics are making significant inroads. The data from ENCODE and GENCODE projects available through UCSC genome browser can be considered as benchmark for comparison and meta-analysis. A pipeline for integrating next generation sequencing data, microarray data, and putting them together with the existing database is discussed. The understanding of cancer genomics is changing the way we approach cancer diagnosis and treatment. To give a better understanding of utilizing available resources' we have chosen oral cancer to show how and what kind of analysis can be done. This review is a computational genomic primer that provides a bird's eye view of computational and bioinformatics' tools currently available to perform integrated genomic and system biology analyses of several carcinoma.

  19. Biological activities of selected peptides: skin penetration ability of copper complexes with peptides.

    Science.gov (United States)

    Mazurowska, Lena; Mojski, Miroslaw

    2008-01-01

    This study concerning the permeability through skin barriers of copper complexes with peptides is an important part of the research on their biological activity. The transport of copper complexes through the skin is essential in treatment of dermatological dysfunctions connected to the deficiency of these elements in the skin. During the last several years, a special interest in transepidermal copper delivery has been observed. This is the reason why copper compounds have been used as active compounds in care cosmetics. Yet, the transport process of copper complexes with tripeptides, glycyl-histidyl-lysine GHK, or gamma-glutamyl-cysteinyl-glycine GSH through the stratum corneum has received very little attention in the literature so far. The penetration ability of GHK-Cu and GSH-Cu through the stratum corneum and the influence of the complexes with tripeptide on the copper ion transport process is the key factor in their cosmetic and pharmaceutical activity. The in vitro penetration process was studied in the model system, a Franz diffusion cell with a liposome membrane, where liquid crystalline systems of physicochemical properties similar to the ones of the intercellular cement of stratum corneum were used as a standard model of a skin barrier. The results obtained demonstrated that copper complexes permeate through the membranes modeling the horny lipid layer and showed the influence of peptides on the dynamics of copper ion diffusion. PMID:18350235

  20. 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.

  1. An Intuitive Automated Modelling Interface for Systems Biology

    Directory of Open Access Journals (Sweden)

    Ozan Kahramanoğulları

    2009-11-01

    Full Text Available We introduce a natural language interface for building stochastic pi calculus models of biological systems. In this language, complex constructs describing biochemical events are built from basic primitives of association, dissociation and transformation. This language thus allows us to model biochemical systems modularly by describing their dynamics in a narrative-style language, while making amendments, refinements and extensions on the models easy. We demonstrate the language on a model of Fc-gamma receptor phosphorylation during phagocytosis. We provide a tool implementation of the translation into a stochastic pi calculus language, Microsoft Research's SPiM.

  2. 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

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

    International Nuclear Information System (INIS)

    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 PrPC. 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 PrPC 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.

  4. Developing mononuclear copper-active-oxygen complexes relevant to reactive intermediates of biological oxidation reactions.

    Science.gov (United States)

    Itoh, Shinobu

    2015-07-21

    Active-oxygen species generated on a copper complex play vital roles in several biological and chemical oxidation reactions. Recent attention has been focused on the reactive intermediates generated at the mononuclear copper active sites of copper monooxygenases such as dopamine β-monooxygenase (DβM), tyramine β-monooxygenase (TβM), peptidylglycine-α-hydroxylating monooxygenase (PHM), and polysaccharide monooxygenases (PMO). In a simple model system, reaction of O2 and a reduced copper(I) complex affords a mononuclear copper(II)-superoxide complex or a copper(III)-peroxide complex, and subsequent H(•) or e(-)/H(+) transfer, which gives a copper(II)-hydroperoxide complex. A more reactive species such as a copper(II)-oxyl radical type species could be generated via O-O bond cleavage of the peroxide complex. However, little had been explored about the chemical properties and reactivity of the mononuclear copper-active-oxygen complexes due to the lack of appropriate model compounds. Thus, a great deal of effort has recently been made to develop efficient ligands that can stabilize such reactive active-oxygen complexes in synthetic modeling studies. In this Account, I describe our recent achievements of the development of a mononuclear copper(II)-(end-on)superoxide complex using a simple tridentate ligand consisting of an eight-membered cyclic diamine with a pyridylethyl donor group. The superoxide complex exhibits a similar structure (four-coordinate tetrahedral geometry) and reactivity (aliphatic hydroxylation) to those of a proposed reactive intermediate of copper monooxygenases. Systematic studies based on the crystal structures of copper(I) and copper(II) complexes of the related tridentate supporting ligands have indicated that the rigid eight-membered cyclic diamine framework is crucial for controlling the geometry and the redox potential, which are prerequisites for the generation of such a unique mononuclear copper(II)-(end-on)superoxide complex

  5. 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.

  6. 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 ...

  7. 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.

  8. 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. PMID:25845304

  9. 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.

  10. 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

  11. 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.

  12. A Free Energy Principle for Biological Systems

    Directory of Open Access Journals (Sweden)

    Friston Karl

    2012-10-01

    Full Text Available This paper describes a free energy principle that tries to explain the ability of biological systems to resist a natural tendency to disorder. It appeals to circular causality of the sort found in synergetic formulations of self-organization (e.g., the slaving principle and models of coupled dynamical systems, using nonlinear Fokker Planck equations. Here, circular causality is induced by separating the states of a random dynamical system into external and internal states, where external states are subject to random fluctuations and internal states are not. This reduces the problem to finding some (deterministic dynamics of the internal states that ensure the system visits a limited number of external states; in other words, the measure of its (random attracting set, or the Shannon entropy of the external states is small. We motivate a solution using a principle of least action based on variational free energy (from statistical physics and establish the conditions under which it is formally equivalent to the information bottleneck method. This approach has proved useful in understanding the functional architecture of the brain. The generality of variational free energy minimisation and corresponding information theoretic formulations may speak to interesting applications beyond the neurosciences; e.g., in molecular or evolutionary biology.

  13. Synchronization and emergence in complex systems

    Indian Academy of Sciences (India)

    Fatihcan M Atay

    2011-11-01

    We show how novel behaviour can emerge in complex systems at the global level through synchronization of the activities of their constituent units. Two mechanisms are suggested for the emergence, namely non-diffusive coupling and time delays. In this way, simple units can synchronize to display complex dynamics, or conversely, simple dynamics may arise from complex constituents.

  14. Chaotic systems in complex phase space

    CERN Document Server

    Bender, Carl M; Hook, Daniel W; Weir, David J

    2008-01-01

    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 behaviors of these two PT-symmetric dynamical models in complex phase space exhibit strong qualitative similarities.

  15. COMPLEX COMPOST AND DETOXICATION OF AGROLANDSCAPE SYSTEMS

    Directory of Open Access Journals (Sweden)

    Belyuchenko I. S.

    2014-03-01

    Full Text Available Toxicity complex compost arises during compiling of organomineral mixtures of various waste of life, agriculture and mineral industries. One of detoxification factors of complex compost is the ability of heavy metal cations to the formation insoluble compounds, which are fixed by clay materials and different disperse systems, and differ markedly by calcium content, acidity and humus soil-absorbing complex

  16. Many-Body Theory for Multi-Agent Complex Systems

    OpenAIRE

    Johnson, Neil F.; Smith, David M. D.; Hui, Pak Ming

    2005-01-01

    Multi-agent complex systems comprising populations of decision-making particles, have wide application across the biological, informational and social sciences. We uncover a formal analogy between these systems' time-averaged dynamics and conventional many-body theory in Physics. Their behavior is dominated by the formation of 'Crowd-Anticrowd' quasiparticles. For the specific example of the Minority Game, our formalism yields analytic expressions which are in excellent agreement with numeric...

  17. Large-scale Complex IT Systems

    CERN Document Server

    Sommerville, Ian; 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 challenges and issues in the development of large-scale complex, software-intensive systems. Central to this is the notion that we cannot separate software from the socio-technical environment in which it is used.

  18. The Feasibility of Systems Thinking in Biology Education

    Science.gov (United States)

    Boersma, Kerst; Waarlo, Arend Jan; Klaassen, Kees

    2011-01-01

    Systems thinking in biology education is an up and coming research topic, as yet with contrasting feasibility claims. In biology education systems thinking can be understood as thinking backward and forward between concrete biological objects and processes and systems models representing systems theoretical characteristics. Some studies claim that…

  19. 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…

  20. Entity grammar systems: a grammatical tool for studying the hierarchical structures of biological systems.

    Science.gov (United States)

    Wang, Yun

    2004-05-01

    The hierarchical structures of biological systems are the typical complex hierarchical dynamical structures in the physical world, the effective investigations on which could not be performed with the existing formal grammar systems. To meet the needs of the investigation on these kinds of systems, especially the emerging field of system biology, a grammatical tool was proposed in the present article. Because the grammatical tool mainly deals with the systems composed of structured entities, they are called entity grammar systems (EGSs). The structure of entities in EGSs have the general form of the objects in the physical world, which means EGSs could be used as a tool to study the complex system composed of many objects with different structures, just like the biological systems. The article contains the formal definition of EGSs and the hierarchy of EGSs, which is congruent with the Chomsky hierarchy. The relationship between EGSs and array grammar systems, graph grammar systems, tree grammar systems, multi-set grammar systems are discussed to show the generative power of EGSs. At the end of the present article, the steps to define new grammar systems with the form of EGS are provided and the possible applicable fields of EGSs are discussed. PMID:15006443

  1. Mueller matrix polarimetry for the characterization of complex random medium like biological tissues

    Indian Academy of Sciences (India)

    Nirmalya Ghosh; Jalpa Soni; M F G Wood; M A Wallenberg; I A Vitkin

    2010-12-01

    The polarization parameters of light scattered from biological tissues contain wealth of morphological and functional information of potential biomedical importance. But, in optically thick turbid media such as tissues, numerous complexities due to multiple scattering and simultaneous occurrences of many polarization events present formidable challenges, in terms of both accurate measurement and unique interpretation of the individual polarimetry characteristics. We have developed and validated an expanded Mueller matrix decomposition approach to overcome this problem. The approach was validated theoretically with a polarization-sensitive Monte Carlo light propagation model and experimentally by recording Mueller matrices from tissue-like complex random medium. In this paper, we discuss our comprehensive turbid polarimetry platform consisting of the experimental polarimetry system, forward Monte Carlo modelling and inverse polar decomposition analysis. Initial biomedical applications of this novel general method for polarimetry analysis in random media are also presented.

  2. Predictive Approaches to Control of Complex Systems

    CERN Document Server

    Karer, Gorazd

    2013-01-01

    A predictive control algorithm uses a model of the controlled system to predict the system behavior for various input scenarios and determines the most appropriate inputs accordingly. Predictive controllers are suitable for a wide range of systems; therefore, their advantages are especially evident when dealing with relatively complex systems, such as nonlinear, constrained, hybrid, multivariate systems etc. However, designing a predictive control strategy for a complex system is generally a difficult task, because all relevant dynamical phenomena have to be considered. Establishing a suitable model of the system is an essential part of predictive control design. Classic modeling and identification approaches based on linear-systems theory are generally inappropriate for complex systems; hence, models that are able to appropriately consider complex dynamical properties have to be employed in a predictive control algorithm. This book first introduces some modeling frameworks, which can encompass the most frequ...

  3. Experimental and Theoretical Studies on Biologically Active Lanthanide (III) Complexes

    Science.gov (United States)

    Kostova, I.; Trendafilova, N.; Georgieva, I.; Rastogi, V. K.; Kiefer, W.

    2008-11-01

    The complexation ability and the binding mode of the ligand coumarin-3-carboxylic acid (HCCA) to La(III), Ce(III), Nd(III), Sm(III), Gd(III) and Dy(III) lanthanide ions (Ln(III)) are elucidated at experimental and theoretical level. The complexes were characterized using elemental analysis, DTA and TGA data as well as 1H NMR and 13C NMR spectra. FTIR and Raman spectroscopic techniques as well as DFT quantum chemical calculations were used for characterization of the binding mode and the structures of lanthanide(III) complexes of HCCA. The metal—ligand binding mode is predicted through molecular modeling and energy estimation of different Ln—CCA structures using B3LYP/6-31G(d) method combined with a large quasi-relativistic effective core potential for lanthanide ion. The energies obtained predict bidentate coordination of CCA- to Ln(III) ions through the carbonylic oxygen and the carboxylic oxygen. Detailed vibrational analysis of HCCA, CCA- and Ln(III) complexes based on both calculated and experimental frequencies confirms the suggested metal—ligand binding mode. The natural bonding analysis predicts strongly ionic character of the Ln(III)-CCA bonding in the- complexes studied. With the relatively resistant tumor cell line K-562 we obtained very interesting in-vitro results which are in accordance with our previously published data concerning the activity of lanthanide(III) complexes with other coumarin derivatives.

  4. Human Metabolic Network: Reconstruction, Simulation, and Applications in Systems Biology

    Science.gov (United States)

    Wu, Ming; Chan, Christina

    2012-01-01

    Metabolism is crucial to cell growth and proliferation. Deficiency or alterations in metabolic functions are known to be involved in many human diseases. Therefore, understanding the human metabolic system is important for the study and treatment of complex diseases. Current reconstructions of the global human metabolic network provide a computational platform to integrate genome-scale information on metabolism. The platform enables a systematic study of the regulation and is applicable to a wide variety of cases, wherein one could rely on in silico perturbations to predict novel targets, interpret systemic effects, and identify alterations in the metabolic states to better understand the genotype-phenotype relationships. In this review, we describe the reconstruction of the human metabolic network, introduce the constraint based modeling approach to analyze metabolic networks, and discuss systems biology applications to study human physiology and pathology. We highlight the challenges and opportunities in network reconstruction and systems modeling of the human metabolic system. PMID:24957377

  5. 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

  6. Dielectric relaxation in biological systems physical principles, methods, and applications

    CERN Document Server

    Feldman, Yuri

    2015-01-01

    This title covers the theoretical basis and practical aspects of the study of dielectric properties of biological systems, such as water, electrolyte and polyelectrolytes, solutions of biological macromolecules, cells suspensions and cellular systems.

  7. 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.; Putten, van der W.H.; Ruiter, de P.C.; Struik, P.C.; Thomma, B.

    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 agricultura

  8. Model checking biological systems described using ambient calculus

    DEFF Research Database (Denmark)

    Mardare, Radu Iulian; Priami, Corrado; Qualia, Paola;

    2005-01-01

    Model checking biological systems described using ambient calculus. In Proc. of the second International Workshop on Computational Methods in Systems Biology (CMSB04), Lecture Notes in Bioinformatics 3082:85-103, Springer, 2005....

  9. Biological Properties Of Benzopyran-Based Platinum (Ii Complexes

    Directory of Open Access Journals (Sweden)

    Malinowska Katarzyna

    2014-04-01

    Full Text Available The aim of the study was to analyze the physicochemical synthesized complex 3 [(1,3- thiazol -2- ylimino methyl]-4H- chromene -4 -one with tetrachloroplatinate(II dipotassium and determination peroxidase activity and glutathione (GPX in red blood cells of cancer patients and healthy subjects. Materials and methods. Tests were carried out with the approval of the Bioethics Committee No. RNN/260/08/KB. Blood was collected into tubes with anticoagulant (heparin lithium. Determination of glutathione peroxidase activity was performed by methods of Little and O’Brien in 20 person groups hospitalized at the Department of General and Colorectal Surgery Veterans General Hospital in Łódź. Results. The study was an increase of activity in the control without the compound and after the introduction of the complex relative to the treatment groups. In healthy subjects, without the use of glutathione peroxidase complex averaged 73.25 ± 23.88 U / g Hb after application of the compound corresponds to the reference group 81.01 ± 25.94 U / g Hb. In contrast, in patients without the use of the complex activity amounted to 42.85 ± 27.49 U / g Hb. In the study group, which uses synthesized complex GPX activity corresponds to 67.72 ± 13.44 U / g Hb. Conclusions. The obtained results underline that the introduction of significant blood antioxidant complex research has a significant impact on the results of the determinations. Statistically significant (p < 0.05 difference occurred in both test and no relation to the administration of the complex in relation to the control of 1. 2.

  10. Self-Organization of Complex Systems

    OpenAIRE

    Paczuski, Maya; Bak, Per

    1999-01-01

    The basic laws of physics are simple, so why is the world complex? The theory of self-organized criticality posits that complex behavior in nature emerges from the dynamics of extended, dissipative systems that evolve through a sequence of meta-stable states into a critical state, with long range spatial and temporal correlations. Minor disturbances lead to intermittent events of all sizes. These events organize the system into a complex state that cannot be reduced to a few degrees of freedo...

  11. Lateral diffusion of lipids in complex biological membranes.

    OpenAIRE

    O'Leary, T. J.

    1987-01-01

    Lateral diffusion of lipids in biological membranes may be influenced by polypeptides, proteins, and other nonlipid membrane constituents. Using concepts from scaled-particle theory, we extend the free-volume model for lipid diffusion to membranes having an arbitrarily large number of components. This theory clarifies the interpretation of the free-volume theory, better reproduces the free-area dependence of lipid lateral diffusion rates, and quantitatively predicts the experimental observati...

  12. About Evaluation of Complex Dynamical Systems

    OpenAIRE

    Dmytro Polishchuk; Olexandr Polishchuk

    2016-01-01

    The methods are proposed for evaluation of complex dynamical systems, choice of their optimal operating modes, determination of optimal operating system from given class of equivalent systems, system's timeline behaviour analysis on the basis of versatile multicriteria and multilevel analysis of behaviour of system's elements.

  13. Integrative systems biology approaches in asthma pharmacogenomics

    OpenAIRE

    Dahlin, Amber; Tantisira, Kelan G.

    2012-01-01

    In order to improve therapeutic outcomes, there is a tremendous need to identify patients who are likely to respond to a given asthma treatment. Pharmacogenomic studies have explained a portion of the variability in drug response and provided an increasing list of candidate genes and SNPs. However, as phenotypic variation arises from a network of complex interactions among genetic and environmental factors, rather than individual genes or SNPs, a multidisciplinary, systems-level approach is r...

  14. Complex Evaluation of Hierarchically-Network Systems

    CERN Document Server

    Polishchuk, Dmytro; Yadzhak, Mykhailo

    2016-01-01

    Methods of complex evaluation based on local, forecasting, aggregated, and interactive evaluation of the state, function quality, and interaction of complex system's objects on the all hierarchical levels is proposed. Examples of analysis of the structural elements of railway transport system are used for illustration of efficiency of proposed approach.

  15. 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 scales

  16. Conceptual Modelling of Complex Production Systems

    OpenAIRE

    Nenad Perši

    2008-01-01

    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 level...

  17. A Statistical Physics Characterization of the Complex Systems Dynamics: Quantifying Complexity from Spatio-Temporal Interactions

    Science.gov (United States)

    Koorehdavoudi, Hana; Bogdan, Paul

    2016-06-01

    Biological systems are frequently categorized as complex systems due to their capabilities of generating spatio-temporal structures from apparent random decisions. In spite of research on analyzing biological systems, we lack a quantifiable framework for measuring their complexity. To fill this gap, in this paper, we develop a new paradigm to study a collective group of N agents moving and interacting in a three-dimensional space. Our paradigm helps to identify the spatio-temporal states of the motion of the group and their associated transition probabilities. This framework enables the estimation of the free energy landscape corresponding to the identified states. Based on the energy landscape, we quantify missing information, emergence, self-organization and complexity for a collective motion. We show that the collective motion of the group of agents evolves to reach the most probable state with relatively lowest energy level and lowest missing information compared to other possible states. Our analysis demonstrates that the natural group of animals exhibit a higher degree of emergence, self-organization and complexity over time. Consequently, this algorithm can be integrated into new frameworks to engineer collective motions to achieve certain degrees of emergence, self-organization and complexity.

  18. A Statistical Physics Characterization of the Complex Systems Dynamics: Quantifying Complexity from Spatio-Temporal Interactions.

    Science.gov (United States)

    Koorehdavoudi, Hana; Bogdan, Paul

    2016-01-01

    Biological systems are frequently categorized as complex systems due to their capabilities of generating spatio-temporal structures from apparent random decisions. In spite of research on analyzing biological systems, we lack a quantifiable framework for measuring their complexity. To fill this gap, in this paper, we develop a new paradigm to study a collective group of N agents moving and interacting in a three-dimensional space. Our paradigm helps to identify the spatio-temporal states of the motion of the group and their associated transition probabilities. This framework enables the estimation of the free energy landscape corresponding to the identified states. Based on the energy landscape, we quantify missing information, emergence, self-organization and complexity for a collective motion. We show that the collective motion of the group of agents evolves to reach the most probable state with relatively lowest energy level and lowest missing information compared to other possible states. Our analysis demonstrates that the natural group of animals exhibit a higher degree of emergence, self-organization and complexity over time. Consequently, this algorithm can be integrated into new frameworks to engineer collective motions to achieve certain degrees of emergence, self-organization and complexity. PMID:27297496

  19. 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.

  20. An Integrated Biological Control System At Hanford

    International Nuclear Information System (INIS)

    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.

  1. Effect of solar activity on the physiological rhythms of biological systems

    International Nuclear Information System (INIS)

    The infradian components, including those with a period of about 3.5, 7, 30 days, are ubiquitously found in biology, from unicells to complex biological organisms. It can be hypothesized that heliogeophysical factors other than the solar visible light, likely at the origin of the circadian system (with a period of about 27 hours), may be responsible for the infradian biosystems. 37 refs

  2. Geometric triangular chiral hexagon crystal-like complexes organization in pathological tissues biological collision order.

    Directory of Open Access Journals (Sweden)

    Jairo A Díaz

    Full Text Available The present study describes and documents self-assembly of geometric triangular chiral hexagon crystal like complex organizations (GTCHC in human pathological tissues. The authors have found this architectural geometric expression at macroscopic and microscopic levels mainly in cancer processes. This study is based essentially on macroscopic and histopathologic analyses of 3000 surgical specimens: 2600 inflammatory lesions and 400 malignant tumours. Geometric complexes identified photographically at macroscopic level were located in the gross surgical specimen, and these areas were carefully dissected. Samples were taken to carry out histologic analysis. Based on the hypothesis of a collision genesis mechanism and because it is difficult to carry out an appropriate methodological observation in biological systems, the authors designed a model base on other dynamic systems to obtain indirect information in which a strong white flash wave light discharge, generated by an electronic device, hits over the lines of electrical conductance structured in helicoidal pattern. In their experimental model, the authors were able to reproduce and to predict polarity, chirality, helicoid geometry, triangular and hexagonal clusters through electromagnetic sequential collisions. They determined that similar events among constituents of extracelular matrix which drive and produce piezoelectric activity are responsible for the genesis of GTCHC complexes in pathological tissues. This research suggests that molecular crystals represented by triangular chiral hexagons derived from a collision-attraction event against collagen type I fibrils emerge at microscopic and macroscopic scales presenting a lateral assembly of each side of hypertrophy helicoid fibers, that represent energy flow in cooperative hierarchically chiral electromagnetic interaction in pathological tissues and arises as a geometry of the equilibrium in perturbed biological systems. Further

  3. Non-Equilibrium Quantum Entanglement in Biological Systems

    Institute of Scientific and Technical Information of China (English)

    LI Hong-Rong; ZHANG Pei; GAO Hong; BI Wen-Ting; ALAMRI M. D.; LI Fu-Li

    2012-01-01

    A non-equilibrium model of a classically driven quantum harmonic oscillator is proposed to explain persistent quantum entanglement in biological systems at ambient temperature. The conditions for periodic entanglement generation are derived. Our results support the evidence that biological systems may have quantum entanglement at biological temperatures.%A non-equilibrium model of a classically driven quantum harmonic oscillator is proposed to explain persistent quantum entanglement in biological systems at ambient temperature.The conditions for periodic entanglement generation are derived.Our results support the evidence that biological systems may have quantum entanglement at biological temperatures.

  4. The Ontologies of Complexity and Learning about Complex Systems

    Science.gov (United States)

    Jacobson, Michael J.; Kapur, Manu; So, Hyo-Jeong; Lee, June

    2011-01-01

    This paper discusses a study of students learning core conceptual perspectives from recent scientific research on complexity using a hypermedia learning environment in which different types of scaffolding were provided. Three comparison groups used a hypermedia system with agent-based models and scaffolds for problem-based learning activities that…

  5. Autocatalysis as the Natural Philosophy Underlying Complexity and Biological Evolution

    Directory of Open Access Journals (Sweden)

    Güngör Gündüz

    2011-06-01

    Full Text Available The importance and different aspects of autocatalysis in evolution was analyzed. The behaviour of autocatalytic reactions mainly the Lotka-Volterra and the Schlögl equations were discussed in terms of phase change, entropy, and their oscillation frequency. The increase of complexity as the general direction of evolution was examined on some patterns in terms of both their entropy and information content. In addition, the relation between stability and functionality, stability and cohesion were discussed. It was concluded that evolution drifts in the direction of increasing complexity as a kind of natural philosophy to counteract the increase of entropy in the universe.

  6. 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.

  7. Are Biological Systems Poised at Criticality?

    Science.gov (United States)

    Mora, Thierry; Bialek, William

    2011-07-01

    Many of life's most fascinating phenomena emerge from interactions among many elements—many amino acids determine the structure of a single protein, many genes determine the fate of a cell, many neurons are involved in shaping our thoughts and memories. Physicists have long hoped that these collective behaviors could be described using the ideas and methods of statistical mechanics. In the past few years, new, larger scale experiments have made it possible to construct statistical mechanics models of biological systems directly from real data. We review the surprising successes of this "inverse" approach, using examples from families of proteins, networks of neurons, and flocks of birds. Remarkably, in all these cases the models that emerge from the data are poised near a very special point in their parameter space—a critical point. This suggests there may be some deeper theoretical principle behind the behavior of these diverse systems.

  8. 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...

  9. 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 ...

  10. Strategies for structuring interdisciplinary education in Systems Biology

    DEFF Research Database (Denmark)

    Cvijovic, Marija; Höfer, Thomas; Aćimović, Jure;

    2016-01-01

    Systems Biology is an approach to biology and medicine that has the potential to lead to a better understanding of how biological properties emerge from the interaction of genes, proteins, molecules, cells and organisms. The approach aims at elucidating how these interactions govern biological fu...

  11. North Mississippi Refuges Complex Biological Program 'Pulse-Check' Review - DRAFT REPORT

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Biological review for the three refuges of the North Mississippi Refuges Complex is presented. Review is based on an assessment of addressing goals and objectives...

  12. New neutral and lipophilic technetium complexes based on a cytectrene moiety. Synthesis, characterization and biological evaluation

    Energy Technology Data Exchange (ETDEWEB)

    El Aissi, Radhia [National Centre of Sciences and Nuclear Technology, Sidi Thabet (Tunisia). Radiopharmaceutical Unit; CNRS, Laboratoire de Synthese et Physico-Chimie de Molecules d' Interet Biologique, SPCMIB, UMR 5068, Toulouse (France); Toulouse Univ., UPS, Laboratoire de Synthese et Physico-Chimie de Molecules d' Interet Biologique, SPCMIB, UMR 5068, Toulouse (France); Malek-Saied, Nadia; Saidi, Mouldi [National Centre of Sciences and Nuclear Technology, Sidi Thabet (Tunisia). Radiopharmaceutical Unit; Mallet-Ladeira, Sonia [Toulouse Univ., UPS et CNRS, FR2599 (France). Inst. de Chimie de Toulouse; Coulais, Yvon [Toulouse Univ. (France). Lab. ' ' Traceurs et traitement de l' image' ' ; Benoist, Eric [CNRS, Laboratoire de Synthese et Physico-Chimie de Molecules d' Interet Biologique, SPCMIB, UMR 5068, Toulouse (France); Toulouse Univ., UPS, Laboratoire de Synthese et Physico-Chimie de Molecules d' Interet Biologique, SPCMIB, UMR 5068, Toulouse (France)

    2015-05-01

    The synthesis, characterization and biological evaluation of five neutral and lipophilic {sup 99m}Tc-complexes, so-called cytectrenes, obtained from N-substitutedferrocenecarboxamide derivatives are reported. N-substituted ferrocenecarboxamide starting materials were obtained in two steps, with good yield and were fully characterized by classical spectroscopic methods including X-ray diffraction analysis for one of them. Using a microwave strategy for the {sup 99m}Tc-radiolabelling step, each cytectrene were obtained quickly (radiolabelling time < 5 min), from modest to good yield. The {sup 99m}Tc-complexes, characterized by HPLC comparison with cold rhenium complex analogues, are stable, neutral and lipophilic (logP{sub o/w} ranged between 1.8 and 2.9). Unfortunately, despite such suitable features, in vivo studies of two of them gave poor results, in terms of brain uptake. Both radiocompounds exhibited the maximum brain accumulation of 0.31% ID/g and 0.26% ID/g at 5 min post-injection, respectively, followed by a very fast washout from the brain (0.06% ID/g and 0.07% ID/g at 30 min post-injection, respectively). Although our ligand systems exhibited high stability against exchange reactions with blood proteins, the high radioactivity level in stomach, increasing with time, suggests in vivo decomposition of our complex to pertechnetate.

  13. Models of complex attitude systems

    DEFF Research Database (Denmark)

    Sørensen, Bjarne Taulo

    production systems was modelled. The analysis was based on data from a cross-cultural survey involving 1931 participants from Belgium, Denmark, Germany and Poland. The survey questionnaire contained measures of personal value orientations and attitudes towards environment and nature, industrial food...... search algorithms and structural equation models. The results suggest that evaluative judgments of the importance of production system attributes are generated in a schematic manner, driven by personal value orientations. The effect of personal value orientations was strong and largely unmediated......, 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...

  14. A systems biology approach for the study of smoking and myocardial infarction

    OpenAIRE

    Xu, Tao

    2015-01-01

    Metabolomics has been proven to be a powerful tool to study complex phenotypes. It can present a snapshot of the current status of metabolism and provide a functional readout of the gene products. Complementing with other ‘omics’ techniques in systems biology studies, the integration of metabolomics with other ‘omics’, e.g. trancriptomics and epigenomics, will help to illustrate complex biological processes which are related to disease and environmental exposure. This thesis presents three...

  15. Multiway modeling and analysis in stem cell systems biology

    Directory of Open Access Journals (Sweden)

    Vandenberg Scott L

    2008-07-01

    Full Text Available Abstract Background Systems biology refers to multidisciplinary approaches designed to uncover emergent properties of biological systems. Stem cells are an attractive target for this analysis, due to their broad therapeutic potential. A central theme of systems biology is the use of computational modeling to reconstruct complex systems from a wealth of reductionist, molecular data (e.g., gene/protein expression, signal transduction activity, metabolic activity, etc.. A number of deterministic, probabilistic, and statistical learning models are used to understand sophisticated cellular behaviors such as protein expression during cellular differentiation and the activity of signaling networks. However, many of these models are bimodal i.e., they only consider row-column relationships. In contrast, multiway modeling techniques (also known as tensor models can analyze multimodal data, which capture much more information about complex behaviors such as cell differentiation. In particular, tensors can be very powerful tools for modeling the dynamic activity of biological networks over time. Here, we review the application of systems biology to stem cells and illustrate application of tensor analysis to model collagen-induced osteogenic differentiation of human mesenchymal stem cells. Results We applied Tucker1, Tucker3, and Parallel Factor Analysis (PARAFAC models to identify protein/gene expression patterns during extracellular matrix-induced osteogenic differentiation of human mesenchymal stem cells. In one case, we organized our data into a tensor of type protein/gene locus link × gene ontology category × osteogenic stimulant, and found that our cells expressed two distinct, stimulus-dependent sets of functionally related genes as they underwent osteogenic differentiation. In a second case, we organized DNA microarray data in a three-way tensor of gene IDs × osteogenic stimulus × replicates, and found that application of tensile strain to a

  16. Temperature-dependent phase transitions in zeptoliter volumes of a complex biological membrane

    Energy Technology Data Exchange (ETDEWEB)

    Nikiforov, Maxim P; Jesse, Stephen; Kalinin, Sergei V [Center for Nanophase Materials Sciences, Oak Ridge National Laboratory, Oak Ridge, TN 37831 (United States); Hohlbauch, Sophia; Proksch, Roger [Asylum Research, Santa Barbara, CA 93117 (United States); King, William P [Department of Mechanical Science and Engineering, University of Illinois Urbana-Champaign, Urbana, IL 61801 (United States); Voitchovsky, Kislon [Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139 (United States); Contera, Sonia Antoranz [Department of Physics, University of Oxford, Parks Road, Oxford OX1 3PU, Oxford (United Kingdom)

    2011-02-04

    Phase transitions in purple membrane have been a topic of debate for the past two decades. In this work we present studies of a reversible transition of purple membrane in the 50-60 deg. C range in zeptoliter volumes under different heating regimes (global heating and local heating). The temperature of the reversible phase transition is 52 {+-} 5 deg. C for both local and global heating, supporting the hypothesis that this transition is mainly due to a structural rearrangement of bR molecules and trimers. To achieve high resolution measurements of temperature-dependent phase transitions, a new scanning probe microscopy-based method was developed. We believe that our new technique can be extended to other biological systems and can contribute to the understanding of inhomogeneous phase transitions in complex systems.

  17. Temperature-dependent phase transitions of a complex biological membrane in zeptoliter volumes

    Energy Technology Data Exchange (ETDEWEB)

    Nikiforov, Maxim [ORNL; Hohlbauch, Sophia [Asylum Research, Santa Barbara, CA; King, William P [University of Illinois, Urbana-Champaign; Voitchovsky, K [Massachusetts Institute of Technology (MIT); Contera, S Antoranz [University of Oxford; Jesse, Stephen [ORNL; Kalinin, Sergei V [ORNL; Proksch, Roger [Asylum Research, Santa Barbara, CA

    2011-01-01

    Phase transitions in purple membrane have been a topic of debate for the past two decades. In this work we present studies of a reversible transition of purple membrane in the 50 60 C range in zeptoliter volumes under different heating regimes (global heating and local heating). The temperature of the reversible phase transition is 52 5 C for both local and global heating, supporting the hypothesis that this transition is mainly due to a structural rearrangement of bR molecules and trimers. To achieve high resolution measurements of temperature-dependent phase transitions, a new scanning probe microscopy-based method was developed. We believe that our new technique can be extended to other biological systems and can contribute to the understanding of inhomogeneous phase transitions in complex systems.

  18. 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 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.

  19. New water-soluble ruthenium(II) cytotoxic complex: biological activity and cellular distribution.

    Science.gov (United States)

    Morais, Tânia S; Santos, Filipa C; Jorge, Tiago F; Côrte-Real, Leonor; Madeira, Paulo J Amorim; Marques, Fernanda; Robalo, M Paula; Matos, António; Santos, Isabel; Garcia, M Helena

    2014-01-01

    A novel water soluble organometallic compound, [RuCp(mTPPMSNa)(2,2'-bipy)][CF3SO3] (TM85, where Cp=η(5)-cyclopentadienyl, mTPPMS=diphenylphosphane-benzene-3-sulfonate and 2,2'-bipy=2,2'-bipyridine) is presented herein. Studies of interactions with relevant proteins were performed to understand the behavior and mode of action of this complex in the biological environment. Electrochemical and fluorescence studies showed that TM85 strongly binds to albumin. Studies carried out to study the formation of TM85 which adducts with ubiquitin and cytochrome c were performed by electrospray ionization mass spectrometry (ESI-MS). Antitumor activity was evaluated against a variety of human cancer cell lines, namely A2780, A2780cisR, MCF7, MDAMB231, HT29, PC3 and V79 non-tumorigenic cells and compared with the reference drug cisplatin. TM85 cytotoxic effect was reduced in the presence of endocytosis modulators at low temperatures, suggesting an energy-dependent mechanism consistent with endocytosis. Ultrastructural analysis by transmission electron microscopy (TEM) revealed that TM85 targets the endomembranar system disrupting the Golgi and also affects the mitochondria. Disruption of plasma membrane observed by flow cytometry could lead to cellular damage and cell death. On the whole, the biological activity evaluated herein combined with the water solubility property suggests that complex TM85 could be a promising anticancer agent. PMID:24145065

  20. 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.

  1. 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.

  2. Detection of timescales in evolving complex systems

    CERN Document Server

    Darst, Richard K; Arenas, Alex; Gómez, Sergio; Saramäki, Jari; Fortunato, Santo

    2016-01-01

    Most complex systems are intrinsically dynamic in nature. The evolution of a dynamic complex system is typically represented as a sequence of snapshots, where each snapshot describes the configuration of the system at a particular instant of time. Then, one may directly follow how the snapshots evolve in time, or aggregate the snapshots within some time intervals to form representative "slices" of the evolution of the system configuration. This is often done with constant intervals, whose duration is based on arguments on the nature of the system and of its dynamics. A more refined approach would be to consider the rate of activity in the system to perform a separation of timescales. However, an even better alternative would be to define dynamic intervals that match the evolution of the system's configuration. To this end, we propose a method that aims at detecting evolutionary changes in the configuration of a complex system, and generates intervals accordingly. We show that evolutionary timescales can be id...

  3. Life Is Simple-Biologic Complexity Is an Epiphenomenon.

    Science.gov (United States)

    Torday, John S

    2016-01-01

    Life originated from unicellular organisms by circumventing the Second Law of Thermodynamics using the First Principles of Physiology, namely negentropy, chemiosmosis and homeostatic regulation of calcium and lipids. It is hypothesized that multicellular organisms are merely contrivances or tools, used by unicellular organisms as agents for the acquisition of epigenetic inheritance. The First Principles of Physiology, which initially evolved in unicellular organisms are the exapted constraints that maintain, sustain and perpetuate that process. To ensure fidelity to this mechanism, we must return to the first principles of the unicellular state as the determinants of the primary level of selection pressure during the life cycle. The power of this approach is reflected by examples of its predictive value. This perspective on life is a "game changer", mechanistically rendering transparent many dogmas, teleologies and tautologies that constrain the current descriptive view of Biology. PMID:27128951

  4. Life Is Simple—Biologic Complexity Is an Epiphenomenon

    Directory of Open Access Journals (Sweden)

    John S. Torday

    2016-04-01

    Full Text Available Life originated from unicellular organisms by circumventing the Second Law of Thermodynamics using the First Principles of Physiology, namely negentropy, chemiosmosis and homeostatic regulation of calcium and lipids. It is hypothesized that multicellular organisms are merely contrivances or tools, used by unicellular organisms as agents for the acquisition of epigenetic inheritance. The First Principles of Physiology, which initially evolved in unicellular organisms are the exapted constraints that maintain, sustain and perpetuate that process. To ensure fidelity to this mechanism, we must return to the first principles of the unicellular state as the determinants of the primary level of selection pressure during the life cycle. The power of this approach is reflected by examples of its predictive value. This perspective on life is a “game changer”, mechanistically rendering transparent many dogmas, teleologies and tautologies that constrain the current descriptive view of Biology.

  5. Life Is Simple—Biologic Complexity Is an Epiphenomenon

    Science.gov (United States)

    Torday, John S.

    2016-01-01

    Life originated from unicellular organisms by circumventing the Second Law of Thermodynamics using the First Principles of Physiology, namely negentropy, chemiosmosis and homeostatic regulation of calcium and lipids. It is hypothesized that multicellular organisms are merely contrivances or tools, used by unicellular organisms as agents for the acquisition of epigenetic inheritance. The First Principles of Physiology, which initially evolved in unicellular organisms are the exapted constraints that maintain, sustain and perpetuate that process. To ensure fidelity to this mechanism, we must return to the first principles of the unicellular state as the determinants of the primary level of selection pressure during the life cycle. The power of this approach is reflected by examples of its predictive value. This perspective on life is a “game changer”, mechanistically rendering transparent many dogmas, teleologies and tautologies that constrain the current descriptive view of Biology. PMID:27128951

  6. 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.

  7. Systems pharmacology of complex diseases

    OpenAIRE

    Hansen, Jens; Zhao, Shan; Iyengar, Ravi

    2011-01-01

    Systems pharmacology approaches can be used to identify and predict drug-induced adverse events. Disease-centered networks within the human interactome allow us to predict which drugs may produce a similar pathophysiology. Such predictions can be tested in animal models.

  8. Coordinated aggregation in complex systems:. an interdisciplinary approach

    Science.gov (United States)

    Basios, V.; Nicolis, S. C.; Deneubourg, J. L.

    2016-09-01

    The study of the topic of guided aggregation in biology brings together decision making, collective motion and the dynamical interplay between individuals and groups. At the same time it meets statistical mechanics and the physics of complex systems in a new paradigmatic thinking. We propose a research platform for implementation and for undertaking systematic studies of coordinated aggregation, in a truly multi- and inter-disciplinary fashion.

  9. 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.

  10. Chaotic systems in complex phase space

    Indian Academy of Sciences (India)

    Carl M Bender; Joshua Feinberg; Daniel W Hook; David J Weir

    2009-09-01

    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 $\\mathcal{PT}$ -symmetric dynamical models in complex phase space exhibit strong qualitative similarities.

  11. 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.

  12. Decoherence and Spin Echo in Biological Systems

    CERN Document Server

    Nesterov, Alexander I

    2015-01-01

    The spin echo approach is extended to include bio-complexes for which the interaction with dynamical noise is strong. Significant restoration of the free induction decay signal due to homogeneous (decoherence) and inhomogeneous (dephasing) broadening is demonstrated analytically and numerically, for both an individual dimer of interacting chlorophylls and for an ensemble of dimers. This approach is based on an exact and closed system of ordinary differential equations that can be easily solved for a wide range of parameters that are relevant for bio-applications.

  13. Quantum integrable systems. Quantitative methods in biology

    CERN Document Server

    Feverati, Giovanni

    2011-01-01

    Quantum integrable systems have very strong mathematical properties that allow an exact description of their energetic spectrum. From the Bethe equations, I formulate the Baxter "T-Q" relation, that is the starting point of two complementary approaches based on nonlinear integral equations. The first one is known as thermodynamic Bethe ansatz, the second one as Kl\\"umper-Batchelor-Pearce-Destri- de Vega. I show the steps toward the derivation of the equations for some of the models concerned. I study the infrared and ultraviolet limits and discuss the numerical approach. Higher rank integrals of motion can be obtained, so gaining some control on the eigenvectors. After, I discuss the Hubbard model in relation to the N = 4 supersymmetric gauge theory. The Hubbard model describes hopping electrons on a lattice. In the second part, I present an evolutionary model based on Turing machines. The goal is to describe aspects of the real biological evolution, or Darwinism, by letting evolve populations of algorithms. ...

  14. The start of systems biology in Ukraine

    Directory of Open Access Journals (Sweden)

    Obolenskaya M. Yu.

    2014-01-01

    Full Text Available The first laboratory of Systems Biology in Ukraine (IMBIG NASU represents a track record of its scientific results. They include the pioneered development of a web-based tool for genome-wide surveys of eukaryotic promoters for the presence of transcription factors binding sites (COTRASIF; the deciphered mechanisms of the fine-tuned and balanced response of primary hepatocytes to interferon alpha levels recorded after partial hepatectomy; the elaboration of a novel method of gene regulatory network inference compatible with GRID environment and the development of a stoichiometric model of folate-related one carbon unit metabolism in human placenta and its application for the characteristics of the system’s behavior as a whole at different human pathologies.

  15. 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...... that were in concordance with their effects in experimental animals. In project II, I profiled the effects on rat liver gene expression levels following exposure to a 14-chemical mixture ± the presence of an endocrine disrupting chemical. This project helped us shed light on the mechanism of action...... of the 14-chemical mixture and the endocrine disrupting chemical. In project III, I modeled a predictive signature for an in vivo endpoint that is sensitive to endocrine disruption. I used publicly available data generated for the purpose of modeling predictive signatures for various in vivo endpoints. From...

  16. Nutritional Systems Biology: Definitions and Approaches

    DEFF Research Database (Denmark)

    Panagiotou, Gianni; Nielsen, Jens

    2009-01-01

    Nutrigenetics and nutrigenomics are nascent areas that are evolving quickly and riding on the wave of “personalized medicine” that is providing opportunities in the discovery and development of nutraceutical compounds. The human genome sequence and sequences of model organisms provide...... will benefit most from, or be placed at risk by, intervention strategies. More accurate assessment of the inputs to human health and the consequences of those inputs measured as accurate transcriptomic, proteomic, and metabolomic analyses would bring personalized health/diet to practice far faster than would...... 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...

  17. 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 ...

  18. 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

  19. On the Calculation of System Entropy in Nonlinear Stochastic Biological Networks

    Directory of Open Access Journals (Sweden)

    Bor-Sen Chen

    2015-10-01

    Full Text Available Biological networks are open systems that can utilize nutrients and energy from their environment for use in their metabolic processes, and produce metabolic products. System entropy is defined as the difference between input and output signal entropy, i.e., the net signal entropy of the biological system. System entropy is an important indicator for living or non-living biological systems, as biological systems can maintain or decrease their system entropy. In this study, system entropy is determined for the first time for stochastic biological networks, and a computation method is proposed to measure the system entropy of nonlinear stochastic biological networks that are subject to intrinsic random fluctuations and environmental disturbances. We find that intrinsic random fluctuations could increase the system entropy, and that the system entropy is inversely proportional to the robustness and stability of the biological networks. It is also determined that adding feedback loops to shift all eigenvalues to the farther left-hand plane of the complex s-domain could decrease the system entropy of a biological network.

  20. Microbial systems biology: New frontiers open to predictive microbiology

    NARCIS (Netherlands)

    S. Brul; F.I.C. Mensonides; K.J. Hellingwerf; M.J. Teixeira De Mattos

    2008-01-01

    The field of Systems Biology is a rapidly evolving area of research. It follows on from the previous experimental and theoretical ‘omics’ revolution in biology. Now that we have through the use of these tools many ‘indices’ of biological systems available the next step is to actually start composing

  1. Complexity of Multi-Modal Transportation and Systems of Systems

    OpenAIRE

    Karcanias, N.; Hessami, A. G.; Alonso, E

    2015-01-01

    The multi-modal transportation comprising diverse infrastructures, means & operations, energy resources, rules & regulations and a broad community of stakeholders constitute a complex yet real candidate for formalisation, analysis and optimization. It is shown that the complexity of the system is best described by viewing the challenges of its complexity as a System of Systems (SoS). The objective of this paper is to make an attempt to define and formalise the loose concept of “System of Syst...

  2. Active impedance matching of complex structural systems

    Science.gov (United States)

    Macmartin, Douglas G.; Miller, David W.; Hall, Steven R.

    1991-01-01

    Viewgraphs on active impedance matching of complex structural systems are presented. Topics covered include: traveling wave model; dereverberated mobility model; computation of dereverberated mobility; control problem: optimal impedance matching; H2 optimal solution; statistical energy analysis (SEA) solution; experimental transfer functions; interferometer actuator and sensor locations; active strut configurations; power dual variables; dereverberation of complex structure; dereverberated transfer function; compensators; and relative power flow.

  3. Thermodynamic modeling of complex systems

    DEFF Research Database (Denmark)

    Liang, Xiaodong

    Offshore reservoirs represent one of the major growth areas of the oil and gas industry, and environmental safety is one of the biggest challenges for the offshore exploration and production. The oil accidents in the Gulf of Mexico in 1979 and 2010 were two of the biggest disasters in history...... 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...

  4. Expert systems guide biological phosphorus removal

    Energy Technology Data Exchange (ETDEWEB)

    Krichten, D.J.; Wilson, K.D.; Tracy, K.D. (Air Products and Chemicals, Inc., Allentown, PA (United States))

    1991-10-01

    There is a large body of knowledge regarding optimum control strategies for new secondary wastewater treatment technology using an anaerobic selector to provide biological phosphorus removal. However, because the selector technology is new and the concepts differ somewhat from those used in conventional activated sludge wastewater treatment, a method of communicating this knowledge to plant operators is needed. Traditional methods such as classroom training and operating manuals are of limited effectiveness. The commonplace availability and low cost of the personal computer (PC) makes it practical to use a computer program to communicate the type of information required to control a wastewater treatment plant. Knowledge-based systems technology, commonly referred to as expert systems (ES) technology, is easy to use, provides useful information regarding a consistent control strategy, relieves the anxiety associated with learning a new process,' and provides instruction for inexperienced personnel. ES technology does not require special formatted input and is therefore easily accessible. All information required by the program is readily available through routine laboratory analysis, common plant instrumentation, or direct user observation. The program was designed for all levels of computer users and will run on all IBM-compatible or Apple MacIntosh systems.

  5. 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

  6. Network, degeneracy and bow tie. Integrating paradigms and architectures to grasp the complexity of the immune system

    OpenAIRE

    Tieri Paolo; Grignolio Andrea; Zaikin Alexey; Mishto Michele; Remondini Daniel; Castellani Gastone C; Franceschi Claudio

    2010-01-01

    Abstract Recently, the network paradigm, an application of graph theory to biology, has proven to be a powerful approach to gaining insights into biological complexity, and has catalyzed the advancement of systems biology. In this perspective and focusing on the immune system, we propose here a more comprehensive view to go beyond the concept of network. We start from the concept of degeneracy, one of the most prominent characteristic of biological complexity, defined as the ability of struct...

  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. 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.

  9. Increase of Organization in Complex Systems

    CERN Document Server

    Georgiev, Georgi Yordanov; 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 - the central processing unit (CPU) of computers. The quantity of organization for several generations of CPUs shows a double exponential rate of change of organization with time. The exact functional dependence has a fine, S-shaped structure, revealing some of the mechanisms of self-organization. The principle of least action helps to explain the mechanism of increase of organization through quantity accumulation and constraint and curvature minimization with an attractor, the least average sum of actions of all elements ...

  10. (R)evolution of complex regulatory systems

    DEFF Research Database (Denmark)

    Linding, Rune

    2010-01-01

    Signaling systems are exciting to study precisely because they are some of the most complex and dynamical systems that we know. The cell needs operational freedom and, thus, many motif-domain interactions might not be "hard-wired" through evolution, but instead may be like the Linux operating sys...... system, where symbolic links can point to files without duplication....

  11. Is the Lean Organisation a Complex System?

    OpenAIRE

    Masai, Pierre; Parrend, Pierre; Toussaint, Nicolas; Collet, Pierre

    2015-01-01

    International audience; 3 Toyota Motor Europe, Bruxelles, Belgium 4 Complex System Digital Campus (UNESCO Unitwin) http://unitwin-cs.org/ Abstract The Lean Organisation enjoys a tremendous success. It was first developed within Toyota Motor Corporation in the Automotive Industry, but was then adopted by many organisations in all fields of human activities. A deeper observation of this success displays behaviours of complex systems: a high number of agents interact ...

  12. 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...

  13. The retail market as a complex system

    OpenAIRE

    Pennacchioli, Diego; Coscia, Michele; Rinzivillo, Salvatore; Giannotti, Fosca; Pedreschi, Dino

    2014-01-01

    Aim of this paper is to introduce the complex system perspective into retail market analysis. Currently, to understand the retail market means to search for local patterns at the micro level, involving the segmentation, separation and profiling of diverse groups of consumers. In other contexts, however, markets are modelled as complex systems. Such strategy is able to uncover emerging regularities and patterns that make markets more predictable, e.g. enabling to predict how much a country's G...

  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. Influence of Complex Refractive Index on Diffuse Reflection of Biological Tissues

    Institute of Scientific and Technical Information of China (English)

    LAI Jian-Cheng; LI Zhen-Hua; HE An-Zhi

    2005-01-01

    @@ Complex refractive indices are introduced to solve various boundary questions at the interfaces when modelling light migration within heterogeneous tissues. Combined with the complex refractive index, Fresnel's formulae are used to describe the reflection and transmission at the interfaces between two heterogeneous tissues layers.Using the Monte Carlo method, the influence of the complex refractive index on diffuse reflection of semi-infinite biological tissues is discussed. The results show that neglecting the imaginary part of the refractive index of tissues will bring a major deviation in the diffuse reflection of semi-infinite biological tissues when its emitting point is apart from the incident point.

  16. 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

  17. 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.

  18. Low angle neutron data acquisition system for molecular biology

    International Nuclear Information System (INIS)

    The low angle spectrometer system utilizing a 2-dimensional position sensitive counter was designed to accommodate a variety of experiments in molecular biology requiring good low angle resolution. Biological structures requiring low angle analysis techniques fall into two groups: non-ordered systems (proteins or protein complexes in solution) and ordered systems with large spacings like muscle, collagen, and membranes. For structural investigations into such systems, data are ideally needed to a low scattering angle of 0.20 at 4.5 A or a minimum Q of 0.005 A-1 (Q = theta . 2π/lambda). Depending on the type of structure, data often extend to the high angle region, say 300. Apart from the low angle requirements, the spectrometer has to have good resolution to resolve diffraction peaks from samples with crystal spacings up to 1000 A or even larger. While it is desirable to build a spectrometer to such scattering conditions, given reactor conditions might not permit this and compromises have to be made between flux, resolution and lowest angle. The low angle spectrometer described here was designed to be used at the HFBR neutron beam pipe working at approximately 4.2 A or at the H4 satellite station working at 2.4 A

  19. Synthesis, characterization and exploration of the catalytic, supramolecular and biological applications of dinuclear complexes

    OpenAIRE

    Johnpeter, Justin Paul Raj; Therrien, Bruno

    2014-01-01

    The work presented in this thesis involves the synthesis and characterization of dinuclear ruthenium, rhodium and iridium complexes. The catalytic, supramolecular and biological applications of these dinuclear complexes will be discussed. In the first part, the synthesis of sawhorse-type diruthenium tetracarbonyl complexes and their catalytic applications in the supercritical carbon dioxide (scCO2) are presented. Synthesis of sawhorse-type molecular tweezers derived from pyrenyl and porphyrin...

  20. 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

  1. Prions: Introducing a Complex Scientific Controversy to a Biology Classroom

    Science.gov (United States)

    Zaitsev, Igor V.

    2009-01-01

    Thomas Kuhn, in "The Structure of Scientific Revolutions," posited that science does not progress by the steady accumulation of knowledge, but rather by a system of competition among paradigms. They vie for supremacy through greater parsimony, explanatory power, and popularity among the community of scientists (Kuhn, 1962). The current…

  2. The system-biological GLOBE 3D Genome Platform. : A new holistic genome viewer for molecular genetics

    NARCIS (Netherlands)

    M. Lesnussa (Michael); F.N. Kepper (Nick); H.J.F.M.M. Eussen (Bert); T.A. Knoch (Tobias)

    2009-01-01

    textabstractGenomes are tremendous co-evolutionary holistic systems for molecular storage, processing and fabrication of information. Their system-biological complexity remains, however, still largely mysterious, despite immense sequencing achievements and huge advances in the understanding of the

  3. 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.

  4. 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.

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

    Science.gov (United States)

    Hussain, Dilshad; Najam-ul-Haq, Muhammad; Jabeen, Fahmida; Ashiq, Muhammad N; Athar, Muhammad; Rainer, Matthias; Huck, Christian W; Bonn, Guenther K

    2013-05-01

    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(3+) and La(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. PMID:23601977

  6. 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

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

    International Nuclear Information System (INIS)

    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 Fe3+ and La3+ 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

  8. Preparation and Biological Properties of Platinum(II Complex-Loaded Copolymer PLA-TPGS

    Directory of Open Access Journals (Sweden)

    Ha Phuong Thu

    2013-01-01

    Full Text Available A new nanodrug system containing bis(menthone thiosemicarbazonato Platinum(II complex (Pt-thiomen encapsulated with the block copolymers polylactide-d-α-tocopheryl polyethylene glycol 1000 succinate (PLA-TPGS was prepared by a modified solvent extraction/evaporation technique. The characteristics of the nanoparticles including surface morphology, size distribution, structure, and biological activities such as antimicrobial and cytotoxic activities were in vitro investigated. The spherical nanoparticles were around 50 nm in size with core-shell structure and narrow-size distribution. The encapsulated Pt-thiomen can avoid interaction with proteins in the blood plasma. The inhibitory activity of Pt-thiomen-loaded PLA-TPGS nanoparticles on the growth of some bacteria, fungi, and Hep-G2 cells suggests a possibility of developing PLA-TPGS-Pt-thiomen nanoparticles as one of the potential chemotherapeutic agents.

  9. Low Complex System for Levitating Ferromagnetic Materials

    Directory of Open Access Journals (Sweden)

    Dahiru Sani Shu'aibu

    2010-06-01

    Full Text Available This paper primarily presents detailed design and implementation of a low complex magnetic levitation system which can be used in laboratory for levitation experiments. The system transfer function was derived from the coenergy and the mathematical model of the state space representation was obtained. The mathematical model showed that, the system is highly non-linear and inherently unstable. Based on simulation, a low complex circuit was designed and implemented to stabilize the system, using MATLAB control tool-box. The developed controller was simple, cheap and effective, capable of controlling weights of different masses at various distances as compared to some controllers in literature.

  10. Systems Biology in Aging: Linking the Old and the Young

    OpenAIRE

    HOU, LEI; Huang, Jialiang; Green, Christopher D.; Boyd-Kirkup, Jerome; Zhang, Wei; Yu, Xiaoming; Gong, Wenxuan; Zhou, Bing; Jing-Dong J Han

    2012-01-01

    Aging can be defined as a process of progressive decline in the physiological capacity of an organism, manifested by accumulated alteration and destabilization at the whole system level. Systems biology approaches offer a promising new perspective to examine the old problem of aging. We begin this review by introducing the concepts of systems biology, and then illustrate the application of systems biology approaches to aging research, from gene expression profiling to network analysis. We the...

  11. 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.

  12. Biological correlates of complex posttraumatic stress disorder—state of research and future directions

    Directory of Open Access Journals (Sweden)

    Zoya Marinova

    2015-04-01

    Full Text Available Complex posttraumatic stress disorder (PTSD presents with clinical features of full or partial PTSD (re-experiencing a traumatic event, avoiding reminders of the event, and a state of hyperarousal together with symptoms from three additional clusters (problems in emotional regulation, negative self-concept, and problems in interpersonal relations. Complex PTSD is proposed as a new diagnostic entity in ICD-11 and typically occurs after prolonged and complex trauma. Here we shortly review current knowledge regarding the biological correlates of complex PTSD and compare it to the relevant findings in PTSD. Recent studies provide support to the validity of complex PTSD as a separate diagnostic entity; however, data regarding the biological basis of the disorder are still very limited at this time. Further studies focused on complex PTSD biological correlates and replication of the initial findings are needed, including neuroimaging, neurobiochemical, genetic, and epigenetic investigations. Identification of altered biological pathways in complex PTSD may be critical to further understand the pathophysiology and optimize treatment strategies.

  13. Tethering Complexes in the Arabidopsis Endomembrane System.

    Science.gov (United States)

    Vukašinović, Nemanja; Žárský, Viktor

    2016-01-01

    Targeting of endomembrane transport containers is of the utmost importance for proper land plant growth and development. Given the immobility of plant cells, localized membrane vesicle secretion and recycling are amongst the main processes guiding proper cell, tissue and whole plant morphogenesis. Cell wall biogenesis and modification are dependent on vectorial membrane traffic, not only during normal development, but also in stress responses and in plant defense against pathogens and/or symbiosis. It is surprising how little we know about these processes in plants, from small GTPase regulation to the tethering complexes that act as their effectors. Tethering factors are single proteins or protein complexes mediating first contact between the target membrane and arriving membrane vesicles. In this review we focus on the tethering complexes of the best-studied plant model-Arabidopsis thaliana. Genome-based predictions indicate the presence of all major tethering complexes in plants that are known from a hypothetical last eukaryotic common ancestor (LECA). The evolutionary multiplication of paralogs of plant tethering complex subunits has produced the massively expanded EXO70 family, indicating a subfunctionalization of the terminal exocytosis machinery in land plants. Interpretation of loss of function (LOF) mutant phenotypes has to consider that related, yet clearly functionally-specific complexes often share some common core subunits. It is therefore impossible to conclude with clarity which version of the complex is responsible for the phenotypic deviations observed. Experimental interest in the analysis of plant tethering complexes is growing and we hope to contribute with this review by attracting even more attention to this fascinating field of plant cell biology. PMID:27243010

  14. Tethering complexes in the Arabidopsis endomembrane system

    Directory of Open Access Journals (Sweden)

    Nemanja eVukasinovic

    2016-05-01

    Full Text Available AbstractTargeting of endomembrane transport containers is of the utmost importance for proper land plant growth and development. Given the immobility of plant cells, localized membrane vesicle secretion and recycling are amongst the main processes guiding proper cell, tissue and whole plant morphogenesis. Cell wall biogenesis and modification are dependent on vectorial membrane traffic, not only during normal development, but also in stress responses and in plant defence against pathogens and/or symbiosis. It is surprising how little we know about these processes in plants, from small GTPase regulation to the tethering complexes that act as their effectors. Tethering factors are single proteins or protein complexes mediating first contact between the target membrane and arriving membrane vesicles. In this review we focus on the tethering complexes of the best-studied plant model – Arabidopsis thaliana. Genome-based predictions indicate the presence of all major tethering complexes in plants that are known from a hypothetical last eukaryotic common ancestor (LECA. The evolutionary multiplication of paralogs of plant tethering complex subunits has produced the massively expanded EXO70 family, indicating a subfunctionalization of the terminal exocytosis machinery in land plants. Interpretation of loss of function (LOF mutant phenotypes has to consider that related, yet clearly functionally-specific complexes often share some common core subunits. It is therefore impossible to conclude with clarity which version of the complex is responsible for the phenotypic deviations observed. Experimental interest in the analysis of plant tethering complexes is growing and we hope to contribute with this review by attracting even more attention to this fascinating field of plant cell biology.

  15. 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.

  16. 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...

  17. Symptoms of complexity in a tourism system

    CERN Document Server

    Baggio, R

    2007-01-01

    Tourism destinations behave as dynamic evolving complex systems, encompassing numerous factors and activities which are interdependent and whose relationships might be highly nonlinear. Traditional research in this field has looked after a linear approach: variables and relationships are monitored in order to forecast future outcomes with simplified models and to derive implications for management organizations. The limitations of this approach have become apparent in many cases, and several authors claim for a new and different attitude. While complex systems ideas are amongst the most promising interdisciplinary research themes emerged in the last few decades, very little has been done so far in the field of tourism. This paper presents a brief overview of the complexity framework as a means to understand structures, characteristics, relationships and explores the implications and contributions of the complexity literature on tourism systems. The objective is to allow the reader to gain a deeper appreciatio...

  18. Eukaryotic Systems Broaden the Scope of Synthetic Biology

    OpenAIRE

    Haynes, Karmella A.; Silver, Pamela A.

    2009-01-01

    Synthetic biology aims to engineer novel cellular functions by assembling well-characterized molecular parts (i.e., nucleic acids and proteins) into biological “devices” that exhibit predictable behavior. Recently, efforts in eukaryotic synthetic biology have sprung from foundational work in bacteria. Designing synthetic circuits to operate reliably in the context of differentiating and morphologically complex cells presents unique challenges and opportunities for progress in the field. This ...

  19. 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

  20. Major Histocompatibility Complex (MHC Markers in Conservation Biology

    Directory of Open Access Journals (Sweden)

    Katherine Belov

    2011-08-01

    Full Text Available 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.

  1. 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...

  2. 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...

  3. 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...

  4. 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....

  5. 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.

  6. Gene gymnastics: Synthetic biology for baculovirus expression vector system engineering.

    Science.gov (United States)

    Vijayachandran, Lakshmi S; Thimiri Govinda Raj, Deepak B; Edelweiss, Evelina; Gupta, Kapil; Maier, Josef; Gordeliy, Valentin; Fitzgerald, Daniel J; Berger, Imre

    2013-01-01

    Most essential activities in eukaryotic cells are catalyzed by large multiprotein assemblies containing up to ten or more interlocking subunits. The vast majority of these protein complexes are not easily accessible for high resolution studies aimed at unlocking their mechanisms, due to their low cellular abundance and high heterogeneity. Recombinant overproduction can resolve this bottleneck and baculovirus expression vector systems (BEVS) have emerged as particularly powerful tools for the provision of eukaryotic multiprotein complexes in high quality and quantity. Recently, synthetic biology approaches have begun to make their mark in improving existing BEVS reagents by de novo design of streamlined transfer plasmids and by engineering the baculovirus genome. Here we present OmniBac, comprising new custom designed reagents that further facilitate the integration of heterologous genes into the baculovirus genome for multiprotein expression. Based on comparative genome analysis and data mining, we herein present a blueprint to custom design and engineer the entire baculovirus genome for optimized production properties using a bottom-up synthetic biology approach. PMID:23328086

  7. ENERGY FLOWS IN COMPLEX ECOLOGICAL SYSTEMS: A REVIEW

    Institute of Scientific and Technical Information of China (English)

    Jiang ZHANG

    2009-01-01

    Energy flow drives the complex systems to evolve. The allometric scaling as the universal energy flow pattern has been found in different scales of ecological systems. It reflects the general power law relationship between flow and store. The underlying mechanisms of energy flow patterns are explained as the branching transportation networks which can be regarded as the result of systematic optimization of a biological target under constraints. Energy flows in the ecological system may be modelled by the food web model and population dynamics on the network. This paper reviews the latest progress on the energy flow patterns, explanatory models for the allometric scaling and modelling approach of flow and network evolution dynamics in ecology. Furthermore, the possibility of generalizing these flow patterns, modelling approaches to other complex systems is discussed.

  8. Ecological complexity in a coffee agroecosystem: spatial heterogeneity, population persistence and biological control.

    Directory of Open Access Journals (Sweden)

    Heidi Liere

    Full Text Available BACKGROUND: Spatial heterogeneity is essential for the persistence of many inherently unstable systems such as predator-prey and parasitoid-host interactions. Since biological interactions themselves can create heterogeneity in space, the heterogeneity necessary for the persistence of an unstable system could be the result of local interactions involving elements of the unstable system itself. METHODOLOGY/PRINCIPAL FINDINGS: Here we report on a predatory ladybird beetle whose natural history suggests that the beetle requires the patchy distribution of the mutualism between its prey, the green coffee scale, and the arboreal ant, Azteca instabilis. Based on known ecological interactions and the natural history of the system, we constructed a spatially-explicit model and showed that the clustered spatial pattern of ant nests facilitates the persistence of the beetle populations. Furthermore, we show that the dynamics of the beetle consuming the scale insects can cause the clustered distribution of the mutualistic ants in the first place. CONCLUSIONS/SIGNIFICANCE: From a theoretical point of view, our model represents a novel situation in which a predator indirectly causes a spatial pattern of an organism other than its prey, and in doing so facilitates its own persistence. From a practical point of view, it is noteworthy that one of the elements in the system is a persistent pest of coffee, an important world commodity. This pest, we argue, is kept within limits of control through a complex web of ecological interactions that involves the emergent spatial pattern.

  9. 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.

  10. GNU MCSim : bayesian statistical inference for SBML-coded systems biology models

    OpenAIRE

    Bois, Frédéric Y.

    2009-01-01

    International audience Statistical inference about the parameter values of complex models, such as the ones routinely developed in systems biology, is efficiently performed through Bayesian numerical techniques. In that framework, prior information and multiple levels of uncertainty can be seamlessly integrated. GNU MCSim was precisely developed to achieve those aims, in a general non-linear differential context. Starting with version 5.3.0, GNU MCSim reads in and simulates Systems Biology...

  11. Exploring Synthetic and Systems Biology at the University of Edinburgh.

    Science.gov (United States)

    Fletcher, Liz; Rosser, Susan; Elfick, Alistair

    2016-06-15

    The Centre for Synthetic and Systems Biology ('SynthSys') was originally established in 2007 as the Centre for Integrative Systems Biology, funded by the Biotechnology and Biological Sciences Research Council (BBSRC) and the Engineering and Physical Sciences Research Council (EPSRC). Today, SynthSys embraces an extensive multidisciplinary community of more than 200 researchers from across the University with a common interest in synthetic and systems biology. Our research is broad and deep, addressing a diversity of scientific questions, with wide ranging impact. We bring together the power of synthetic biology and systems approaches to focus on three core thematic areas: industrial biotechnology, agriculture and the environment, and medicine and healthcare. In October 2015, we opened a newly refurbished building as a physical hub for our new U.K. Centre for Mammalian Synthetic Biology funded by the BBSRC/EPSRC/MRC as part of the U.K. Research Councils' Synthetic Biology for Growth programme.

  12. 3D-dynamic visualization of complex molecular cell biology processes : 1-year university students' understanding of visualizations of signal transduction

    OpenAIRE

    Jacobsson, Johan Lars Henrik

    2008-01-01

    This study deals with the use of 3D-dynamic visualizations for teaching complex molecular cell biology concepts. The focus is on signal transduction, which is a concept that constitutes an important part of biological systems. 3D-dynamic visualizations (animations) were produced and shown for a total of 24 students attending a course in molecular cell biology at Karlstad University, Sweden. Data were collected by questionnaires and interviews which were structured around the understandability...

  13. 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

    which for example occur in photosynthesis, cellular respiration, DNA repair, and possibly magnetic field sensing. Quantum biology uses computation to model biological interactions in light of quantum mechanical effects and has primarily developed over the past decade as a result of convergence between...

  14. Phase transitions in fluids and biological systems

    Science.gov (United States)

    Sipos, Maksim

    In this thesis, I consider systems from two seemingly different fields: fluid dynamics and microbial ecology. In these systems, the unifying features are the existences of global non-equilibrium steady states. I consider generic and statistical models for transitions between these global states, and I relate the model results with experimental data. A theme of this thesis is that these rather simple, minimal models are able to capture a lot of functional detail about complex dynamical systems. In Part I, I consider the transition between laminar and turbulent flow. I find that quantitative and qualitative features of pipe flow experiments, the superexponential lifetime and the splitting of turbulent puffs, and the growth rate of turbulent slugs, can all be explained by a coarse-grained, phenomenological model in the directed percolation universality class. To relate this critical phenomena approach closer to the fluid dynamics, I consider the transition to turbulence in the Burgers equation, a simplified model for Navier-Stokes equations. Via a transformation to a model of directed polymers in a random medium, I find that the transition to Burgers turbulence may also be in the directed percolation universality class. This evidence implies that the turbulent-to-laminar transition is statistical in nature and does not depend on details of the Navier-Stokes equations describing the fluid flow. In Part II, I consider the disparate subject of microbial ecology where the complex interactions within microbial ecosystems produce observable patterns in microbe abundance, diversity and genotype. In order to be able to study these patterns, I develop a bioinformatics pipeline to multiply align and quickly cluster large microbial metagenomics datasets. I also develop a novel metric that quantifies the degree of interactions underlying the assembly of a microbial ecosystem, particularly the transition between neutral (random) and niche (deterministic) assembly. I apply this

  15. 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...

  16. 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.

  17. Are large complex economic systems unstable ?

    CERN Document Server

    Sinha, Sitabhra

    2010-01-01

    Although classical economic theory is based on the concept of stable equilibrium, real economic systems appear to be always out of equilibrium. Indeed, they share many of the dynamical features of other complex systems, e.g., ecological food-webs. We focus on the relation between increasing complexity of the economic network and its stability with respect to small perturbations in the dynamical variables associated with the constituent nodes. Inherent delays and multiple time-scales suggest that economic systems will be more likely to exhibit instabilities as their complexity is increased even though the speed at which transactions are conducted has increased many-fold through technological developments. Analogous to the birth of nonlinear dynamics from Poincare's work on the question of whether the solar system is stable, we suggest that similar theoretical developments may arise from efforts by econophysicists to understand the mechanisms by which instabilities arise in the economy.

  18. Vacuum Ultraviolet Photoionization of Complex Chemical Systems

    Science.gov (United States)

    Kostko, Oleg; Bandyopadhyay, Biswajit; Ahmed, Musahid

    2016-05-01

    Tunable vacuum ultraviolet (VUV) radiation coupled to mass spectrometry is applied to the study of complex chemical systems. The identification of novel reactive intermediates and radicals is revealed in flame, pulsed photolysis, and pyrolysis reactors, leading to the elucidation of spectroscopy, reaction mechanisms, and kinetics. Mass-resolved threshold photoelectron photoion coincidence measurements provide unprecedented access to vibrationally resolved spectra of free radicals present in high-temperature reactors. Photoionization measurements in water clusters, nucleic acid base dimers, and their complexes with water provide signatures of proton transfer in hydrogen-bonded and π-stacked systems. Experimental and theoretical methods to track ion-molecule reactions and fragmentation pathways in intermolecular and intramolecular hydrogen-bonded systems in sugars and alcohols are described. Photoionization of laser-ablated molecules, clusters, and their reaction products inform thermodynamics and spectroscopy that are relevant to astrochemistry and catalysis. New directions in coupling VUV radiation to interrogate complex chemical systems are discussed.

  19. 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

  20. Process Simulation of Complex Biological Pathways in Physical Reactive Space and Reformulated for Massively Parallel Computing Platforms.

    Science.gov (United States)

    Ganesan, Narayan; Li, Jie; Sharma, Vishakha; Jiang, Hanyu; Compagnoni, Adriana

    2016-01-01

    Biological systems encompass complexity that far surpasses many artificial systems. Modeling and simulation of large and complex biochemical pathways is a computationally intensive challenge. Traditional tools, such as ordinary differential equations, partial differential equations, stochastic master equations, and Gillespie type methods, are all limited either by their modeling fidelity or computational efficiency or both. In this work, we present a scalable computational framework based on modeling biochemical reactions in explicit 3D space, that is suitable for studying the behavior of large and complex biological pathways. The framework is designed to exploit parallelism and scalability offered by commodity massively parallel processors such as the graphics processing units (GPUs) and other parallel computing platforms. The reaction modeling in 3D space is aimed at enhancing the realism of the model compared to traditional modeling tools and framework. We introduce the Parallel Select algorithm that is key to breaking the sequential bottleneck limiting the performance of most other tools designed to study biochemical interactions. The algorithm is designed to be computationally tractable, handle hundreds of interacting chemical species and millions of independent agents by considering all-particle interactions within the system. We also present an implementation of the framework on the popular graphics processing units and apply it to the simulation study of JAK-STAT Signal Transduction Pathway. The computational framework will offer a deeper insight into various biological processes within the cell and help us observe key events as they unfold in space and time. This will advance the current state-of-the-art in simulation study of large scale biological systems and also enable the realistic simulation study of macro-biological cultures, where inter-cellular interactions are prevalent.

  1. Commentary: Systems Biology and Its Relevance to Alcohol Research

    OpenAIRE

    Guo, Q. Max; Zakhari, Sam

    2008-01-01

    Systems biology, a new scientific discipline, aims to study the behavior of a biological organization or process in order to understand the function of a dynamic system. This commentary will put into perspective topics discussed in this issue of Alcohol Research & Health, provide insight into why alcohol-induced disorders exemplify the kinds of conditions for which a systems biological approach would be fruitful, and discuss the opportunities and challenges facing alcohol researchers.

  2. 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...

  3. Influence of low intensity laser radiation on different biological systems

    OpenAIRE

    Tsivunchyk, Olga S.

    2004-01-01

    Abstract There are a lot of examples and contradictory results concerning influence of low intensity laser irradiation (LILI) on biological objects. In this work with a number of experiments the influence of LILI on different biological systems was investigated. For the carried out experiments the following biological objects and systems were used: * different enzymes of anti-oxidant system of animals (i.e. catalase, superoxide-di...

  4. Advanced Systems Biology Methods in Drug Discovery and Translational Biomedicine

    OpenAIRE

    Jun Zou; Ming-Wu Zheng; Gen Li; Zhi-Guang Su

    2013-01-01

    Systems biology is in an exponential development stage in recent years and has been widely utilized in biomedicine to better understand the molecular basis of human disease and the mechanism of drug action. Here, we discuss the fundamental concept of systems biology and its two computational methods that have been commonly used, that is, network analysis and dynamical modeling. The applications of systems biology in elucidating human disease are highlighted, consisting of human disease networ...

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

    Energy Technology Data Exchange (ETDEWEB)

    Manno, D; Filippo, E; Fiore, R; Serra, A [Dipartimento di Scienza dei Materiali, Universita del Salento, Lecce (Italy); Urso, E; Rizzello, A; Maffia, M [Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, Universita del Salento, Lecce (Italy)

    2010-04-23

    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{sup 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{sup 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.

  6. Particlelike wave packets in complex scattering systems

    Science.gov (United States)

    Gérardin, Benoît; Laurent, Jérôme; Ambichl, Philipp; Prada, Claire; Rotter, Stefan; Aubry, Alexandre

    2016-07-01

    A wave packet undergoes a strong spatial and temporal dispersion while propagating through a complex medium. This wave scattering is often seen as a nightmare in wave physics whether it be for focusing, imaging, or communication purposes. Controlling wave propagation through complex systems is thus of fundamental interest in many areas, ranging from optics or acoustics to medical imaging or telecommunications. Here, we study the propagation of elastic waves in a cavity and a disordered waveguide by means of laser interferometry. From the direct experimental access to the time-delay matrix of these systems, we demonstrate the existence of particlelike wave packets that remain focused in time and space throughout their complex trajectory. Due to their limited dispersion, their selective excitation will be crucially relevant for all applications involving selective wave focusing and efficient information transfer through complex media.

  7. Self-organization in complex systems as decision making

    CERN Document Server

    Yukalov, V I

    2014-01-01

    The idea is advanced that self-organization in complex systems can be treated as decision making (as it is performed by humans) and, vice versa, decision making is nothing but a kind of self-organization in the decision maker nervous systems. A mathematical formulation is suggested based on the definition of probabilities of system states, whose particular cases characterize the probabilities of structures, patterns, scenarios, or prospects. In this general framework, it is shown that the mathematical structures of self-organization and of decision making are identical. This makes it clear how self-organization can be seen as an endogenous decision making process and, reciprocally, decision making occurs via an endogenous self-organization. The approach is illustrated by phase transitions in large statistical systems, crossovers in small statistical systems, evolutions and revolutions in social and biological systems, structural self-organization in dynamical systems, and by the probabilistic formulation of c...

  8. Ecological Systems as Complex Systems: Challenges for an Emerging Science

    Directory of Open Access Journals (Sweden)

    Lael Parrott

    2010-03-01

    Full Text Available Complex systems science has contributed to our understanding of ecology in important areas such as food webs, patch dynamics and population fluctuations. This has been achieved through the use of simple measures that can capture the difference between order and disorder and simple models with local interactions that can generate surprising behaviour at larger scales. However, close examination reveals that commonly applied definitions of complexity fail to accommodate some key features of ecological systems, a fact that will limit the contribution of complex systems science to ecology. We highlight these features of ecological complexity—such as diversity, cross-scale interactions, memory and environmental variability—that continue to challenge classical complex systems science. Further advances in these areas will be necessary before complex systems science can be widely applied to understand the dynamics of ecological systems.

  9. 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.

  10. On Phenomenology of Complex Scientific Systems

    CERN Document Server

    Shiltsev, Vladimir

    2011-01-01

    Performance evolution of a number of complex scientific and technical systems demonstrate exponential progress with time exp(+t/C) . The speed of progress C - a measure of difficulty and complexity - is analyzed for high energy elementary particle colliders, astrophysical searches for galaxies and exoplanets, protein structure determination and compared with computers and thermonuclear fusion reactors. An explanation of the characteristic exponential progress is offered.

  11. 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

  12. MEMBRANE COMPUTING AS THE PARADIGM FOR MODELING SYSTEMS BIOLOGY

    Directory of Open Access Journals (Sweden)

    Ravie Chandren Muniyandi

    2013-01-01

    Full Text Available Membrane computing is a field in computer science that is inspired from the structure and the processes of living cells and is being considered as an alternative in solving the limitations in conventional mathematical approaches by taking into consideration its essential features that are of interest for research in systems biology. Advancements in computability make it feasible to handle huge volumes of data in biology and propose a new and better approach using a discreet computer science model, such as membrane computing. In this respect, membrane-computing abilities, to enhance the understanding of the system level of biological systems, have been explored. This study discusses experiences in applying membrane computing in modeling biological systems as well as possibilities of incorporating membrane computing into other computer science paradigms to enhance the use of membrane computing in systems biology. Experiences in modeling aspects of systems biology with membrane computing demonstrate additional advantages and possibilities compared with conventional methods. However, they are not yet used widely to model or simulate biological processes or systems. A general framework of modeling and verifying biological systems using membrane computing is essential as a guideline for biologists in their research in systems biology.

  13. 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...

  14. TissueCypher™: A systems biology approach to anatomic pathology

    Directory of Open Access Journals (Sweden)

    Jeffrey W Prichard

    2015-01-01

    Full Text Available Background: Current histologic methods for diagnosis are limited by intra- and inter-observer variability. Immunohistochemistry (IHC methods are frequently used to assess biomarkers to aid diagnoses, however, IHC staining is variable and nonlinear and the manual interpretation is subjective. Furthermore, the biomarkers assessed clinically are typically biomarkers of epithelial cell processes. Tumors and premalignant tissues are not composed only of epithelial cells but are interacting systems of multiple cell types, including various stromal cell types that are involved in cancer development. The complex network of the tissue system highlights the need for a systems biology approach to anatomic pathology, in which quantification of system processes is combined with informatics tools to produce actionable scores to aid clinical decision-making. Aims: Here, we describe a quantitative, multiplexed biomarker imaging approach termed TissueCypher™ that applies systems biology to anatomic pathology. Applications of TissueCypher™ in understanding the tissue system of Barrett's esophagus (BE and the potential use as an adjunctive tool in the diagnosis of BE are described. Patients and Methods: The TissueCypher™ Image Analysis Platform was used to assess 14 epithelial and stromal biomarkers with known diagnostic significance in BE in a set of BE biopsies with nondysplastic BE with reactive atypia (RA, n = 22 and Barrett's with high-grade dysplasia (HGD, n = 17. Biomarker and morphology features were extracted and evaluated in the confirmed BE HGD cases versus the nondysplastic BE cases with RA. Results: Multiple image analysis features derived from epithelial and stromal biomarkers, including immune biomarkers and morphology, showed significant differences between HGD and RA. Conclusions: The assessment of epithelial cell abnormalities combined with an assessment of cellular changes in the lamina propria may serve as an adjunct to conventional

  15. 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.

  16. Evolution of complexity in RNA-like replicator systems

    Directory of Open Access Journals (Sweden)

    Hogeweg Paulien

    2008-03-01

    Full Text Available Abstract Background The evolution of complexity is among the most important questions in biology. The evolution of complexity is often observed as the increase of genetic information or that of the organizational complexity of a system. It is well recognized that the formation of biological organization – be it of molecules or ecosystems – is ultimately instructed by the genetic information, whereas it is also true that the genetic information is functional only in the context of the organization. Therefore, to obtain a more complete picture of the evolution of complexity, we must study the evolution of both information and organization. Results Here we investigate the evolution of complexity in a simulated RNA-like replicator system. The simplicity of the system allows us to explicitly model the genotype-phenotype-interaction mapping of individual replicators, whereby we avoid preconceiving the functionality of genotypes (information or the ecological organization of replicators in the model. In particular, the model assumes that interactions among replicators – to replicate or to be replicated – depend on their secondary structures and base-pair matching. The results showed that a population of replicators, originally consisting of one genotype, evolves to form a complex ecosystem of up to four species. During this diversification, the species evolve through acquiring unique genotypes with distinct ecological functionality. The analysis of this diversification reveals that parasitic replicators, which have been thought to destabilize the replicator's diversity, actually promote the evolution of diversity through generating a novel "niche" for catalytic replicators. This also makes the current replicator system extremely stable upon the evolution of parasites. The results also show that the stability of the system crucially depends on the spatial pattern formation of replicators. Finally, the evolutionary dynamics is shown to

  17. 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.

  18. Mathematical and Statistical Modeling in Cancer Systems Biology

    Directory of Open Access Journals (Sweden)

    Rachael eHageman Blair

    2012-06-01

    Full Text Available Cancer is a major health problem with high mortality rates. In the post-genome era, investigators have access to massive amounts of rapidly accumulating high-throughput data in publicly available databases, some of which are exclusively devoted to housing Cancer data. However, data interpretation efforts have not kept pace with data collection, and gained knowledge is not necessarily translating into better diagnoses and treatments. A fundamental problem is to integrate and interpret data to further our understanding in Cancer Systems Biology. Viewing cancer as a network provides insights into the complex mechanisms underlying the disease. Mathematical and statistical models provide an avenue for cancer network modeling. In this article, we review two widely used modeling paradigms: deterministic metabolic models and statistical graphical models. The strength of these approaches lies in their flexibility and predictive power. Once a model has been validated, it can be used to make predictions and generate hypotheses. We describe a number of diverse applications to Cancer Biology, including, the system-wide effects of drug-treatments, disease prognosis, tumor classification, forecasting treatment outcomes, and survival predictions.

  19. 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.

  20. 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.

  1. Systems biology by the rules: hybrid intelligent systems for pathway modeling and discovery

    Directory of Open Access Journals (Sweden)

    Bosl William J

    2007-02-01

    Full Text Available Abstract Background Expert knowledge in journal articles is an important source of data for reconstructing biological pathways and creating new hypotheses. An important need for medical research is to integrate this data with high throughput sources to build useful models that span several scales. Researchers traditionally use mental models of pathways to integrate information and development new hypotheses. Unfortunately, the amount of information is often overwhelming and these are inadequate for predicting the dynamic response of complex pathways. Hierarchical computational models that allow exploration of semi-quantitative dynamics are useful systems biology tools for theoreticians, experimentalists and clinicians and may provide a means for cross-communication. Results A novel approach for biological pathway modeling based on hybrid intelligent systems or soft computing technologies is presented here. Intelligent hybrid systems, which refers to several related computing methods such as fuzzy logic, neural nets, genetic algorithms, and statistical analysis, has become ubiquitous in engineering applications for complex control system modeling and design. Biological pathways may be considered to be complex control systems, which medicine tries to manipulate to achieve desired results. Thus, hybrid intelligent systems may provide a useful tool for modeling biological system dynamics and computational exploration of new drug targets. A new modeling approach based on these methods is presented in the context of hedgehog regulation of the cell cycle in granule cells. Code and input files can be found at the Bionet website: www.chip.ord/~wbosl/Software/Bionet. Conclusion This paper presents the algorithmic methods needed for modeling complicated biochemical dynamics using rule-based models to represent expert knowledge in the context of cell cycle regulation and tumor growth. A notable feature of this modeling approach is that it allows biologists

  2. 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. PMID:25493908

  3. 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.

  4. Developing optimal input design strategies in cancer systems biology with applications to microfluidic device engineering

    OpenAIRE

    Maiwald Thomas; Bellomo Domenico; Menolascina Filippo; Bevilacqua Vitoantonio; Ciminelli Caterina; Paradiso Angelo; Tommasi Stefania

    2009-01-01

    Abstract Background Mechanistic models are becoming more and more popular in Systems Biology; identification and control of models underlying biochemical pathways of interest in oncology is a primary goal in this field. Unfortunately the scarce availability of data still limits our understanding of the intrinsic characteristics of complex pathologies like cancer: acquiring information for a system understanding of complex reaction networks is time consuming and expensive. Stimulus response ex...

  5. 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.

  6. Energy Flows in Low-Entropy Complex Systems

    CERN Document Server

    Chaisson, Eric J

    2015-01-01

    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 t...

  7. 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

  8. The Physics of Complex Systems in Cuba

    Science.gov (United States)

    Sotolongo-Costa, Oscar

    In relating the circumstances that led to the birth and development of the physics of complex systems in Cuba, it is difficult to avoid being anecdotal—particularly because of the difficult times during which this research started. Cuban eclecticism, whose spectrum extends from religious syncretism to world-class medicine, seems quite coherent with the field of complex systems, characterized by the synergy of diverse fields. Such a combination, however, in the beginning seemed to be quite removed from the physicists' standard research dogmas.

  9. From precision polymers to complex materials and systems

    Science.gov (United States)

    Lutz, Jean-François; Lehn, Jean-Marie; Meijer, E. W.; Matyjaszewski, Krzysztof

    2016-05-01

    Complex chemical systems, such as living biological matter, are highly organized structures based on discrete molecules in constant dynamic interactions. These natural materials can evolve and adapt to their environment. By contrast, man-made materials exhibit simpler properties. In this Review, we highlight that most of the necessary elements for the development of more complex synthetic matter are available today. Using modern strategies, such as controlled radical polymerizations, supramolecular polymerizations or stepwise synthesis, polymers with precisely controlled molecular structures can be synthesized. Moreover, such tailored polymers can be folded or self-assembled into defined nanoscale morphologies. These self-organized macromolecular objects can be at thermal equilibrium or can be driven out of equilibrium. Recently, in the latter case, interesting dynamic materials have been developed. However, this is just a start, and more complex adaptive materials are anticipated.

  10. Systems biology and bioinformatics in aging research: a workshop report.

    Science.gov (United States)

    Fuellen, Georg; Dengjel, Jörn; Hoeflich, Andreas; Hoeijemakers, Jan; Kestler, Hans A; Kowald, Axel; Priebe, Steffen; Rebholz-Schuhmann, Dietrich; Schmeck, Bernd; Schmitz, Ulf; Stolzing, Alexandra; Sühnel, Jürgen; Wuttke, Daniel; Vera, Julio

    2012-12-01

    In an "aging society," health span extension is most important. As in 2010, talks in this series of meetings in Rostock-Warnemünde demonstrated that aging is an apparently very complex process, where computational work is most useful for gaining insights and to find interventions that counter aging and prevent or counteract aging-related diseases. The specific topics of this year's meeting entitled, "RoSyBA: Rostock Symposium on Systems Biology and Bioinformatics in Ageing Research," were primarily related to "Cancer and Aging" and also had a focus on work funded by the German Federal Ministry of Education and Research (BMBF). The next meeting in the series, scheduled for September 20-21, 2013, will focus on the use of ontologies for computational research into aging, stem cells, and cancer. Promoting knowledge formalization is also at the core of the set of proposed action items concluding this report.

  11. 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.

  12. 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.

  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. 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.

  15. Understanding Complex Construction Systems Through Modularity

    DEFF Research Database (Denmark)

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

    2014-01-01

    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...... 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...... 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....

  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. Approximate bayesian parameter inference for dynamical systems in systems biology

    International Nuclear Information System (INIS)

    This paper proposes to use approximate instead of exact stochastic simulation algorithms for approximate Bayesian parameter inference of dynamical systems in systems biology. It first presents the mathematical framework for the description of systems biology models, especially from the aspect of a stochastic formulation as opposed to deterministic model formulations based on the law of mass action. In contrast to maximum likelihood methods for parameter inference, approximate inference method- share presented which are based on sampling parameters from a known prior probability distribution, which gradually evolves toward a posterior distribution, through the comparison of simulated data from the model to a given data set of measurements. The paper then discusses the simulation process, where an over- view is given of the different exact and approximate methods for stochastic simulation and their improvements that we propose. The exact and approximate simulators are implemented and used within approximate Bayesian parameter inference methods. Our evaluation of these methods on two tasks of parameter estimation in two different models shows that equally good results are obtained much faster when using approximate simulation as compared to using exact simulation. (Author)

  18. Implementation of Complex Biological Logic Circuits Using Spatially Distributed Multicellular Consortia

    OpenAIRE

    Javier Macia; Romilde Manzoni; Núria Conde; Arturo Urrios; Eulàlia de Nadal; Ricard Solé; Francesc Posas

    2016-01-01

    Engineered synthetic biological devices have been designed to perform a variety of functions from sensing molecules and bioremediation to energy production and biomedicine. Notwithstanding, a major limitation of in vivo circuit implementation is the constraint associated to the use of standard methodologies for circuit design. Thus, future success of these devices depends on obtaining circuits with scalable complexity and reusable parts. Here we show how to build complex computational devices...

  19. Building momentum for systems and synthetic biology in India

    OpenAIRE

    Krishnan, Remya; Manjaly-Antony, Lijo Anto; Dhar, Pawan K.

    2010-01-01

    Biological systems are inherently noisy. Predicting the outcome of a perturbation is extremely challenging. Traditional reductionist approach of describing properties of parts, vis-a-vis higher level behaviour has led to enormous understanding of fundamental molecular level biology. This approach typically consists of converting genes into junk (knock-down) and garbage (knock-out) and observe how a system responds. To enable broader understanding of biological dynamics, an integrated computat...

  20. Global optimization in systems biology: stochastic methods and their applications

    OpenAIRE

    Balsa-Canto, Eva; Banga, Julio R.; Egea, José A.; Villaverde, A. F.; Hijas-Liste, G. M.

    2012-01-01

    Mathematical optimization is at the core of many problems in systems biology: (1) as the underlying hypothesis for model development, (2) in model identification, or (3) in the computation of optimal stimulation procedures to synthetically achieve a desired biological behavior. These problems are usually formulated as nonlinear programing problems (NLPs) with dynamic and algebraic constraints. However the nonlinear and highly constrained nature of systems biology models, together with the usu...

  1. Systems biology in aging: linking the old and the young.

    Science.gov (United States)

    Hou, Lei; Huang, Jialiang; Green, Christopher D; Boyd-Kirkup, Jerome; Zhang, Wei; Yu, Xiaoming; Gong, Wenxuan; Zhou, Bing; Han, Jing-Dong J

    2012-11-01

    Aging can be defined as a process of progressive decline in the physiological capacity of an organism, manifested by accumulated alteration and destabilization at the whole system level. Systems biology approaches offer a promising new perspective to examine the old problem of aging. We begin this review by introducing the concepts of systems biology, and then illustrate the application of systems biology approaches to aging research, from gene expression profiling to network analysis. We then introduce the network that can be constructed using known lifespan and aging regulators, and conclude with a look forward to the future of systems biology in aging research. In summary, systems biology is not only a young field that may help us understand aging at a higher level, but also an important platform that can link different levels of knowledge on aging, moving us closer to a more comprehensive control of systematic decline during aging. PMID:23633915

  2. 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...

  3. Some biologically active oxovanadium(IV) complexes of triazole derived Schiff bases: their synthesis, characterization and biological properties.

    Science.gov (United States)

    Chohan, Zahid H; Sumrra, Sajjad H

    2010-10-01

    A series of biologically active oxovanadium(IV) complexes of triazole derived Schiff bases L(1)-L(5) have been synthesized and characterized by their physical, analytical, and spectral data. The synthesized ligands potentially act as bidentate, in which the oxygen of furfural and nitrogen of azomethine coordinate with the oxovanadium atom to give a stoichiometry of vanadyl complexes 1:2 (M:L) in a square-pyramidal geometry. In vitro antibacterial and antifungal activities on different species of pathogenic bacteria (E. coli, S. flexneri, P. aeruginosa, S. typhi, S. aureus, and B. subtilis) and fungi (T. longifusus, C. albicans, A. flavus, M. canis, F. solani, and C. glabrata) have been studied. All compounds showed moderate to significant antibacterial activity against one or more bacterial strains and good antifungal activity against most of the fungal strains. The brine shrimp bioassay was also carried out to check the cytotoxicity of coordinated and uncoordinated synthesized compounds. PMID:20429776

  4. Energy Consumption Monitoring System for Large Complexes

    Science.gov (United States)

    Jorge, André; Guerreiro, João; Pereira, Pedro; Martins, João; Gomes, Luís

    This paper describes the development of an open source system for monitoring and data acquisition of several energy analyzers. The developed system is based on a computer with Internet/Intranet connection by means of RS485 using Modbus RTU as communication protocol. The monitoring/metering system was developed for large building complexes and was validated in the Faculdade de Ciências e Tecnologia University campus. The system considers two distinct applications. The first one allows the user to verify, in real time, the energy consumption of any department in the complex, produce load diagrams, tables and print, email or save all available data. The second application keeps records of active/reactive energy consumption in order to verify the existence of some anomalous situation, and also monthly charge energy consumption to each corresponding department.

  5. 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 ...

  6. Systems biology of neutrophil differentiation and immune response

    DEFF Research Database (Denmark)

    Theilgaard-Mönch, Kim; Porse, Bo T; Borregaard, Niels

    2005-01-01

    Systems biology has emerged as a new scientific field, which aims at investigating biological processes at the genomic and proteomic levels. Recent studies have unravelled aspects of neutrophil differentiation and immune responses at the systems level using high-throughput technologies...

  7. 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.

  8. 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

  9. Complex systems modeling by cellular automata

    NARCIS (Netherlands)

    J. Kroc; P.M.A. Sloot

    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, an

  10. Complex evolutionary systems in behavioral finance

    NARCIS (Netherlands)

    C. Hommes; F. Wagener

    2008-01-01

    Traditional finance is built on the rationality paradigm. This chapter discusses simple models from an alternative approach in which financial markets are viewed as complex evolutionary systems. Agents are boundedly rational and base their investment decisions upon market forecasting heuristics. Pri

  11. Circadian systems : different levels of complexity

    NARCIS (Netherlands)

    Roenneberg, Till; Merrow, Martha

    2001-01-01

    After approximately 50 years of circadian research, especially in selected circadian model systems (Drosophila, Neurospora, Gonyaulax and, more recently, cyanobacteria and mammals), we appreciate the enormous complexity of the circadian programme in organisms and cells, as well as in physiological a

  12. Ensemble annealing of complex physical systems

    OpenAIRE

    Habeck, Michael

    2015-01-01

    Algorithms for simulating complex physical systems or solving difficult optimization problems often resort to an annealing process. Rather than simulating the system at the temperature of interest, an annealing algorithm starts at a temperature that is high enough to ensure ergodicity and gradually decreases it until the destination temperature is reached. This idea is used in popular algorithms such as parallel tempering and simulated annealing. A general problem with annealing methods is th...

  13. Biologic

    CERN Document Server

    Kauffman, L H

    2002-01-01

    In this paper we explore the boundary between biology and the study of formal systems (logic). In the end, we arrive at a summary formalism, a chapter in "boundary mathematics" where there are not only containers but also extainers ><, entities open to interaction and distinguishing the space that they are not. The boundary algebra of containers and extainers is to biologic what boolean algebra is to classical logic. We show how this formalism encompasses significant parts of the logic of DNA replication, the Dirac formalism for quantum mechanics, formalisms for protein folding and the basic structure of the Temperley Lieb algebra at the foundations of topological invariants of knots and links.

  14. Dependency visualization for complex system understanding

    Energy Technology Data Exchange (ETDEWEB)

    Smart, J.A.C.

    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 orgnizational 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.

  15. 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...

  16. 78 FR 58311 - Complex Issues in Developing Drug and Biological Products for Rare Diseases; Public Workshop...

    Science.gov (United States)

    2013-09-23

    ... for Rare Diseases; Public Workshop; Request for Comments AGENCY: Food and Drug Administration, HHS... for Rare Diseases.'' The purpose of the public workshop is twofold: To discuss complex issues in clinical trials for developing drug and biological products (``drugs'') for rare diseases,...

  17. Mathematical modeling of the evolution of a simple biological system

    Digital Repository Service at National Institute of Oceanography (India)

    Gonsalves, M.J.B.D.; Neetu, S.; Krishnan, K.P.; Attri, K.; LokaBharathi, P.A.

    physical system, where a model usually can be developed from well established fundamental principles, in case of biological systems such principles are not always available offering an opportunity for innovation. The success of the innovation, of course...

  18. Membrane Tethering Complexes in the Endosomal System.

    Science.gov (United States)

    Spang, Anne

    2016-01-01

    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 class C core vacuole/endosome tethering (CORVET) complex, while fusion of late endosomes with lysosomes depends on the homotypic fusion and vacuole protein sorting (HOPS) complex. Recycling through the trans-Golgi network (TGN) and to the plasma membrane is facilitated by the Golgi associated retrograde protein (GARP) and endosome-associated recycling protein (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, proteins 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. PMID:27243003

  19. Nutritional Systems Biology Modeling: From Molecular Mechanisms to Physiology

    Science.gov (United States)

    de Graaf, Albert A.; Freidig, Andreas P.; De Roos, Baukje; Jamshidi, Neema; Heinemann, Matthias; Rullmann, Johan A.C.; Hall, Kevin D.; Adiels, Martin; van Ommen, Ben

    2009-01-01

    The use of computational modeling and simulation has increased in many biological fields, but despite their potential these techniques are only marginally applied in nutritional sciences. Nevertheless, recent applications of modeling have been instrumental in answering important nutritional questions from the cellular up to the physiological levels. Capturing the complexity of today's important nutritional research questions poses a challenge for modeling to become truly integrative in the consideration and interpretation of experimental data at widely differing scales of space and time. In this review, we discuss a selection of available modeling approaches and applications relevant for nutrition. We then put these models into perspective by categorizing them according to their space and time domain. Through this categorization process, we identified a dearth of models that consider processes occurring between the microscopic and macroscopic scale. We propose a “middle-out” strategy to develop the required full-scale, multilevel computational models. Exhaustive and accurate phenotyping, the use of the virtual patient concept, and the development of biomarkers from “-omics” signatures are identified as key elements of a successful systems biology modeling approach in nutrition research—one that integrates physiological mechanisms and data at multiple space and time scales. PMID:19956660

  20. Nutritional systems biology modeling: from molecular mechanisms to physiology.

    Directory of Open Access Journals (Sweden)

    Albert A de Graaf

    2009-11-01

    Full Text Available The use of computational modeling and simulation has increased in many biological fields, but despite their potential these techniques are only marginally applied in nutritional sciences. Nevertheless, recent applications of modeling have been instrumental in answering important nutritional questions from the cellular up to the physiological levels. Capturing the complexity of today's important nutritional research questions poses a challenge for modeling to become truly integrative in the consideration and interpretation of experimental data at widely differing scales of space and time. In this review, we discuss a selection of available modeling approaches and applications relevant for nutrition. We then put these models into perspective by categorizing them according to their space and time domain. Through this categorization process, we identified a dearth of models that consider processes occurring between the microscopic and macroscopic scale. We propose a "middle-out" strategy to develop the required full-scale, multilevel computational models. Exhaustive and accurate phenotyping, the use of the virtual patient concept, and the development of biomarkers from "-omics" signatures are identified as key elements of a successful systems biology modeling approach in nutrition research--one that integrates physiological mechanisms and data at multiple space and time scales.