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. Systems biology: confronting the complexity of cancer.

    Science.gov (United States)

    Gentles, Andrew J; Gallahan, Daniel

    2011-09-15

    The AACR-NCI Conference "Systems Biology: Confronting the Complexity of Cancer" took place from February 27 to March 2, 2011, in San Diego, CA. Several themes resonated during the meeting, notably (i) the need for better methods to distill insights from large-scale networks, (ii) the importance of integrating multiple data types in constructing more realistic models, (iii) challenges in translating insights about tumorigenic mechanisms into therapeutic interventions, and (iv) the role of the tumor microenvironment, at the physical, cellular, and molecular levels. The meeting highlighted concrete applications of systems biology to cancer, and the value of collaboration between interdisciplinary researchers in attacking formidable problems.

  3. Life: An Introduction to Complex Systems Biology

    CERN Document Server

    Kaneko, Kunihiko

    2006-01-01

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

  4. Complex biological and bio-inspired systems

    Energy Technology Data Exchange (ETDEWEB)

    Ecke, Robert E [Los Alamos National Laboratory

    2009-01-01

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

  5. Integrative Systems Biology: Elucidating Complex Traits

    DEFF Research Database (Denmark)

    Pers, Tune Hannes

    product itself. My doctoral studies have been focused on the development of integrative approaches to identify systemic risk-modifying and disease-causing patterns. ey have been rooted in the hypothesis that data integration of complementary data sets may yield additional etiologic insights compared...... traits and disease. e esis is structured as follows. Chapter  presents a few introductory remarks to integrative systems biology, and Chapter  gives a brief description of human genetic variation and GWA analysis. Chapters - present the main topics in the esis (integrative methodologies...... to analyses conducted within a single type of data. e first line of research presented here outlines two integrative methodologies designed to identify etiological pathways and susceptibility genes. In Paper I, my coworkers and I present an integrative approach that interrogates protein complexes...

  6. Conceptual Foundations of Systems Biology Explaining Complex Cardiac Diseases

    Directory of Open Access Journals (Sweden)

    George E. Louridas

    2017-02-01

    Full Text Available Systems biology is an important concept that connects molecular biology and genomics with computing science, mathematics and engineering. An endeavor is made in this paper to associate basic conceptual ideas of systems biology with clinical medicine. Complex cardiac diseases are clinical phenotypes generated by integration of genetic, molecular and environmental factors. Basic concepts of systems biology like network construction, modular thinking, biological constraints (downward biological direction and emergence (upward biological direction could be applied to clinical medicine. Especially, in the field of cardiology, these concepts can be used to explain complex clinical cardiac phenotypes like chronic heart failure and coronary artery disease. Cardiac diseases are biological complex entities which like other biological phenomena can be explained by a systems biology approach. The above powerful biological tools of systems biology can explain robustness growth and stability during disease process from modulation to phenotype. The purpose of the present review paper is to implement systems biology strategy and incorporate some conceptual issues raised by this approach into the clinical field of complex cardiac diseases. Cardiac disease process and progression can be addressed by the holistic realistic approach of systems biology in order to define in better terms earlier diagnosis and more effective therapy.

  7. Conceptual Foundations of Systems Biology Explaining Complex Cardiac Diseases.

    Science.gov (United States)

    Louridas, George E; Lourida, Katerina G

    2017-02-21

    Systems biology is an important concept that connects molecular biology and genomics with computing science, mathematics and engineering. An endeavor is made in this paper to associate basic conceptual ideas of systems biology with clinical medicine. Complex cardiac diseases are clinical phenotypes generated by integration of genetic, molecular and environmental factors. Basic concepts of systems biology like network construction, modular thinking, biological constraints (downward biological direction) and emergence (upward biological direction) could be applied to clinical medicine. Especially, in the field of cardiology, these concepts can be used to explain complex clinical cardiac phenotypes like chronic heart failure and coronary artery disease. Cardiac diseases are biological complex entities which like other biological phenomena can be explained by a systems biology approach. The above powerful biological tools of systems biology can explain robustness growth and stability during disease process from modulation to phenotype. The purpose of the present review paper is to implement systems biology strategy and incorporate some conceptual issues raised by this approach into the clinical field of complex cardiac diseases. Cardiac disease process and progression can be addressed by the holistic realistic approach of systems biology in order to define in better terms earlier diagnosis and more effective therapy.

  8. 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 ...

  9. 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...

  10. Complexity and the reductionism-holism debate in systems biology.

    Science.gov (United States)

    Mazzocchi, Fulvio

    2012-01-01

    Reductionism has largely influenced the development of science, culminating in its application to molecular biology. An increasing number of novel research findings have, however, shattered this view, showing how the molecular-reductionist approach cannot entirely handle the complexity of biological systems. Within this framework, the advent of systems biology as a new and more integrative field of research is described, along with the form which has taken on the debate of reductionism versus holism. Such an issue occupies a central position in systems biology, and nonetheless it is not always clearly delineated. This partly occurs because different dimensions (ontological, epistemological, methodological) are involved, and yet the concerned ones often remain unspecified. Besides, within systems biology different streams can be distinguished depending on the degree of commitment to embrace genuine systemic principles. Some useful insights into the future development of this discipline might be gained from the tradition of complexity and self-organization. This is especially true with regards the idea of self-reference, which incorporated into the organizational scheme is able to generate autonomy as an emergent property of the biological whole.

  11. 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.

  12. 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...

  13. 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

  14. A complex biological system: the fly's visual module.

    Science.gov (United States)

    Baptista, Murilo S; de Almeida, Lirio O B; Slaets, Jan F W; Köberle, Roland; Grebogi, Celso

    2008-02-13

    Is the characterization of biological systems as complex systems in the mathematical sense a fruitful assertion? In this paper we argue in the affirmative, although obviously we do not attempt to confront all the issues raised by this question. We use the fly's visual system as an example and analyse our experimental results of one particular neuron in the fly's visual system from this point of view. We find that the motion-sensitive 'H1' neuron, which converts incoming signals into a sequence of identical pulses or 'spikes', encodes the information contained in the stimulus into an alphabet composed of a few letters. This encoding occurs on multilayered sets, one of the features attributed to complex systems. The conversion of intervals between consecutive occurrences of spikes into an alphabet requires us to construct a generating partition. This entails a one-to-one correspondence between sequences of spike intervals and words written in the alphabet. The alphabet dynamics is multifractal both with and without stimulus, though the multifractality increases with the stimulus entropy. This is in sharp contrast to models generating independent spike intervals, such as models using Poisson statistics, whose dynamics is monofractal. We embed the support of the probability measure, which describes the distribution of words written in this alphabet, in a two-dimensional space, whose topology can be reproduced by an M-shaped map. This map has positive Lyapunov exponents, indicating a chaotic-like encoding.

  15. 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.

  16. Approach of Complex-Systems Biology to Reproduction and Evolution

    Science.gov (United States)

    Kaneko, Kunihiko

    Two basic issues in biology - the origin of life and evolution of phenotypes - are discussed on the basis of statistical physics and dynamical systems. In section "A Bridge Between Catalytic Reaction Networks and Reproducing Cells", we survey recent developments in the origin of reproducing cells from an ensemble of catalytic reactions. After surveying several models of catalytic reaction networks briefly, we provide possible answers to the following three questions: (1) How are nonequilibrium states sustained in catalytic reaction dynamics? (2) How is recursive production of a cell maintaining composition of a variety of chemicals possible? (3) How does a specific molecule species carry information for heredity? In section "Evolution", general relationships between plasticity, robustness, and evolvability are presented in terms of phenotypic fluctuations. First, proportionality between evolution speed, phenotypic plasticity, and isogenic phenotypic fluctuation is proposed by extending the fluctuation-response relationship in physics. We then derive a general proportionality relationship between the phenotypic fluctuations of epigenetic and genetic origin: the former is the variance of phenotype due to noise in the developmental process, and the latter due to genetic mutation. The relationship also suggests a link between robustness to noise and to mutation. These relationships are confirmed in models of gene expression dynamics, as well as in laboratory experiments, and then are explained by a theory based on an evolutionary stability hypothesis For both sections "A Bridge Between Catalytic Reaction Networks and Reproducing Cells" and "Evolution", consistency between two levels of hierarchy (i.e., molecular and cellular, or genetic and phenotypic levels) is stressed as a principle for complex-systems biology.

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

    DEFF Research Database (Denmark)

    Green, Sara; Serban, Maria; Scholl, Raphael;

    2017-01-01

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

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

    Science.gov (United States)

    Yuan, Bing

    2016-12-01

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

  19. Complex systems in pulmonary medicine: a systems biology approach to lung disease.

    Science.gov (United States)

    Kaminsky, David A; Irvin, Charles G; Sterk, Peter J

    2011-06-01

    The lung is a highly complex organ that can only be understood by integrating the many aspects of its structure and function into a comprehensive view. Such a view is provided by a systems biology approach, whereby the many layers of complexity, from the molecular genetic, to the cellular, to the tissue, to the whole organ, and finally to the whole body, are synthesized into a working model of understanding. The systems biology approach therefore relies on the expertise of many disciplines, including genomics, proteomics, metabolomics, physiomics, and, ultimately, clinical medicine. The overall structure and functioning of the lung cannot be predicted from studying any one of these systems in isolation, and so this approach highlights the importance of emergence as the fundamental feature of systems biology. In this paper, we will provide an overview of a systems biology approach to lung disease by briefly reviewing the advances made at many of these levels, with special emphasis on recent work done in the realm of pulmonary physiology and the analysis of clinical phenotypes.

  20. Bioinspired Concepts: Unified Theory for Complex Biological and Engineering Systems

    Science.gov (United States)

    2006-01-01

    long cycles , we achieve equality in (4) by essentially using the operating scheme of the Carnot heat engine. This is a physical hard limit: It is...control theory, and computational complexity (classically associated with names such as Carnot , Shannon, Bode, and Turing) all assume incompat- ible...substantially extended from an analytic tool of reverse -engineering TCP congestion control to a general approach to understand in- teractions across layers

  1. Information Complexity and Biology

    Science.gov (United States)

    Bagnoli, Franco; Bignone, Franco A.; Cecconi, Fabio; Politi, Antonio

    Kolmogorov contributed directly to Biology in essentially three problems: the analysis of population dynamics (Lotka-Volterra equations), the reaction-diffusion formulation of gene spreading (FKPP equation), and some discussions about Mendel's laws. However, the widely recognized importance of his contribution arises from his work on algorithmic complexity. In fact, the limited direct intervention in Biology reflects the generally slow growth of interest of mathematicians towards biological issues. From the early work of Vito Volterra on species competition, to the slow growth of dynamical systems theory, contributions to the study of matter and the physiology of the nervous system, the first 50-60 years have witnessed important contributions, but as scattered pieces apparently uncorrelated, and in branches often far away from Biology. Up to the 40' it is hard to see the initial loose build up of a convergence, for those theories that will become mainstream research by the end of the century, and connected by the study of biological systems per-se.

  2. Bioinspired Concepts: Unified Theory for Complex Biological and Engineering Systems

    Science.gov (United States)

    2001-01-01

    Proceedings of the American Control Conference (ACC), Boston, MA. 2004. A. Papachristodoulou. Analysis of Nonlinear Time Delay Systems Using the...Sum of Squares Decomposition. Proceedings of the American Control Conference (ACC), Boston, MA. 2004. S. Prajna, A. Papachristodoulou, P. Seiler, P. A...12. H. El-Samad, M. Khammash, H. Kurata, and J. C. Doyle. Robustness analysis of the heat shock response in E. coli. In Proceedings of

  3. 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.

  4. 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

  5. Quantitative correlation of the in vitro biological effect with parameters of molecular complexation in mutagen-interceptor systems.

    Science.gov (United States)

    Buchelnikov, Anatoly S; Evstigneev, Maxim P

    2014-09-21

    According to the theory of interceptor-protector action a quantitative link between the physico-chemical parameters of molecular complexation and in vitro biological effect in aromatic drug-interceptor systems must exist. In the present communication such link between relative change in mutagenicity of IQ-type aromatic mutagens on addition of aromatic interceptor molecules with equilibrium hetero-association constants of mutagen-interceptor complexation has been found using the published in vitro data in bacteria cell systems.

  6. 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 ...

  7. 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. 

  8. 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

  9. 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."

  10. Controllability of Complex Systems

    Science.gov (United States)

    Slotine, Jean-Jacques

    2013-03-01

    We review recent work on controllability of complex systems. We also discuss the interplay of our results with questions of synchronization, and point out key directions of future research. Work done in collaboration with Yang-Yu Liu, Center for Complex Network Research and Departments of Physics, Computer Science and Biology, Northeastern University and Center for Cancer Systems Biology, Dana-Farber Cancer Institute; and Albert-László Barabási, Center for Complex Network Research and Departments of Physics, Computer Science and Biology, Northeastern University; Center for Cancer Systems Biology, Dana-Farber Cancer Institute; and Department of Medicine, Brigham and Women's Hospital, Harvard Medical School.

  11. 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.

  12. [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.

  13. Nutritional Systems Biology

    DEFF Research Database (Denmark)

    Jensen, Kasper

    sites of diet on the disease pathway. We propose a framework for interrogating the critical targets in colon cancer process and identifying plant-based dietary interventions as important modifiers using a systems chemical biology approach. The fifth chapter of the thesis is on discovering of novel anti...... number of thoroughly selected targets. Our need for fundamental understanding of the building blocks of the complex biological systems had been the main reason for the reductionist approach that was mainly applied in the past to elucidate these systems. Nowadays, it is widely recognized that systems...... components with biological systems and their connection to health and disease. The database will be enriched with predicted interactions between food components and protein targets, based on their structural and pharmacophore similarity with known small molecule ligands. Further to this, the associations...

  14. 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...

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

    Science.gov (United States)

    Pezzulo, Giovanni; Levin, Michael

    2016-11-01

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

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

    Science.gov (United States)

    2016-01-01

    It is widely assumed in developmental biology and bioengineering that optimal understanding and control of complex living systems follows from models of molecular events. The success of reductionism has overshadowed attempts at top-down models and control policies in biological systems. However, other fields, including physics, engineering and neuroscience, have successfully used the explanations and models at higher levels of organization, including least-action principles in physics and control-theoretic models in computational neuroscience. Exploiting the dynamic regulation of pattern formation in embryogenesis and regeneration requires new approaches to understand how cells cooperate towards large-scale anatomical goal states. Here, we argue that top-down models of pattern homeostasis serve as proof of principle for extending the current paradigm beyond emergence and molecule-level rules. We define top-down control in a biological context, discuss the examples of how cognitive neuroscience and physics exploit these strategies, and illustrate areas in which they may offer significant advantages as complements to the mainstream paradigm. By targeting system controls at multiple levels of organization and demystifying goal-directed (cybernetic) processes, top-down strategies represent a roadmap for using the deep insights of other fields for transformative advances in regenerative medicine and systems bioengineering. PMID:27807271

  17. A novel procedure for the identification of chaos in complex biological systems

    Science.gov (United States)

    Bazeia, D.; Pereira, M. B. P. N.; Brito, A. V.; Oliveira, B. F. De; Ramos, J. G. G. S.

    2017-03-01

    We demonstrate the presence of chaos in stochastic simulations that are widely used to study biodiversity in nature. The investigation deals with a set of three distinct species that evolve according to the standard rules of mobility, reproduction and predation, with predation following the cyclic rules of the popular rock, paper and scissors game. The study uncovers the possibility to distinguish between time evolutions that start from slightly different initial states, guided by the Hamming distance which heuristically unveils the chaotic behavior. The finding opens up a quantitative approach that relates the correlation length to the average density of maxima of a typical species, and an ensemble of stochastic simulations is implemented to support the procedure. The main result of the work shows how a single and simple experimental realization that counts the density of maxima associated with the chaotic evolution of the species serves to infer its correlation length. We use the result to investigate others distinct complex systems, one dealing with a set of differential equations that can be used to model a diversity of natural and artificial chaotic systems, and another one, focusing on the ocean water level.

  18. Flower Morphology, Pollination Biology and Mating System of the Complex Flower of Vigna caracalla (Fabaceae: Papilionoideae)

    Science.gov (United States)

    Etcheverry, Angela Virginia; Alemán, Maria Mercedes; Fleming, Trinidad Figueroa

    2008-01-01

    Background and Aims Vigna caracalla has the most complex flower among asymmetrical Papilionoideae. The objective of this study was to understand the relationships among floral characteristics, specialization, mating system and the role of floral visitors under different ecological contexts. Methods Five populations were studied in north-western Argentina, from 700 to 1570 m a.s.l. Anthesis, colour and odour patterns, stigmatic receptivity, visitors and pollination mechanism were examined and mating-system experiments were performed. Key Results The petals are highly modified and the keel shows 3·75–5·25 revolutions. The sense of asymmetry was always left-handed. Hand-crosses showed that V. caracalla is self-compatible, but depends on pollinators to set seeds. Hand-crossed fruits were more successful than hand-selfed ones, with the exception of the site at the highest elevation. Bombus morio (queens and workers), Centris bicolor, Eufriesea mariana and Xylocopa eximia trigger the pollination mechanism (a ‘brush type’). The greatest level of self-compatibility and autonomous self-pollination were found at the highest elevation, together with the lowest reproductive success and number of pollinators (B. morio workers only). Conclusions Self-fertilization may have evolved in the peripheral population at the highest site of V. caracalla because of the benefits of reproductive assurance under reduced pollinator diversity. PMID:18587133

  19. 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....

  20. 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.

  1. Understanding biological complexity: lessons from the past.

    Science.gov (United States)

    Weiss, James N; Qu, Zhilin; Garfinkel, Alan

    2003-01-01

    Advances in molecular biology now permit complex biological systems to be tracked at an exquisite level of detail. The information flow is so great, however, that using intuition alone to draw connections is unrealistic. Thus, the need to integrate mathematical biology with experimental biology is greater than ever. To achieve this integration, obstacles that have traditionally prevented effective communication between theoreticians and experimentalists must be overcome, so that experimentalists learn the language of mathematics and dynamical modeling and theorists learn the language of biology. Fifty years ago Alan Hodgkin and Andrew Huxley published their quantitative model of the nerve action potential; in the same year, Alan Turing published his work on pattern formation in activator-inhibitor systems. These classic studies illustrate two ends of the spectrum in mathematical biology: the detailed model approach and the minimal model approach. When combined, they are highly synergistic in analyzing the mechanisms underlying the behavior of complex biological systems. Their effective integration will be essential for unraveling the physical basis of the mysteries of life.

  2. Insights into Biological Complexity from Simple Foundations.

    Science.gov (United States)

    Albergante, L; Liu, D; Palmer, S; Newman, T J

    2016-01-01

    We discuss an overtly "simple approach" to complex biological systems borrowing selectively from theoretical physics. The approach is framed by three maxims, and we show examples of its success in two different applications: investigating cellular robustness at the level of gene regulatory networks and quantifying rare events of DNA replication errors.

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

    Science.gov (United States)

    Coveney, Peter V; Fowler, Philip W

    2005-09-22

    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 examples of systems biology, are modelled by sets of nonlinear coupled differential equations, which have to be solved numerically. A major difficulty with this approach is that all the parameters within these equations are not usually known. Coupled models that include biomolecular detail could help solve this problem. Coupling models across large ranges of length- and time-scales is central to describing complex systems and therefore to biology. Such coupling may be performed in at least two different ways, which we refer to as hierarchical and hybrid multiscale modelling. While limited progress has been made in the former case, the latter is only beginning to be addressed systematically. These modelling methods are expected to bring numerous benefits to biology, for example, the properties of a system could be studied over a wider range of length- and time-scales, a key aim of systems biology. Multiscale models couple behaviour at the molecular biological level to that at the cellular level, thereby providing a route for calculating many unknown parameters as well as investigating the effects at, for example, the cellular level, of small changes at the biomolecular level, such as a genetic mutation or the presence of a drug. The modelling and simulation of biomolecular systems is itself very computationally intensive; we describe a recently developed hybrid continuum-molecular model, HybridMD, and its associated molecular insertion algorithm, which point the way towards the

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

    Science.gov (United States)

    Smolke, Christina D; Silver, Pamela A

    2011-03-18

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

  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. Computational Systems Chemical Biology

    OpenAIRE

    Oprea, Tudor I.; Elebeoba E. May; 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).

  7. Complexity through Recombination: From Chemistry to Biology

    Directory of Open Access Journals (Sweden)

    Carolina Díaz Arenas

    2010-12-01

    Full Text Available Recombination is a common event in nature, with examples in physics, chemistry, and biology. This process is characterized by the spontaneous reorganization of structural units to form new entities. Upon reorganization, the complexity of the overall system can change. In particular the components of the system can now experience a new response to externally applied selection criteria, such that the evolutionary trajectory of the system is altered. In this work we explore the link between chemical and biological forms of recombination. We estimate how the net system complexity changes, through analysis of RNA-RNA recombination and by mathematical modeling. Our results underscore the importance of recombination in the origins of life on the Earth and its subsequent evolutionary divergence.

  8. 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.

  9. Systems biology: a biologist's viewpoint.

    Science.gov (United States)

    Bose, Biplab

    2013-12-01

    The debate over reductionism and antireductionism in biology is very old. Even the systems approach in biology is more than five decades old. However, mainstream biology, particularly experimental biology, has broadly sidestepped those debates and ideas. Post-genome data explosion and development of high-throughput techniques led to resurfacing of those ideas and debates as a new incarnation called Systems Biology. Though experimental biologists have co-opted systems biology and hailed it as a paradigm shift, it is practiced in different shades and understood with divergent meanings. Biology has certain questions linked with organization of multiple components and processes. Often such questions involve multilevel systems. Here in this essay we argue that systems theory provides required framework and abstractions to explore those questions. We argue that systems biology should follow the logical and mathematical approach of systems theory and transmogrification of systems biology to mere collection of higher dimensional data must be avoided. Therefore, the questions that we ask and the priority of those questions should also change. Systems biology should focus on system-level properties and investigate complexity without shying away from it.

  10. Biological conversion system

    Science.gov (United States)

    Scott, C.D.

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

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

    Directory of Open Access Journals (Sweden)

    Paolo Martini

    2013-11-01

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

  12. 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.

  13. Multifrequency EPR Spectroscopy: A Toolkit for the Characterization of Mono- and Di-nuclear Metal Ion Centers in Complex Biological Systems

    Science.gov (United States)

    Hanson, Graeme R.

    Metalloenzymes are ubiquitous in nature containing complex metal ion cofactors intimately involved in the enzymes' biological function. The application of multifrequency continuous wave and orientation selective pulsed EPR in conjunction with computer simulation and density functional theory calculations has proven to be a powerful toolkit for the geometric and electronic structural characterization of these metal ion cofactors in the resting enzyme, enzyme-substrate and -product complexes, which in turn provides a detailed understanding of the enzymes' catalytic mechanism. In this chapter, a brief description of the multifrequency EPR toolkit used to structurally (geometric and electronic) characterize metal ion binding sites in complex biological systems and its application in the structural characterization of (i) molybdenum containing enzymes and model complexes, (ii) mono- and di-nuclear copper(II) cyclic peptide complexes (marine and synthetic analogues) and (iii) dinuclear metal ion centers in purple acid phosphatases will be presented.

  14. [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.

  15. 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

  16. Introduction to systems biology

    NARCIS (Netherlands)

    Bruggeman, F.J.; Hornberg, J.J.; Boogerd, F.C.; Westerhoff, H.V.; Boogerd, F.C.; Bruggeman, F.J.; Hofmeyr, J.H.S.; Westerhoff, H.V.

    2007-01-01

    The developments in the molecular biosciences have made possible a shift to combined molecular and system-level approaches to biological research under the name of Systems Biology. It integrates many types of molecular knowledge, which can best be achieved by the synergistic use of models and experi

  17. 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.

  18. [Medical applications of systems biology].

    Science.gov (United States)

    Demongeot, Jacques

    2009-01-01

    We illustrate in this review some applications of systems biology in the medical and biological areas. After a brief summary of time scales experienced by medical -observations and of the general scheme of dynamic systems, we describe how some techniques underlying the complex systems theory can be applied to model medical issues in immunology, medical genetics, developmental morphogenesis, biochemistry, epidemiology, telemedecine and multiple platforms of expertise. In concluding, we will discuss the issue of "clinomics" coupling clinical and -omics data in a unique patient-specific file.

  19. Bridging the gap between systems biology and synthetic biology.

    Science.gov (United States)

    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, systems biology provides the knowledge necessary for the development of synthetic biology tools, which in turn facilitates the manipulation and understanding of complex biological systems. Thus, the combination of systems and synthetic biology has huge potential for studying and engineering microbes, especially to perform advanced tasks, such as producing biofuels. Although there have been very few studies in integrating systems and synthetic biology, existing examples have demonstrated great power in extending microbiological capabilities. This review focuses on recent efforts in microbiological genomics, transcriptomics, proteomics, and metabolomics, aiming to fill the gap between systems and synthetic biology.

  20. Systems biology approach to bioremediation

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-06-01

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

  1. 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.

  2. 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.

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

    Science.gov (United States)

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

    2014-04-24

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

  4. 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.

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

    Science.gov (United States)

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

    2015-10-01

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

  6. Towards Systems Biology of Mycotoxin Regulation

    OpenAIRE

    Christof Rampitsch; Rajagopal Subramaniam

    2013-01-01

    Systems biology is a scientific approach that integrates many scientific disciplines to develop a comprehensive understanding of biological phenomena, thus allowing the prediction and accurate simulation of complex biological behaviors. It may be presumptuous to write about toxin regulation at the level of systems biology, but the last decade of research is leading us closer than ever to this approach. Past research has delineated multiple levels of regulation in the pathways leading to the b...

  7. Systems biology in molecular psychiatry.

    Science.gov (United States)

    Gebicke-Haerter, P J

    2008-09-01

    The last ten to fifteen years have seen a remarkable shift of research strategies from hypothesis-driven, reductionistic to data driven, hypothesis-free approaches. This tendency has become evident after completion of the sequencing of the human genome, when publications under the label systems biology have been skyrocketing. This shift marks a gradual revision of scientific understanding of biological systems. Whilst the former has been component-oriented, precluding elements that do not belong to the hypothesis, the latter try to extract information from the whole system in the first place. Only with this information at hand, data driven strategies develop hypotheses. Data driven strategies unearth the immense complexity of biological systems and, hence, necessitate computer-aided support. Mathematical tools derived from chaos theory appear to be applicable in biological systems, but require significant improvements. The combination of high throughput data collection with in silico modelling of molecular or higher order systems can markedly extend our understanding of onset and progression of diseases. Undoubtedly, systems thinking in brain research is the greatest challenge for the years to come.

  8. 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 ‘‘...

  9. Theoretical aspects of Systems Biology.

    Science.gov (United States)

    Bizzarri, Mariano; Palombo, Alessandro; Cucina, Alessandra

    2013-05-01

    The natural world consists of hierarchical levels of complexity that range from subatomic particles and molecules to ecosystems and beyond. This implies that, in order to explain the features and behavior of a whole system, a theory might be required that would operate at the corresponding hierarchical level, i.e. where self-organization processes take place. In the past, biological research has focused on questions that could be answered by a reductionist program of genetics. The organism (and its development) was considered an epiphenomenona of its genes. However, a profound rethinking of the biological paradigm is now underway and it is likely that such a process will lead to a conceptual revolution emerging from the ashes of reductionism. This revolution implies the search for general principles on which a cogent theory of biology might rely. Because much of the logic of living systems is located at higher levels, it is imperative to focus on them. Indeed, both evolution and physiology work on these levels. Thus, by no means Systems Biology could be considered a 'simple' 'gradual' extension of Molecular Biology.

  10. 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…

  11. Systems biology of industrial microorganisms.

    Science.gov (United States)

    Papini, Marta; Salazar, Margarita; Nielsen, Jens

    2010-01-01

    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.

  12. 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.

  13. 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.

  14. An application of Ag(III) complex chemiluminescence system for the determination of enoxacin in capsule and biological fluid.

    Science.gov (United States)

    Chen, Peiyun; Sun, Hanwen

    2010-01-01

    Ag(III) complex chemiluminescence (CL) system was applied for the determination of enoxacin (ENX). The CL conditions of [Ag(HIO(6))(2)](5-)-H(2)SO(4)-ENX systems without any luminescence reagent were investigated and optimized. Under the optimized conditions, the CL intensity was proportional to the concentration of ENX in the range from 6.6 × 10(-5) to 3.3 × 10(-3) g/L. The limit of detection (s/n = 3) was 2.0 × 10(-5) g/L. The recovery of ENX from the spiked pharmaceutical preparations was in the range of 82.9-108% with a relative standard deviation of 1.9-3.0%. For spiked serum and urine samples the recovery of ENX was in the range of 83.7-110% with a relative standard deviation of 1.1-2.8%. The proposed method was applied successfully to the determination of the drug in capsule, serum and urine samples.

  15. Ecological Complexity and the Success of Fungal Biological Control Agents

    Directory of Open Access Journals (Sweden)

    Guy R. Knudsen

    2014-01-01

    Full Text Available Fungal biological control agents against plant pathogens, especially those in soil, operate within physically, biologically, and spatially complex systems by means of a variety of trophic and nontrophic interspecific interactions. However, the biocontrol agents themselves are also subject to the same types of interactions, which may reduce or in some cases enhance their efficacy against target plant pathogens. Characterization of these ecologically complex systems is challenging, but a number of tools are available to help unravel this complexity. Several of these tools are described here, including the use of molecular biology to generate biocontrol agents with useful marker genes and then to quantify these agents in natural systems, epifluorescence and confocal laser scanning microscopy to observe their presence and activity in situ, and spatial statistics and computer simulation modeling to evaluate and predict these activities in heterogeneous soil habitats.

  16. 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.

  17. 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.

  18. Carbon nanomaterials in biological systems

    Energy Technology Data Exchange (ETDEWEB)

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

    2007-09-19

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

  19. Systems biology in animal sciences

    NARCIS (Netherlands)

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

    2011-01-01

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

  20. Effect of fermented non-starch polysaccharide complexes on sorption of heavy metal ions in biological systems

    Directory of Open Access Journals (Sweden)

    L. E. Glagoleva

    2013-01-01

    Full Text Available Hydrolytic action enzyme for modification of nonstarch polysaccharide complexes was developed and studied their influence on sorption activity in relation to heavy metals in biosystem.

  1. Network dynamics and systems biology

    Science.gov (United States)

    Norrell, Johannes A.

    The physics of complex systems has grown considerably as a field in recent decades, largely due to improved computational technology and increased availability of systems level data. One area in which physics is of growing relevance is molecular biology. A new field, systems biology, investigates features of biological systems as a whole, a strategy of particular importance for understanding emergent properties that result from a complex network of interactions. Due to the complicated nature of the systems under study, the physics of complex systems has a significant role to play in elucidating the collective behavior. In this dissertation, we explore three problems in the physics of complex systems, motivated in part by systems biology. The first of these concerns the applicability of Boolean models as an approximation of continuous systems. Studies of gene regulatory networks have employed both continuous and Boolean models to analyze the system dynamics, and the two have been found produce similar results in the cases analyzed. We ask whether or not Boolean models can generically reproduce the qualitative attractor dynamics of networks of continuously valued elements. Using a combination of analytical techniques and numerical simulations, we find that continuous networks exhibit two effects---an asymmetry between on and off states, and a decaying memory of events in each element's inputs---that are absent from synchronously updated Boolean models. We show that in simple loops these effects produce exactly the attractors that one would predict with an analysis of the stability of Boolean attractors, but in slightly more complicated topologies, they can destabilize solutions that are stable in the Boolean approximation, and can stabilize new attractors. Second, we investigate ensembles of large, random networks. Of particular interest is the transition between ordered and disordered dynamics, which is well characterized in Boolean systems. Networks at the

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

    Science.gov (United States)

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

    2016-01-01

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

  3. 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...

  4. Systems biology: experimental design.

    Science.gov (United States)

    Kreutz, Clemens; Timmer, Jens

    2009-02-01

    Experimental design has a long tradition in statistics, engineering and life sciences, dating back to the beginning of the last century when optimal designs for industrial and agricultural trials were considered. In cell biology, the use of mathematical modeling approaches raises new demands on experimental planning. A maximum informative investigation of the dynamic behavior of cellular systems is achieved by an optimal combination of stimulations and observations over time. In this minireview, the existing approaches concerning this optimization for parameter estimation and model discrimination are summarized. Furthermore, the relevant classical aspects of experimental design, such as randomization, replication and confounding, are reviewed.

  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. Industrial systems biology.

    Science.gov (United States)

    Otero, José Manuel; Nielsen, Jens

    2010-02-15

    The chemical industry is currently undergoing a dramatic change driven by demand for developing more sustainable processes for the production of fuels, chemicals, and materials. In biotechnological processes different microorganisms can be exploited, and the large diversity of metabolic reactions represents a rich repository for the design of chemical conversion processes that lead to efficient production of desirable products. However, often microorganisms that produce a desirable product, either naturally or because they have been engineered through insertion of heterologous pathways, have low yields and productivities, and in order to establish an economically viable process it is necessary to improve the performance of the microorganism. Here metabolic engineering is the enabling technology. Through metabolic engineering the metabolic landscape of the microorganism is engineered such that there is an efficient conversion of the raw material, typically glucose, to the product of interest. This process may involve both insertion of new enzymes activities, deletion of existing enzyme activities, but often also deregulation of existing regulatory structures operating in the cell. In order to rapidly identify the optimal metabolic engineering strategy the industry is to an increasing extent looking into the use of tools from systems biology. This involves both x-ome technologies such as transcriptome, proteome, metabolome, and fluxome analysis, and advanced mathematical modeling tools such as genome-scale metabolic modeling. Here we look into the history of these different techniques and review how they find application in industrial biotechnology, which will lead to what we here define as industrial systems biology.

  7. Complexity, Systems, and Software

    Science.gov (United States)

    2014-08-14

    complex ( Hidden issues; dumbs down operator) 11 Complexity, Systems, and Software Sarah Sheard August 14, 2014 © 2014 Carnegie...August 14, 2014 © 2014 Carnegie Mellon University Addressing Complexity in SoSs Source: SEBOK Wiki System Con truer Strateglc Context

  8. 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.

  9. Introducing systems biology for nursing science.

    Science.gov (United States)

    Founds, Sandra A

    2009-07-01

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

  10. 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.

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

    Science.gov (United States)

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

    2010-03-01

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

  12. Complex metabolic network of 1,3-propanediol transport mechanisms and its system identification via biological robustness.

    Science.gov (United States)

    Guo, Yanjie; Feng, Enmin; Wang, Lei; Xiu, Zhilong

    2014-04-01

    The bioconversion of glycerol to 1,3-propanediol (1,3-PD) by Klebsiella pneumoniae (K. pneumoniae) can be characterized by an intricate metabolic network of interactions among biochemical fluxes, metabolic compounds, key enzymes and genetic regulation. Since there are some uncertain factors in the fermentation, especially the transport mechanisms of 1,3-PD across cell membrane, the metabolic network contains multiple possible metabolic systems. Considering the genetic regulation of dha regulon and inhibition of 3-hydroxypropionaldehyde to the growth of cells, we establish a 14-dimensional nonlinear hybrid dynamical system aiming to determine the most possible metabolic system and the corresponding optimal parameter. The existence, uniqueness and continuity of solutions are discussed. Taking the robustness index of the intracellular substances together as a performance index, a system identification model is proposed, in which 1,395 continuous variables and 90 discrete variables are involved. The identification problem is decomposed into two subproblems and a parallel particle swarm optimization procedure is constructed to solve them. Numerical results show that it is most possible that 1,3-PD passes the cell membrane by active transport coupled with passive diffusion.

  13. 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

  14. Robust design of biological circuits: evolutionary systems biology approach.

    Science.gov (United States)

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

    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 fluctuations and environmental molecular noise from the cellular context in the host cell. Based on evolutionary systems biology algorithm, the design parameters of target gene circuits can evolve to specific values in order to robustly track a desired biologic function in spite of intrinsic and environmental noise. The fitness function is selected to be inversely proportional to the tracking error so that the evolutionary biological circuit can achieve the optimal tracking mimicking the evolutionary process of a gene circuit. Finally, several design examples are given in silico with the Monte Carlo simulation to illustrate the design procedure and to confirm the robust performance of the proposed design method. The result shows that the designed gene circuits can robustly track desired behaviors with minimal errors even with nontrivial intrinsic and external noise.

  15. Using learning networks to understand complex systems: a case study of biological, geophysical and social research in the Amazon.

    Science.gov (United States)

    Barlow, Jos; Ewers, Robert M; Anderson, Liana; Aragao, Luiz E O C; Baker, Tim R; Boyd, Emily; Feldpausch, Ted R; Gloor, Emanuel; Hall, Anthony; Malhi, Yadvinder; Milliken, William; Mulligan, Mark; Parry, Luke; Pennington, Toby; Peres, Carlos A; Phillips, Oliver L; Roman-Cuesta, Rosa Maria; Tobias, Joseph A; Gardner, Toby A

    2011-05-01

    Developing high-quality scientific research will be most effective if research communities with diverse skills and interests are able to share information and knowledge, are aware of the major challenges across disciplines, and can exploit economies of scale to provide robust answers and better inform policy. We evaluate opportunities and challenges facing the development of a more interactive research environment by developing an interdisciplinary synthesis of research on a single geographic region. We focus on the Amazon as it is of enormous regional and global environmental importance and faces a highly uncertain future. To take stock of existing knowledge and provide a framework for analysis we present a set of mini-reviews from fourteen different areas of research, encompassing taxonomy, biodiversity, biogeography, vegetation dynamics, landscape ecology, earth-atmosphere interactions, ecosystem processes, fire, deforestation dynamics, hydrology, hunting, conservation planning, livelihoods, and payments for ecosystem services. Each review highlights the current state of knowledge and identifies research priorities, including major challenges and opportunities. We show that while substantial progress is being made across many areas of scientific research, our understanding of specific issues is often dependent on knowledge from other disciplines. Accelerating the acquisition of reliable and contextualized knowledge about the fate of complex pristine and modified ecosystems is partly dependent on our ability to exploit economies of scale in shared resources and technical expertise, recognise and make explicit interconnections and feedbacks among sub-disciplines, increase the temporal and spatial scale of existing studies, and improve the dissemination of scientific findings to policy makers and society at large. Enhancing interaction among research efforts is vital if we are to make the most of limited funds and overcome the challenges posed by addressing large

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

    Science.gov (United States)

    Phair, Robert D

    2014-11-05

    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.

  17. 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.

  18. In silico cell biology and biochemistry: a systems biology approach

    OpenAIRE

    Camacho, Diogo Mayo

    2007-01-01

    In the post-"omic" era the analysis of high-throughput data is regarded as one of the major challenges faced by researchers. One focus of this data analysis is uncovering biological network topologies and dynamics. It is believed that this kind of research will allow the development of new mathematical models of biological systems as well as aid in the improvement of already existing ones. The work that is presented in this dissertation addresses the problem of the analysis of highly complex ...

  19. 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...

  20. Complex systems: physics beyond physics

    Science.gov (United States)

    Holovatch, Yurij; Kenna, Ralph; Thurner, Stefan

    2017-03-01

    Complex systems are characterised by specific time-dependent interactions among their many constituents. As a consequence they often manifest rich, non-trivial and unexpected behaviour. Examples arise both in the physical and non-physical worlds. 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 physicists' 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 conceptualised 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 representation of texts as evolutionary objects. We discuss why these areas form complex systems in the above sense. We argue that there exists plenty of new ground for physicists to explore and that methodical and conceptual progress is needed most.

  1. 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 ...

  2. 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.

  3. Computer algebra in systems biology

    CERN Document Server

    Laubenbacher, Reinhard

    2007-01-01

    Systems biology focuses on the study of entire biological systems rather than on their individual components. With the emergence of high-throughput data generation technologies for molecular biology and the development of advanced mathematical modeling techniques, this field promises to provide important new insights. At the same time, with the availability of increasingly powerful computers, computer algebra has developed into a useful tool for many applications. This article illustrates the use of computer algebra in systems biology by way of a well-known gene regulatory network, the Lac Operon in the bacterium E. coli.

  4. Hierarchical structure of biological systems

    Science.gov (United States)

    Alcocer-Cuarón, Carlos; Rivera, Ana L; Castaño, Victor M

    2014-01-01

    A general theory of biological systems, based on few fundamental propositions, allows a generalization of both Wierner and Berthalanffy approaches to theoretical biology. Here, a biological system is defined as a set of self-organized, differentiated elements that interact pair-wise through various networks and media, isolated from other sets by boundaries. Their relation to other systems can be described as a closed loop in a steady-state, which leads to a hierarchical structure and functioning of the biological system. Our thermodynamical approach of hierarchical character can be applied to biological systems of varying sizes through some general principles, based on the exchange of energy information and/or mass from and within the systems. PMID:24145961

  5. 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....

  6. 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),...

  7. Optical Complex Systems 2008

    Science.gov (United States)

    Brun, Guillaume

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

  8. Fostering synergy between cell biology and systems biology

    OpenAIRE

    2015-01-01

    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...

  9. System-of-Systems Complexity

    Directory of Open Access Journals (Sweden)

    Hermann Kopetz

    2013-11-01

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

  10. Validation of systems biology models

    NARCIS (Netherlands)

    Hasdemir, D.

    2015-01-01

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

  11. 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...

  12. Modeling Complex Systems

    CERN Document Server

    Boccara, Nino

    2010-01-01

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

  13. 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.

  14. 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...

  15. Systems biology of human atherosclerosis.

    Science.gov (United States)

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

    2014-01-01

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

  16. Text mining for systems biology.

    Science.gov (United States)

    Fluck, Juliane; Hofmann-Apitius, Martin

    2014-02-01

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

  17. 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...

  18. Ten questions about systems biology

    DEFF Research Database (Denmark)

    Joyner, Michael J; Pedersen, Bente K

    2011-01-01

    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......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...

  19. 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.

  20. Systems Biology and Stem Cell Pluripotency

    DEFF Research Database (Denmark)

    Mashayekhi, Kaveh; Hall, Vanessa; Freude, Kristine

    2016-01-01

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

  1. Systems Biology and Synthetic Biology: A New Epoch for Toxicology Research

    OpenAIRE

    Mark T. Mc Auley; Hyunok Choi; Kathleen Mooney; Emily Paul; Miller, Veronica M.

    2015-01-01

    Systems biology and synthetic biology are emerging disciplines which are becoming increasingly utilised in several areas of bioscience. Toxicology is beginning to benefit from systems biology and we suggest in the future that is will also benefit from synthetic biology. Thus, a new era is on the horizon. This review illustrates how a suite of innovative techniques and tools can be applied to understanding complex health and toxicology issues. We review limitations confronted by the traditiona...

  2. Managing Complex Dynamical Systems

    Science.gov (United States)

    Cox, John C.; Webster, Robert L.; Curry, Jeanie A.; Hammond, Kevin L.

    2011-01-01

    Management commonly engages in a variety of research designed to provide insight into the motivation and relationships of individuals, departments, organizations, etc. This paper demonstrates how the application of concepts associated with the analysis of complex systems applied to such data sets can yield enhanced insights for managerial action.

  3. 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...

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. 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.  

  9. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-03-01

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

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

    Science.gov (United States)

    Wolkenhauer, O

    2001-09-01

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

  12. Network biology concepts in complex disease comorbidities

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  13. Building multivariate systems biology models

    NARCIS (Netherlands)

    Kirwan, G.M.; Johansson, E.; Kleemann, R.; Verheij, E.R.; Wheelock, A.M.; Goto, S.; Trygg, J.; Wheelock, C.E.

    2012-01-01

    Systems biology methods using large-scale "omics" data sets face unique challenges: integrating and analyzing near limitless data space, while recognizing and removing systematic variation or noise. Herein we propose a complementary multivariate analysis workflow to both integrate "omics" data from

  14. Complex adaptive systems ecology

    DEFF Research Database (Denmark)

    Sommerlund, Julie

    2003-01-01

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

  15. Stochastic simulation in systems biology.

    Science.gov (United States)

    Székely, Tamás; Burrage, Kevin

    2014-11-01

    Natural systems are, almost by definition, heterogeneous: this can be either a boon or an obstacle to be overcome, depending on the situation. Traditionally, when constructing mathematical models of these systems, heterogeneity has typically been ignored, despite its critical role. However, in recent years, stochastic computational methods have become commonplace in science. They are able to appropriately account for heterogeneity; indeed, they are based around the premise that systems inherently contain at least one source of heterogeneity (namely, intrinsic heterogeneity). In this mini-review, we give a brief introduction to theoretical modelling and simulation in systems biology and discuss the three different sources of heterogeneity in natural systems. Our main topic is an overview of stochastic simulation methods in systems biology. There are many different types of stochastic methods. We focus on one group that has become especially popular in systems biology, biochemistry, chemistry and physics. These discrete-state stochastic methods do not follow individuals over time; rather they track only total populations. They also assume that the volume of interest is spatially homogeneous. We give an overview of these methods, with a discussion of the advantages and disadvantages of each, and suggest when each is more appropriate to use. We also include references to software implementations of them, so that beginners can quickly start using stochastic methods for practical problems of interest.

  16. 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.

  17. [Research progress of cardiac systems biology].

    Science.gov (United States)

    Wang, Juan; Shang, Tong

    2009-04-01

    Systems Biology is one of the most widely discussed fields among emerging post-genomic disciplines. Medical systems biology is an important component of systems biology. The goals of medical systems biology are gaining a complete understanding of human body in normal and disease states. Driven by the great importance of cardiovascular diseases, cardiac systems biology is improving rapidly. This review provides an overview of major themes in the developing field of cardiac systems biology, including some of the high-throughput experiments and strategies used to integrate the datasets, various types of computational approaches used for developing useful quantitative models, and successful examples, future directions of cardiac systems biology.

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

    Science.gov (United States)

    Chen, Bor-Sen; Wu, Chia-Chou

    2013-10-11

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

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

    Directory of Open Access Journals (Sweden)

    Bor-Sen Chen

    2013-10-01

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

  20. Handling Biological Complexity Using Kron Reduction

    NARCIS (Netherlands)

    Jayawardhana, Bayu; Rao, Shodhan; Sikkema, Ward; Bakker, Barbara; Camlibel, Kanat; Julius, Agung; Pasumarthy, Ramkrishna; Scherpen, Jacquelien

    2015-01-01

    We revisit a model reduction method for detailed-balanced chemical reaction networks based on Kron reduction on the graph of complexes. The resulting reduced model preserves a number of important properties of the original model, such as, the kinetics law and identity of the chemical species. For de

  1. 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.

  2. 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.

  3. Analyzing the Biology on the System Level

    OpenAIRE

    Tong, Wei

    2016-01-01

    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,...

  4. Systems biology solutions for biochemical production challenges

    DEFF Research Database (Denmark)

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

    2017-01-01

    There is an urgent need to significantly accelerate the development of microbial cell factories to produce fuels and chemicals from renewable feedstocks in order to facilitate the transition to a biobased society. Methods commonly used within the field of systems biology including omics character......There is an urgent need to significantly accelerate the development of microbial cell factories to produce fuels and chemicals from renewable feedstocks in order to facilitate the transition to a biobased society. Methods commonly used within the field of systems biology including omics...... characterization, genome-scale metabolic modeling, and adaptive laboratory evolution can be readily deployed in metabolic engineering projects. However, high performance strains usually carry tens of genetic modifications and need to operate in challenging environmental conditions. This additional complexity...... compared to basic science research requires pushing systems biology strategies to their limits and often spurs innovative developments that benefit fields outside metabolic engineering. Here we survey recent advanced applications of systems biology methods in engineering microbial production strains...

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. [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.

  10. 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.

  11. 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...

  12. 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.

  13. 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.

  14. Using Simple Manipulatives to Improve Student Comprehension of a Complex Biological Process: Protein Synthesis

    Science.gov (United States)

    Guzman, Karen; Bartlett, John

    2012-01-01

    Biological systems and living processes involve a complex interplay of biochemicals and macromolecular structures that can be challenging for undergraduate students to comprehend and, thus, misconceptions abound. Protein synthesis, or translation, is an example of a biological process for which students often hold many misconceptions. This article…

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

    DEFF Research Database (Denmark)

    Fletcher, Eugene; Krivoruchko, Anastasia; Nielsen, Jens

    2016-01-01

    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...

  16. 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.

  17. 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.

  18. Decavanadate effects in biological systems.

    Science.gov (United States)

    Aureliano, Manuel; Gândara, Ricardo M C

    2005-05-01

    Vanadium biological studies often disregarded the formation of decameric vanadate species known to interact, in vitro, with high-affinity with many proteins such as myosin and sarcoplasmic reticulum calcium pump and also to inhibit these biochemical systems involved in energy transduction. Moreover, very few in vivo animal studies involving vanadium consider the contribution of decavanadate to vanadium biological effects. Recently, it has been shown that an acute exposure to decavanadate but not to other vanadate oligomers induced oxidative stress and a different fate in vanadium intracellular accumulation. Several markers of oxidative stress analyzed on hepatic and cardiac tissue were monitored after in vivo effect of an acute exposure (12, 24 h and 7 days), to a sub-lethal concentration (5 mM; 1 mg/kg) of two vanadium solutions ("metavanadate" and "decavanadate"). It was observed that "decavanadate" promote different effects than other vanadate oligomers in catalase activity, glutathione content, lipid peroxidation, mitochondrial superoxide anion production and vanadium accumulation, whereas both solutions seem to equally depress reactive oxygen species (ROS) production as well as total intracellular reducing power. Vanadium is accumulated in mitochondria in particular when "decavanadate" is administered. These recent findings, that are now summarized, point out the decameric vanadate species contributions to in vivo and in vitro effects induced by vanadium in biological systems.

  19. A Systems Biology Starter Kit for Arenaviruses

    Directory of Open Access Journals (Sweden)

    Magali E. Droniou-Bonzom

    2012-12-01

    Full Text Available Systems biology approaches in virology aim to integrate viral and host biological networks, and thus model the infection process. The growing availability of high-throughput “-omics” techniques and datasets, as well as the ever-increasing sophistication of in silico modeling tools, has resulted in a corresponding rise in the complexity of the analyses that can be performed. The present study seeks to review and organize published evidence regarding virus-host interactions for the arenaviruses, from alterations in the host proteome during infection, to reported protein-protein interactions. In this way, we hope to provide an overview of the interplay between arenaviruses and the host cell, and lay the foundations for complementing current arenavirus research with a systems-level approach.

  20. A systems biology starter kit for arenaviruses.

    Science.gov (United States)

    Droniou-Bonzom, Magali E; Cannon, Paula M

    2012-12-01

    Systems biology approaches in virology aim to integrate viral and host biological networks, and thus model the infection process. The growing availability of high-throughput “-omics” techniques and datasets, as well as the ever-increasing sophistication of in silico modeling tools, has resulted in a corresponding rise in the complexity of the analyses that can be performed. The present study seeks to review and organize published evidence regarding virus-host interactions for the arenaviruses, from alterations in the host proteome during infection, to reported protein-protein interactions. In this way, we hope to provide an overview of the interplay between arenaviruses and the host cell, and lay the foundations for complementing current arenavirus research with a systems-level approach.

  1. 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...

  2. An Automated Biological Dosimetry System

    Science.gov (United States)

    Lorch, T.; Bille, J.; Frieben, M.; Stephan, G.

    1986-04-01

    The scoring of structural chromosome aberrations in peripheral human blood lymphocytes can be used in biological dosimetry to estimate the radiation dose which an individual has received. Especially the dicentric chromosome is a rather specific indicator for an exposure to ionizing radiation. For statistical reasons, in the low dose range a great number of cells must be analysed, which is a very tedious task. The resulting high cost of a biological dose estimation limits the application of this method to cases of suspected irradiation for which physical dosimetry is not possible or not sufficient. Therefore an automated system has been designed to do the major part of the routine work. It uses a standard light microscope with motorized scanning stage, a Plumbicon TV-camera, a real-time hardware preprocessor, a binary and a grey level image buffer system. All computations are performed by a very powerful multi-microprocessor-system (POLYP) based on a MIMD-architecture. The task of the automated system can be split in finding the metaphases (see Figure 1) at low microscope magnification and scoring dicentrics at high magnification. The metaphase finding part has been completed and is now in routine use giving good results. The dicentric scoring part is still under development.

  3. Small RNA biology is systems biology.

    Science.gov (United States)

    Jost, Daniel; Nowojewski, Andrzej; Levine, Erel

    2011-01-01

    During the last decade small regulatory RNA (srRNA) emerged as central players in the regulation of gene expression in all kingdoms of life. Multiple pathways for srRNA biogenesis and diverse mechanisms of gene regulation may indicate that srRNA regulation evolved independently multiple times. However, small RNA pathways share numerous properties, including the ability of a single srRNA to regulate multiple targets. Some of the mechanisms of gene regulation by srRNAs have significant effect on the abundance of free srRNAs that are ready to interact with new targets. This results in indirect interactions among seemingly unrelated genes, as well as in a crosstalk between different srRNA pathways. Here we briefly review and compare the major srRNA pathways, and argue that the impact of srRNA is always at the system level. We demonstrate how a simple mathematical model can ease the discussion of governing principles. To demonstrate these points we review a few examples from bacteria and animals.

  4. 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...

  5. [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.

  6. Systems biology of ageing and longevity.

    Science.gov (United States)

    Kirkwood, Thomas B L

    2011-01-12

    Ageing is intrinsically complex, being driven by multiple causal mechanisms. Each mechanism tends to be partially supported by data indicating that it has a role in the overall cellular and molecular pathways underlying the ageing process. However, the magnitude of this role is usually modest. The systems biology approach combines (i) data-driven modelling, often using the large volumes of data generated by functional genomics technologies, and (ii) hypothesis-driven experimental studies to investigate causal pathways and identify their parameter values in an unusually quantitative manner, which enables the contributions of individual mechanisms and their interactions to be better understood, and allows for the design of experiments explicitly to test the complex predictions arising from such models. A clear example of the success of the systems biology approach in unravelling the complexity of ageing can be seen in recent studies on cell replicative senescence, revealing interactions between mitochondrial dysfunction, telomere erosion and DNA damage. An important challenge also exists in connecting the network of (random) damage-driven proximate mechanisms of ageing with the higher level (genetically specified) signalling pathways that influence longevity. This connection is informed by actions of natural selection on the determinants of ageing and longevity.

  7. 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.

  8. Tunable promoters in systems biology

    DEFF Research Database (Denmark)

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

    2005-01-01

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

  9. Systems biology of Microbial Communities

    Energy Technology Data Exchange (ETDEWEB)

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

    2008-04-11

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

  10. KPFM and PFM of Biological Systems

    Energy Technology Data Exchange (ETDEWEB)

    Rodriguez, Brian [University College, Dublin; Kalinin, Sergei V [ORNL

    2011-01-01

    Surface potentials and electrostatic interactions in biological systems are a key element of cellular regulation and interaction. Examples include cardiac and muscular activity, voltage-gated ion channels, protein folding and assembly, and electroactive cells and electrotransduction. The coupling between electrical, mechanical, and chemical signals and responses in cellular systems necessitates the development of tools capable of measuring the distribution of charged species, surface potentials, and mechanical responses to applied electrical stimuli and vice versa, ultimately under physiological conditions. In this chapter, applications of voltage-modulated atomic force microscopy (AFM) methods including Kelvin probe force microscopy (KPFM) and piezoresponse force microscopy (PFM) to biological systems are discussed. KPFM is a force-sensitive non-contact or intermittent-contact mode AFM technique that allows electrostatic interactions and surface potentials to be addressed. Beyond long-range electrostatic interactions, the application of bias can lead to a mechanical response, e.g., due to linear piezoelectric coupling in polar biopolymers or via more complex electrotransduction and redox pathways in other biosystems. The use and development of PFM, based on direct electromechanical detection, to biological systems will also be addressed. The similarities and limitations of measuring surface potentials and electromechanical coupling in solution will be outlined.

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

    NARCIS (Netherlands)

    MacLeod, Miles; Nersessian, Nancy J.

    2016-01-01

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

  12. Systems biology characterization of engineered tissues.

    Science.gov (United States)

    Rajagopalan, Padmavathy; Kasif, Simon; Murali, T M

    2013-01-01

    Tissue engineering and molecular systems biology are inherently interdisciplinary fields that have been developed independently so far. In this review, we first provide a brief introduction to tissue engineering and to molecular systems biology. Next, we highlight some prominent applications of systems biology techniques in tissue engineering. Finally, we outline research directions that can successfully blend these two fields. Through these examples, we propose that experimental and computational advances in molecular systems biology can lead to predictive models of bioengineered tissues that enhance our understanding of bioengineered systems. In turn, the unique challenges posed by tissue engineering will usher in new experimental techniques and computational advances in systems biology.

  13. 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...

  14. 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

  15. 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.

  16. Waves in complex systems

    Science.gov (United States)

    Xie, Hang

    The theme of this thesis is the study of wave phenomena in complex systems. In particular, the following three topics constitute the foci of my research. The first topic involves the generalization of an electronic transport mechanism commonly observed in disordered media, fluctuation induced tunneling conduction, by considering tunneling through not just insulating potential barriers, but also narrow conducting channels. Here the wave nature of the electron implies that a narrow conduction channel can act as an electronic waveguide, with a cutoff transverse dimension that is half the Fermi wavelength. My research involves the study of electronic transport through finite-length conducting channels with transverse dimensions below the cutoff. Such narrow conduction channel may be physically realized by chains of single conducting atoms, for example. At small voltage bias across the conduction channel, only tunneling transport is possible at zero temperature. But at finite temperatures some of the electrons with energies above the Fermi level can ballistically transport across the channel. By considering both tunneling and thermal activation mechanisms, with thermally-generated (random) voltage bias across the narrow channel, we obtained a temperature-dependent conductivity behavior that is in good agreement with the measured two-lead conductance of RuO2 and IrO2 nanowires. Furthermore, by considering high applied voltage across the nano conduction channels, our model predicts interesting electronic Fabry-Perot behavior whose experimental verification is presently underway. The second topic involves the study of the Hall effect in mesoscopic samples. In particular, we are interested in the possibility of enhancing the Hall effect by nano-patterning samples of 2D electron gas. Through numerical solution of the Schrodinger equation in the presence of a magnetic field, mesoscopic transport behavior is obtained for samples with given geometric patterns of the

  17. Temperature Dependence of Biological Tissues Complex Permitivity at Microwave Frequencies

    Directory of Open Access Journals (Sweden)

    Dagmar Faktorova

    2008-01-01

    Full Text Available In the paper an universal overview of polarizing mechanisms with an emphasis on dipolar materials as the investigated tissues are regarded. Experimental apparatus is presented with giving its specificity as well as the method used at calculation of complex permittivity. The experimental part is aimed at temperature dependence of complex permittivity measurement of pig biological tissues with different properties. Experimental results are presented graphically with the commentary for courses of particular tissues.

  18. Temperature Dependence of Biological Tissues Complex Permitivity at Microwave Frequencies

    OpenAIRE

    Dagmar Faktorova

    2008-01-01

    In the paper an universal overview of polarizing mechanisms with an emphasis on dipolar materials as the investigated tissues are regarded. Experimental apparatus is presented with giving its specificity as well as the method used at calculation of complex permittivity. The experimental part is aimed at temperature dependence of complex permittivity measurement of pig biological tissues with different properties. Experimental results are presented graphically with the commentary for courses o...

  19. 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.

  20. Quantum Effects in Biological Systems

    Science.gov (United States)

    Roy, Sisir

    2014-07-01

    The debates about the trivial and non-trivial effects in biological systems have drawn much attention during the last decade or so. What might these non-trivial sorts of quantum effects be? There is no consensus so far among the physicists and biologists regarding the meaning of "non-trivial quantum effects". However, there is no doubt about the implications of the challenging research into quantum effects relevant to biology such as coherent excitations of biomolecules and photosynthesis, quantum tunneling of protons, van der Waals forces, ultrafast dynamics through conical intersections, and phonon-assisted electron tunneling as the basis for our sense of smell, environment assisted transport of ions and entanglement in ion channels, role of quantum vacuum in consciousness. Several authors have discussed the non-trivial quantum effects and classified them into four broad categories: (a) Quantum life principle; (b) Quantum computing in the brain; (c) Quantum computing in genetics; and (d) Quantum consciousness. First, I will review the above developments. I will then discuss in detail the ion transport in the ion channel and the relevance of quantum theory in brain function. The ion transport in the ion channel plays a key role in information processing by the brain.

  1. 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…

  2. 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.

  3. 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.

  4. 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.

  5. Study of the structure and dynamics of complex biological networks

    Science.gov (United States)

    Samal, Areejit

    2008-12-01

    In this thesis, we have studied the large scale structure and system level dynamics of certain biological networks using tools from graph theory, computational biology and dynamical systems. We study the structure and dynamics of large scale metabolic networks inside three organisms, Escherichia coli, Saccharomyces cerevisiae and Staphylococcus aureus. We also study the dynamics of the large scale genetic network controlling E. coli metabolism. We have tried to explain the observed system level dynamical properties of these networks in terms of their underlying structure. Our studies of the system level dynamics of these large scale biological networks provide a different perspective on their functioning compared to that obtained from purely structural studies. Our study also leads to some new insights on features such as robustness, fragility and modularity of these large scale biological networks. We also shed light on how different networks inside the cell such as metabolic networks and genetic networks are interrelated to each other.

  6. 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.

  7. 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...

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

    OpenAIRE

    Hana Koorehdavoudi; Paul Bogdan

    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 t...

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

    Science.gov (United States)

    Bochynek, Thomas; Robson, Simon K A

    2014-01-01

    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.

  10. 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.

  11. 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.

  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. 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

  14. Biologically inspired autonomouse system; Seibutsugata jiritsu system

    Energy Technology Data Exchange (ETDEWEB)

    Yuta, S. [Tsukuba Univ., Ibaraki (Japan)

    1996-04-10

    The intelligence robot was begun to try to make up a machine to imitate the human intelligent actions as a model of human thoughts. However, robots created with the results of traditional artificial intelligence based on the logical knowledge impression and logic judgement have been found to be unable to realize the usual actions conducted by humans and animals even though having superior brains or remembrances. Research on `The biological inspired autonomous robots` in the intelligence robots, aims to peruse a method to realize on a machine not for high class intelligence capable to execute logical thoughts down by human but for intelligence corresponding to ability response to environment autonomously and to live in a given environment which is had even by animals except human being. Here is examined on the non-human biological type robot and its intelligence under a center of research on the biological inspired autonomous system in the intelligence robots, and is outlined on their research field. 2 refs., 1 fig.

  15. Measuring Complexity of SAP Systems

    Directory of Open Access Journals (Sweden)

    Ilja Holub

    2016-10-01

    Full Text Available The paper discusses the reasons of complexity rise in ERP system SAP R/3. It proposes a method for measuring complexity of SAP. Based on this method, the computer program in ABAP for measuring complexity of particular SAP implementation is proposed as a tool for keeping ERP complexity under control. The main principle of the measurement method is counting the number of items or relations in the system. The proposed computer program is based on counting of records in organization tables in SAP.

  16. 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,...

  17. 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...

  18. 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.

  19. Applicability of Computational Systems Biology in Toxicology

    DEFF Research Database (Denmark)

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

    2014-01-01

    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...... 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...

  20. 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.

  1. 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.

  2. Gold complexes with benzimidazole derivatives: synthesis, characterization and biological studies.

    Science.gov (United States)

    Mota, Vinicius Zamprogno; de Carvalho, Gustavo Senra Gonçalves; da Silva, Adilson David; Costa, Luiz Antônio Sodré; de Almeida Machado, Patrícia; Coimbra, Elaine Soares; Ferreira, Carmen Veríssima; Shishido, Silvia Mika; Cuin, Alexandre

    2014-02-01

    Synthesis, characterization, DFT studies and biological assays of new gold(I) and gold(III) complexes of benzimidazole are reported. Molecular and structural characterizations of the compounds were based on elemental (C, H and N) and thermal (TG-DTA) analyses, and FT-IR and UV-Visible spectroscopic measurements. The structures of complexes were proposed based DFT calculations. The benzimidazole compounds (Lig1 and Lig2) and the gold complexes were tested against three Leishmania species related to cutaneous manifestations of leishmaniasis. The free benzimidazole compounds showed no leishmanicidal activity. On the other hand, the gold(I and III) complexes have shown to possess significant activity against Leishmania in both stages of parasite, and the gold(III) complex with Lig2 exhibited expressive leishmanicidal activity with IC50 values below 5.7 μM. Also, the gold complexes showed high leishmania selectivity. The gold(I) complex with Lig1, for example, is almost 50 times more toxic for the parasite than for macrophages. Besides the leishmanicidal activity, all complexes exhibited toxic effect against SK-Mel 103 and Balb/c 3T3, cancer cells.

  3. Methods of information geometry in computational system biology (consistency between chemical and biological evolution).

    Science.gov (United States)

    Astakhov, Vadim

    2009-01-01

    Interest in simulation of large-scale metabolic networks, species development, and genesis of various diseases requires new simulation techniques to accommodate the high complexity of realistic biological networks. Information geometry and topological formalisms are proposed to analyze information processes. We analyze the complexity of large-scale biological networks as well as transition of the system functionality due to modification in the system architecture, system environment, and system components. The dynamic core model is developed. The term dynamic core is used to define a set of causally related network functions. Delocalization of dynamic core model provides a mathematical formalism to analyze migration of specific functions in biosystems which undergo structure transition induced by the environment. The term delocalization is used to describe these processes of migration. We constructed a holographic model with self-poetic dynamic cores which preserves functional properties under those transitions. Topological constraints such as Ricci flow and Pfaff dimension were found for statistical manifolds which represent biological networks. These constraints can provide insight on processes of degeneration and recovery which take place in large-scale networks. We would like to suggest that therapies which are able to effectively implement estimated constraints, will successfully adjust biological systems and recover altered functionality. Also, we mathematically formulate the hypothesis that there is a direct consistency between biological and chemical evolution. Any set of causal relations within a biological network has its dual reimplementation in the chemistry of the system environment.

  4. 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.

  5. 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.

  6. Anomaly Detection for Complex Systems

    Data.gov (United States)

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

  7. 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.

  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. Systems biology and cardiac arrhythmias.

    Science.gov (United States)

    Grace, Andrew A; Roden, Dan M

    2012-10-27

    During the past few years, the development of effective, empirical technologies for treatment of cardiac arrhythmias has exceeded the pace at which detailed knowledge of the underlying biology has accumulated. As a result, although some clinical arrhythmias can be cured with techniques such as catheter ablation, drug treatment and prediction of the risk of sudden death remain fairly primitive. The identification of key candidate genes for monogenic arrhythmia syndromes shows that to bring basic biology to the clinic is a powerful approach. Increasingly sophisticated experimental models and methods of measurement, including stem cell-based models of human cardiac arrhythmias, are being deployed to study how perturbations in several biologic pathways can result in an arrhythmia-prone heart. The biology of arrhythmia is largely quantifiable, which allows for systematic analysis that could transform treatment strategies that are often still empirical into management based on molecular evidence.

  10. Multi-scale modelling and simulation in systems biology.

    Science.gov (United States)

    Dada, Joseph O; Mendes, Pedro

    2011-02-01

    The aim of systems biology is to describe and understand biology at a global scale where biological functions are recognised as a result of complex mechanisms that happen at several scales, from the molecular to the ecosystem. Modelling and simulation are computational tools that are invaluable for description, prediction and understanding these mechanisms in a quantitative and integrative way. Therefore the study of biological functions is greatly aided by multi-scale methods that enable the coupling and simulation of models spanning several spatial and temporal scales. Various methods have been developed for solving multi-scale problems in many scientific disciplines, and are applicable to continuum based modelling techniques, in which the relationship between system properties is expressed with continuous mathematical equations or discrete modelling techniques that are based on individual units to model the heterogeneous microscopic elements such as individuals or cells. In this review, we survey these multi-scale methods and explore their application in systems biology.

  11. 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.

  12. Systems Biology and Ecology of Streamlined Bacterioplankton

    Science.gov (United States)

    Giovannoni, S. J.

    2014-12-01

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

  13. Micro-separation toward systems biology.

    Science.gov (United States)

    Liu, Bi-Feng; Xu, Bo; Zhang, Guisen; Du, Wei; Luo, Qingming

    2006-02-17

    Current biology is experiencing transformation in logic or philosophy that forces us to reevaluate the concept of cell, tissue or entire organism as a collection of individual components. Systems biology that aims at understanding biological system at the systems level is an emerging research area, which involves interdisciplinary collaborations of life sciences, computational and mathematical sciences, systems engineering, and analytical technology, etc. For analytical chemistry, developing innovative methods to meet the requirement of systems biology represents new challenges as also opportunities and responsibility. In this review, systems biology-oriented micro-separation technologies are introduced for comprehensive profiling of genome, proteome and metabolome, characterization of biomolecules interaction and single cell analysis such as capillary electrophoresis, ultra-thin layer gel electrophoresis, micro-column liquid chromatography, and their multidimensional combinations, parallel integrations, microfabricated formats, and nano technology involvement. Future challenges and directions are also suggested.

  14. 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

  15. 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.

  16. 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...

  17. 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.

  18. 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.

  19. 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

  20. 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.

  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. Yeast systems biology to unravel the network of life

    DEFF Research Database (Denmark)

    Mustacchi, Roberta; Hohmann, S; Nielsen, Jens

    2006-01-01

    Systems biology focuses on obtaining a quantitative description of complete biological systems, even complete cellular function. In this way, it will be possible to perform computer-guided design of novel drugs, advanced therapies for treatment of complex diseases, and to perform in silico design...... of advanced cell factories for production of fuels, chemicals, food ingredients and pharmaceuticals. The yeast Saccharomyces cerevisiae represents an excellent model system; the density of biological information available on this organism allows it to serve as a eukaryotic model for studying human diseases....... Furthermore, it serves as an industrial workhorse for production of a wide range of chemicals and pharmaceuticals. Systems biology involves the combination of novel experimental techniques from different disciplines as well as functional genomics, bioinformatics and mathematical modelling, and hence no single...

  3. Software for systems biology: from tools to integrated platforms.

    Science.gov (United States)

    Ghosh, Samik; Matsuoka, Yukiko; Asai, Yoshiyuki; Hsin, Kun-Yi; Kitano, Hiroaki

    2011-11-03

    Understanding complex biological systems requires extensive support from software tools. Such tools are needed at each step of a systems biology computational workflow, which typically consists of data handling, network inference, deep curation, dynamical simulation and model analysis. In addition, there are now efforts to develop integrated software platforms, so that tools that are used at different stages of the workflow and by different researchers can easily be used together. This Review describes the types of software tools that are required at different stages of systems biology research and the current options that are available for systems biology researchers. We also discuss the challenges and prospects for modelling the effects of genetic changes on physiology and the concept of an integrated platform.

  4. Kirigami artificial muscles with complex biologically inspired morphologies

    Science.gov (United States)

    Sareh, Sina; Rossiter, Jonathan

    2013-01-01

    In this paper we present bio-inspired smart structures which exploit the actuation of flexible ionic polymer composites and the kirigami design principle. Kirigami design is used to convert planar actuators into active 3D structures capable of large out-of-plane displacement and that replicate biological mechanisms. Here we present the burstbot, a fluid control and propulsion mechanism based on the atrioventricular cuspid valve, and the vortibot, a spiral actuator based on Vorticella campanula, a ciliate protozoa. Models derived from biological counterparts are used as a platform for design optimization and actuator performance measurement. The symmetric and asymmetric fluid interactions of the burstbot are investigated and the effectiveness in fluid transport applications is demonstrated. The vortibot actuator is geometrically optimized as a camera positioner capable of 360° scanning. Experimental results for a one-turn spiral actuator show complex actuation derived from a single degree of freedom control signal.

  5. 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.

  6. Systems Biology of Metabolism: A Driver for Developing Personalized and Precision Medicine

    DEFF Research Database (Denmark)

    Nielsen, Jens

    2017-01-01

    Systems biology uses mathematical models to analyze large datasets and simulate system behavior. It enables integrative analysis of different types of data and can thereby provide new insight into complex biological systems. Here will be discussed the challenges of using systems medicine for adva......Systems biology uses mathematical models to analyze large datasets and simulate system behavior. It enables integrative analysis of different types of data and can thereby provide new insight into complex biological systems. Here will be discussed the challenges of using systems medicine...

  7. 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.

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

    Science.gov (United States)

    Degrazio, Dominick

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

  9. 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...

  10. 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.

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

    CERN Document Server

    Prisecaru, V I

    2004-01-01

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

  12. 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.

  13. 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.

  14. Responses to Low Doses of Ionizing Radiation in Biological Systems

    OpenAIRE

    Feinendegen, Ludwig E.; Pollycove, Myron; Sondhaus, Charles A.

    2004-01-01

    Biological tissues operate through cells that act together within signaling networks. These assure coordinated cell function in the face of constant exposure to an array of potentially toxic agents, externally from the environment and endogenously from metabolism. Living tissues are indeed complex adaptive systems.

  15. 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.

  16. Integrating Biological Systems in the Process Dynamics and Control Curriculum

    Science.gov (United States)

    Parker, Robert S.; Doyle, Francis J.; Henson, Michael A.

    2006-01-01

    The evolution of the chemical engineering discipline motivates a re-evaluation of the process dynamics and control curriculum. A key requirement of future courses will be the introduction of theoretical concepts and application examples relevant to emerging areas, notably complex biological systems. We outline the critical concepts required to…

  17. The rational design of biological complexity: a deceptive metaphor.

    Science.gov (United States)

    Van Regenmortel, Marc H V

    2007-03-01

    Biologists often claim that they follow a rational design strategy when their research is based on molecular knowledge of biological systems. This claim implies that their knowledge of the innumerable causal connections present in biological systems is sufficient to allow them to deduce and predict the outcome of their experimental interventions. The design metaphor is shown to originate in human intentionality and in the anthropomorphic fallacy of interpreting objects, events, and the behavior of all living organisms in terms of goals and purposes. Instead of presenting rational design as an effective research strategy, it would be preferable to acknowledge that advances in biomedicine are nearly always derived from empirical observations based on trial and error experimentation. The claim that rational design is an effective research strategy was tested in the case of current attempts to develop synthetic vaccines, in particular against human immunodeficiency virus. It was concluded that in this field of biomedicine, trial and error experimentation is more likely to succeed than a rational design approach. Current developments in systems biology may give us eventually a better understanding of the immune system and this may enable us in the future to develop improved vaccines.

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

    Science.gov (United States)

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

    2014-03-24

    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, AbDesigner (http://helixweb.nih.gov/AbDesigner/), to help researchers select optimal peptide immunogens for antibody generation against relatively disordered regions of target proteins. Here we describe AbDesigner in terms of its features, comparing it to other software tools, and use it to design three antibodies against kidney disease-related proteins in human, viz. nephrin, podocin, and apolipoprotein L1.

  19. 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.

  20. Carbon Nanotubes – Interactions with Biological Systems

    OpenAIRE

    Reis, Joana; Capela-Silva, Fernando; Potes, José; Fonseca, Alexandra; Oliveira, Mónica; Kanagaraj, Subramani; Marques, António Torres

    2011-01-01

    his book chapter discusses the prospective biomedical applications of carbon nanotubes based materials, the impact of carbon nanotubes properties in the interaction with biological systems. Protein adsorption, impact on cell viability and cytokine production are explored. Potential respiratory and dermal toxicity are reviewed, as the difficulties on studying the biological response. In face of recent studies, special attention is drawn upon promising orthopaedic use.

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

    Directory of Open Access Journals (Sweden)

    Putty-Reddy Sudhir

    2016-03-01

    Full Text Available 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.

  2. Discovering large network motifs from a complex biological network

    Energy Technology Data Exchange (ETDEWEB)

    Terada, Aika; Sese, Jun, E-mail: terada@sel.is.ocha.ac.j, E-mail: sesejun@is.ocha.ac.j [Department of Computer Science, Ochanomizu University, 2-1-1 Ohtsuka, Bunkyo-ku, Tokyo 112-8610 (Japan)

    2009-12-01

    Graph structures representing relationships between entries have been studied in statistical analysis, and the results of these studies have been applied to biological networks, whose nodes and edges represent proteins and the relationships between them, respectively. Most of the studies have focused on only graph structures such as scale-free properties and cliques, but the relationships between nodes are also important features since most of the proteins perform their functions by connecting to other proteins. In order to determine such relationships, the problem of network motif discovery has been addressed; network motifs are frequently appearing graph structures in a given graph. However, the methods for network motif discovery are highly restrictive for the application to biological network because they can only be used to find small network motifs or they do not consider noise and uncertainty in observations. In this study, we introduce a new index to measure network motifs called AR index and develop a novel algorithm called ARIANA for finding large motifs even when the network has noise. Experiments using a synthetic network verify that our method can find better network motifs than an existing algorithm. By applying ARIANA to a real complex biological network, we find network motifs associated with regulations of start time of cell functions and generation of cell energies and discover that the cell cycle proteins can be categorized into two different groups.

  3. Lectures in Complex Systems (1991)

    Science.gov (United States)

    1992-08-05

    T. Hecht, A. Hiibler, and E. Luscher . "Skalengesetze fur den Maximalen Energieaustausch Nichtlinearer Gekoppelter Systeme." Natur- wissenschaften 74...1987): 336. 4. Eisenhammer, T. A., A. Hiibler, T. Geisel, and E. LUscher . "Scaling Behavior of the Maximum Energy Exchange Between Coupled Anharmonic...Chaos in the Forced Pendulum." Phys. Rev. A 26 (1982): 3483. 7. Hiibler, A and E. Luscher . "Resonant Stimulation and Control of Complex Systems." Helv

  4. Quantum contextuality in complex systems

    CERN Document Server

    Cabello, Adan

    2010-01-01

    We show that, for a system of several qubits, there is an inequality for the correlations between three compatible dichotomic measurements which must be satisfied by any noncontextual theory, but is violated by any quantum state. Remarkably, the violation grows exponentially with the number of qubits, and the tolerated error per correlation also increases with the number of qubits, showing that state-independent quantum contextuality is experimentally observable in complex systems.

  5. Biological Systems, Energy Sources, and Biology Teaching. Biology and Human Welfare.

    Science.gov (United States)

    Tribe, Michael; Pritchard, Alan J.

    This five-chapter document (part of a series on biology and human welfare) focuses on biological systems as energy sources and on the teaching of this subject area. Chapter 1 discusses various topics related to energy and ecology, including biomass, photosynthesis and world energy balances, energy flow through ecosystems, and others. Chapter 2…

  6. 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

  7. 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.

  8. Systems Biology and Synthetic Biology: A New Epoch for Toxicology Research

    Directory of Open Access Journals (Sweden)

    Mark T. Mc Auley

    2015-01-01

    Full Text Available Systems biology and synthetic biology are emerging disciplines which are becoming increasingly utilised in several areas of bioscience. Toxicology is beginning to benefit from systems biology and we suggest in the future that is will also benefit from synthetic biology. Thus, a new era is on the horizon. This review illustrates how a suite of innovative techniques and tools can be applied to understanding complex health and toxicology issues. We review limitations confronted by the traditional computational approaches to toxicology and epidemiology research, using polycyclic aromatic hydrocarbons (PAHs and their effects on adverse birth outcomes as an illustrative example. We introduce how systems toxicology (and their subdisciplines, genomic, proteomic, and metabolomic toxicology will help to overcome such limitations. In particular, we discuss the advantages and disadvantages of mathematical frameworks that computationally represent biological systems. Finally, we discuss the nascent discipline of synthetic biology and highlight relevant toxicological centred applications of this technique, including improvements in personalised medicine. We conclude this review by presenting a number of opportunities and challenges that could shape the future of these rapidly evolving disciplines.

  9. 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.

  10. Disorder in Complex Human System

    Science.gov (United States)

    Akdeniz, K. Gediz

    2011-11-01

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

  11. 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...

  12. 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.

  13. Systems and synthetic biology as emerging technosciences

    Directory of Open Access Journals (Sweden)

    Karen Kastenhofer

    2016-12-01

    Full Text Available Systems and synthetic biology can be understood as emerging technosciences. Both are characteristically shaped by promises and visions, a certain logic and function of labelling, specific forms of social organisation, an embedding in specific regimes of funding and innovation as well as a characteristic matrix of orientations within research practice. This characteristic constitution of systems and synthetic biology has fundamental consequences for scientific practice, its analysis and its governance.

  14. Design and control strategies for CELSS - Integrating mechanistic paradigms and biological complexities

    Science.gov (United States)

    Moore, B., III; Kaufmann, R.; Reinhold, C.

    1981-01-01

    Systems analysis and control theory consideration are given to simulations of both individual components and total systems, in order to develop a reliable control strategy for a Controlled Ecological Life Support System (CELSS) which includes complex biological components. Because of the numerous nonlinearities and tight coupling within the biological component, classical control theory may be inadequate and the statistical analysis of factorial experiments more useful. The range in control characteristics of particular species may simplify the overall task by providing an appropriate balance of stability and controllability to match species function in the overall design. The ultimate goal of this research is the coordination of biological and mechanical subsystems in order to achieve a self-supporting environment.

  15. BioFNet: biological functional network database for analysis and synthesis of biological systems.

    Science.gov (United States)

    Kurata, Hiroyuki; Maeda, Kazuhiro; Onaka, Toshikazu; Takata, Takenori

    2014-09-01

    In synthetic biology and systems biology, a bottom-up approach can be used to construct a complex, modular, hierarchical structure of biological networks. To analyze or design such networks, it is critical to understand the relationship between network structure and function, the mechanism through which biological parts or biomolecules are assembled into building blocks or functional networks. A functional network is defined as a subnetwork of biomolecules that performs a particular function. Understanding the mechanism of building functional networks would help develop a methodology for analyzing the structure of large-scale networks and design a robust biological circuit to perform a target function. We propose a biological functional network database, named BioFNet, which can cover the whole cell at the level of molecular interactions. The BioFNet takes an advantage in implementing the simulation program for the mathematical models of the functional networks, visualizing the simulated results. It presents a sound basis for rational design of biochemical networks and for understanding how functional networks are assembled to create complex high-level functions, which would reveal design principles underlying molecular architectures.

  16. 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.

    Directory of Open Access Journals (Sweden)

    Philipp Widmann

    Full Text Available 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

  17. GPU-powered Simulation Methodologies for Biological Systems

    Directory of Open Access Journals (Sweden)

    Dario Pescini

    2013-09-01

    Full Text Available The study of biological systems witnessed a pervasive cross-fertilization between experimental investigation and computational methods. This gave rise to the development of new methodologies, able to tackle the complexity of biological systems in a quantitative manner. Computer algorithms allow to faithfully reproduce the dynamics of the corresponding biological system, and, at the price of a large number of simulations, it is possible to extensively investigate the system functioning across a wide spectrum of natural conditions. To enable multiple analysis in parallel, using cheap, diffused and highly efficient multi-core devices we developed GPU-powered simulation algorithms for stochastic, deterministic and hybrid modeling approaches, so that also users with no knowledge of GPUs hardware and programming can easily access the computing power of graphics engines.

  18. Modeling of biological intelligence for SCM system optimization.

    Science.gov (United States)

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

    2012-01-01

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

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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)

    2012-01-01

    The invention provides systems and methods for manipulating, e.g., optimizing and controlling, biological systems, e.g., for eliciting a more desired biological response of biological sample, such as a tissue, organ, and/or a cell. In one aspect, systems and methods of the invention operate 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, e.g., a bioreactor. In alternative aspects, systems include a device for sustaining cells or tissue samples, one or more actuators for stimulating the samples via biochemical, electromagnetic, thermal, mechanical, and/or optical stimulation, one or more sensors for measuring a biological response signal of the samples resulting from the stimulation of the sample. 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 compositions and methods of the invention can be used, e.g., to for systems optimization of any biological manufacturing or experimental system, e.g., bioreactors for proteins, e.g., therapeutic proteins, polypeptides or peptides for vaccines, and the like, small molecules (e.g., antibiotics), polysaccharides, lipids, and the like. Another use of the apparatus and methods includes combination drug therapy, e.g. optimal drug cocktail, directed cell proliferations and differentiations, e.g. in tissue engineering, e.g. neural progenitor cells differentiation, and discovery of key parameters in complex biological systems.

  7. Phytoestrogen Biological Actions on Mammalian Reproductive System and Cancer Growth

    OpenAIRE

    Zhao, E; Mu, Qing

    2010-01-01

    Phytoestrogens are a family of diverse polyphenolic compounds derived from nature plant that structurally or functionally mimic circulating estrogen in the mammalian reproductive system. They induce estrogenic and anti-estrogenic effects in the brain-pituitary-gonad axis (a principal endocrine system involving in reproductive regulation) and peripheral reproductive organs. The dichotomy of phytoestrogen-mediated actions elucidates that they play the biological activities via complex mechanism...

  8. Complex Phenomena in Nanoscale Systems

    CERN Document Server

    Casati, Giulio

    2009-01-01

    Nanoscale physics has become one of the rapidly developing areas of contemporary physics because of its direct relevance to newly emerging area, nanotechnologies. Nanoscale devices and quantum functional materials are usually constructed based on the results of fundamental studies on nanoscale physics. Therefore studying physical phenomena in nanosized systems is of importance for progressive development of nanotechnologies. In this context study of complex phenomena in such systems and using them for controlling purposes is of great practical importance. Namely, such studies are brought together in this book, which contains 27 papers on various aspects of nanoscale physics and nonlinear dynamics.

  9. 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

  10. First steps in computational systems biology: A practical session in metabolic modeling and simulation.

    Science.gov (United States)

    Reyes-Palomares, Armando; Sánchez-Jiménez, Francisca; Medina, Miguel Ángel

    2009-05-01

    A comprehensive understanding of biological functions requires new systemic perspectives, such as those provided by systems biology. Systems biology approaches are hypothesis-driven and involve iterative rounds of model building, prediction, experimentation, model refinement, and development. Developments in computer science are allowing for ever faster numerical simulations of mathematical models. Mathematical modeling plays an essential role in new systems biology approaches. As a complex, integrated system, metabolism is a suitable topic of study for systems biology approaches. However, up until recently, this topic has not been properly covered in biochemistry courses. This communication reports the development and implementation of a practical lesson plan on metabolic modeling and simulation.

  11. 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.

  12. 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.

  13. 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.

  14. Natural production of biological optical systems

    Science.gov (United States)

    Choi, Seung Ho; Kim, Young L.

    2015-03-01

    Synthesis and production in nature often provide ideas to design and fabricate advanced biomimetic photonic materials and structures, leading to excellent physical properties and enhanced performance. In addition, the recognition and utilization of natural or biological substances have been typical routes to develop biocompatible and biodegradable materials for medical applications. In this respect, biological lasers utilizing such biomaterials and biostructures have been received considerable attention, given a variety of implications and potentials for bioimaging, biosensing, implantation, and therapy. However, without relying on industrial facilities, eco-friendly massive production of such optical components or systems has not yet been investigated. We show examples of bioproduction of biological lasers using agriculture and fisheries. We anticipate that such approaches will open new possibilities for scalable eco-friendly `green' production of biological photonics components and systems.

  15. Encyclopedia of complexity and systems science

    OpenAIRE

    2012-01-01

    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 n...

  16. Computer Simulation and Computabiblity of Biological Systems

    CERN Document Server

    Baianu, I C

    2004-01-01

    The ability to simulate a biological organism by employing a computer is related to the ability of the computer to calculate the behavior of such a dynamical system, or the "computability" of the system. However, the two questions of computability and simulation are not equivalent. Since the question of computability can be given a precise answer in terms of recursive functions, automata theory and dynamical systems, it will be appropriate to consider it first. The more elusive question of adequate simulation of biological systems by a computer will be then addressed and a possible connection between the two answers given will be considered as follows. A symbolic, algebraic-topological "quantum computer" (as introduced in Baianu, 1971b) is here suggested to provide one such potential means for adequate biological simulations based on QMV Quantum Logic and meta-Categorical Modeling as for example in a QMV-based, Quantum-Topos (Baianu and Glazebrook,2004.

  17. 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...

  18. 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.

  19. 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.

  20. 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.

  1. 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...

  2. Adaptive neural-based fuzzy modeling for biological systems.

    Science.gov (United States)

    Wu, Shinq-Jen; Wu, Cheng-Tao; Chang, Jyh-Yeong

    2013-04-01

    The inverse problem of identifying dynamic biological networks from their time-course response data set is a cornerstone of systems biology. Hill and Michaelis-Menten model, which is a forward approach, provides local kinetic information. However, repeated modifications and a large amount of experimental data are necessary for the parameter identification. S-system model, which is composed of highly nonlinear differential equations, provides the direct identification of an interactive network. However, the identification of skeletal-network structure is challenging. Moreover, biological systems are always subject to uncertainty and noise. Are there suitable candidates with the potential to deal with noise-contaminated data sets? Fuzzy set theory is developed for handing uncertainty, imprecision and complexity in the real world; for example, we say "driving speed is high" wherein speed is a fuzzy variable and high is a fuzzy set, which uses the membership function to indicate the degree of a element belonging to the set (words in Italics to denote fuzzy variables or fuzzy sets). Neural network possesses good robustness and learning capability. In this study we hybrid these two together into a neural-fuzzy modeling technique. A biological system is formulated to a multi-input-multi-output (MIMO) Takagi-Sugeno (T-S) fuzzy system, which is composed of rule-based linear subsystems. Two kinds of smooth membership functions (MFs), Gaussian and Bell-shaped MFs, are used. The performance of the proposed method is tested with three biological systems.

  3. 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.

  4. Metabolic Scaling in Complex Living Systems

    Directory of Open Access Journals (Sweden)

    Douglas S. Glazier

    2014-10-01

    Full Text Available In this review I show that four major kinds of theoretical approaches have been used to explain the scaling of metabolic rate in cells, organisms and groups of organisms in relation to system size. They include models focusing on surface-area related fluxes of resources and wastes (including heat, internal resource transport, system composition, and various processes affecting resource demand, all of which have been discussed extensively for nearly a century or more. I argue that, although each of these theoretical approaches has been applied to multiple levels of biological organization, none of them alone can fully explain the rich diversity of metabolic scaling relationships, including scaling exponents (log-log slopes that vary from ~0 to >1. Furthermore, I demonstrate how a synthetic theory of metabolic scaling can be constructed by including the context-dependent action of each of the above modal effects. This “contextual multimodal theory” (CMT posits that various modulating factors (including metabolic level, surface permeability, body shape, modes of thermoregulation and resource-transport, and other internal and external influences affect the mechanistic expression of each theoretical module. By involving the contingent operation of several mechanisms, the “meta-mechanistic” CMT differs from most metabolic scaling theories that are deterministically mechanistic. The CMT embraces a systems view of life, and as such recognizes the open, dynamic nature and complex hierarchical and interactive organization of biological systems, and the importance of multiple (upward, downward and reciprocal causation, biological regulation of resource supply and demand and their interaction, and contingent internal (system and external (environmental influences on metabolic scaling, all of which are discussed. I hope that my heuristic attempt at building a unifying theory of metabolic scaling will not only stimulate further testing of all of the

  5. Aspergilli: Systems biology and industrial applications

    DEFF Research Database (Denmark)

    Knuf, Christoph; Nielsen, Jens

    2012-01-01

    possible to implement systems biology tools to advance metabolic engineering. These tools include genome-wide transcription analysis and genome-scale metabolic models. Herein, we review achievements in the field and highlight the impact of Aspergillus systems biology on industrial biotechnology....... genetic modifications has enabled the use of metabolic engineering strategies. Genome sequencing of Aspergilli was originally trailing behind developments in the field of bacteria and yeasts, but with the recent availability of genome sequences for several industrially relevant Aspergilli, it has become...

  6. 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.

  7. 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.

  8. MicroRNA-regulated networks: the perfect storm for classical molecular biology, the ideal scenario for systems biology.

    Science.gov (United States)

    Vera, Julio; Lai, Xin; Schmitz, Ulf; Wolkenhauer, Olaf

    2013-01-01

    MicroRNAs (miRNAs) are involved in many regulatory pathways some of which are complex networks enriched in regulatory motifs like positive or negative feedback loops or coherent and incoherent feedforward loops. Their complexity makes the understanding of their regulation difficult and the interpretation of experimental data cumbersome. In this book chapter we claim that systems biology is the appropriate approach to investigate the regulation of these miRNA-regulated networks. Systems biology is an interdisciplinary approach by which biomedical questions on biochemical networks are addressed by integrating experiments with mathematical modelling and simulation. We here introduce the foundations of the systems biology approach, the basic theoretical and computational tools used to perform model-based analyses of miRNA-regulated networks and review the scientific literature in systems biology of miRNA regulation, with a focus on cancer.

  9. Controlling Complex Systems and Developing Dynamic Technology

    Science.gov (United States)

    Avizienis, Audrius Victor

    In complex systems, control and understanding become intertwined. Following Ilya Prigogine, we define complex systems as having control parameters which mediate transitions between distinct modes of dynamical behavior. From this perspective, determining the nature of control parameters and demonstrating the associated dynamical phase transitions are practically equivalent and fundamental to engaging with complexity. In the first part of this work, a control parameter is determined for a non-equilibrium electrochemical system by studying a transition in the morphology of structures produced by an electroless deposition reaction. Specifically, changing the size of copper posts used as the substrate for growing metallic silver structures by the reduction of Ag+ from solution under diffusion-limited reaction conditions causes a dynamical phase transition in the crystal growth process. For Cu posts with edge lengths on the order of one micron, local forces promoting anisotropic growth predominate, and the reaction produces interconnected networks of Ag nanowires. As the post size is increased above 10 microns, the local interfacial growth reaction dynamics couple with the macroscopic diffusion field, leading to spatially propagating instabilities in the electrochemical potential which induce periodic branching during crystal growth, producing dendritic deposits. This result is interesting both as an example of control and understanding in a complex system, and as a useful combination of top-down lithography with bottom-up electrochemical self-assembly. The second part of this work focuses on the technological development of devices fabricated using this non-equilibrium electrochemical process, towards a goal of integrating a complex network as a dynamic functional component in a neuromorphic computing device. Self-assembled networks of silver nanowires were reacted with sulfur to produce interfacial "atomic switches": silver-silver sulfide junctions, which exhibit

  10. Cancer systems biology and modeling: microscopic scale and multiscale approaches.

    Science.gov (United States)

    Masoudi-Nejad, Ali; Bidkhori, Gholamreza; Hosseini Ashtiani, Saman; Najafi, Ali; Bozorgmehr, Joseph H; Wang, Edwin

    2015-02-01

    Cancer has become known as a complex and systematic disease on macroscopic, mesoscopic and microscopic scales. Systems biology employs state-of-the-art computational theories and high-throughput experimental data to model and simulate complex biological procedures such as cancer, which involves genetic and epigenetic, in addition to intracellular and extracellular complex interaction networks. In this paper, different systems biology modeling techniques such as systems of differential equations, stochastic methods, Boolean networks, Petri nets, cellular automata methods and agent-based systems are concisely discussed. We have compared the mentioned formalisms and tried to address the span of applicability they can bear on emerging cancer modeling and simulation approaches. Different scales of cancer modeling, namely, microscopic, mesoscopic and macroscopic scales are explained followed by an illustration of angiogenesis in microscopic scale of the cancer modeling. Then, the modeling of cancer cell proliferation and survival are examined on a microscopic scale and the modeling of multiscale tumor growth is explained along with its advantages.

  11. 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.

  12. 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.

  13. 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.

  14. Mathematical Control of Complex Systems 2013

    OpenAIRE

    Zidong Wang; Hamid Reza Karimi; Bo Shen; Jun Hu; Hongli Dong; Xiao He

    2014-01-01

    Mathematical control of complex systems have already become an ideal research area for control engineers, mathematicians, computer scientists, and biologists to understand, manage, analyze, and interpret functional information/dynamical behaviours from real-world complex dynamical systems, such as communication systems, process control, environmental systems, intelligent manufacturing systems, transportation systems, and structural systems. This special issue aims to bring together the latest...

  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. Nonlinear Waves in Complex Systems

    DEFF Research Database (Denmark)

    2007-01-01

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

  17. 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.

  18. 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.

  19. 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.

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

    Science.gov (United States)

    Joslyn, C

    2001-01-01

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

  1. 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.

  2. 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

  3. Nutritional Systems Biology: Definitions and Approaches

    DEFF Research Database (Denmark)

    Panagiotou, Gianni; Nielsen, Jens

    2009-01-01

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

  4. 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...... of a system thereby suggesting new ways of thinking specific toxicological endpoints. Furthermore, computational methods can serve as valuable input for the hypothesis generating phase of the preparations of a research project....

  5. 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.

  6. 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.

  7. Biological Indicator Systems in Floodplains - a Review

    Science.gov (United States)

    Dziock, Frank; Henle, Klaus; Foeckler, Francis; Follner, Klaus; Scholz, Mathias

    2006-08-01

    Based on a literature review, the different approaches to biological indicator systems in floodplains are summarised. Four general categories of bioindication are defined and proposed here: 1. Classification indicators, 2.1 Environmental indicators, 2.2 Biodiversity indicators, 3. Valuation indicators. Furthermore, existing approaches in floodplains are classified according to the four categories. Relevant and widely used approaches in floodplains are explained in more detail. The results of the RIVA project are put into the context of these indication approaches. It is concluded that especially functional assessment approaches using biological traits of the species can be seen as very promising and deserve more attention by conservation biologists and floodplain ecologists.

  8. 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.

  9. Complex systems in aeolian geomorphology

    Science.gov (United States)

    Baas, Andreas C. W.

    2007-11-01

    Aeolian geomorphology provides a rich ground for investigating Earth surface processes and landforms as complex systems. Sand transport by wind is a classic dissipative process with non-linear dynamics, while dune field evolution is a prototypical self-organisation phenomenon. Both of these broad areas of aeolian geomorphology are discussed and analysed in the context of complexity and a systems approach. A feedback loop analysis of the aeolian boundary-layer-flow/sediment-transport/bedform interactions, based on contemporary physical models, reveals that the system is fundamentally unstable (or at most meta-stable) and likely to exhibit chaotic behaviour. Recent field-experimental research on aeolian streamers and spatio-temporal transport patterns, however, indicates that sand transport by wind may be wholly controlled by a self-similar turbulence cascade in the boundary layer flow, and that key aspects of transport event time-series can be fully reproduced from a combination of (self-organised) 1/ f forcing, motion threshold, and saltation inertia. The evolution of various types of bare-sand dunes and dune field patterns have been simulated successfully with self-organising cellular automata that incorporate only simplified physically-based interactions (rules). Because of their undefined physical scale, however, it not clear whether they in fact simulate ripples (bedforms) or dunes (landforms), raising fundamental cross-cutting questions regarding the difference between aeolian dunes, impact ripples, and subaqueous (current) ripples and dunes. An extended cellular automaton (CA) model, currently under development, incorporates the effects of vegetation in the aeolian environment and is capable of simulating the development of nebkhas, blow-outs, and parabolic coastal dunes. Preliminary results indicate the potential for establishing phase diagrams and attractor trajectories for vegetated aeolian dunescapes. Progress is limited, however, by a serious lack of

  10. Newton, laplace, and the epistemology of systems biology.

    Science.gov (United States)

    Bittner, Michael L; Dougherty, Edward R

    2012-01-01

    For science, theoretical or applied, to significantly advance, researchers must use the most appropriate mathematical methods. A century and a half elapsed between Newton's development of the calculus and Laplace's development of celestial mechanics. One cannot imagine the latter without the former. Today, more than three-quarters of a century has elapsed since the birth of stochastic systems theory. This article provides a perspective on the utilization of systems theory as the proper vehicle for the development of systems biology and its application to complex regulatory diseases such as cancer.

  11. Collaboration in Complex Medical Systems

    Science.gov (United States)

    Xiao, Yan; Mankenzie, Colin F.

    1998-01-01

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

  12. 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.

  13. 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

  14. Witnessing Quantum Coherence: from solid-state to biological systems

    CERN Document Server

    Li, Che-Ming; Chen, Yueh-Nan; Chen, Guang-Yin; Nori, Franco; 10.1038/srep00885

    2012-01-01

    Quantum coherence is one of the primary non-classical features of quantum systems. While protocols such as the Leggett-Garg inequality (LGI) and quantum tomography can be used to test for the existence of quantum coherence and dynamics in a given system, unambiguously detecting inherent "quantumness" still faces serious obstacles in terms of experimental feasibility and efficiency, particularly in complex systems. Here we introduce two "quantum witnesses" to efficiently verify quantum coherence and dynamics in the time domain, without the expense and burden of non-invasive measurements or full tomographic processes. Using several physical examples, including quantum transport in solid-state nanostructures and in biological organisms, we show that these quantum witnesses are robust and have a much finer resolution in their detection window than the LGI has. These robust quantum indicators may assist in reducing the experimental overhead in unambiguously verifying quantum coherence in complex systems.

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. Set membership experimental design for biological systems

    Directory of Open Access Journals (Sweden)

    Marvel Skylar W

    2012-03-01

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

  20. Set membership experimental design for biological systems

    Science.gov (United States)

    2012-01-01

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

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. Reduction of Subjective and Objective System Complexity

    Science.gov (United States)

    Watson, Michael D.

    2015-01-01

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

  6. 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.

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

    Directory of Open Access Journals (Sweden)

    Atsushi eFukushima

    2014-11-01

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

  8. Dynamic sensitivity analysis of biological systems

    Directory of Open Access Journals (Sweden)

    Chang Maw

    2008-12-01

    Full Text Available Abstract Background A mathematical model to understand, predict, control, or even design a real biological system is a central theme in systems biology. A dynamic biological system is always modeled as a nonlinear ordinary differential equation (ODE system. How to simulate the dynamic behavior and dynamic parameter sensitivities of systems described by ODEs efficiently and accurately is a critical job. In many practical applications, e.g., the fed-batch fermentation systems, the system admissible input (corresponding to independent variables of the system can be time-dependent. The main difficulty for investigating the dynamic log gains of these systems is the infinite dimension due to the time-dependent input. The classical dynamic sensitivity analysis does not take into account this case for the dynamic log gains. Results We present an algorithm with an adaptive step size control that can be used for computing the solution and dynamic sensitivities of an autonomous ODE system simultaneously. Although our algorithm is one of the decouple direct methods in computing dynamic sensitivities of an ODE system, the step size determined by model equations can be used on the computations of the time profile and dynamic sensitivities with moderate accuracy even when sensitivity equations are more stiff than model equations. To show this algorithm can perform the dynamic sensitivity analysis on very stiff ODE systems with moderate accuracy, it is implemented and applied to two sets of chemical reactions: pyrolysis of ethane and oxidation of formaldehyde. The accuracy of this algorithm is demonstrated by comparing the dynamic parameter sensitivities obtained from this new algorithm and from the direct method with Rosenbrock stiff integrator based on the indirect method. The same dynamic sensitivity analysis was performed on an ethanol fed-batch fermentation system with a time-varying feed rate to evaluate the applicability of the algorithm to realistic

  9. Method for photo-altering a biological system to improve biological effect

    Science.gov (United States)

    Hill, Richard A.; Doiron, Daniel R.; Crean, David H.

    2000-08-01

    Photodynamic therapy is a new adjunctive therapy for filtration surgery that does not use chemotherapy agents or radiation, but uses pharmacologically-active sensitizing compounds to produce a titratable, localized, transient, post operative avascular conjunctiva. A photosensitizing agent in a biological system is selectively activated by delivering the photosensitive agent to the biological system and laser activating only a spatially selected portion of the delivered photosensitive agent. The activated portion of the photosensitive agent reacts with the biological system to obtain a predetermined biological effect. As a result, an improved spatial disposition and effectuation of the biological effect by the photosensitive agent in the biological system is achieved.

  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. 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.

  12. 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.

  13. Role of the ESCRT Complexes in Telomere Biology

    Directory of Open Access Journals (Sweden)

    Anna K. Dieckmann

    2016-11-01

    Full Text Available Eukaryotic chromosomal ends are protected by telomeres from fusion, degradation, and unwanted double-strand break repair events. Therefore, telomeres preserve genome stability and integrity. Telomere length can be maintained by telomerase, which is expressed in most human primary tumors but is not expressed in the majority of somatic cells. Thus, telomerase may be a highly relevant anticancer drug target. Genome-wide studies in the yeast Saccharomyces cerevisiae identified a set of genes associated with telomere length maintenance (TLM genes. Among the tlm mutants with short telomeres, we found a strong enrichment for those affecting vacuolar and endosomal traffic (particularly the endosomal sorting complex required for transport [ESCRT] pathway. Here, we present our results from investigating the surprising link between telomere shortening and the ESCRT machinery. Our data show that the whole ESCRT system is required to safeguard proper telomere length maintenance. We propose a model of impaired end resection resulting in too little telomeric overhang, such that Cdc13 binding is prevented, precluding either telomerase recruitment or telomeric overhang protection.

  14. 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

  15. 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

  16. Systems biology and its potential role in radiobiology.

    Science.gov (United States)

    Feinendegen, Ludwig; Hahnfeldt, Philip; Schadt, Eric E; Stumpf, Michael; Voit, Eberhard O

    2008-02-01

    About a century ago, Conrad Röentgen discovered X-rays, and Henri Becquerel discovered a new phenomenon, which Marie and Pierre Curie later coined as radio-activity. Since their seminal work, we have learned much about the physical properties of radiation and its effects on living matter. Alas, the more we discover, the more we appreciate the complexity of the biological processes that are triggered by radiation exposure and eventually lead (or do not lead) to disease. Equipped with modern biological methods of high-throughput experimentation, imaging, and vastly increased computational prowess, we are now entering an era where we can piece some of the multifold aspects of radiation exposure and its sequelae together, and develop a more systemic understanding of radiogenic effects such as radio-carcinogenesis than has been possible in the past. It is evident from the complexity of even the known processes that such an understanding can only be gained if it is supported by mathematical models. At this point, the construction of comprehensive models is hampered both by technical inadequacies and a paucity of appropriate data. Nonetheless, some initial steps have been taken already and the generally increased interest in systems biology may be expected to speed up future progress. In this context, we discuss in this article examples of relatively small, yet very useful models that elucidate selected aspects of the effects of exposure to ionizing radiation and may shine a light on the path before us.

  17. 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.

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

    CERN Document Server

    Stanley, H

    2014-01-01

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

  19. 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 ...

  20. 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…

  1. 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…

  2. Systems Biology Toolbox for MATLAB: a computational platform for research in systems biology.

    Science.gov (United States)

    Schmidt, Henning; Jirstrand, Mats

    2006-02-15

    We present a Systems Biology Toolbox for the widely used general purpose mathematical software MATLAB. The toolbox offers systems biologists an open and extensible environment, in which to explore ideas, prototype and share new algorithms, and build applications for the analysis and simulation of biological and biochemical systems. Additionally it is well suited for educational purposes. The toolbox supports the Systems Biology Markup Language (SBML) by providing an interface for import and export of SBML models. In this way the toolbox connects nicely to other SBML-enabled modelling packages. Models are represented in an internal model format and can be described either by entering ordinary differential equations or, more intuitively, by entering biochemical reaction equations. The toolbox contains a large number of analysis methods, such as deterministic and stochastic simulation, parameter estimation, network identification, parameter sensitivity analysis and bifurcation analysis.

  3. In situ characterization of nanoparticle biomolecular interactions in complex biological media by flow cytometry

    Science.gov (United States)

    Lo Giudice, Maria Cristina; Herda, Luciana M.; Polo, Ester; Dawson, Kenneth A.

    2016-11-01

    Nanoparticles interacting with, or derived from, living organisms are almost invariably coated in a variety of biomolecules presented in complex biological milieu, which produce a bio-interface or `biomolecular corona' conferring a biological identity to the particle. Biomolecules at the surface of the nanoparticle-biomolecule complex present molecular fragments that may be recognized by receptors of cells or biological barriers, potentially engaging with different biological pathways. Here we demonstrate that using intense fluorescent reporter binders, in this case antibodies bound to quantum dots, we can map out the availability of such recognition fragments, allowing for a rapid and meaningful biological characterization. The application in microfluidic flow, in small detection volumes, with appropriate thresholding of the detection allows the study of even complex nanoparticles in realistic biological milieu, with the emerging prospect of making direct connection to conditions of cell level and in vivo experiments.

  4. Is Echo a complex adaptive system?

    Science.gov (United States)

    Smith, R M; Bedau, M A

    2000-01-01

    We evaluate whether John Holland's Echo model exemplifies his theory of complex adaptive systems. After reviewing Holland's theory of complex adaptive systems and describing his Escho model, we describe and explain the characteristic evolutionary behavior observed in a series of Echo model runs. We conclude that Echo lacks the diversity of hierarchically organized aggregates that typify complex adaptive systems, and we explore possible explanations for this failure.

  5. 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

  6. 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.

  7. Biological systems in high magnetic field

    Science.gov (United States)

    Yamagishi, A.

    1990-12-01

    Diamagnetic orientation of biological systems have been investigated theoretically and experimentally. Fibrinogen, one of blood proteins, were polymerized in static high magnetic fields up to 8 T. Clotted gels composed of oriented fibrin fibers were obtained even in a field as low as 1 T. Red blood cells (RBC) show full orientation with their plane parallel to the applied field of 4 T. It is confirmed experimentally that the magnetic orientation of RBC is caused by diamagnetic anisotropy. Full orientation is also obtained with blood platelet in a field of 3 T.

  8. 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.......g., the effects of receptor defects or drug delivery mechanisms. The property of sequential realisability. which is closely related to the function of biochemical pathways, is addressed by a variant of traditional Data Flow Analysis (DFA). This so-called ‘Pathway Analysis’ computes safe approximations to the set...

  9. Methylene Diphosphonate Chemical and Biological control of MDP complex

    CERN Document Server

    Aungurarat, A

    2000-01-01

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

  10. 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.

  11. 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.

  12. 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.

  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. 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

  15. 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...

  16. 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.......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....

  17. 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.

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

    NARCIS (Netherlands)

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

    2009-01-01

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

  19. 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.

  20. Application of computational systems biology to explore environmental toxicity hazards

    DEFF Research Database (Denmark)

    Audouze, Karine Marie Laure; Grandjean, Philippe

    2011-01-01

    Background: Computer-based modeling is part of a new approach to predictive toxicology.Objectives: We investigated the usefulness of an integrated computational systems biology approach in a case study involving the isomers and metabolites of the pesticide dichlorodiphenyltrichloroethane (DDT......) to ascertain their possible links to relevant adverse effects.Methods: We extracted chemical-protein association networks for each DDT isomer and its metabolites using ChemProt, a disease chemical biology database that includes both binding and gene expression data, and we explored protein-protein interactions...... using a human interactome network. To identify associated dysfunctions and diseases, we integrated protein-disease annotations into the protein complexes using the Online Mendelian Inheritance in Man database and the Comparative Toxicogenomics Database.Results: We found 175 human proteins linked to p,p´-DDT...

  1. Optical sensors and their applications for probing biological systems

    DEFF Research Database (Denmark)

    Palanco, Marta Espina

    and mammalian cells. First, we performed Surface Enhanced Raman Spectroscopy (SERS) studies on intact plant materials via using silver plasmonic nanostructures. Our studies showed strong Raman signals which resemble to the presence of typical constituents such as carbohydrates, proteins and lipids of different......There is a great interest in exploring and developing new optical sensitive methodologies for probing complex biological systems. In this project we developed non-invasive and sensitive biosensor strategies for studying physiologically relevant chemical and physical properties of plant...... biological sample to provide a SERS-template where silver nanoparticles can grow, thus providing a new insight into SERS-based sensors for chemically sensing in-situ plant constituents. Optical manipulation techniques have been used to investigate mechanical properties of soft membrane cells, i.e. mammalian...

  2. 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

  3. Rapid searches for complex patterns in biological molecules.

    OpenAIRE

    Abarbanel, R M; Wieneke, P R; Mansfield, E; Jaffe, D A; Brutlag, D L

    1984-01-01

    The intrinsic redundancy of genetic information makes searching for patterns in biological sequences a difficult task. We have designed an interactive self-documenting computer program called QUEST that allows rapid searching of large DNA and protein data banks for highly redundant consensus sequences or character patterns. QUEST uses a concise language for specifying character patterns containing several levels of ambiguity and pattern arrangement. Examples of the use of this program for seq...

  4. Study of complex molecules of biological interest with synchrotron radiation

    Energy Technology Data Exchange (ETDEWEB)

    Prince, K.C. [Elettra-Sincrotrone Trieste, Strada Statale 14–km 163,5 in AREA Science Park, I-34149 Trieste (Italy); Istituto Officina dei Materiali, Consiglio Nazionale delle Ricerche, in Area Science Park, I-34149 Trieste (Italy); Molecular Model Discovery Laboratory, Faculty of Science, Engineering and Technology, Swinburne University of Technology, Hawthorn, Melbourne, Victoria, 3122 (Australia); Bolognesi, P., E-mail: paola.bolognesi@cnr.it [CNR-ISM, Area della Ricerca di Roma 1, Via Salaria Km. 29,300, Monterotondo (Roma) (Italy); Feyer, V. [Elettra-Sincrotrone Trieste, Strada Statale 14–km 163,5 in AREA Science Park, I-34149 Trieste (Italy); Research Center Jülich, Peter Grünberg Institute (PGI-6), 52425 Jülich (Germany); Plekan, O. [Elettra-Sincrotrone Trieste, Strada Statale 14–km 163,5 in AREA Science Park, I-34149 Trieste (Italy); Avaldi, L. [CNR-ISM, Area della Ricerca di Roma 1, Via Salaria Km. 29,300, Monterotondo (Roma) (Italy)

    2015-10-15

    Synchrotron radiation and synchrotron based spectroscopic techniques have found important applications in the study of isolated molecular species of biological interest. In this paper, some examples of spectroscopic and dynamic studies of amino acids and small peptides, nucleobases and pharmaceuticals are reviewed. Opportunities offered by the advent of new radiation sources combined with novel methods for the production of beams of these molecules are also discussed.

  5. Multi-agent and complex systems

    CERN Document Server

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

    2017-01-01

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

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

    Science.gov (United States)

    Díaz, Jairo A; Jaramillo, Natalia A; Murillo, Mauricio F

    2007-12-12

    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 interdisciplinary studies must

  7. 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

  8. 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.

  9. Modeling delayed processes in biological systems

    Science.gov (United States)

    Feng, Jingchen; Sevier, Stuart A.; Huang, Bin; Jia, Dongya; Levine, Herbert

    2016-09-01

    Delayed processes are ubiquitous in biological systems and are often characterized by delay differential equations (DDEs) and their extension to include stochastic effects. DDEs do not explicitly incorporate intermediate states associated with a delayed process but instead use an estimated average delay time. In an effort to examine the validity of this approach, we study systems with significant delays by explicitly incorporating intermediate steps. We show that such explicit models often yield significantly different equilibrium distributions and transition times as compared to DDEs with deterministic delay values. Additionally, different explicit models with qualitatively different dynamics can give rise to the same DDEs revealing important ambiguities. We also show that DDE-based predictions of oscillatory behavior may fail for the corresponding explicit model.

  10. 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.

  11. A Review: Protein Interaction & Behavior Assessment in Host Cells after Novel Drug Compound Administration using Systems Biology Approach

    OpenAIRE

    Yesha Modi; Harsh Shinde; Natasha Navet; Richa Arya; Nikita Sushil Kumar; Kanika Mehrotra; Fariya Khan; Satyam Khanna; Ruchi Narula

    2014-01-01

    To understand complex biological systems requires the integration of experimental and computational research; in other words systems biology approach. Computational biology, through via different software helps in exploration more than one gene expression at a time and also understanding the connectivity, Systems Biology provides a powerful foundation from which to address critical scientific questions head-on. The reviews in this Insight cover many different aspects of this energetic field, ...

  12. 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

  13. 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.

  14. On System Complexity: Identification, Measurement, and Management

    OpenAIRE

    Casti, J.L.

    1985-01-01

    Attempts to axiomatize and formalize system complexity all leave a feeling of basic incompleteness and a sense of failure to grasp important aspects of the problem. This paper examines some of the root causes of these failures and outlines a framework for the consideration of complexity as an implicate, rather than explicate, property of systems in interaction.

  15. Modeling complex work systems - method meets reality

    OpenAIRE

    Veer, van der, C.G.; Hoeve, Machteld; Lenting, Bert F.

    1996-01-01

    Modeling an existing task situation is often a first phase in the (re)design of information systems. For complex systems design, this model should consider both the people and the organization involved, the work, and situational aspects. Groupware Task Analysis (GTA) as part of a method for the design of complex systems, has been applied in a situation of redesign of a Dutch public administration system. The most feasible method to collect information in this case was ethnography, the resulti...

  16. Designing the Cloud-based DOE Systems Biology Knowledgebase

    Energy Technology Data Exchange (ETDEWEB)

    Lansing, Carina S.; Liu, Yan; Yin, Jian; Corrigan, Abigail L.; Guillen, Zoe C.; Kleese van Dam, Kerstin; Gorton, Ian

    2011-09-01

    Systems Biology research, even more than many other scientific domains, is becoming increasingly data-intensive. Not only have advances in experimental and computational technologies lead to an exponential increase in scientific data volumes and their complexity, but increasingly such databases themselves are providing the basis for new scientific discoveries. To engage effectively with these community resources, integrated analyses, synthesis and simulation software is needed, regularly supported by scientific workflows. In order to provide a more collaborative, community driven research environment for this heterogeneous setting, the Department of Energy (DOE) has decided to develop a federated, cloud based cyber infrastructure - the Systems Biology Knowledgebase (Kbase). Pacific Northwest National Laboratory (PNNL) with its long tradition in data intensive science lead two of the five initial pilot projects, these two focusing on defining and testing the basic federated cloud-based system architecture and develop a prototype implementation. Hereby the community wide accessibility of biological data and the capability to integrate and analyze this data within its changing research context were seen as key technical functionalities the Kbase needed to enable. In this paper we describe the results of our investigations into the design of a cloud based federated infrastructure for: (1) Semantics driven data discovery, access and integration; (2) Data annotation, publication and sharing; (3) Workflow enabled data analysis; and (4) Project based collaborative working. We describe our approach, exemplary use cases and our prototype implementation that demonstrates the feasibility of this approach.

  17. Models of complex attitude systems

    DEFF Research Database (Denmark)

    Sørensen, Bjarne Taulo

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

  18. [Systems biology is a bridge of integrated traditional Chinese and Western medicine].

    Science.gov (United States)

    Chen, Hai-Bin; Cheng, Hai-Bo; Lu, Wei; Zhou, Hong-Guang; Wu, Mian-Hua

    2013-01-01

    The integration of Chinese medicine (CM) and Western medicine (WM) is the only way for the development of medicine, and it is the best form for unifying systems theory and reductionism. In this paper, systems biology and its application in medical research were discussed. The authors put forward that systems biology may possibly interpret the scientific connotation of the complex theoretic systems of CM, which will make WM to well know the human body and disease. We hold that systems biology is a bridge of integrated CM and WM.

  19. 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.

  20. Change and Identity in Complex Systems

    Directory of Open Access Journals (Sweden)

    John Collier

    2005-06-01

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

  1. Social networks as embedded complex adaptive systems.

    Science.gov (United States)

    Benham-Hutchins, Marge; Clancy, Thomas R

    2010-09-01

    As systems evolve over time, their natural tendency is to become increasingly more complex. Studies in the field of complex systems have generated new perspectives on management in social organizations such as hospitals. Much of this research appears as a natural extension of the cross-disciplinary field of systems theory. This is the 15th in a series of articles applying complex systems science to the traditional management concepts of planning, organizing, directing, coordinating, and controlling. In this article, the authors discuss healthcare social networks as a hierarchy of embedded complex adaptive systems. The authors further examine the use of social network analysis tools as a means to understand complex communication patterns and reduce medical errors.

  2. Web API for biology with a workflow navigation system.

    Science.gov (United States)

    Kwon, Yeondae; Shigemoto, Yasumasa; Kuwana, Yoshikazu; Sugawara, Hideaki

    2009-07-01

    DNA Data Bank of Japan (DDBJ) provides Web-based systems for biological analysis, called Web APIs for biology (WABI). So far, we have developed over 20 SOAP services and several workflows that consist of a series of method invocations. In this article, we present newly developed services of WABI, that is, REST-based Web services, additional workflows and a workflow navigation system. Each Web service and workflow can be used as a complete service or a building block for programmers to construct more complex information processing systems. The workflow navigation system aims to help non-programming biologists perform analysis tasks by providing next applicable services on Web browsers according to the output of a previously selected service. With this function, users can apply multiple services consecutively only by following links without any programming or manual copy-and-paste operations on Web browsers. The listed services are determined automatically by the system referring to the dictionaries of service categories, the input/output types of services and HTML tags. WABI and the workflow navigation system are freely accessible at http://www.xml.nig.ac.jp/index.html and http://cyclamen.ddbj.nig.ac.jp/, respectively.

  3. 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...

  4. 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 ...

  5. 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...

  6. 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.

  7. Parametric ordering of complex systems

    CERN Document Server

    Binder, P M

    1993-01-01

    Cellular automata (CA) dynamics are ordered in terms of two global parameters, computable {\\sl a priori} from the description of rules. While one of them (activity) has been used before, the second one is new; it estimates the average sensitivity of rules to small configurational changes. For two well-known families of rules, the Wolfram complexity Classes cluster satisfactorily. The observed simultaneous occurrence of sharp and smooth transitions from ordered to disordered dynamics in CA can be explained with the two-parameter diagram.

  8. 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.

  9. 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.

  10. 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.

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

    Science.gov (United States)

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

    2016-10-25

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

  12. 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.

  13. 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.

  14. 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. ...

  15. Biosensors for antioxidant evaluation in biological systems.

    Science.gov (United States)

    Mello, Lucilene Dornelles; Kisner, Alexandre; Goulart, Marilia Oliveira Fonseca; Kubota, Lauro Tatsuo

    2013-02-01

    The prevention of oxidative reactions in a biological medium as well as the role of reactive oxygen species (ROS) in chronic degenerative diseases are questions that continue to be investigated. Electrochemical biosensors have shown attractive features to evaluate the oxidative stress condition at a level comparable to chromatographic and spectroscopic techniques. The biosensors developed so far are based on direct analysis of specific indicators such as biomarkers of oxidative stress on the monitoring of reactive oxygen species the free radicals in cells or tissues, aiming to obtain a correlation between the index obtained from these indicators with the oxidative stress levels in cells. In this review we will provide an overview of the development of electrochemical biosensors to evaluate the content of antioxidants and reactive oxygen species in physiological systems. Some discussion regarding the analysis of antioxidant capacity at the single cell level is also presented.

  16. 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.

  17. Workshop on Nonlinear Phenomena in Complex Systems

    CERN Document Server

    1989-01-01

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

  18. 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......., Denmark, demonstrates the system can be used for automatic welding of complex products in one-of-a-kind production....

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. Spectroscopic study of molecular structure, antioxidant activity and biological effects of metal hydroxyflavonol complexes

    Science.gov (United States)

    Samsonowicz, Mariola; Regulska, Ewa

    2017-02-01

    Flavonols with varied hydroxyl substitution can act as strong antioxidants. Thanks to their ability to chelate metals as well as to donate hydrogen atoms they have capacity to scavenge free radicals. Their metal complexes are often more active in comparison with free ligands. They exhibit interesting biological properties, e.g. anticancer, antiphlogistic and antibacterial. The relationship between molecular structure and their biological properties was intensively studied using spectroscopic methods (UV-Vis, IR, Raman, NMR, ESI-MS). The aim of this paper is review on spectroscopic analyses of molecular structure and biological activity of hydroxyflavonol metal complexes.

  4. 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.

  5. 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.

  6. 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.

  7. 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 ...

  8. Data Analysis of Complex Systems

    Science.gov (United States)

    2011-06-01

    Based on Color Brown: Unbleached White: Bleached Colored: Bleached and dyed or pigmented Based on Usage Industrial: Packaging, wrapping...Based on Raw Material Wood: Contain fibers from wood Agricultural residue: Fibers from straw , grass or other annual plants Recycled: Recycle or...screening process, small contaminants such as plastic and adhesives are removed. The amount of debris that is removed from the system depends on the

  9. Systems biology strategies to study lipidomes in health and disease.

    Science.gov (United States)

    Hyötyläinen, Tuulia; Orešič, Matej

    2014-07-01

    Lipids are a diverse group of metabolites that have many key biological functions, acting as structural components of cell membranes, energy storage sources and intermediates in signaling pathways. Due to their importance lipids are under tight homeostatic control and exhibit spatial and dynamic complexity at multiple levels. It is thus not surprising that altered lipid metabolism plays important roles in the pathogenesis of most of the common diseases. Lipidomics emerged as a discipline which is dedicated to global study of lipidomes, including pathways and networks of lipids in biological systems. When studying the lipidomes at a systems level, one of the key challenges is how to address the lipid functionality at many physiological levels, from metabolic and signaling pathways to spatial systems such as cellular membranes and lipoprotein particles. Besides the better analytical techniques to study lipids, computational techniques have started to emerge which enable modeling of lipidomes in their spatial and dynamic context. Together, the recent methodological advances in lipidomics have a potential to open novel avenues for predictive and preventive medicine. This review focuses on progress in systems approaches to study lipids in health and disease, with specific emphasis on clinical applications.

  10. 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.

  11. 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.

  12. 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

  13. 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

  14. Hypoxia-inducible factor 3 biology: complexities and emerging themes.

    Science.gov (United States)

    Duan, Cunming

    2016-02-15

    The hypoxia-inducible factor (HIF) family has three distinct members in most vertebrates. All three HIFs consist of a unique and oxygen-labile α-subunit and a common and stable β-subunit. While HIF-1 and HIF-2 function as master regulators of the transcriptional response to hypoxia, much less is known about HIF-3. The HIF-3α gene gives rise to multiple HIF-3α variants due to the utilization of different promoters, different transcription initiation sites, and alternative splicing. These HIF-3α variants are expressed in different tissues, at different developmental stages, and are differentially regulated by hypoxia and other factors. Recent studies suggest that different HIF-3α variants have different and even opposite functions. There is strong evidence that full-length HIF-3α protein functions as an oxygen-regulated transcription activator and that it activates a unique transcriptional program in response to hypoxia. Many HIF-3α target genes have been identified. While some short HIF-3α variants act as dominant-negative regulators of HIF-1/2α actions, other HIF-3α variants can inhibit HIF-1/2α actions by competing for the common HIF-β. There are also a number of HIF-3α variants yet to be explored. Future studies of these naturally occurring HIF-3α variants will provide new and important insights into HIF biology and may lead to the development of new therapeutic strategies.

  15. A systems biology perspective of wine fermentations.

    Science.gov (United States)

    Pizarro, Francisco; Vargas, Felipe A; Agosin, Eduardo

    2007-11-01

    The yeast Saccharomyces cerevisiae is an important industrial microorganism. Nowadays, it is being used as a cell factory for the production of pharmaceuticals such as insulin, although this yeast has long been utilized in the bakery to raise dough, and in the production of alcoholic beverages, fermenting the sugars derived from rice, wheat, barley, corn and grape juice. S. cerevisiae has also been extensively used as a model eukaryotic system. In the last decade, genomic techniques have revealed important features of its molecular biology. For example, DNA array technologies are routinely used for determining gene expression levels in cells under different physiological conditions or environmental stimuli. Laboratory strains of S. cerevisiae are different from wine strains. For instance, laboratory yeasts are unable to completely transform all the sugar in the grape must into ethanol under winemaking conditions. In fact, standard culture conditions are usually very different from winemaking conditions, where multiple stresses occur simultaneously and sequentially throughout the fermentation. The response of wine yeasts to these stimuli differs in some aspects from laboratory strains, as suggested by the increasing number of studies in functional genomics being conducted on wine strains. In this paper we review the most recent applications of post-genomic techniques to understand yeast physiology in the wine industry. We also report recent advances in wine yeast strain improvement and propose a reference framework for integration of genomic information, bioinformatic tools and molecular biology techniques for cellular and metabolic engineering. Finally, we discuss the current state and future perspectives for using 'modern' biotechnology in the wine industry.

  16. 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

  17. Dynamical Systems and Control Theory Inspired by Molecular Biology

    Science.gov (United States)

    2014-10-02

    in both bacterial and eukaryotic signaling pathways. A common theme in the systems biology literature is that certain systems whose output variables...AFRL-OSR-VA-TR-2014-0282 DYNAMICAL SYSTEMS AND CONTROL THEORY INSPIRED BY MOLECULAR BIOLOGY Eduardo Sontag RUTGERS THE STATE UNIVERSITY OF NEW JERSEY...Standard Form 298 (Re . 8-98) v Prescribed by ANSI Std. Z39.18 DYNAMICAL SYSTEMS AND CONTROL THEORY INSPIRED BY MOLECULAR BIOLOGY AFOSR FA9550-11-1-0247

  18. 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.

  19. Exoproteomics: exploring the world around biological systems.

    Science.gov (United States)

    Armengaud, Jean; Christie-Oleza, Joseph A; Clair, Gérémy; Malard, Véronique; Duport, Catherine

    2012-10-01

    The term 'exoproteome' describes the protein content that can be found in the extracellular proximity of a given biological system. These proteins arise from cellular secretion, other protein export mechanisms or cell lysis, but only the most stable proteins in this environment will remain in abundance. It has been shown that these proteins reflect the physiological state of the cells in a given condition and are indicators of how living systems interact with their environments. High-throughput proteomic approaches based on a shotgun strategy, and high-resolution mass spectrometers, have modified the authors' view of exoproteomes. In the present review, the authors describe how these new approaches should be exploited to obtain the maximum useful information from a sample, whatever its origin. The methodologies used for studying secretion from model cell lines derived from eukaryotic, multicellular organisms, virulence determinants of pathogens and environmental bacteria and their relationships with their habitats are illustrated with several examples. The implication of such data, in terms of proteogenomics and the discovery of novel protein functions, is discussed.

  20. Programmable temperature control system for biological materials

    Science.gov (United States)

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

    1982-01-01

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

  1. 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.

  2. 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.

  3. 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 ...

  4. Optimal sensor configuration for complex systems

    DEFF Research Database (Denmark)

    Sadegh, Payman; Spall, J. C.

    1998-01-01

    Considers the problem of sensor configuration for complex systems. Our approach involves definition of an appropriate optimality criterion or performance measure, and description of an efficient and practical algorithm for achieving the optimality objective. The criterion for optimal sensor...

  5. Systems biology in the context of big data and networks.

    Science.gov (United States)

    Altaf-Ul-Amin, Md; Afendi, Farit Mochamad; Kiboi, Samuel Kuria; Kanaya, Shigehiko

    2014-01-01

    Science is going through two rapidly changing phenomena: one is the increasing capabilities of the computers and software tools from terabytes to petabytes and beyond, and the other is the advancement in high-throughput molecular biology producing piles of data related to genomes, transcriptomes, proteomes, metabolomes, interactomes, and so on. Biology has become a data intensive science and as a consequence biology and computer science have become complementary to each other bridged by other branches of science such as statistics, mathematics, physics, and chemistry. The combination of versatile knowledge has caused the advent of big-data biology, network biology, and other new branches of biology. Network biology for instance facilitates the system-level understanding of the cell or cellular components and subprocesses. It is often also referred to as systems biology. The purpose of this field is to understand organisms or cells as a whole at various levels of functions and mechanisms. Systems biology is now facing the challenges of analyzing big molecular biological data and huge biological networks. This review gives an overview of the progress in big-data biology, and data handling and also introduces some applications of networks and multivariate analysis in systems biology.

  6. 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.

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

    Directory of Open Access Journals (Sweden)

    P. Kavitha

    2016-01-01

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

  8. 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

  9. 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

    Various biological processes involve the conversion of energy into forms that are usable for chemical transformations and are quantum mechanical in nature. Such processes involve light absorption, excited electronic states formation, excitation energy transfer, electrons and protons tunnelling...... 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...... quantum physics and biology. In this paper we consider electron transfer in biological processes, from a theoretical view-point; namely in terms of quantum mechanical and semi-classical models. We systematically characterize the interactions between the moving electron and its biological environment...

  10. 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

  11. 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.

  12. Thermodynamic modeling of complex systems

    DEFF Research Database (Denmark)

    Liang, Xiaodong

    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......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....... Contrary to earlier theories, the oil is not only present on the surface, but also in great volumes both in the water column and on the seafloor, which indicates that we do not know enough about how oil behaves in water and interacts with it. Sonar detection is one of the most important and necessary...

  13. 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…

  14. Understanding health from a complex systems perspective.

    Science.gov (United States)

    Topolski, Stefan

    2009-08-01

    Doctors often use theory to inform medical practice. The current bio-psycho-social model of health may be advanced still further with theoretical rigour. Traditional fields of thermodynamics and newer fields of non-linear dynamics including chaos theory and complex systems science can inform our understanding of the complexity of human health, illness and disease. Commonly accepted aspects of human health may be projected as probabilities over time creating curves of human health potential. Maximum health may be represented by maximum functional complexity. Complexity's relationship to entropy and energy can produce a complex surface that better models the human experience of health and illness from birth to death. Such a potential health trajectory uniting complexity and entropy expands upon earlier theories of health while allowing for unusual predictions and the novel opportunity to test and validate this model of human health.

  15. 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.

  16. 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.

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

    Science.gov (United States)

    Edwards, Lindsay M; Thiele, Ines

    2013-03-22

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

  18. 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.

  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. 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.

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

    Science.gov (United States)

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

    2015-09-04

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

  2. 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.

  3. 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.

  4. 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.

  5. 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...

  6. 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...

  7. 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.

  8. 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.

  9. 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...

  10. Complex and adaptive dynamical systems a primer

    CERN Document Server

    Gros, Claudius

    2007-01-01

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

  11. 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...

  12. 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...

  13. 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

  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. 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....

  16. 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

  17. Hierarchical structure of biological systems: A bioengineering approach

    OpenAIRE

    Alcocer-Cuarón, Carlos; Rivera, Ana L; Castaño, Victor M.

    2013-01-01

    A general theory of biological systems, based on few fundamental propositions, allows a generalization of both Wierner and Berthalanffy approaches to theoretical biology. Here, a biological system is defined as a set of self-organized, differentiated elements that interact pair-wise through various networks and media, isolated from other sets by boundaries. Their relation to other systems can be described as a closed loop in a steady-state, which leads to a hierarchical structure and function...

  18. Radionuclide Imaging Technologies for Biological Systems

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-05-14

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

  19. 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.

  20. The apoptotic machinery as a biological complex system: analysis of its omics and evolution, identification of candidate genes for fourteen major types of cancer, and experimental validation in CML and neuroblastoma

    Directory of Open Access Journals (Sweden)

    Li Destri Giovanni

    2009-04-01

    Full Text Available Abstract Background Apoptosis is a critical biological phenomenon, executed under the guidance of the Apoptotic Machinery (AM, which allows the physiologic elimination of terminally differentiated, senescent or diseased cells. Because of its relevance to BioMedicine, we have sought to obtain a detailed characterization of AM Omics in Homo sapiens, namely its Genomics and Evolution, Transcriptomics, Proteomics, Interactomics, Oncogenomics, and Pharmacogenomics. Methods This project exploited the methodology commonly used in Computational Biology (i.e., mining of many omics databases of the web as well as the High Throughput biomolecular analytical techniques. Results In Homo sapiens AM is comprised of 342 protein-encoding genes (possessing either anti- or pro-apoptotic activity, or a regulatory function and 110 MIR-encoding genes targeting them: some have a critical role within the system (core AM nodes, others perform tissue-, pathway-, or disease-specific functions (peripheral AM nodes. By overlapping the cancer type-specific AM mutation map in the fourteen most frequent cancers in western societies (breast, colon, kidney, leukaemia, liver, lung, neuroblastoma, ovary, pancreas, prostate, skin, stomach, thyroid, and uterus to their transcriptome, proteome and interactome in the same tumour type, we have identified the most prominent AM molecular alterations within each class. The comparison of the fourteen mutated AM networks (both protein- as MIR-based has allowed us to pinpoint the hubs with a general and critical role in tumour development and, conversely, in cell physiology: in particular, we found that some of these had already been used as targets for pharmacological anticancer therapy. For a better understanding of the relationship between AM molecular alterations and pharmacological induction of apoptosis in cancer, we examined the expression of AM genes in K562 and SH-SY5Y after anticancer treatment. Conclusion We believe that our data

  1. Synthesis, spectral and thermal studies of some transition metal mixed ligand complexes: modeling of equilibrium composition and biological activity.

    Science.gov (United States)

    Neelakantan, M A; Sundaram, M; Nair, M Sivasankaran

    2011-09-01

    Several mixed ligand Ni(II), Cu(II) and Zn(II) complexes of 2-amino-3-hydroxypyridine (AHP) and imidazoles viz., imidazole (him), benzimidazole (bim), histamine (hist) and L-histidine (his) have been synthesized and characterized by elemental and spectral (vibrational, electronic, 1H NMR and EPR) data as well as by magnetic moment values. On the basis of elemental analysis and molar conductance values, all the complexes can be formulated as [MAB]Cl except histidine complexes as MAB. Thermogravimetric studies reveal the presence of coordinated water molecules in most of the complexes. From the magnetic measurements and electronic spectral data, octahedral structure was proposed for Ni(II) and Cu(II)-AHP-his, tetrahedral for Cu(II)-AHP-him/bim/hist, but square planar for the Cu(II)-AHP complex. The g∥/A∥ calculated supports tetrahedral environment around the Cu(II) in Cu(II)-AHP-him/bim/hist and distorted octahedral for Cu(II)-AHP-his complexes. The morphology of the reported metal complexes was investigated by scanning electron micrographs (SEM). The potentiometric study has been performed in aqueous solution at 37 °C and I=0.15 mol dm(-3) NaClO4. MABH, MAB and MAB2 species has been identified in the present systems. Proton dissociation constants of AHP and stability constants of metal complexes were determined using MINIQUAD-75. The most probable structure of the mixed ligand species is discussed based upon their stability constants. The in vitro biological activity of the complexes was tested against the Gram positive and Gram negative bacteria, fungus and yeast. The oxidative DNA cleavage studies of the complexes were performed using gel electrophoresis method. Cu(II) complexes have been found to promote DNA cleavage in presence of biological reductant such as ascorbate and oxidant like hydrogen peroxide.

  2. Synthesis, spectral and thermal studies of some transition metal mixed ligand complexes: Modeling of equilibrium composition and biological activity

    Science.gov (United States)

    Neelakantan, M. A.; Sundaram, M.; Nair, M. Sivasankaran

    2011-09-01

    Several mixed ligand Ni(II), Cu(II) and Zn(II) complexes of 2-amino-3-hydroxypyridine (AHP) and imidazoles viz., imidazole (him), benzimidazole (bim), histamine (hist) and L-histidine (his) have been synthesized and characterized by elemental and spectral (vibrational, electronic, 1H NMR and EPR) data as well as by magnetic moment values. On the basis of elemental analysis and molar conductance values, all the complexes can be formulated as [MAB]Cl except histidine complexes as MAB. Thermogravimetric studies reveal the presence of coordinated water molecules in most of the complexes. From the magnetic measurements and electronic spectral data, octahedral structure was proposed for Ni(II) and Cu(II)-AHP-his, tetrahedral for Cu(II)-AHP-him/bim/hist, but square planar for the Cu(II)-AHP complex. The g∥/ A∥ calculated supports tetrahedral environment around the Cu(II) in Cu(II)-AHP-him/bim/hist and distorted octahedral for Cu(II)-AHP-his complexes. The morphology of the reported metal complexes was investigated by scanning electron micrographs (SEM). The potentiometric study has been performed in aqueous solution at 37 °C and I = 0.15 mol dm -3 NaClO 4. MABH, MAB and MAB 2 species has been identified in the present systems. Proton dissociation constants of AHP and stability constants of metal complexes were determined using MINIQUAD-75. The most probable structure of the mixed ligand species is discussed based upon their stability constants. The in vitro biological activity of the complexes was tested against the Gram positive and Gram negative bacteria, fungus and yeast. The oxidative DNA cleavage studies of the complexes were performed using gel electrophoresis method. Cu(II) complexes have been found to promote DNA cleavage in presence of biological reductant such as ascorbate and oxidant like hydrogen peroxide.

  3. Toward metabolic engineering in the context of system biology and synthetic biology: advances and prospects.

    Science.gov (United States)

    Liu, Yanfeng; Shin, Hyun-dong; Li, Jianghua; Liu, Long

    2015-02-01

    Metabolic engineering facilitates the rational development of recombinant bacterial strains for metabolite overproduction. Building on enormous advances in system biology and synthetic biology, novel strategies have been established for multivariate optimization of metabolic networks in ensemble, spatial, and dynamic manners such as modular pathway engineering, compartmentalization metabolic engineering, and metabolic engineering guided by genome-scale metabolic models, in vitro reconstitution, and systems and synthetic biology. Herein, we summarize recent advances in novel metabolic engineering strategies. Combined with advancing kinetic models and synthetic biology tools, more efficient new strategies for improving cellular properties can be established and applied for industrially important biochemical production.

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

    Directory of Open Access Journals (Sweden)

    Banga Julio R

    2006-11-01

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

  5. 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...

  6. 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.

  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. Modeling complex work systems - method meets reality

    NARCIS (Netherlands)

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

    1996-01-01

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

  9. (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...

  10. Controlled ecological life support system - biological problems

    Science.gov (United States)

    Moore, B., III (Editor); Macelroy, R. D. (Editor)

    1982-01-01

    The general processes and controls associated with two distinct experimental paradigms are examined. Specific areas for research related to biotic production (food production) and biotic decomposition (waste management) are explored. The workshop discussions were directed toward Elemental cycles and the biological factors that affect the transformations of nutrients into food, of food material into waste, and of waste into nutrients were discussed. To focus on biological issues, the discussion assumed that (1) food production would be by biological means (thus excluding chemical synthesis), (2) energy would not be a limiting factor, and (3) engineering capacity for composition and leak rate would be adequate.

  11. 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.

  12. 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.

  13. 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.

  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. 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.

  16. 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.

  17. An Efficient Machine Learning Approach To Low-Complexity Filtering In Biological Sequences

    Energy Technology Data Exchange (ETDEWEB)

    Barber, Christopher A; Oehmen, Christopher S

    2012-06-09

    Biological sequences contain low-complexity regions (LCRs) which produce superfluous matches in homology searches, and lead to slow execution of database search algorithms such as BLAST. These regions are efficiently identified by low-complexity filtering algorithms such as SDUST and SEG, which are included in the BLAST tool-suite. These algorithms target differing notions of complexity, so an algorithm which combines their sensitivities is pursued. A variety of features are derived from these algorithms, as well as a new filtering algorithm based on Lempel-Ziv complexity. Artificial sequences with known LCRs are used to train and evaluate an SVM classifier, which significantly outperforms the standalone filtering algorithms.

  18. The self as a complex dynamic system

    Directory of Open Access Journals (Sweden)

    Sarah Mercer

    2011-04-01

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

  19. 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

  20. 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.

  1. 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.

  2. Sender–receiver systems and applying information theory for quantitative synthetic biology

    Science.gov (United States)

    Barcena Menendez, Diego; Senthivel, Vivek Raj; Isalan, Mark

    2015-01-01

    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. PMID:25282688

  3. Complex Features in Lotka-Volterra Systems with Behavioral Adaptation

    Science.gov (United States)

    Tebaldi, Claudio; Lacitignola, Deborah

    Lotka-Volterra systems have played a fundamental role for mathematical modelling in many branches of theoretical biology and proved to describe, at least qualitatively, the essential features of many phenomena, see for example Murray [Murray 2002]. Furthermore models of that kind have been considered successfully also in quite different and less mathematically formalized context: Goodwin' s model of economic growth cycles [Goodwin 1967] and urban dynamics [Dendrinos 1992] are only two of a number of examples. Such systems can certainly be defined as complex ones and in fact the aim of modelling was essentially to clarify mechanims rather than to provide actual precise simulations and predictions. With regards to complex systems, we recall that one of their main feature, no matter of the specific definition one has in mind, is adaptation, i. e. the ability to adjust.

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

    Science.gov (United States)

    Wu, Hao; Tremaroli, Valentina; Bäckhed, Fredrik

    2015-12-01

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

  5. 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.

  6. Systems biology studies of Aspergilli - from sequence to science

    DEFF Research Database (Denmark)

    Andersen, Mikael Rørdam

    2008-01-01

    The recent dawn of the new biological mindset called systems biology has put forth a new way of analyzing and understanding biology. Carried by the notion that no element of a cell is an island, systems biology takes a holistic approach, and attempts to understand life as systems that have co...... a few. The recent publication of the genome sequences of several filamentous fungi of the Aspergillus species (Aspergilli), has, along with the accumulation of years of reductionist studies, been a catalyst for the application of systems biology to this interesting group of fungi. Among the genome...... biology approach has been applied to a wide range of issues. These tools include the compilation of data from literature on A. niger enzymes to form a re-constructed metabolic network and model of metabolism, allowing assessment of the industrial production potential of metabolites from this fungus. Based...

  7. Complexity of some problems concerning L systems

    DEFF Research Database (Denmark)

    Jones, Neil D.; Skyum, Sven

    1979-01-01

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

  8. 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.

  9. Systems biology studies of Aspergilli - from sequence to science

    OpenAIRE

    Andersen, Mikael Rørdam; Nielsen, Jens; Nielsen, Michael Lynge

    2008-01-01

    The recent dawn of the new biological mindset called systems biology has put forth a new way of analyzing and understanding biology. Carried by the notion that no element of a cell is an island, systems biology takes a holistic approach, and attempts to understand life as systems that have co-evolved and not as a haphazardly compiled list of parts. This has been made possible by the socalled genomic revolution — the sequencing of the genomic DNA of a rapidly increasing number of organisms — a...

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. Meat science: From proteomics to integrated omics towards system biology.

    Science.gov (United States)

    D'Alessandro, Angelo; Zolla, Lello

    2013-01-14

    Since the main ultimate goal of farm animal raising is the production of proteins for human consumption, research tools to investigate proteins play a major role in farm animal and meat science. Indeed, proteomics has been applied to the field of farm animal science to monitor in vivo performances of livestock animals (growth performances, fertility, milk quality etc.), but also to further our understanding of the molecular processes at the basis of meat quality, which are largely dependent on the post mortem biochemistry of the muscle, often in a species-specific way. Post mortem alterations to the muscle proteome reflect the biological complexity of the process of "muscle to meat conversion," a process that, despite decades of advancements, is all but fully understood. This is mainly due to the enormous amounts of variables affecting meat tenderness per se, including biological factors, such as animal species, breed specific-characteristic, muscle under investigation. However, it is rapidly emerging that the tender meat phenotype is not only tied to genetics (livestock breeding selection), but also to extrinsic factors, such as the rearing environment, feeding conditions, physical activity, administration of hormonal growth promotants, pre-slaughter handling and stress, post mortem handling. From this intricate scenario, biochemical approaches and systems-wide integrated investigations (metabolomics, transcriptomics, interactomics, phosphoproteomics, mathematical modeling), which have emerged as complementary tools to proteomics, have helped establishing a few milestones in our understanding of the events leading from muscle to meat conversion. The growing integration of omics disciplines in the field of systems biology will soon contribute to take further steps forward.

  15. Global sensitivity and identifiability implications in systems biology

    OpenAIRE

    Dobre, Simona; Bastogne, Thierry; Richard, Alain

    2010-01-01

    International audience; In systems biology, a common approach to model biological processes is to use large systems of differential equations.The associated parameter estimation problem requires to prior handle identifiability and sensitivity issues in a practical biological framework. The lack of method to assess global practical identifiability has leaded us to analyze and establish bridges between global sensitivity and identifiability measures. Specifically, we are interested in deriving ...

  16. Complex system modelling for veterinary epidemiology.

    Science.gov (United States)

    Lanzas, Cristina; Chen, Shi

    2015-02-01

    The use of mathematical models has a long tradition in infectious disease epidemiology. The nonlinear dynamics and complexity of pathogen transmission pose challenges in understanding its key determinants, in identifying critical points, and designing effective mitigation strategies. Mathematical modelling provides tools to explicitly represent the variability, interconnectedness, and complexity of systems, and has contributed to numerous insights and theoretical advances in disease transmission, as well as to changes in public policy, health practice, and management. In recent years, our modelling toolbox has considerably expanded due to the advancements in computing power and the need to model novel data generated by technologies such as proximity loggers and global positioning systems. In this review, we discuss the principles, advantages, and challenges associated with the most recent modelling approaches used in systems science, the interdisciplinary study of complex systems, including agent-based, network and compartmental modelling. Agent-based modelling is a powerful simulation technique that considers the individual behaviours of system components by defining a set of rules that govern how individuals ("agents") within given populations interact with one another and the environment. Agent-based models have become a recent popular choice in epidemiology to model hierarchical systems and address complex spatio-temporal dynamics because of their ability to integrate multiple scales and datasets.

  17. 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...

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

    Directory of Open Access Journals (Sweden)

    Lenka Kucková

    2015-01-01

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

  19. 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.

  20. 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...